Demonstration of the analgesic efficacy and dose-response of acetylsalicylic acid with pseudoephedrine.

PubMed

Schachtel, Bernard P; Voelker, Michael; Sanner, Kathleen M; Gagney, Diana; Bey, Mary; Schachtel, Emily J; Becka, Michael

2010-12-01

To determine acute analgesia by acetylsalicylic acid (ASA) when combined with pseudoephedrine (PSE) in patients with upper respiratory tract infection (URTI), we used the sore throat pain model to measure single-dose effects of ASA 500 mg/PSE 30 mg, ASA 1000 mg/PSE 60 mg, and acetaminophen (APAP) 1000 mg/PSE 60 mg (serving as a positive control). Under double-blind, randomized, placebo-controlled conditions, 640 adult patients with confirmed acute pharyngitis and rhinosinusitis associated with URTI rated throat pain intensity and relief at intervals over 6 hours. Efficacy was demonstrated for both doses of ASA/PSE compared with placebo for all end points, including total pain relief and summed pain intensity differences, beginning at 20 minutes on both scales (all P < .05), and the efficacy of APAP/PSE compared with placebo was confirmed (P < .01). Greater differences in pain relief and intensity were also demonstrated between the higher and lower doses of ASA/PSE (P < .05), in particular, among 329 patients with severe pain, as well as between ASA 1000 mg/PSE 60 mg and APAP 1000 mg/PSE 60 mg (P < .05). No serious adverse events were reported. This study demonstrates that ASA is a well-tolerated and effective analgesic in 500- and 1000-mg doses when combined with pseudoephedrine.

Clinical efficacy of moxifloxacin versus comparator therapies for community-acquired pneumonia caused by Legionella spp.

PubMed

Garau, J; Fritsch, A; Arvis, P; Read, R C

2010-08-01

The aim of this study was to compare outcomes for patients with community-acquired pneumonia (CAP) caused by Legionella spp. following treatment with moxifloxacin or a range of comparator antimicrobial agents. Data were pooled from four sequential I.V./P.O. trials of moxifloxacin in the treatment of CAP. Comparators were ceftriaxone +/- erythromycin, amoxicillin/clavulanate +/- clarithromycin, trovafloxacin, levofloxacin, or ceftriaxone + levofloxacin. Legionella infection was diagnosed by culture, urine antigen testing and/or serology. Clinical success rates for the efficacy-valid (per protocol) populations were recorded at the test-of-cure visit (5-30 days post-therapy). Severity of CAP was determined using the modified American Thoracic Society criteria.Of 1786 efficacy-valid patients, 33 (1.8%) had documented infection with Legionella spp. (moxifloxacin: n=13; comparator: n=20). Of these, 30 cases were identified by serology and/or urine antigen detection and 3 by respiratory culture. The success rate of moxifloxacin vs. comparator therapy was 92.3% vs. 80.0% for the I.V./P.O. trials.Sequential (I.V./P.O.) moxifloxacin demonstrated clinical efficacy that was at least as good as that of comparator treatments for the treatment of CAP due to Legionella.

A Comparative Analysis of Perceptions of Pharmacy Students’ Stress and Stressors across Two Multicampus Universities

PubMed Central

Gaither, Caroline A.; Crawford, Stephanie Y.; Tieman, Jami

2016-01-01

Objective. To compare perceived levels of stress, stressors, and academic self-efficacy among students at two multicampus colleges of pharmacy. Methods. A survey instrument using previously validated items was developed and administered to first-year, second-year, and third-year pharmacy students at two universities with multiple campuses in spring 2013. Results. Eight hundred twenty students out of 1115 responded (73.5% response rate). Institutional differences were found in perceived student stress levels, self-efficacy, and stress-related causes. An interaction effect was demonstrated between institution and campus type (main or branch) for perceived stress and self-efficacy although campus type alone did not demonstrate a direct effect. Institutional and campus differences existed in awareness of campus counseling services, as did a few differences in coping methods. Conclusion. Stress measures were similar for pharmacy students at main or branch campuses. Institutional differences in student stress might be explained by instructional methods, campus support services, institutional climate, and nonuniversity factors. PMID:27402985

A Comparative Analysis of Perceptions of Pharmacy Students' Stress and Stressors across Two Multicampus Universities.

PubMed

Awé, Clara; Gaither, Caroline A; Crawford, Stephanie Y; Tieman, Jami

2016-06-25

Objective. To compare perceived levels of stress, stressors, and academic self-efficacy among students at two multicampus colleges of pharmacy. Methods. A survey instrument using previously validated items was developed and administered to first-year, second-year, and third-year pharmacy students at two universities with multiple campuses in spring 2013. Results. Eight hundred twenty students out of 1115 responded (73.5% response rate). Institutional differences were found in perceived student stress levels, self-efficacy, and stress-related causes. An interaction effect was demonstrated between institution and campus type (main or branch) for perceived stress and self-efficacy although campus type alone did not demonstrate a direct effect. Institutional and campus differences existed in awareness of campus counseling services, as did a few differences in coping methods. Conclusion. Stress measures were similar for pharmacy students at main or branch campuses. Institutional differences in student stress might be explained by instructional methods, campus support services, institutional climate, and nonuniversity factors.

Hyperhidrosis: Anatomy, Pathophysiology and Treatment with Emphasis on the Role of Botulinum Toxins

PubMed Central

Lakraj, Amanda-Amrita D.; Moghimi, Narges; Jabbari, Bahman

2013-01-01

Clinical features, anatomy and physiology of hyperhidrosis are presented with a review of the world literature on treatment. Level of drug efficacy is defined according to the guidelines of the American Academy of Neurology. Topical agents (glycopyrrolate and methylsulfate) are evidence level B (probably effective). Oral agents (oxybutynin and methantheline bromide) are also level B. In a total of 831 patients, 1 class I and 2 class II blinded studies showed level B efficacy of OnabotulinumtoxinA (A/Ona), while 1 class I and 1 class II study also demonstrated level B efficacy of AbobotulinumtoxinA (A/Abo) in axillary hyperhidrosis (AH), collectively depicting Level A evidence (established) for botulinumtoxinA (BoNT-A). In a comparator study, A/Ona and A/Inco toxins demonstrated comparable efficacy in AH. For IncobotulinumtoxinA (A/Inco) no placebo controlled studies exist; thus, efficacy is Level C (possibly effective) based solely on the aforementioned class II comparator study. For RimabotulinumtoxinB (B/Rima), one class III study has suggested Level U efficacy (insufficient data). In palmar hyperhidrosis (PH), there are 3 class II studies for A/Ona and 2 for A/Abo (individually and collectively level B for BoNT-A) and no blinded study for A/Inco (level U). For B/Rima the level of evidence is C (possibly effective) based on 1 class II study. Botulinum toxins (BoNT) provide a long lasting effect of 3–9 months after one injection session. Studies on BoNT-A iontophoresis are emerging (2 class II studies; level B); however, data on duration and frequency of application is inconsistent. PMID:23612753

Application of Volatile Antifungal Plant Essential Oils for Controlling Pepper Fruit Anthracnose by Colletotrichum gloeosporioides

PubMed Central

Hong, Jeum Kyu; Yang, Hye Ji; Jung, Heesoo; Yoon, Dong June; Sang, Mee Kyung; Jeun, Yong-Chull

2015-01-01

Anthracnose caused by Colletotrichum gloeosporioides has been destructive during pepper fruit production in outdoor fields in Korea. In vitro antifungal activities of 15 different plant essential oils or its components were evaluated during conidial germination and mycelial growth of C. gloeosporioides. In vitro conidial germination was most drastically inhibited by vapour treatments with carvacrol, cinnamon oil, trans-cinnamaldehyde, citral, p-cymene and linalool. Inhibition of the mycelial growth by indirect vapour treatment with essential oils was also demonstrated compared with untreated control. Carvacrol, cinnamon oil, trans-cinnamaldehyde, citral and eugenol were among the most inhibitory plant essential oils by the indirect antifungal efficacies. Plant protection efficacies of the plant essential oils were demonstrated by reduced lesion diameter on the C. gloeosporioides-inoculated immature green pepper fruits compared to the inoculated control fruits without any plant essential oil treatment. In planta test showed that all plant essential oils tested in this study demonstrated plant protection efficacies against pepper fruit anthracnose with similar levels. Thus, application of different plant essential oils can be used for eco-friendly disease management of anthracnose during pepper fruit production. PMID:26361475

Does cognitive reappraisal reduce anxiety? A daily diary study of a micro-intervention with individuals with high social anxiety.

PubMed

Kivity, Yogev; Huppert, Jonathan D

2016-03-01

To examine emotion regulation (ER) among individuals with high (HSA) and low social anxiety (LSA) and the effects of 1 week of practiced cognitive reappraisal using self-report, daily diary measures and lab tasks. HSAs received reappraisal (HSA-R; n = 43) or monitoring (HSA-M; n = 40) instructions. LSAs received monitoring instructions (LSA-M; n = 41). Self-report measures of social anxiety and ER, and a lab task of reappraisal were administered at baseline and after 1 week. Daily diaries of anxiety and ER were also collected. At baseline, HSAs compared with LSAs reported lower self-efficacy of reappraisal and higher frequency and self-efficacy of suppression, but no differences emerged in the reappraisal task. Following the intervention, the HSA-R compared with the HSA-M reported lower symptom severity, greater self-efficacy of reappraisal but equal daily anxiety. HSA-R used reappraisal mostly combined with suppression (74.76% of situations). Post hoc analyses demonstrated that clinical diagnosis, but not severity, moderated the intervention effect. The results demonstrate the efficacy of a short intervention in social anxiety, and provide additional areas of research for improving its treatment. (c) 2016 APA, all rights reserved).

Titanium-nitride-oxide-coated coronary stents: insights from the available evidence.

PubMed

Karjalainen, Pasi P; Nammas, Wail

2017-06-01

Coating of stent surface with a biocompatible material is suggested to improve stent safety profile. A proprietary process was developed to coat titanium-nitride-oxide on the stent surface, based on plasma technology that uses the nano-synthesis of gas and metal. Preclinical in vitro and in vivo investigation confirmed blood compatibility of titanium (nitride-) oxide films. Titanium-nitride-oxide-coated stents demonstrated a better angiographic outcome, compared with bare-metal stents at mid-term follow-up; however, they failed to achieve non-inferiority for angiographic outcome versus second-generation drug-eluting stents. Observational studies showed adequate clinical outcome at mid-term follow-up. Non-randomized studies showed an outcome of titanium-nitride-oxide-coated stents comparable to - or better than - first-generation drug-eluting stents at long-term follow-up. Two randomized controlled trials demonstrated comparable efficacy outcome, and a better safety outcome of titanium-nitride-oxide-coated stents versus drug-eluting stents at long-term follow-up. Evaluation by optical coherence tomography at mid-term follow-up revealed better neointimal strut coverage associated with titanium-nitride-oxide-coated stents versus drug-eluting stents; yet, neointimal hyperplasia thickness was greater. Key messages Stents coated with titanium-nitride-oxide demonstrated biocompatibility in preclinical studies: they inhibit platelet and fibrin deposition, and reduce neointimal growth. In observational and non-randomized studies, titanium-nitride-oxide-coated stents were associated with adequate safety and efficacy outcome. In randomized trials of patients with acute coronary syndrome, titanium-nitride-oxide-coated stents were associated with a better safety outcome, compared with drug-eluting stents; efficacy outcome was comparable.

Quantifying the Impact of Natural Immunity on Rotavirus Vaccine Efficacy Estimates: A Clinical Trial in Dhaka, Bangladesh (PROVIDE) and a Simulation Study.

PubMed

Rogawski, Elizabeth T; Platts-Mills, James A; Colgate, E Ross; Haque, Rashidul; Zaman, K; Petri, William A; Kirkpatrick, Beth D

2018-03-05

The low efficacy of rotavirus vaccines in clinical trials performed in low-resource settings may be partially explained by acquired immunity from natural exposure, especially in settings with high disease incidence. In a clinical trial of monovalent rotavirus vaccine in Bangladesh, we compared the original per-protocol efficacy estimate to efficacy derived from a recurrent events survival model in which children were considered naturally exposed and potentially immune after their first rotavirus diarrhea (RVD) episode. We then simulated trial cohorts to estimate the expected impact of prior exposure on efficacy estimates for varying rotavirus incidence rates and vaccine efficacies. Accounting for natural immunity increased the per-protocol vaccine efficacy estimate against severe RVD from 63.1% (95% confidence interval [CI], 33.0%-79.7%) to 70.2% (95% CI, 44.5%-84.0%) in the postvaccination period, and original year 2 efficacy was underestimated by 14%. The simulations demonstrated that this expected impact increases linearly with RVD incidence, will be greatest for vaccine efficacies near 50%, and can reach 20% in settings with high incidence and low efficacy. High rotavirus incidence leads to predictably lower vaccine efficacy estimates due to the acquisition of natural immunity in unvaccinated children, and this phenomenon should be considered when comparing efficacy estimates across settings. NCT01375647.

Efficacy of Pharmacist Based Diabetes Educational Interventions on Clinical Outcomes of Adults With Type 2 Diabetes Mellitus: A Network Meta-Analysis.

PubMed

Bukhsh, Allah; Khan, Tahir M; Lee, Shaun W H; Lee, Learn-Han; Chan, Kok-Gan; Goh, Bey-Hing

2018-01-01

Background: Comparative efficacy of different pharmacist based interventions on glycemic control of type 2 diabetes patients is unclear. This review aimed to evaluate and compare the efficacy of different pharmacist based interventions on clinical outcomes of type 2 diabetes patients. Methods: A systematic search was conducted across five databases from date of database inception to September 2017. All randomized clinical trials evaluating the efficacy of pharmacist based interventions on type 2 diabetes patients were included for network meta-analysis (NMA). The protocol is available with PROSPERO (CRD42017078854). Results: A total of 43 studies, involving 6259 type 2 diabetes patients, were included. NMA demonstrated that all interventions significantly lowered glycosylated hemoglobin (HbA1c) levels compared to usual care, but there was no statistical evidence from this study that one intervention was significantly better than the other for reducing HbA1c levels. Pharmacist based diabetes education plus pharmaceutical care showed maximum efficacy for reducing HbA1c levels [-0.86, 95% CI -0.983, -0.727; p < 0.001]. Pharmacist based diabetes education plus pharmaceutical care was observed to be statistically significant in lowering levels of systolic blood pressure [-4.94; 95%CI -8.65, -1.23] and triglycerides levels [-0.26, 95%CI -0.51, -0.01], as compared to the interventions which involved diabetes education by pharmacist, and for body mass index (BMI) [-0.57; 95%CI -1.25, -0.12] in comparison to diabetes education by health care team involving pharmacist as member. Conclusion: The findings of this review demonstrate that all interventions had a significantly positive effect on HbA1c, but there was no statistical evidence from this study that one intervention was significantly better than the other for achieving glycemic control.Pharmacist based diabetes education plus pharmaceutical care showed maximum efficacy on HbA1c and rest of the clinical outcomes.

Online diabetes self-management program: a randomized study.

PubMed

Lorig, Kate; Ritter, Philip L; Laurent, Diana D; Plant, Kathryn; Green, Maurice; Jernigan, Valarie Blue Bird; Case, Siobhan

2010-06-01

We hypothesized that people with type 2 diabetes in an online diabetes self-management program, compared with usual-care control subjects, would 1) demonstrate reduced A1C at 6 and 18 months, 2) have fewer symptoms, 3) demonstrate increased exercise, and 4) have improved self-efficacy and patient activation. In addition, participants randomized to listserve reinforcement would have better 18-month outcomes than participants receiving no reinforcement. A total of 761 participants were randomized to 1) the program, 2) the program with e-mail reinforcement, or 3) were usual-care control subjects (no treatment). This sample included 110 American Indians/Alaska Natives (AI/ANs). Analyses of covariance models were used at the 6- and 18-month follow-up to compare groups. At 6 months, A1C, patient activation, and self-efficacy were improved for program participants compared with usual care control subjects (P < 0.05). There were no changes in other health or behavioral indicators. The AI/AN program participants demonstrated improvements in health distress and activity limitation compared with usual-care control subjects. The subgroup with initial A1C >7% demonstrated stronger improvement in A1C (P = 0.01). At 18 months, self-efficacy and patient activation were improved for program participants. A1C was not measured. Reinforcement showed no improvement. An online diabetes self-management program is acceptable for people with type 2 diabetes. Although the results were mixed they suggest 1) that the program may have beneficial effects in reducing A1C, 2) AI/AN populations can be engaged in and benefit from online interventions, and 3) our follow-up reinforcement appeared to have no value.

Impact of pediatric exclusivity on drug labeling and demonstrations of efficacy.

PubMed

Wharton, Gerold T; Murphy, M Dianne; Avant, Debbie; Goldsmith, John V; Chai, Grace; Rodriguez, William J; Eisenstein, Eric L

2014-08-01

Besides vaccines and otitis media medicines, most products prescribed for children have not been studied in the pediatric population. To remedy this, Congress enacted legislation in 1997, known as pediatric exclusivity (PE), which provides 6 months of additional market protection to drug sponsors in exchange for studying their products in children. We reviewed requests for pediatric studies and subsequent labeling for drugs granted PE from 1998 through 2012. Regression analysis estimates the probability of demonstrating efficacy in PE trials. Variables include therapeutic group, year of exclusivity, product sales, initiation process, and small disease population. From 1998 through 2012, the US Food and Drug Administration issued 401 pediatric study requests. For 189 drugs, studies were completed and granted exclusivity. A total of 173 drugs (92%) received new pediatric labeling, with 108 (57%) receiving a new or expanded pediatric indication. Three drugs had non-efficacy trials. Efficacy was not established for 78 drugs. Oncology, cardiovascular, and endocrine drugs were less likely to demonstrate efficacy (P < .01) compared with gastrointestinal and pain/anesthesia drugs. Drugs studied later in the program were less likely to demonstrate efficacy (P < .05). Sales, initiation process, and small disease population were not significant predictors. Most drugs (173; 92%) granted exclusivity added pediatric information to their labeling as a result of PE, with 108 (57%) receiving a new or expanded pediatric indication. Therapeutic area and year of exclusivity influenced the likelihood of obtaining a pediatric indication. Positive and negative outcomes continue to inform the construct of future pediatric trials. Copyright © 2014 by the American Academy of Pediatrics.

A comparative clinical study evaluating stain removal efficacy of a new sensitivity whitening dentifrice compared to commercially available whitening dentifrices.

PubMed

Hughes, Nathan; Maggio, Brenda; Sufi, Farzana; Mason, Stephen; Kleber, Carl J

2009-01-01

To assess the extrinsic stain removal efficacy of a new sensitivity dentifrice containing sodium tripolyphosphate (STP) to marketed whitening toothpastes after six weeks of product use. This was a single-center, double-blind, stratified, six-week clinical study comparing the reduction in stain area and intensity of Sensodyne Extra Whitening to Crest Maximum Strength Sensitivity Protection Whitening plus Scope and Colgate Tartar Control Plus Whitening Mint dentifrice, as measured by MacPherson's Modification of the Lobene Stain Index (MMLSI) in a forced stain model. Two-hundred and ninety-five subjects completed the study. Tooth stain MMSLI scores showed significant differences between Sensodyne and Crest dentifrices in favor of Sensodyne for all surface sites (p = 0.014), and individually for facial (p = 0.023), lingual (p = 0.027), and interproximal (p = 0.014) surfaces. No significant statistical differences between Sensodyne and Colgate dentifrices were observed for any of the surfaces. Results from this stain removal clinical study demonstrate significant extrinsic stain removal efficacy for all dentifrices relative to baseline. Significant differences between the two marketed sensitivity whitening dentifrices were demonstrated in favor of the new Sensodyne Sensitivity Whitening dentifrice.

Ziprasidone and amisulpride effectively treat negative symptoms of schizophrenia: results of a 12-week, double-blind study.

PubMed

Olié, Jean-Pierre; Spina, Edoardo; Murray, Stephen; Yang, Ruoyong

2006-05-01

We compared the efficacy of ziprasidone and amisulpride in the treatment of negative symptoms and overall psychopathology in subjects who had chronic schizophrenia with predominantly negative symptoms. This multicentre, 12-week, double-blind study randomly assigned subjects with predominantly negative-symptom schizophrenia [i.e. Positive and Negative Syndrome Scale (PANSS) Negative Subscale score >or=6 points greater than Positive Subscale score] to ziprasidone (40-80 mg b.i.d.; n=60) or amisulpride (50-100 mg b.i.d.; n=63). The primary efficacy variable was the change from baseline in PANSS Negative Subscale score. Secondary efficacy variables included change in scores for PANSS Total, Global Assessment of Functioning, Brief Psychiatric Rating Scale derived from PANSS Total and Core, Clinical Global Impression (CGI)-Severity and CGI-Improvement. For the change in PANSS Negative Subscale score, a ratio to assess the equivalence of the treatment groups was calculated from the least squares mean changes from baseline, with equivalence claimed if the lower limit of the 95% confidence interval of the ratio exceeded 0.60. Mean daily dose, adjusted for differential numbers of subjects and differential days between visits, was 118.0 mg for ziprasidone and 144.7 mg for amisulpride. Mean PANSS Negative Subscale scores improved over the 12-week treatment period for intent-to-treat subjects, evaluable subjects (subjects with >or=4 weeks of double-blind treatment and no protocol deviations) and completers in both treatment groups. Ziprasidone demonstrated efficacy comparable to amisulpride in improving negative symptoms and global psychopathology. The groups demonstrated comparable improvements in secondary efficacy variables. Both agents were generally well tolerated, with comparably low incidences of movement disorders. In subjects with negative symptom-prominent schizophrenia, ziprasidone in mean daily doses of 118 mg was equivalent to amisulpride in mean daily doses of 148 mg in ameliorating negative symptoms and comparable in improving overall psychopathology and global illness severity.

The relationships of information efficacy and media literacy skills to knowledge and self-efficacy for health-related decision making.

PubMed

Austin, Erica Weintraub; Pinkleton, Bruce E; Austin, Bruce W; Van de Vord, Rebecca

2012-01-01

To compare the extent to which information efficacy (confidence for acquiring useful information) and media literacy skills predict knowledge and self-efficacy for preventing or treating the health threat of influenza. A random-sample survey of 1,379 residential students enrolled at a northwestern public university was conducted in fall 2009. Students accessed an Internet survey through a link provided in an e-mail. Students who self-diagnosed correctly demonstrated higher levels of media literacy skills than those who self-diagnosed incorrectly. Among those who self-diagnosed incorrectly, the only predictor of knowledge was accessibility of information sources; low accessibility was associated with reduced knowledge. Information efficacy predicted self-efficacy for both groups. The results illustrate the limitations of information efficacy in the absence of media literacy skills. To decrease health risks, college health practitioners should promote media literacy while also ensuring easy access to high-quality information.

Comparative efficacy of disease-modifying therapies for patients with relapsing remitting multiple sclerosis: Systematic review and network meta-analysis.

PubMed

Fogarty, Emer; Schmitz, Susanne; Tubridy, Niall; Walsh, Cathal; Barry, Michael

2016-09-01

Randomised studies have demonstrated efficacy of disease-modifying therapies in relapsing remitting multiple sclerosis (RRMS). However it is unclear how the magnitude of treatment efficacy varies across all currently available therapies. To perform a systematic review and network meta-analysis to evaluate the comparative efficacy of available therapies in reducing relapses and disability progression in RRMS. A systematic review identified 28 randomised, placebo-controlled and direct comparative trials. A network meta-analysis was conducted within a Bayesian framework to estimate comparative annualised relapse rates (ARR) and risks of disability progression (defined by both a 3-month, and 6-month confirmation interval). Potential sources of treatment-effect modification from study-level covariates and baseline risk were evaluated through meta-regression methods. The Surface Under the Cumulative RAnking curve (SUCRA) method was used to provide a ranking of treatments for each outcome. The magnitude of ARR reduction varied between 15-36% for all interferon-beta products, glatiramer acetate and teriflunomide, and from 50 to 69% for alemtuzumab, dimethyl fumarate, fingolimod and natalizumab. The risk of disability progression (3-month) was reduced by 19-28% with interferon-beta products, glatiramer acetate, fingolimod and teriflunomide, by 38-45% for pegylated interferon-beta, dimethyl fumarate and natalizumab and by 68% with alemtuzumab. Broadly similar estimates for the risk of disability progression (6-month), with the exception of interferon-beta-1b 250mcg which was much more efficacious based on this definition. Alemtuzumab and natalizumab had the highest SUCRA scores (97% and 95% respectively) for ARR, while ranking for disability progression varied depending on the definition of the outcome. Interferon-beta-1b 250mcg ranked among the most efficacious treatments for disability progression confirmed after six months (92%) and among the least efficacious when the outcome was confirmed after three months (30%). No significant modification of relative treatment effects was identified from study-level covariates or baseline risk. Compared with placebo, clear reductions in ARR with disease-modifying therapies were accompanied by more uncertain changes in disability progression. The magnitude of the reduction and the uncertainty associated with treatment effects varied between DMTs. While natalizumab and alemtuzumab demonstrated consistently high ranking across outcomes, with older interferon-beta and glatiramer acetate products ranking lowest, variation in disability progression definitions lead to variation in the relative ranking of treatments. Rigorously conducted comparative studies are required to fully evaluate the comparative treatment effects of disease modifying therapies for RRMS. Copyright © 2016 Elsevier B.V. All rights reserved.

A double-blind, randomized, placebo/active controlled crossover evaluation of the efficacy and safety of Ritalin ® LA in children with attention-deficit/hyperactivity disorder in a laboratory classroom setting.

PubMed

Schulz, Eberhard; Fleischhaker, Christian; Hennighausen, Klaus; Heiser, Philip; Oehler, Klaus-Uwe; Linder, Martin; Haessler, Frank; Huss, Michael; Warnke, Andreas; Schmidt, Martin; Schulte-Markworth, Michael; Sieder, Christian; Klatt, Jan; Tracik, Ferenc

2010-10-01

The primary objective of this study was to demonstrate efficacy of Ritalin(®) LA 20 mg by showing superiority to placebo and noninferiority to Medikinet(®) Retard in a laboratory classroom setting. Secondary objectives included safety/tolerability and further efficacy parameters. A total of 147 children with attention-deficit/hyperactivity disorder (ADHD) diagnosed by the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS) and aged 6-14 (81% males) and known to be methylphenidate (MPH) responders were enrolled in this multicenter, double-blind, randomized, placebo/active-controlled, three-period (7 days each) crossover study. The Swanson, Kotlin, Agler, M-Flynn, and Pelham (SKAMP) scale was used for efficacy ratings. The mean of SKAMP Combined ratings performed at 10:30 a.m., at 12:00 a.m., and at 1:30 p.m. was defined as the primary parameter. In all, 146 patients completed all treatment periods. Intensity and frequency of adverse events were comparable between the two formulations. Ritalin(®) LA demonstrated superiority compared to placebo (p<0.0001). The observed difference in the SKAMP scores between Ritalin(®) LA and Medikinet(®) Retard between the hours 1.5 until 4.5 did not exceed the noninferiority margin (p=0.0003); therefore, the difference is regarded as not clinically relevant. Similar results were obtained for the secondary efficacy variables. Ritalin(®) LA is an efficacious, well-tolerated treatment option for children aged 6-14 with ADHD.

Alginate-immobilized bentonite clay: adsorption efficacy and reusability for Cu(II) removal from aqueous solution.

PubMed

Tan, Wei Shang; Ting, Adeline Su Yien

2014-05-01

This study evaluated the use of alginate-immobilized bentonite to remove Cu(II) as an alternative to mitigate clogging problems. The adsorption efficacy (under the influence of time, pH and initial Cu(II) concentration) and reusability of immobilized-bentonite (1% w/v bentonite) was tested against plain alginate beads. Results revealed that immobilized bentonite demonstrated significantly higher sorption efficacy compared to plain alginate beads with 114.70 and 94.04 mg Cu(II) adsorbed g(-1) adsorbent, respectively. Both sorbents were comparable in other aspects where sorption equilibrium was achieved within 6 h, with optimum pH between pH 4 and 5 for adsorption, displayed maximum adsorption capacity at initial Cu(II) concentrations of 400 mg l(-1), and demonstrated excellent reusability potential with desorption greater than 90% throughout three consecutive adsorption-desorption cycles. Both sorbents also conformed to Langmuir isotherm and pseudo-second order kinetic model. Immobilized bentonite is therefore recommended for use in water treatments to remove Cu(II) without clogging the system. Copyright © 2013 Elsevier Ltd. All rights reserved.

Planning a Stigmatized Nonvisible Illness Disclosure: Applying the Disclosure Decision-Making Model

PubMed Central

Choi, Soe Yoon; Venetis, Maria K.; Greene, Kathryn; Magsamen-Conrad, Kate; Checton, Maria G.; Banerjee, Smita C.

2016-01-01

This study applied the disclosure decision-making model (DD-MM) to explore how individuals plan to disclose nonvisible illness (Study 1), compared to planning to disclose personal information (Study 2). Study 1 showed that perceived stigma from the illness negatively predicted disclosure efficacy; closeness predicted anticipated response (i.e., provision of support) although it did not influence disclosure efficacy; disclosure efficacy led to reduced planning, with planning leading to scheduling. Study 2 demonstrated that when information was considered to be intimate, it negatively influenced disclosure efficacy. Unlike the model with stigma (Study 1), closeness positively predicted both anticipated response and disclosure efficacy. The rest of the hypothesized relationships showed a similar pattern to Study 1: disclosure efficacy reduced planning, which then positively influenced scheduling. Implications of understanding stages of planning for stigmatized information are discussed. PMID:27662447

Planning a Stigmatized Nonvisible Illness Disclosure: Applying the Disclosure Decision-Making Model.

PubMed

Choi, Soe Yoon; Venetis, Maria K; Greene, Kathryn; Magsamen-Conrad, Kate; Checton, Maria G; Banerjee, Smita C

2016-11-16

This study applied the disclosure decision-making model (DD-MM) to explore how individuals plan to disclose nonvisible illness (Study 1), compared to planning to disclose personal information (Study 2). Study 1 showed that perceived stigma from the illness negatively predicted disclosure efficacy; closeness predicted anticipated response (i.e., provision of support) although it did not influence disclosure efficacy; disclosure efficacy led to reduced planning, with planning leading to scheduling. Study 2 demonstrated that when information was considered to be intimate, it negatively influenced disclosure efficacy. Unlike the model with stigma (Study 1), closeness positively predicted both anticipated response and disclosure efficacy. The rest of the hypothesized relationships showed a similar pattern to Study 1: disclosure efficacy reduced planning, which then positively influenced scheduling. Implications of understanding stages of planning for stigmatized information are discussed.

The Chicago Parent Program: Comparing 1-Year Outcomes for African American and Latino Parents of Young Children

PubMed Central

Breitenstein, Susan M.; Gross, Deborah; Fogg, Louis; Ridge, Alison; Garvey, Christine; Julion, Wrenetha; Tucker, Sharon

2012-01-01

Data were merged from two prevention randomized trials testing 1-year outcomes of a parenting skills program, the Chicago Parent Program (CPP), and comparing its effects for African-American (n=291) versus Latino (n=213) parents and their preschool children. Compared to controls, intervention parents had improved self-efficacy, used less corporal punishment and more consistent discipline, and demonstrated more positive parenting. Intervention children had greater reductions in behavior problems based on parent-report, teacher-report, and observation. Although improvements from CPP were evident for parents in both racial/ethnic groups, Latino parents reported greater improvements in their children’s behavior and in parenting self-efficacy but exhibited greater decreases in praise. Findings support the efficacy of the CPP for African American and Latino parents and young children from low-income urban communities. PMID:22622598

The Chicago Parent Program: comparing 1-year outcomes for African American and Latino parents of young children.

PubMed

Breitenstein, Susan M; Gross, Deborah; Fogg, Louis; Ridge, Alison; Garvey, Christine; Julion, Wrenetha; Tucker, Sharon

2012-10-01

Data were merged from two prevention randomized trials testing 1-year outcomes of a parenting skills program, the Chicago Parent Program (CPP) and comparing its effects for African-American (n = 291) versus Latino (n = 213) parents and their preschool children. Compared to controls, intervention parents had improved self-efficacy, used less corporal punishment and more consistent discipline, and demonstrated more positive parenting. Intervention children had greater reductions in behavior problems based on parent-report, teacher-report, and observation. Although improvements from the CPP were evident for parents in both racial/ethnic groups, Latino parents reported greater improvements in their children's behavior and in parenting self-efficacy but exhibited greater decreases in praise. Findings support the efficacy of the CPP for African American and Latino parents and young children from low-income urban communities. Copyright © 2012 Wiley Periodicals, Inc.

Treatment of Adolescent Panic Disorder: A Nonrandomized Comparison of Intensive versus Weekly CBT

ERIC Educational Resources Information Center

Chase, Rhea M.; Whitton, Sarah W.; Pincus, Donna B.

2012-01-01

This study compared the relative efficacy of intensive versus weekly panic control treatment (PCT) for adolescent panic disorder with agoraphobia (PDA). Twenty-six adolescents participated in weekly sessions and 25 received intensive treatment involving daily sessions. Both groups demonstrated significant and comparable reductions in panic…

Anti-Cancer Efficacy of Silybin Derivatives - A Structure-Activity Relationship

PubMed Central

Agarwal, Chapla; Wadhwa, Ritambhara; Deep, Gagan; Biedermann, David; Gažák, Radek; Křen, Vladimír; Agarwal, Rajesh

2013-01-01

Silybin or silibinin, a flavonolignan isolated from Milk thistle seeds, is one of the popular dietary supplements and has been extensively studied for its antioxidant, hepatoprotective and anti-cancer properties. We have envisioned that potency of silybin could be further enhanced through suitable modification/s in its chemical structure. Accordingly, here, we synthesized and characterized a series of silybin derivatives namely 2,3-dehydrosilybin (DHS), 7-O-methylsilybin (7OM), 7-O-galloylsilybin (7OG), 7,23-disulphatesilybin (DSS), 7-O-palmitoylsilybin (7OP), and 23-O-palmitoylsilybin (23OP); and compared their anti-cancer efficacy using human bladder cancer HTB9, colon cancer HCT116 and prostate carcinoma PC3 cells. In all the 3 cell lines, DHS, 7OM and 7OG demonstrated better growth inhibitory effects and compared to silybin, while other silybin derivatives showed lesser or no efficacy. Next, we prepared the optical isomers (A and B) of silybin, DHS, 7OM and 7OG, and compared their anti-cancer efficacy. Isomers of these three silybin derivatives also showed better efficacy compared with respective silybin isomers, but in each, there was no clear cut silybin A versus B isomer activity preference. Further studies in HTB cells found that DHS, 7OM and 7OG exert better apoptotic activity than silibinin. Clonogenic assays in HTB9 cells further confirmed that both the racemic mixtures as well as pure optical isomers of DHS, 7OM and 7OG were more effective than silybin. Overall, these results clearly suggest that the anti-cancer efficacy of silybin could be significantly enhanced through structural modifications, and identify strong anti-cancer efficacy of silybin derivatives, namely DHS, 7OM, and 7OG, signifying that their efficacy and toxicity should be evaluated in relevant pre-clinical cancer models in rodents. PMID:23555889

Evaluation of the efficacy of ChAd63-MVA vectored vaccines expressing circumsporozoite protein and ME-TRAP against controlled human malaria infection in malaria-naive individuals.

PubMed

Hodgson, Susanne H; Ewer, Katie J; Bliss, Carly M; Edwards, Nick J; Rampling, Thomas; Anagnostou, Nicholas A; de Barra, Eoghan; Havelock, Tom; Bowyer, Georgina; Poulton, Ian D; de Cassan, Simone; Longley, Rhea; Illingworth, Joseph J; Douglas, Alexander D; Mange, Pooja B; Collins, Katharine A; Roberts, Rachel; Gerry, Stephen; Berrie, Eleanor; Moyle, Sarah; Colloca, Stefano; Cortese, Riccardo; Sinden, Robert E; Gilbert, Sarah C; Bejon, Philip; Lawrie, Alison M; Nicosia, Alfredo; Faust, Saul N; Hill, Adrian V S

2015-04-01

Circumsporozoite protein (CS) is the antigenic target for RTS,S, the most advanced malaria vaccine to date. Heterologous prime-boost with the viral vectors simian adenovirus 63 (ChAd63)-modified vaccinia virus Ankara (MVA) is the most potent inducer of T-cells in humans, demonstrating significant efficacy when expressing the preerythrocytic antigen insert multiple epitope-thrombospondin-related adhesion protein (ME-TRAP). We hypothesized that ChAd63-MVA containing CS may result in a significant clinical protective efficacy. We conducted an open-label, 2-site, partially randomized Plasmodium falciparum sporozoite controlled human malaria infection (CHMI) study to compare the clinical efficacy of ChAd63-MVA CS with ChAd63-MVA ME-TRAP. One of 15 vaccinees (7%) receiving ChAd63-MVA CS and 2 of 15 (13%) receiving ChAd63-MVA ME-TRAP achieved sterile protection after CHMI. Three of 15 vaccinees (20%) receiving ChAd63-MVA CS and 5 of 15 (33%) receiving ChAd63-MVA ME-TRAP demonstrated a delay in time to treatment, compared with unvaccinated controls. In quantitative polymerase chain reaction analyses, ChAd63-MVA CS was estimated to reduce the liver parasite burden by 69%-79%, compared with 79%-84% for ChAd63-MVA ME-TRAP. ChAd63-MVA CS does reduce the liver parasite burden, but ChAd63-MVA ME-TRAP remains the most promising antigenic insert for a vectored liver-stage vaccine. Detailed analyses of parasite kinetics may allow detection of smaller but biologically important differences in vaccine efficacy that can influence future vaccine development. NCT01623557. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Robenacoxib vs. carprofen for the treatment of canine osteoarthritis; a randomized, noninferiority clinical trial.

PubMed

Reymond, N; Speranza, C; Gruet, P; Seewald, W; King, J N

2012-04-01

Robenacoxib is a member of the coxib class of nonsteroidal anti-inflammatory drugs (NSAID), with high selectivity for the cyclooxygenase (COX)-2 isoform of COX. In this study, the efficacy and tolerability of robenacoxib were compared with those of carprofen in canine osteoarthritis in a multi-centre, prospective, randomized, blinded, positive-controlled noninferiority clinical trial. Both drugs were administered orally once daily at recommended dosages: robenacoxib at 1-2 mg/kg (n = 125 dogs) and racemic carprofen at 2-4 mg/kg (n = 63 dogs) for a total of 12 weeks. The efficacy of the test compounds was assessed by veterinary investigators and owners using numerical rating scales at baseline and days 7, 14, 28, 56 and 84. In both groups, all scores were significantly (P < 0.0001) improved compared with baseline at all time points (days 7-84). Robenacoxib had noninferior efficacy to carprofen for the primary endpoint, the global functional disability, both for all dogs and for the subgroup of dogs in which robenacoxib was not administered during meals. Noninferiority was also demonstrated for three of six veterinary investigator secondary endpoints and four of six owner efficacy endpoints. For haematology and clinical chemistry variables, there were some significant differences from baseline levels but no differences between groups. There were no differences between groups in the frequencies of adverse events, which were reported in 46% dogs with robenacoxib and 52% with carprofen (P = 0.44), which were most frequently mild events affecting the gastrointestinal tract. In conclusion, noninferior efficacy and tolerability of robenacoxib compared with carprofen was demonstrated in dogs with osteoarthritis. © 2011 Blackwell Publishing Ltd.

Efficacy of hormone therapy with and without methyltestosterone augmentation of venlafaxine in the treatment of postmenopausal depression: a double-blind controlled pilot study.

PubMed

Dias, Rodrigo S; Kerr-Corrêa, Florence; Moreno, Ricardo A; Trinca, Luzia A; Pontes, Anagloria; Halbe, Hans W; Gianfaldoni, Arlete; Dalben, Ivete S

2006-01-01

This study evaluated the augmentation of venlafaxine with hormone therapy in the treatment of postmenopausal depression. The hormones evaluated were estrogen (0.625 mg) in combination with medroxyprogesterone acetate (2.5 mg) and methyltestosterone (2.5 mg). Seventy-two menopausal women (mean age: 53.6 +/- 4.27 years) diagnosed with depression (Montgomery-Asberg Depression Rating Scale [MADRS] scores > or = 20) were treated with venlafaxine and one of the following hormone therapy combinations, in a double-blind regimen: estrogen + medroxyprogesterone + methyltestosterone (group 1, n = 20); estrogen + medroxyprogesterone acetate (group 2, n = 20); methyltestosterone only (group 3, n = 16); and no hormone therapy (group 4, n = 16). Study duration was 24 weeks. Primary efficacy outcome was remission according to the MADRS, whereas secondary efficacy measures included the Clinical Global Impression (CGI), Blatt-Kupperman Index, and Women's Health Questionnaire (WHQ). Forty-eight patients completed the study. All groups showed significant improvement from baseline. Group 3 demonstrated significant improvement on the MADRS compared with placebo (group 4) at weeks 20 (P = 0.048) and 24 (P = 0.030); effect size 8.04 (0.83; 15.26) (P = 0.029), but also had the highest dropout rate. Groups 1 and 3 had significant CGI improvement rates compared with placebo: 42.23% (P = 0.012) and 44.45% (P = 0.08), respectively. There were no differences in the WHQ or BKI scores among the groups. Methyltestosterone 2.5 mg had the highest effect size compared with placebo, but the high dropout rate prevented its efficacy from being determined. Estrogen plus medroxyprogesterone, combined with methyltestosterone or otherwise, demonstrated a trend toward increased efficacy of venlafaxine. Further larger-scale clinical trials are needed to elucidate the findings of this pilot study.

Safety and efficacy of a novel Prunus domestica extract (Sitoprin, CR002) on testosterone-induced benign prostatic hyperplasia (BPH) in male Wistar rats.

PubMed

Swaroop, Anand; Bagchi, Manashi; Kumar, Pawan; Preuss, Harry G; Bagchi, Debasis

2015-01-01

The efficacy of a novel Prunus domestica bark extract (Sitoprin, CR002) was investigated on testosterone propionate (TP)-induced benign prostatic hyperplasia (BPH) in male Wistar rats. BPH was induced by daily subcutaneous administration of TP (3.0 mg/kg) over a period of 15 days (interim sacrifice group) and for an additional 21 days (terminal sacrifice group). We evaluated the dose-dependent efficacy (0, 50, 100 and 200 mg/kg body weight/day) of CR002 and a control group against BPH, and compared with a reference standard Prunus africana extract (CR001). Extensive clinical examinations were carried out on days 1, 7, 14, 21, 28 and 35 of treatment period to determine the onset, duration and severity of clinical signs. Clinical pathology, hematology, biochemistry and histopathology were performed on days 15 and 35, prior to necropsy. Animals were fasted overnight prior to blood collection. Prostate glands and tissues were examined. On day 36, histopathology of ventral prostrate of control rats demonstrates single layer of columnar mucin secreting epithelial cells along with a lumen occupied with eosinophilic secretion. In contrast, CR002 and CR001 groups (100 and 200 mg/kg/day) exhibited no hyperplasia and proliferation of epithelial cells. Prostate histopathology of these treated groups was comparable with control rats. The hyperplasia and hypertrophy of prostrate was reduced to single-layered cell indicating the efficacy of CR002 and CR001. Overall, results demonstrate that CR002 exhibits therapeutic efficacy/activity in TP-induced BPH in rats, which is comparable to CR001.

Fungi Associated with the Hemlock Woolly Adelgid, Adelges tsugae, and Assessment of Entomopathogenic Isolates for Management

PubMed Central

Reid, W.R.; Parker, B.L.; Gouli, S.Y.; Skinner, M.; Gouli, V.V.; Teillon, H.B.

2010-01-01

Fungi associated with the hemlock wooly adelgid, Adelges tsugae Annand (Hemiptera: Adelgidae), were collected throughout the eastern USA and southern China. Twenty fungal genera were identified, as were 79 entomopathogenic isolates, including: Lecanicillium lecanii (Zimmermann) (Hypocreales: Insertae sedis), Isaria farinosa (Holm: Fries.) (Cordycipitaceae), Beauveria bassiana (Balasamo) (Hyphomycetes), and Fusarium spp (Nectriaceae). The remaining fungal genera associated with insect cadavers were similar for both the USA and China collections, although the abundance of Acremonium (Hypocreaceae) was greater in China. The entomopathogenic isolates were assayed for efficacy against Myzus persicae (Sulzer) (Homoptera: Aphididae) and yielded mortality ranging from 3 to 92%. Ten isolates demonstrating the highest efficacy were further assessed for efficacy against field-collected A. tsugae under laboratory conditions. Overall, two B. bassiana, one L. lecanii, and a strain of Metarhizium anisopliae (Metchnikoff) (Hypocreales: Clavicipitaceae), demonstrated significantly higher efficacy against A. tsugae than the others. Isolates were further evaluated for conidial production, germination rate and colony growth at four temperatures representative of field conditions. All isolates were determined to be mesophiles with optimal temperature between 25–30° C. In general, conidial production increased with temperature, though two I. farinosa produced significantly more conidia at cooler temperatures. When efficacy values were compared with conidial production and temperature tolerances, Agricultural Research Service Collection of Entomopathogenic Fungi (ARSEF) 1080, 5170, and 5798 had characteristics comparable to the industrial B. bassiana strain GHA. PMID:20672977

Efficacy of Single and Combined Antibiotic Treatments of Anthrax in Rabbits.

PubMed

Weiss, Shay; Altboum, Zeev; Glinert, Itai; Schlomovitz, Josef; Sittner, Assa; Bar-David, Elad; Kobiler, David; Levy, Haim

2015-12-01

Respiratory anthrax is a fatal disease in the absence of early treatment with antibiotics. Rabbits are highly susceptible to infection with Bacillus anthracis spores by intranasal instillation, succumbing within 2 to 4 days postinfection. This study aims to test the efficiency of antibiotic therapy to treat systemic anthrax in this relevant animal model. Delaying the initiation of antibiotic administration to more than 24 h postinfection resulted in animals with systemic anthrax in various degrees of bacteremia and toxemia. As the onset of symptoms in humans was reported to start on days 1 to 7 postexposure, delaying the initiation of treatment by 24 to 48 h (time frame for mass distribution of antibiotics) may result in sick populations. We evaluated the efficacy of antibiotic administration as a function of bacteremia levels at the time of treatment initiation. Here we compare the efficacy of treatment with clarithromycin, amoxicillin-clavulanic acid (Augmentin), imipenem, vancomycin, rifampin, and linezolid to the previously reported efficacy of doxycycline and ciprofloxacin. We demonstrate that treatment with amoxicillin-clavulanic acid, imipenem, vancomycin, and linezolid were as effective as doxycycline and ciprofloxacin, curing rabbits exhibiting bacteremia levels of up to 10(5) CFU/ml. Clarithromycin and rifampin were shown to be effective only as a postexposure prophylactic treatment but failed to treat the systemic (bacteremic) phase of anthrax. Furthermore, we evaluate the contribution of combined treatment of clindamycin and ciprofloxacin, which demonstrated improvement in efficacy compared to ciprofloxacin alone. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Biofilm disruption with rotating microrods enhances antimicrobial efficacy

NASA Astrophysics Data System (ADS)

Mair, Lamar O.; Nacev, Aleksandar; Hilaman, Ryan; Stepanov, Pavel Y.; Chowdhury, Sagar; Jafari, Sahar; Hausfeld, Jeffrey; Karlsson, Amy J.; Shirtliff, Mark E.; Shapiro, Benjamin; Weinberg, Irving N.

2017-04-01

Biofilms are a common and persistent cause of numerous illnesses. Compared to planktonic microbes, biofilm residing cells often demonstrate significant resistance to antimicrobial agents. Thus, methods for dislodging cells from the biofilm may increase the antimicrobial susceptibility of such cells, and serve as a mechanical means of increasing antimicrobial efficacy. Using Aspergillus fumigatus as a model microbe, we magnetically rotate microrods in and around biofilm. We show that such rods can improve the efficacy of antimicrobial Amphotericin B treatments in vitro. This work represents a first step in using kinetic magnetic particle therapy for disrupting fungal biofilms.

Systematic Review with Network Meta-Analysis: Comparative Efficacy of Biologics in the Treatment of Moderately to Severely Active Ulcerative Colitis.

PubMed

Vickers, Adrian D; Ainsworth, Claire; Mody, Reema; Bergman, Annika; Ling, Caroline S; Medjedovic, Jasmina; Smyth, Michael

2016-01-01

Biological therapies are increasingly used to treat ulcerative colitis (UC). To compare the efficacy of biologics in adults with moderately-to-severely active UC, stratified by prior exposure to anti-tumour necrosis factor (anti-TNF) therapy. A systematic literature review was undertaken to identify studies of biologics approved for UC. Network meta-analysis was conducted for endpoints at induction and maintenance. Seven studies were included in the meta-analysis of induction treatment for anti-TNF therapy-naïve patients. All biologics were more effective than placebo in inducing clinical response, clinical remission, and mucosal healing. Infliximab demonstrated a statistically significant improvement over adalimumab in clinical response (odds ratio [OR] [95% credible interval (CrI)]: 2.19 [1.35-3.55]), clinical remission (OR [95% CrI]: 2.81 [1.49-5.49]), and mucosal healing (OR [95% CrI]: 2.23 [1.21-4.14]); there were no other significant differences between biologics for induction efficacy. Five studies were included in the meta-analysis of maintenance treatment, two studies rerandomised responder patients at end of induction, and three followed the same patients 'straight through'. To account for design differences, the number of responders at end of induction was assumed to be equivalent to the number rerandomised. Vedolizumab showed significantly different durable clinical response from comparators (OR [95% CrI] infliximab 3.18 [1.14-9.20], golimumab 2.33 [1.04-5.41], and adalimumab 3.96 [1.67-9.84]). In anti-TNF therapy-experienced patients, only vedolizumab and adalimumab could be compared. At induction, no significant differences in efficacy were seen. During maintenance, vedolizumab showed significantly improved rates of mucosal healing versus adalimumab (OR [95% CrI]: 6.72 [1.36-41.0]). This study expands the understanding of comparative efficacies of biologic treatments for UC, encompassing outcomes and populations not previously studied. All biologic treatments were effective for UC during induction. Vedolizumab demonstrated possible clinical benefits in the maintenance setting versus all comparators, irrespective of prior anti-TNF exposure and after adjusting for differences in study design.

Rifaximin and eluxadoline - newly approved treatments for diarrhea-predominant irritable bowel syndrome: what is their role in clinical practice alongside alosetron?

PubMed

Cash, Brooks D; Lacy, Brian E; Rao, Tharaknath; Earnest, David L

2016-01-01

Diarrhea-predominant irritable bowel syndrome (IBS-D) is a common functional gastrointestinal condition in which patients experience abdominal pain, diarrhea, bloating, cramps, flatulence, fecal urgency, and incontinence. We review two recently approved therapies that focus on treating underlying pathogenic mechanisms of IBS-D: (1) the non-absorbable antibiotic rifaximin, and (2) the opioid receptor agonist/antagonist eluxadoline. We compare the safety and efficacy data emerging from rifaximin and eluxadoline registration trials with safety and efficacy data from the alosetron clinical development program. The rifaximin and eluxadoline clinical development programs for IBS-D have demonstrated significant improvement in IBS-D endpoints compared to placebo. Direct comparison of primary endpoint results from the alosetron, rifaximin, and eluxadoline pivotal trials is not possible; however, general estimates of efficacy can be made, and these demonstrate similar and significantly greater responses to 'adequate relief' and a composite endpoint of abdominal pain/stool form for each agent compared to placebo. With the recent approval in the United States of rifaximin and eluxadoline for IBS-D, how should clinicians employ these agents? We suggest that they be utilized sequentially, taking into consideration patient symptoms and severity, prior medical history, mode of action, cost, availability, managed care coverage, and adverse event profiles.

Novel Composite Efficacy Measure To Demonstrate the Rationale and Efficacy of Combination Antiviral–Anti-Inflammatory Treatment for Recurrent Herpes Simplex Labialis

PubMed Central

Levin, Myron J.; Tyring, Stephen K.; Spruance, Spotswood L.

2014-01-01

Historically, the primary target for research and treatment of recurrent herpes simplex labialis (HSL) has been limited to inhibiting herpes simplex virus (HSV) replication. Antiviral monotherapy, however, has proven only marginally effective in curtailing the duration and severity of recurrent lesions. Recently, the role of inflammation in the progression and resolution of recurrences has been identified as an additional target. This was evaluated in a randomized study comparing combination topical 5% acyclovir-1% hydrocortisone cream (AHC) with 5% acyclovir alone (AC; in the AHC vehicle) and the vehicle. The efficacy of each topical therapy was evaluated for cumulative lesion size—a novel composite efficacy endpoint incorporating episode duration, lesion area, and proportion of nonulcerative lesions. In that study, cumulative lesion area was significantly decreased with AHC compared with AC (25% decrease; P < 0.05) and the vehicle (50% decrease; P < 0.0001). As research continues in this arena, cumulative lesion area should be included as a measure of efficacy in clinical trials of recurrent HSL therapies. PMID:24342632

Efficacy of Pharmacist Based Diabetes Educational Interventions on Clinical Outcomes of Adults With Type 2 Diabetes Mellitus: A Network Meta-Analysis

PubMed Central

Bukhsh, Allah; Khan, Tahir M.; Lee, Shaun W. H.; Lee, Learn-Han; Chan, Kok-Gan; Goh, Bey-Hing

2018-01-01

Background: Comparative efficacy of different pharmacist based interventions on glycemic control of type 2 diabetes patients is unclear. This review aimed to evaluate and compare the efficacy of different pharmacist based interventions on clinical outcomes of type 2 diabetes patients. Methods: A systematic search was conducted across five databases from date of database inception to September 2017. All randomized clinical trials evaluating the efficacy of pharmacist based interventions on type 2 diabetes patients were included for network meta-analysis (NMA). The protocol is available with PROSPERO (CRD42017078854). Results: A total of 43 studies, involving 6259 type 2 diabetes patients, were included. NMA demonstrated that all interventions significantly lowered glycosylated hemoglobin (HbA1c) levels compared to usual care, but there was no statistical evidence from this study that one intervention was significantly better than the other for reducing HbA1c levels. Pharmacist based diabetes education plus pharmaceutical care showed maximum efficacy for reducing HbA1c levels [−0.86, 95% CI −0.983, −0.727; p < 0.001]. Pharmacist based diabetes education plus pharmaceutical care was observed to be statistically significant in lowering levels of systolic blood pressure [−4.94; 95%CI −8.65, −1.23] and triglycerides levels [−0.26, 95%CI −0.51, −0.01], as compared to the interventions which involved diabetes education by pharmacist, and for body mass index (BMI) [−0.57; 95%CI −1.25, −0.12] in comparison to diabetes education by health care team involving pharmacist as member. Conclusion: The findings of this review demonstrate that all interventions had a significantly positive effect on HbA1c, but there was no statistical evidence from this study that one intervention was significantly better than the other for achieving glycemic control.Pharmacist based diabetes education plus pharmaceutical care showed maximum efficacy on HbA1c and rest of the clinical outcomes. PMID:29692730

Ibandronate treatment for osteoporosis: rationale, preclinical, and clinical development of extended dosing regimens.

PubMed

Epstein, Solomon

2006-03-01

Ibandronate is a potent nitrogen-containing bisphosphonate available as a once-monthly oral formulation for the treatment and prevention of osteoporosis. Preclinical experiments with estrogen-depleted rats, dogs, and monkeys demonstrated the efficacy of daily and intermittent ibandronate dosing. Initial clinical trials explored the optimal dosing regimens for oral administration in humans. The Oral Ibandronate Osteoporosis Vertebral Fracture Trial in North America and Europe (BONE) and Monthly Oral Ibandronate in Ladies (MOBILE) trials demonstrated that long-term daily and intermittent administration of ibandronate was efficacious for increasing bone mineral density, reducing markers of bone turnover, and preventing fractures, while maintaining bone quality. These preclinical and clinical ibandronate trials provided progressive evidence that a simple, long interval dosing regimen could offer efficacy and safety comparable with currently available bisphosphonates. It is anticipated that once-monthly ibandronate may have a positive impact on patient adherence, and ultimately, on fracture protection in osteoporotic women.

Efficacy and safety of herbal medicines in treating gastric ulcer: a review.

PubMed

Bi, Wei-Ping; Man, Hui-Bin; Man, Mao-Qiang

2014-12-07

Gastric ulcer is a common disorder of the digestive system. Current therapeutic regimens largely rely on Western medicine. However, numerous studies have demonstrated that herbal medicines can effectively treat gastric ulcer in humans and various animal models via divergent mechanisms. This review updates the efficacy and safety of herbal medicines in treating gastric ulcer, and the mechanisms of their action in humans and animal models. Studies have demonstrated that the efficacy of herbal medicines is comparable or superior to that of drugs such as omeprazole or cimetidine in humans and animal models, and herbal medicines display fewer adverse effects. The mechanisms by which herbal medicines benefit gastric ulcer include stimulation of mucous cell proliferation, anti-oxidation, and inhibition of gastric acid secretion and H(+)/K(+)-ATPase activity. Some herbal medicines also exhibit antimicrobial properties. Utilization of herbal medicines could be a valuable alternative to treat gastric ulcer in humans effectively, with few adverse effects.

New drugs: evidence relating to their therapeutic value after introduction to the market.

PubMed

Ujeyl, Mariam; Schlegel, Claudia; Walter, Siegbert; Gundert-Remy, Ursula

2012-02-01

Drug approval is based on three criteria: quality, efficacy, and safety. We investigated the types of study design and statistical methods employed to demonstrate safety and efficacy of proprietary medicinal products (PMPs) that were approved for use in the European Union through the centralized procedure. We retrospectively analyzed the European Public Assessment Reports of PMPs that the European Medicinal Agency approved, either initially or for extended indications, in 2009 and 2010. Data were analyzed for 39 PMPs: 64% of these were new active substances, and 36% were approved for extended indications. 46% of the PMPs had been studied in an active-control trial. In only 28%, superiority of the new PMPs compared to active control had been tested. 46% of the approvals included testing of a patient-relevant primary endpoint. The median size of population used to demonstrate safety was 1700 persons. The centralized procedure does not require comparative information from active-control trials. Accordingly, as our descriptive analysis revealed, this information is often not available at the time of market introduction. Pivotal studies only rarely clearly demonstrate an added therapeutic value of a new PMP compared to existing alternatives.

Efficacy and Safety of Brexpiprazole (OPC-34712) as Maintenance Treatment in Adults with Schizophrenia: a Randomized, Double-Blind, Placebo-Controlled Study.

PubMed

Fleischhacker, W Wolfgang; Hobart, Mary; Ouyang, John; Forbes, Andy; Pfister, Stephanie; McQuade, Robert D; Carson, William H; Sanchez, Raymond; Nyilas, Margareta; Weiller, Emmanuelle

2017-01-01

Brexpiprazole has previously demonstrated efficacy in acute schizophrenia trials. The objective of this trial was to assess the efficacy, safety, and tolerability of maintenance treatment with brexpiprazole in adults with schizophrenia. Patients with an acute exacerbation of psychotic symptoms were converted to brexpiprazole (1-4mg/d) over 1 to 4 weeks and entered a single-blind stabilization phase. Those patients who met stability criteria for 12 weeks were randomized 1:1 to double-blind maintenance treatment with either brexpiprazole (at their stabilization dose) or placebo for up to 52 weeks. The primary efficacy endpoint was the time from randomization to impending relapse. Safety and tolerability were also assessed. A total of 524 patients were enrolled, 202 of whom were stabilized on brexpiprazole and randomized to brexpiprazole (n=97) or placebo (n=105). Efficacy was demonstrated at a prespecified interim analysis (conducted after 45 events), and so the trial was terminated early. The final analysis showed that time to impending relapse was statistically significantly delayed with brexpiprazole treatment compared with placebo (P<.0001, log-rank test). The hazard ratio for the final analysis was 0.292 (95% confidence interval: 0.156, 0.548); mean dose at last visit, 3.6mg. The proportion of patients meeting the criteria for impending relapse was 13.5% with brexpiprazole and 38.5% with placebo (P<.0001). During the maintenance phase, the incidence of adverse events was comparable to placebo. or patients with schizophrenia already stabilized on brexpiprazole, maintenance treatment with brexpiprazole was efficacious, with a favorable safety profile. © The Author 2016. Published by Oxford University Press on behalf of CINP.

UPDATE ON NEUROPHARMACOLOGICAL TREATMENTS FOR ALCOHOLISM: SCIENTIFIC BASIS AND CLINICAL FINDINGS

PubMed Central

JOHNSON, BANKOLE A.

2008-01-01

The past decade has seen an expansion of research and knowledge on pharmacotherapy for the treatment of alcohol dependence. The Food and Drug Administration (FDA)–approved medications naltrexone and acamprosate have shown mixed results in clinical trials. Oral naltrexone and naltrexone depot formulations have generally demonstrated efficacy at treating alcohol dependence, but their treatment effect size is small, and more research is needed to compare the effects of different doses on drinking outcome. Acamprosate has demonstrated efficacy for treating alcohol dependence in European trials, but with a small effect size. In U.S. trials, acamprosate has not proved to be efficacious. Research continues to explore which types of alcohol-dependent individual would benefit the most from treatment with naltrexone or acamprosate. The combination of the two medications demonstrated efficacy for treating alcohol dependence in one European study but not in a multi-site U.S. study. Another FDA-approved medication, disulfiram, is an aversive agent that does not diminish craving for alcohol. Disulfiram is most effective when given to those who are highly compliant or who are receiving their medication under supervision. Of the non-approved medications, topiramate is among the most promising, with a medium effect size in clinical trials. Another promising medication, baclofen, has shown efficacy in small trials. Serotonergic agents such as selective serotonin reuptake inhibitors and the serotonin-3 receptor antagonist, ondansetron, appear to be efficacious only among certain genetic subtypes of alcoholic. As neuroscientific research progresses, other promising medications, as well as medication combinations, for treating alcohol dependence continue to be explored. PMID:17880925

One-month comparative efficacy of three topical ectoparasiticides against adult brown dog ticks (Rhipicephalus sanguineus sensu lato) on mixed-bred dogs in controlled environment.

PubMed

Varloud, Marie; Fourie, Josephus J

2015-05-01

This study was designed to compare the therapeutic and residual efficacy for 1 month of three topical ectoparasiticides on mixed-bred dogs against the brown dog tick, Rhipicephalus sanguineus. Adult dogs (n = 32, 10.8-18.4 kg BW) were allocated to 4 groups (n = 8) and infested with 50 adult ticks on days -8, -2, 7, 14, 21, and 28. Within each group, dogs were treated topically on day 0 with a control solution (CS), Vectra 3D (DPP), Frontline Plus (FM), or K9 Advantix (IP). Ticks were enumerated on dogs 24 h after treatment and each subsequent tick infestation by in situ thumb count assessment without removal and at 48 h by combing and removal. Acaricidal efficacy was calculated using arithmetic means for all 24 and 48 h tick count assessments. From 42 to 56% of the total, infested ticks were found on dogs 48 h post-challenge in the CS group. Therapeutic efficacy for all treatments ranged from 45.5 to 64.6% after 48 h of infestation. Residual efficacy after FM treatment was consistently lower compared to DPP or IP treatments at the 24 h assessments on days 8, 22, 23, and 29. Residual efficacy measured at this last time point was 94.8% for DPP, 83.1% for IP, and 46.9% for FM. This study demonstrates that permethrin-based formulations (DPP and IP) provided a quicker onset of residual protection against brown dog ticks compared to FM. Although DPP and IP are both permethrin-based formulations, DPP exhibited consistently higher residual acaricidal efficacies and was the only treatment that provided >90% protection for 1 month at 24 h post challenge.

HIV prevention trial design in an era of effective pre-exposure prophylaxis.

PubMed

Cutrell, Amy; Donnell, Deborah; Dunn, David T; Glidden, David V; Grobler, Anneke; Hanscom, Brett; Stancil, Britt S; Meyer, R Daniel; Wang, Ronnie; Cuffe, Robert L

2017-01-01

Pre-exposure prophylaxis (PrEP) has demonstrated remarkable effectiveness protecting at-risk individuals from HIV-1 infection. Despite this record of effectiveness, concerns persist about the diminished protective effect observed in women compared with men and the influence of adherence and risk behaviors on effectiveness in targeted subpopulations. Furthermore, the high prophylactic efficacy of the first PrEP agent, tenofovir disoproxil fumarate/emtricitabine (TDF/FTC), presents challenges for demonstrating the efficacy of new candidates. Trials of new agents would typically require use of non-inferiority (NI) designs in which acceptable efficacy for an experimental agent is determined using pre-defined margins based on the efficacy of the proven active comparator (i.e. TDF/FTC) in placebo-controlled trials. Setting NI margins is a critical step in designing registrational studies. Under- or over-estimation of the margin can call into question the utility of the study in the registration package. The dependence on previous placebo-controlled trials introduces the same issues as external/historical controls. These issues will need to be addressed using trial design features such as re-estimated NI margins, enrichment strategies, run-in periods, crossover between study arms, and adaptive re-estimation of sample sizes. These measures and other innovations can help to ensure that new PrEP agents are made available to the public using stringent standards of evidence.

Efficacy of Curcuma for Treatment of Osteoarthritis

PubMed Central

Perkins, Kimberly; Sahy, William; Beckett, Robert D.

2016-01-01

The objective of this review is to identify, summarize, and evaluate clinical trials to determine the efficacy of curcuma in the treatment of osteoarthritis. A literature search for interventional studies assessing efficacy of curcuma was performed, resulting in 8 clinical trials. Studies have investigated the effect of curcuma on pain, stiffness, and functionality in patients with knee osteoarthritis. Curcuma-containing products consistently demonstrated statistically significant improvement in osteoarthritis-related endpoints compared with placebo, with one exception. When compared with active control, curcuma-containing products were similar to nonsteroidal anti-inflammatory drugs, and potentially to glucosamine. While statistical significant differences in outcomes were reported in a majority of studies, the small magnitude of effect and presence of major study limitations hinder application of these results. Further rigorous studies are needed prior to recommending curcuma as an effective alternative therapy for knee osteoarthritis. PMID:26976085

The value of irbesartan in the management of hypertension.

PubMed

Bramlage, Peter; Durand-Zaleski, Isabelle; Desai, Nisha; Pirk, Olaf; Hacker, Caroline

2009-08-01

Elevated blood pressure levels are highly prevalent and are a major reason for cardiovascular events and thus place a significant financial burden on healthcare systems worldwide. Guidelines recommend five first-line anti-hypertensive drug classes, but compelling indications may indicate favoring one drug class over another. Angiotensin receptor blockers (ARBs) have demonstrated a blood pressure lowering efficacy which is at least comparable with other drug classes, including ACE inhibitors (ACE-I), beta-blockers, calcium channel blockers and diuretics. They have, in addition, a lower side effect profile than other drug classes and patients on ARBs are more persistent with therapy. Compelling indications for the use of ARBs are heart failure, post-myocardial infarction, diabetic nephropathy, proteinuria/microalbuminuria, left ventricular hypertrophy, atrial fibrillation, metabolic syndrome and ACE-I induced cough. The ARB irbesartan has demonstrated a high efficacy in lowering blood pressure, which has been shown to be at least comparable with ACE-Is and superior to other ARBs such as losartan and valsartan. This translated into a better cost-effectiveness for irbesartan than for valsartan and losartan in the treatment of hypertension. In addition, irbesartan has been shown to be effective in both early and late stage diabetic nephropathy. It has further demonstrated considerable cost savings over standard therapy including beta-blockers, diuretics and non-dihydropyridine calcium channel blockers at all stages of kidney disease. Based on efficacy data from the Irbesartan Diabetic Nephropathy Trial and Reduction of Endpoints in NIDDM (non insulin dependant diabetes melitis) with the Angiotensin II Antagonist Losartan Study, it has also demonstrated cost savings over losartan in late stage renal disease. While both losartan and irbesartan are registered for the treatment of late stage diabetic nephropathy, irbesartan is also registered for early stage diabetic nephropathy in the EU. In summary, the data from randomized clinical trials on the efficacy of antihypertensive drugs provides an indication of their real value to patients. In addition observational data from clinical practice and proven end-organ protection in diabetic nephropathy provides further evidence of the true value of irbesartan compared to other ARBs in the treatment of hypertension.

The immunization site of cytokine-secreting tumor cell vaccines influences the trafficking of tumor-specific T lymphocytes and antitumor efficacy against regional tumors.

PubMed

Chang, Chun-Jung; Tai, Kuo-Feng; Roffler, Steve; Hwang, Lih-Hwa

2004-11-15

Tumor cells engineered to secrete cytokines, referred to as tumor cell vaccines, can often generate systemic antitumor immunity and, in many cases, cause tumor regression. We compared the efficacy of s.c. immunization or intrahepatic immunization of GM-CSF-expressing tumor cell vaccines on the growth of s.c. or orthotopic liver tumors. A chemically transformed hepatic epithelial cell line, GP7TB, derived from Fischer 344 rats, was used to generate tumor models and tumor cell vaccines. Our results demonstrated that two s.c. injections of an irradiated tumor cell vaccine significantly controlled the growth of s.c. tumors, but was completely ineffective against orthotopic liver tumors. Effector cell infiltration in liver tumors was markedly reduced compared with s.c. tumors. Enhanced apoptosis of some effector cells was observed in the liver tumors compared with the s.c. tumors. Furthermore, the T cells induced by s.c. immunization preferentially migrated to s.c. tumor sites, as demonstrated by adoptive transfer experiments. In contrast, intrahepatic immunization, using parental tumor cells admixed with adenoviruses carrying the GM-CSF gene, yielded significantly better therapeutic effects on the liver tumors than on the s.c. tumors. Adoptive transfer experiments further confirmed that the T cells induced by liver immunization preferentially migrated to the liver tumor sites. Our results demonstrate that distinct T cell populations are induced by different immunization routes. Thus, the homing behavior of T cells depends on the route of immunization and is an important factor determining the efficacy of immunotherapy for regional tumors.

Substituted N-aryl-6-pyrimidinones: A new class of potent, selective, and orally active p38 MAP kinase inhibitors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Devadas, Balekudru; Selness, Shaun R.; Xing, Li

2012-02-28

A novel series of highly potent and selective p38 MAP kinase inhibitors was developed originating from a substituted N-aryl-6-pyrimidinone scaffold. SAR studies coupled with in vivo evaluations in rat arthritis model culminated in the identification of 10 with excellent oral efficacy. Compound 10 exhibited a significantly enhanced dissolution rate compared to 1, translating to a high oral bioavailability (>90%) in rat. In animal studies 10 inhibited LPS-stimulated production of tumor necrosis factor-{alpha} in a dose-dependent manner and demonstrated robust efficacy comparable to dexamethasone in a rat streptococcal cell wall-induced arthritis model.

Assessment of the efficacy and safety profiles of aspirin and acetaminophen with codeine: results from 2 randomized, controlled trials in individuals with tension-type headache and postoperative dental pain.

PubMed

Gatoulis, Sergio C; Voelker, Michael; Fisher, Matt

2012-01-01

Aspirin is a widely used NSAID that has been extensively studied in numerous conditions. Nonprescription analgesics, such as aspirin, are frequently used for a wide variety of common ailments, including conditions such as dental pain and tension-type headache. We sought to compare the efficacy and safety profiles of aspirin, acetaminophen with codeine, and placebo in the treatment of post-operative dental pain and tension-type headache. These were 2 randomized, double-blind, placebo-controlled, single-dose clinical trials that assigned participants (2:2:1) to receive either aspirin (1000 mg), acetaminophen (300 mg) with codeine (30 mg), or placebo. The primary efficacy end point was the sum of pain intensity differences from baseline (SPID) over 6 hours for the dental pain study and over 4 hours for the tension-type headache study. Other common analgesic measures, in addition to safety, were also evaluated. The results of the dental pain study for aspirin and acetaminophen with codeine suggest statistically significant efficacy for all measures compared with placebo at all time points. Aspirin provided statistically significant efficacy compared with acetaminophen with codeine for SPID(0-4) (P = 0.028). In the tension-type headache study, aspirin and acetaminophen with codeine provided statistically significant efficacy compared with placebo for SPID(0-4) and SPID(0-6) (P < 0.001) and for total pain relief (P < 0.001). There were no significant differences between aspirin and acetaminophen with codeine at any evaluation of SPID (P ≥ 0.070), complete relief (P ≥ 0.179), or time to meaningful relief (P ≥ 0.245). Regarding safety, there were no statistically significant differences between treatment groups in the incidence of adverse events in the dental pain and tension-type headache studies. These 2 randomized, double-blind, placebo-controlled studies demonstrate that treatment with aspirin (1000 mg) provides statistically significant analgesic efficacy compared with placebo use and comparable efficacy with acetaminophen (300 mg) with codeine (30 mg) therapy after impacted third molar extraction and in tension- type headache. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

Evaluation of a kojic acid, emblica extract, and glycolic acid formulation compared with hydroquinone 4% for skin lightening.

PubMed

Draelos, Zoe Diana; Yatskayer, Margarita; Bhushan, Pragya; Pillai, Sreekumar; Oresajo, Christian

2010-09-01

Hydroquinone has been the standard prescription agent for skin lightening; however, its use recently has become controversial. Hydroquinone is banned in Europe and parts of Asia because of potential long-term consequences, including carcinogenesis when orally consumed. These concerns have stimulated research to develop alternative skin lightening agents with efficacy comparable to hydroquinone but with a better safety profile. This double-blind study examined the skin lightening ability of a topical formulation containing kojic acid, emblica extract, and glycolic acid compared with prescription generic hydroquinone cream 4%. Eighty multiethnic participants with mild to moderate facial dyschromia were randomly assigned to use the study product or hydroquinone 4% twice daily for 12 weeks to evaluate product efficacy, tolerability, and safety using investigator assessment, participant assessment, and dermospectrophotometry. Study results demonstrated efficacy parity between the study product and hydroquinone 4%. Thus this novel skin lightening preparation is an alternative to hydroquinone 4% for participants with mild to moderate facial dyschromia.

Fasting during Ramadan: efficacy, safety, and patient acceptability of vildagliptin in diabetic patients.

PubMed

Aziz, Kamran Ma

2015-01-01

Diabetes management during Ramadan fasting is challenging to the physician in terms of minimizing the risk of hypoglycemia. As compared to oral hypoglycemic agents (OHAs) and sulfonylureas (SUs), which carry a higher and significant risk of hypoglycemia, newer antidiabetic agents such as dipeptidyl peptidase-4 (DPP-4) inhibitors have demonstrated lower risk of hypoglycemia during Ramadan fasting, with better patient compliance. In addition to diabetes education and pre-Ramadan assessments, the physician should also consider use of DPP-4 inhibitors (such as vildagliptin) during Ramadan fasting to minimize the risk of hypoglycemia in type 2 diabetic subjects. Severe episodes of hypoglycemia have been demonstrated in recent research and clinical trials with OHAs/SUs. Conversely, these research observations have also demonstrated comparative safety and efficacy with lower risk of hypoglycemia associated with vildagliptin. Current research review has collected evidence-based clinical trials and observations for the drug vildagliptin to minimize the risk of hypoglycemia during Ramadan fasting, while at the same time focusing the role of diabetes self-management education (DSME), pre-Ramadan assessments, and patient care.

Fasting during Ramadan: efficacy, safety, and patient acceptability of vildagliptin in diabetic patients

PubMed Central

Aziz, Kamran MA

2015-01-01

Diabetes management during Ramadan fasting is challenging to the physician in terms of minimizing the risk of hypoglycemia. As compared to oral hypoglycemic agents (OHAs) and sulfonylureas (SUs), which carry a higher and significant risk of hypoglycemia, newer antidiabetic agents such as dipeptidyl peptidase-4 (DPP-4) inhibitors have demonstrated lower risk of hypoglycemia during Ramadan fasting, with better patient compliance. In addition to diabetes education and pre-Ramadan assessments, the physician should also consider use of DPP-4 inhibitors (such as vildagliptin) during Ramadan fasting to minimize the risk of hypoglycemia in type 2 diabetic subjects. Severe episodes of hypoglycemia have been demonstrated in recent research and clinical trials with OHAs/SUs. Conversely, these research observations have also demonstrated comparative safety and efficacy with lower risk of hypoglycemia associated with vildagliptin. Current research review has collected evidence-based clinical trials and observations for the drug vildagliptin to minimize the risk of hypoglycemia during Ramadan fasting, while at the same time focusing the role of diabetes self-management education (DSME), pre-Ramadan assessments, and patient care. PMID:25931826

A Randomized, Placebo-Controlled Study of Once-Daily Atomoxetine in the School Setting in Children with ADHD

ERIC Educational Resources Information Center

Weiss, Margaret; Tannock, Rosemary; Kratochvil, Christopher; Dunn, David; Velez-Borras, Jesus; Thomason, Christine; Tamura, Roy; Kelsey, Douglas; Stevens, Linda; Allen, Albert J.

2005-01-01

Objective: Five studies have demonstrated the effectiveness of atomoxetine compared with placebo in reducing symptoms of attention-deficit/hyperactivity disorder (ADHD) based on parent reports. The primary objective of this clinical trial was to assess the efficacy of once-daily atomoxetine compared with placebo using teacher reports. Method: One…

Ethinyl estradiol and levonorgestrel in a transdermal contraceptive delivery system.

PubMed

Sriprasert, Intira; Stanczyk, Frank Z; Archer, David F

2015-01-01

The new transdermal contraceptive delivery system (TCDS) developed by Agile Therapeutics containing ethinyl estradiol and levonorgestrel (EE/LNG) is a reversible contraceptive method that maintains stable serum levels of both estrogen and progestin, and has efficacy similar to that of combination oral contraceptives (COC). We provided information of this new TCDS compared with the only TCDS available on the market that contains EE and norelgestromin, and has a higher EE exposure than a COC with 35 µg of EE potentially increasing the risk of venous thromboembolism. The article will summarize finding from clinical studies Phase I, II and III of EE/LNG TCDS. The development of the lower dose EE/LNG TCDS has demonstrated less EE exposure. The serum levels of EE and LNG were stable and comparable between various application sites and daily life conditions. Moreover, the EE/LNG TCDS showed comparable efficacy among obese and non-obese users. However, the Pearl index of this EE/LNG TCDS is questionable and the problem of compliance is a potential confounder of the results. The current Phase III efficacy study will contribute to a further evaluation of compliance and efficacy and will be completed in 2016.

Comparative efficacy of chloroquine and sulphadoxine--pyrimethamine in pregnant women and children: a meta-analysis.

PubMed

Kalanda, Gertrude C; Hill, Jenny; Verhoeff, Francine H; Brabin, Bernard J

2006-05-01

To compare the efficacy of chloroquine and sulphadoxine-pyremethamine against Plasmodium falciparum infection in pregnant women and in children from the same endemic areas of Africa, with the aim of determining the level of correspondence in efficacy determinations in these two risk groups. Meta-analysis of nine published and unpublished in vivo antimalarial efficacy studies in pregnant women and in children across five African countries. Pregnant women (all gravidae) were more likely to be sensitive than children to both chloroquine (odds ratio: 2.07; 95% confidence interval: 1.5, 2.9) and sulphadoxine-pyrimethamine (odds ratio: 2.66; 95% confidence interval: 11.1, 6.7). Pregnant women demonstrated an almost uniform increased sensitivity for peripheral parasite clearance at day 14 compared with children. This finding was consistent across a wide range of drug sensitivities. Primigravidae at day 14 showed lower clearance to antimalarial drugs than multigravidae (P<0.05). There was no significant difference between parasite clearance in primigravidae and in children. The greater drug sensitivity in pregnant women probably indicates differences in host susceptibility rather than parasite resistance. Parasite sensitivity patterns in children may be a suitable guide to antimalarial policy in pregnant women.

The moderating effect of self-efficacy on normal-weight, overweight, and obese children's math achievement: a longitudinal analysis.

PubMed

Kranjac, Ashley Wendell

2015-03-01

Increased body weight is associated with decreased cognitive function in school-aged children. The role of self-efficacy in shaping the connection between children's educational achievement and obesity-related comorbidities has not been examined to date. Evidence of the predictive ability of self-efficacy in children is demonstrated in cognitive tasks, including math achievement scores. This study examined the relationship between self-efficacy and math achievement in normal weight, overweight, and obese children. I hypothesized that overweight and obese children with higher self-efficacy will be less affected in math achievement than otherwise comparable children with lower self-efficacy. I tested this prediction with multilevel growth modeling techniques using the ECLS-K 1998-1999 survey data, a nationally representative sample of children. Increased self-efficacy moderates the link between body weight and children's math achievement by buffering the risks that increased weight status poses to children's cognitive function. My findings indicate that self-efficacy moderates math outcomes in overweight, but not obese, children. Copyright © 2015 Elsevier Ltd. All rights reserved.

An evaluation of choice on instructional efficacy and individual preferences among children with autism.

PubMed

Toussaint, Karen A; Kodak, Tiffany; Vladescu, Jason C

2016-03-01

The current study compared the differential effects of choice and no-choice reinforcement conditions on skill acquisition. In addition, we assessed preference for choice-making opportunities with 3 children with autism, using a modified concurrent-chains procedure. We replicated the experiment with 2 participants. The results indicated that choice-making opportunities increased treatment efficacy for 2 of the 3 participants, and all 3 participants demonstrated a preference for choice-making opportunities. © 2015 Society for the Experimental Analysis of Behavior.

Vitamin D and depression: a systematic review and meta-analysis comparing studies with and without biological flaws.

PubMed

Spedding, Simon

2014-04-11

Efficacy of Vitamin D supplements in depression is controversial, awaiting further literature analysis. Biological flaws in primary studies is a possible reason meta-analyses of Vitamin D have failed to demonstrate efficacy. This systematic review and meta-analysis of Vitamin D and depression compared studies with and without biological flaws. The systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The literature search was undertaken through four databases for randomized controlled trials (RCTs). Studies were critically appraised for methodological quality and biological flaws, in relation to the hypothesis and study design. Meta-analyses were performed for studies according to the presence of biological flaws. The 15 RCTs identified provide a more comprehensive evidence-base than previous systematic reviews; methodological quality of studies was generally good and methodology was diverse. A meta-analysis of all studies without flaws demonstrated a statistically significant improvement in depression with Vitamin D supplements (+0.78 CI +0.24, +1.27). Studies with biological flaws were mainly inconclusive, with the meta-analysis demonstrating a statistically significant worsening in depression by taking Vitamin D supplements (-1.1 CI -0.7, -1.5). Vitamin D supplementation (≥800 I.U. daily) was somewhat favorable in the management of depression in studies that demonstrate a change in vitamin levels, and the effect size was comparable to that of anti-depressant medication.

Dronedarone: current evidence and future questions.

PubMed

Schafer, Jeremy A; Kjesbo, Nicole K; Gleason, Patrick P

2010-01-01

Atrial fibrillation (AF) is the most common sustained arrhythmia, affecting more than 2.2 million Americans. ACC/AHA/ESC guidelines for the management of patients with AF recommend amiodarone for maintaining sinus rhythm. Dronedarone is a derivative of amiodarone indicated for the treatment of AF. To provide an overview of dronedarone with a focus on the phase III trials and discuss unresolved questions of dronedarone. A literature search was conducted via the PubMed database using the keyword "dronedarone." Search was limited to human trials in english. The FDA website was searched for briefing documents and subcommittee meetings on dronedarone. Clinicaltrials.gov was searched with the keyword dronedarone for upcoming or unpublished clinical trials. Five phase III trials are available for dronedarone: ANDROMEDA, EURIDIS/ADONIS, ATHENA, ERATO, and DIONYSIS. EURIDIS/ADONIS and ATHENA demonstrated a reduction AF recurrence with dronedarone compared to placebo. The ANDROMEDA trial recruited patients with recent hospitalization for heart failure and was terminated due to an excess of deaths in the dronedarone group. The DIONYSIS trial was a comparative effectiveness trial that demonstrated less efficacy for dronedarone but improved tolerability compared to amiodarone. Dronedarone represents an option in the management of AF in select patients. Dronedarone is not appropriate in patients with recently decompensated heart failure or those treated with strong CYP3A4 inhibitors or medications prolonging the QT interval. Dronedarone appears to have improved tolerability at the expense of decreased efficacy when compared to amiodarone. Questions remain on the long-term safety, use in patients with heart failure, retreatment after dronedarone or amiodarone failure, and comparative efficacy with a rate control strategy.

Efficacy of anti-osteoporotic medications in patients with type 1 and 2 diabetes mellitus: a systematic review.

PubMed

Anagnostis, Panagiotis; Paschou, Stavroula A; Gkekas, Nifon N; Artzouchaltzi, Aikaterini-Maria; Christou, Konstantinos; Stogiannou, Dimitrios; Vryonidou, Andromachi; Potoupnis, Michael; Goulis, Dimitrios G

2018-06-01

Both type 1 (T1DM) and type 2 diabetes mellitus (T2DM) have been associated with bone fragility and increased fracture risk. However, little is known regarding the effect of anti-osteoporotic treatment on bone mineral density (BMD) and/or fracture risk in these patients. We aimed to systematically investigate the efficacy of anti-osteoporotic medications in patients with diabetes in comparison with non-diabetic subjects. MEDLINE and Scopus databases were searched (up to 31st October 2017). Nine studies fulfilled the pre-defined inclusion criteria [patients with T2DM (n = 8) or either T1DM or T2DM (n = 1)]. Regarding fracture risk, five studies were identified. Alendronate demonstrated comparable vertebral anti-fracture efficacy in patients with and without diabetes (n = 2), whereas non-vertebral fracture risk was either the same (n = 1) or higher in diabetic patients (n = 1). Raloxifene also demonstrated comparable vertebral anti-fracture efficacy in both groups (n = 2), without any effect on non-vertebral fractures in either group. In one study, diabetic patients exposed to raloxifene demonstrated the same vertebral and non-vertebral fracture risk with non-diabetic patients. Teriparatide (n = 1) demonstrated the same non-vertebral fracture rates in both patients with and without T2DM. Regarding BMD, equal increases in spine BMD were observed with alendronate (n = 4), risedronate (n = 1), and teriparatide (n = 1). With respect to hip BMD, similar increases were observed with teriparatide (n = 1), whereas data regarding alendronate were controversial (n = 3). No eligible study was found for zoledronic acid, ibandronate, strontium ranelate, denosumab, or bazedoxifene. The presence of diabetes does not alter anti-osteoporotic treatment response, regarding BMD increase and vertebral fracture risk reduction.

Topical adapalene gel 0.1% vs. isotretinoin gel 0.05% in the treatment of acne vulgaris: a randomized open-label clinical trial.

PubMed

Ioannides, D; Rigopoulos, D; Katsambas, A

2002-09-01

Topical application of isotretinoin and adapalene has proved effective in treating acne vulgaris. Both drugs demonstrate therapeutic advantages and less irritancy over tretinoin, the most widely used treatment for acne. They both act as retinoid agonists, but differ in their affinity profile for nuclear and cytosolic retinoic acid receptors. To compare the efficacy and tolerability of adapalene gel 0.1% and isotretinoin gel 0.05% in the treatment of acne vulgaris of the face, in a randomized open-label clinical trial. Eighty patients were enrolled and were instructed to apply adapalene gel 0.1% or isotretinoin gel 0.05% once daily over a 12-week treatment period. Efficacy determination included noninflammatory and inflammatory lesion counts by the investigator and global evaluation of improvement. Cutaneous tolerance was assessed by determining erythema, scaling and burning with pruritus. Adapalene and isotretinoin gels were highly effective in treating facial acne. Adapalene gel produced greater reductions in noninflammatory and inflammatory lesion counts than did isotretinoin gel, but differences between treatments were not statistically significant. Adapalene gel was significantly better tolerated than isotretinoin gel during the whole treatment period. The two gels studied demonstrated comparable efficacy. When adapalene and isotretinoin were compared, significantly lower skin irritation was noted with adapalene, indicating that adapalene may begin a new era of treatment with low-irritant retinoids.

Curcumin uptake enhancement using low dose light illumination during incubation in Candida albicans

NASA Astrophysics Data System (ADS)

Romano, Renan A.; Pratavieira, Sebastião.; da Silva, Ana P.; Kurachi, Cristina; Bagnato, Vanderlei S.; Guimarães, Francisco E. G.

2017-07-01

A new PDI protocol is presented in this study. C. albicans cells pre-illuminated with a low dose light demonstrated an increase of curcumin uptake when compared to dark incubation, leading to a higher PDI efficacy.

Antimicrobial Efficacy of Multipurpose Disinfecting Solutions in the Presence of Contact Lenses and Lens Cases.

PubMed

Gabriel, Manal M; McAnally, Cindy; Bartell, John

2018-03-01

The aim of this study was to use antimicrobial efficacy endpoint methodology to determine compatibility of multipurpose disinfecting solutions (MPSs), lens cases, and hydrogel lenses for disinfection (AEEMC) against International Organization for Standardization (ISO)-specified microorganisms and clinical ocular isolates of Stenotrophomonas maltophilia. Six MPSs (PQ/Aldox 1, 2, and 3; PQ/Alexidine; PQ/PHMB; and PHMB) were challenged against ISO-specified microorganisms and S. maltophilia using the AEEMC test. AEEMC tests were performed with and without balafilcon A, etafilcon A, and senofilcon A lenses in lens cases with organic soil. Exposure times included disinfection time (DT) and 24 hr. Additionally, all six MPSs were challenged with two strains of S. maltophilia, based on the ISO Stand-alone test. The efficacy against bacteria for PQ/Aldox and PQ/Alexidine MPSs was not diminished by the presence of lenses. The efficacy of PQ/PHMB and PHMB MPSs against Serratia marcescens was significantly reduced compared with the no-lens control at DT for at least one lens type. The PHMB MPS with lenses present also demonstrated reduced efficacy against Staphylococcus aureus at DT versus the control. PQ/Aldox MPSs retained activity against Fusarium solani with lenses present; however, all other test MPSs demonstrated reduced F. solani efficacy at DT with lenses present. With lenses, all MPSs showed reduced efficacy against Candida albicans. AEEMC antimicrobial efficacy test results vary based on challenge microorganism, contact lenses, and MPS biocide systems. This study highlights the importance of evaluating MPSs for compatibility with lenses and lens cases.

Antimicrobial Efficacy of Multipurpose Disinfecting Solutions in the Presence of Contact Lenses and Lens Cases

PubMed Central

McAnally, Cindy; Bartell, John

2018-01-01

Objective: The aim of this study was to use antimicrobial efficacy endpoint methodology to determine compatibility of multipurpose disinfecting solutions (MPSs), lens cases, and hydrogel lenses for disinfection (AEEMC) against International Organization for Standardization (ISO)–specified microorganisms and clinical ocular isolates of Stenotrophomonas maltophilia. Methods: Six MPSs (PQ/Aldox 1, 2, and 3; PQ/Alexidine; PQ/PHMB; and PHMB) were challenged against ISO-specified microorganisms and S. maltophilia using the AEEMC test. AEEMC tests were performed with and without balafilcon A, etafilcon A, and senofilcon A lenses in lens cases with organic soil. Exposure times included disinfection time (DT) and 24 hr. Additionally, all six MPSs were challenged with two strains of S. maltophilia, based on the ISO Stand-alone test. Results: The efficacy against bacteria for PQ/Aldox and PQ/Alexidine MPSs was not diminished by the presence of lenses. The efficacy of PQ/PHMB and PHMB MPSs against Serratia marcescens was significantly reduced compared with the no-lens control at DT for at least one lens type. The PHMB MPS with lenses present also demonstrated reduced efficacy against Staphylococcus aureus at DT versus the control. PQ/Aldox MPSs retained activity against Fusarium solani with lenses present; however, all other test MPSs demonstrated reduced F. solani efficacy at DT with lenses present. With lenses, all MPSs showed reduced efficacy against Candida albicans. Conclusions: AEEMC antimicrobial efficacy test results vary based on challenge microorganism, contact lenses, and MPS biocide systems. This study highlights the importance of evaluating MPSs for compatibility with lenses and lens cases. PMID:27598555

Gender role attitudes, relationship efficacy, and self-disclosure in intimate relationships.

PubMed

Horne, Rebecca M; Johnson, Matthew D

2018-01-01

Drawing from the intimacy process model and data from 5,042 individuals who remained partnered across Waves 1 and 2 of the German Panel Analysis of Intimate Relationships and Family Dynamics (pairfam), this study examined the contributions of traditional gender role attitudes and relationship efficacy in predicting levels of self-disclosure within an intimate relationship. Independent samples t-tests demonstrated females scored higher than males on self-disclosure and relationship efficacy measures but lower on traditional gender role attitudes. An ordinary least squares regression analysis revealed relationship efficacy was a stronger predictor of self-disclosure compared to traditional gender role attitudes, which were not associated with self-disclosure. The findings suggest attitudes with an interpersonal motivational system may be especially important for setting the intimacy process into motion within an intimate union.

Effects of a simulated emergency airway management education program on the self-efficacy and clinical performance of intensive care unit nurses.

PubMed

Han, Myong-Ja; Lee, Ju-Ry; Shin, Yu-Jung; Son, Jeong-Suk; Choi, Eun-Joo; Oh, Yun-Hee; Lee, Soon-Haeng; Choi, Hye-Ran

2017-12-21

To examine the effects of a simulated emergency airway management education program on the self-efficacy and clinical performance among nurses in intensive care units. A one-group, pre- and post-test design was used. Thirty-five nurses who were working in adult intensive care units participated in this study. The simulation education program included lectures, skill demonstration, skill training, team-based practice, and debriefing. Self-efficacy and clinical performance questionnaires were completed before the program and 1 week after its completion. The data were analyzed by using descriptive statistics and the paired t-test to compare the mean differences between the pre-test and post-test. The scores before and after education were compared. After education, there was a significant improvement in the nurses' self-efficacy and clinical performance in emergency airway management situations. Simulation education effectively improved the self-efficacy and clinical performance of the nurses who were working in intensive care units. Based on the program for clinical nurses within a hospital, it will provide information that might advance clinical nursing education. © 2017 Japan Academy of Nursing Science.

Efficacy of Curcuma for Treatment of Osteoarthritis.

PubMed

Perkins, Kimberly; Sahy, William; Beckett, Robert D

2017-01-01

The objective of this review is to identify, summarize, and evaluate clinical trials to determine the efficacy of curcuma in the treatment of osteoarthritis. A literature search for interventional studies assessing efficacy of curcuma was performed, resulting in 8 clinical trials. Studies have investigated the effect of curcuma on pain, stiffness, and functionality in patients with knee osteoarthritis. Curcuma-containing products consistently demonstrated statistically significant improvement in osteoarthritis-related endpoints compared with placebo, with one exception. When compared with active control, curcuma-containing products were similar to nonsteroidal anti-inflammatory drugs, and potentially to glucosamine. While statistical significant differences in outcomes were reported in a majority of studies, the small magnitude of effect and presence of major study limitations hinder application of these results. Further rigorous studies are needed prior to recommending curcuma as an effective alternative therapy for knee osteoarthritis. © The Author(s) 2016.

Efficacy and tolerability of brivaracetam compared to lacosamide, eslicarbazepine acetate, and perampanel as adjunctive treatments in uncontrolled focal epilepsy: Results of an indirect comparison meta-analysis of RCTs.

PubMed

Brigo, Francesco; Bragazzi, Nicola Luigi; Nardone, Raffaele; Trinka, Eugen

2016-11-01

Brivaracetam (BRV), eslicarbazepine acetate (ESL), lacosamide (LCM), and perampanel (PER) have been recently marketed as adjunctive treatments for focal onset seizures. To date, no randomized controlled trial (RCT) has directly compared BRV with ESL, LCM, or PER. To compare BRV with the other add-on AEDs in patients with uncontrolled focal epilepsy, estimating their efficacy and tolerability through an adjusted, common-reference based indirect comparison meta-analysis. We systematically searched RCTs in which add-on treatment with ESL or LCM in patients with focal onset seizures have been compared with placebo. Efficacy and tolerability outcomes were considered. Random-effects Mantel-Haenszel meta-analyses were performed to obtain odds ratios (ORs) for the efficacy of BRV, LCM, ESL, or PER versus placebo. Adjusted indirect comparisons were then made between BRV and the other three AEDs using the obtained results, comparing the minimum and the highest effective recommended daily dose of each drug. Seventeen RCTs, with a total of 4971 patients were included. After adjusting for dose-effects, indirect comparisons showed no difference between BRV and LCM, ESL, or PER for responder rate and seizure freedom. Lower adverse events were observed with high dose BRV compared to high dose ESL or PER, but no difference was found in withdrawing because of adverse events. Indirect comparisons do not demonstrate a significant difference in efficacy between add-on BRV and LCM, ESL, or PER in focal epilepsy, and might suggest a better tolerability of BRV than ESL, and possibly also PER, at the highest effective recommended dose. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

The efficacy and integrity of shape memory alloy staples and bone anchors with ligament tethers in the fusionless treatment of experimental scoliosis.

PubMed

Braun, John T; Akyuz, Ephraim; Ogilvie, James W; Bachus, Kent N

2005-09-01

Scoliosis is a complex three-dimensional deformity with limited treatment options. Current treatments present potential problems that may be addressed with use of fusionless techniques for the correction of scoliosis. However, there are few data comparing the efficacy of different fusionless implant strategies in controlling scoliosis or on the integrity of rigid compared with flexible devices in an in vivo setting over time. The objective of this study was to compare the efficacy and integrity of rigid and flexible anterior thoracic tethers used to treat experimental scoliosis. Experimental scoliosis was created in twenty-four Spanish Cross-X female goats and was subsequently treated with either anterior shape memory alloy staples or anterior ligament tethers attached to bone anchors. Serial radiographs were analyzed to determine the efficacy of the implants in controlling scoliosis progression as well as the integrity of the implants at study completion. After the goats were killed, the implants were analyzed with use of three quantitative indices of implant integrity and implant pullout testing. Over the treatment period, scoliosis progressed from 77.3 degrees to 94.3 degrees in the goats treated with staples and was corrected from 73.4 degrees to 69.9 degrees in the goats treated with bone anchors, with loosening of eighteen of forty-two staples (two of the eighteen dislodged) and evidence of drift in two of forty-nine anchors. Histologic sections revealed a consistent halo of fibrous tissue around the staple tines but well-fixed bone anchors at all sites. Pullout testing demonstrated that bone anchors had greater strength than staples initially and at the study completion, with an increase in bone anchor fixation over the course of the study. In this scoliosis model, the flexible ligament tethers attached to bone anchors demonstrated greater efficacy and integrity than the more rigid shape memory alloy staples.

Systematic Review with Network Meta-Analysis: Comparative Efficacy of Biologics in the Treatment of Moderately to Severely Active Ulcerative Colitis

PubMed Central

Vickers, Adrian D.; Ainsworth, Claire; Mody, Reema; Bergman, Annika; Ling, Caroline S.; Medjedovic, Jasmina; Smyth, Michael

2016-01-01

Background Biological therapies are increasingly used to treat ulcerative colitis (UC). Aim To compare the efficacy of biologics in adults with moderately-to-severely active UC, stratified by prior exposure to anti-tumour necrosis factor (anti-TNF) therapy. Methods A systematic literature review was undertaken to identify studies of biologics approved for UC. Network meta-analysis was conducted for endpoints at induction and maintenance. Results Seven studies were included in the meta-analysis of induction treatment for anti-TNF therapy-naïve patients. All biologics were more effective than placebo in inducing clinical response, clinical remission, and mucosal healing. Infliximab demonstrated a statistically significant improvement over adalimumab in clinical response (odds ratio [OR] [95% credible interval (CrI)]: 2.19 [1.35–3.55]), clinical remission (OR [95% CrI]: 2.81 [1.49–5.49]), and mucosal healing (OR [95% CrI]: 2.23 [1.21–4.14]); there were no other significant differences between biologics for induction efficacy. Five studies were included in the meta-analysis of maintenance treatment, two studies rerandomised responder patients at end of induction, and three followed the same patients ‘straight through’. To account for design differences, the number of responders at end of induction was assumed to be equivalent to the number rerandomised. Vedolizumab showed significantly different durable clinical response from comparators (OR [95% CrI] infliximab 3.18 [1.14–9.20], golimumab 2.33 [1.04–5.41], and adalimumab 3.96 [1.67–9.84]). In anti-TNF therapy-experienced patients, only vedolizumab and adalimumab could be compared. At induction, no significant differences in efficacy were seen. During maintenance, vedolizumab showed significantly improved rates of mucosal healing versus adalimumab (OR [95% CrI]: 6.72 [1.36–41.0]). Conclusions This study expands the understanding of comparative efficacies of biologic treatments for UC, encompassing outcomes and populations not previously studied. All biologic treatments were effective for UC during induction. Vedolizumab demonstrated possible clinical benefits in the maintenance setting versus all comparators, irrespective of prior anti-TNF exposure and after adjusting for differences in study design. PMID:27776175

Efficacy of antidepressive medication for depression in Parkinson disease: a network meta-analysis

PubMed Central

Zhuo, Chuanjun; Xue, Rong; Luo, Lanlan; Ji, Feng; Tian, Hongjun; Qu, Hongru; Lin, Xiaodong; Jiang, Ronghuan; Tao, Ran

2017-01-01

Abstract Background: Parkinson disease (PD) was considered as the 2nd most prevalent neurodegenerative disorder after Alzheimer disease, while depression is a prevailing nonmotor symptom of PD. Typically used antidepression medication includes tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRI), serotonin and norepinephrine reuptake inhibitors (SNRI), monoamine-oxidase inhibitors (MAOI), and dopamine agonists (DA). Our study aimed at evaluating the efficacy of antidepressive medications for depression of PD. Methods: Web of Science, PubMed, Embase, and the Cochrane library were searched for related articles. Traditional meta-analysis and network meta-analysis (NMA) were performed with outcomes including depression score, UPDRS-II, UPDRS-III, and adverse effects. Surface under the cumulative ranking curve (SUCRA) was also performed to illustrate the rank probabilities of different medications on various outcomes. The consistency of direct and indirect evidence was also assessed by node-splitting method. Results: Results of traditional pairwise meta-analysis were performed. Concerning depression score, significant improvement was observed in AD, MAOI, SSRI, and SNRI compared with placebo. NMA was performed and more information could be obtained. DA was illustrated to be effective over placebo concerning UPDRS-III, MAOI, and SNRI. DA demonstrated a better prognosis in UPDRS-II scores compared with placebo and MAOI. However, DA and SSRI demonstrated a significant increase in adverse effects compared with placebo. The SUCRA value was calculated to evaluate the ranking probabilities of all medications on investigated outcomes, and the consistency between direct and indirect evidences was assessed by node-splitting method. Conclusion: SSRI had a satisfying efficacy for the depression of PD patients and could improve activities of daily living and motor function of patient but the adverse effects are unneglectable. SNRI are the safest medication with high efficacy for depression as well while other outcomes are relatively poor. PMID:28562526

Treatment of Chronic Hepatitis C in Patients Receiving Opioid Agonist Therapy: A Review of Best Practice.

PubMed

Norton, Brianna L; Akiyama, Matthew J; Zamor, Philippe J; Litwin, Alain H

2018-06-01

Injection drug use is the most common transmission route for hepatitis C. High rates of infection are observed among individuals on opioid agonist therapy. Although people who inject drugs carry the highest burden, few have initiated treatment. We present a comprehensive review of the evidence on the efficacy of HCV medications, drug-drug interactions, and barriers to and models of care. Studies have demonstrated comparable efficacy for individuals who are on opioid agonist therapy compared with those who are not. We propose that a strategy of treatment and cure-as-prevention is imperative in this population to curb the hepatitis C epidemic. Copyright © 2018 Elsevier Inc. All rights reserved.

The Activity of Antimicrobial Surfaces Varies by Testing Protocol Utilized

PubMed Central

Campos, Matias D.; Zucchi, Paola C.; Phung, Ann; Leonard, Steven N.; Hirsch, Elizabeth B.

2016-01-01

Background Contaminated hospital surfaces are an important source of nosocomial infections. A major obstacle in marketing antimicrobial surfaces is a lack of efficacy data based on standardized testing protocols. Aim We compared the efficacy of multiple testing protocols against several “antimicrobial” film surfaces. Methods Four clinical isolates were used: one Escherichia coli, one Klebsiella pneumoniae, and two Staphylococcus aureus strains. Two industry methods (modified ISO 22196 and ASTM E2149), a “dried droplet”, and a “transfer” method were tested against two commercially available antimicrobial films, one film in development, an untreated control, and a positive (silver) control film. At 2 (only ISO) and 24 hours following inoculation, bacteria were collected from film surfaces and enumerated. Results Compared to untreated films in all protocols, there were no significant differences in recovery on either commercial brand at 2 or 24 hours after inoculation. The silver surface demonstrated significant microbicidal activity (mean loss 4.9 Log10 CFU/ml) in all methods and time points with the exception of 2 hours in the ISO protocol and the transfer method. Using our novel droplet method, no differences between placebo and active surfaces were detected. The surface in development demonstrated variable activity depending on method, organism, and time point. The ISO demonstrated minimal activity at 2 hours but significant activity at 24 hours (mean 4.5 Log10 CFU/ml difference versus placebo). The ASTEM protocol exhibited significant differences in recovery of staphylococci (mean 5 Log10 CFU/ml) but not Gram-negative isolates (10 fold decrease). Minimal activity was observed with this film in the transfer method. Conclusions Varying results between protocols suggested that efficacy of antimicrobial surfaces cannot be easily and reproducibly compared. Clinical use should be considered and further development of representative methods is needed. PMID:27494336

In vivo cardiac cellular reprogramming efficacy is enhanced by angiogenic preconditioning of the infarcted myocardium with vascular endothelial growth factor.

PubMed

Mathison, Megumi; Gersch, Robert P; Nasser, Ahmed; Lilo, Sarit; Korman, Mallory; Fourman, Mitchell; Hackett, Neil; Shroyer, Kenneth; Yang, Jianchang; Ma, Yupo; Crystal, Ronald G; Rosengart, Todd K

2012-12-01

In situ cellular reprogramming offers the possibility of regenerating functional cardiomyocytes directly from scar fibroblasts, obviating the challenges of cell implantation. We hypothesized that pretreating scar with gene transfer of the angiogenic vascular endothelial growth factor (VEGF) would enhance the efficacy of this strategy. Gata4, Mef2c, and Tbx5 (GMT) administration via lentiviral transduction was demonstrated to transdifferentiate rat fibroblasts into (induced) cardiomyocytes in vitro by cardiomyocyte marker studies. Fisher 344 rats underwent coronary ligation and intramyocardial administration of an adenovirus encoding all 3 major isoforms of VEGF (AdVEGF-All6A(+)) or an AdNull control vector (n=12/group). Lentivirus encoding GMT or a GFP control was administered to each animal 3 weeks later, followed by histologic and echocardiographic analyses. GMT administration reduced the extent of fibrosis by half compared with GFP controls (12 ± 2% vs 24 ± 3%, P<0.01) and reduced the number of myofibroblasts detected in the infarct zone by 4-fold. GMT-treated animals also demonstrated greater density of cardiomyocyte-specific marker beta myosin heavy chain 7(+) cells compared with animals receiving GFP with or without VEGF (P<0.01). Ejection fraction was significantly improved after GMT vs GFP administration (12 ± 3% vs -7 ± 3%, P<0.01). Eight (73%) GFP animals but no GMT animals demonstrated decreased ejection fraction during this interval (P<0.01). Also, improvement in ejection fraction was 4-fold greater in GMT/VEGF vs GMT/null animals (17 ± 2% vs 4 ± 1%, P<0.05). VEGF administration to infarcted myocardium enhances the efficacy of GMT-mediated cellular reprogramming in improving myocardial function and reducing the extent of myocardial fibrosis compared with the use of GMT or VEGF alone.

Efficacy and safety of herbal medicines in treating gastric ulcer: A review

PubMed Central

Bi, Wei-Ping; Man, Hui-Bin; Man, Mao-Qiang

2014-01-01

Gastric ulcer is a common disorder of the digestive system. Current therapeutic regimens largely rely on Western medicine. However, numerous studies have demonstrated that herbal medicines can effectively treat gastric ulcer in humans and various animal models via divergent mechanisms. This review updates the efficacy and safety of herbal medicines in treating gastric ulcer, and the mechanisms of their action in humans and animal models. Studies have demonstrated that the efficacy of herbal medicines is comparable or superior to that of drugs such as omeprazole or cimetidine in humans and animal models, and herbal medicines display fewer adverse effects. The mechanisms by which herbal medicines benefit gastric ulcer include stimulation of mucous cell proliferation, anti-oxidation, and inhibition of gastric acid secretion and H(+)/K(+)-ATPase activity. Some herbal medicines also exhibit antimicrobial properties. Utilization of herbal medicines could be a valuable alternative to treat gastric ulcer in humans effectively, with few adverse effects. PMID:25493014

Pharmacokinetics of Intranasal Scopolamine Gel Formulation (Inscop)

NASA Technical Reports Server (NTRS)

Boyd, Jason L.; Du, Brian; Daniels, Vernie; Simmons, Rita; Buckey, Jay; Putcha, Lakshmi

2009-01-01

Space Motion Sickness (SMS) is commonly experienced by astronauts and often requires treatment with medications during early flight days of space missions. Orally administered scopolamine is commonly used by astronauts to prevent SMS. Bioavailability of oral (PO) SMS medications is often low and highly variable. Intranasal (IN) administration of medications achieves higher and more reliable bioavailability than from an equivalent PO dose. Methods: To test the safety and reliability of INSCOP, two clinical studies were performed, a dose escalation study and a comparison study administering INSCOP during normal ambulation and head down tilt bedrest. Efficacy was evaluated by testing INSCOP with two, different motion sickness inducing paradigms. Results: Preliminary results indicate that INSCOP demonstrates linear pharmacokinetics and a low side effect profile. In head down tilt bedrest, relative bioavailability of INSCOP was increased for females at both doses (0.2 and 0.4 mg) and for males at the higher dose (0.4 mg) but is reduced at the lower dose (0.2 mg) compared to normal ambulation. INSCOP displays gender specific differences during ABR. One of the treatment efficacy trials conducted at Dartmouth Hitchcock Medical Center demonstrated that INSCOP is efficacious at both doses (0.2 and 0.4 mg) in suppressing motion sickness symptoms as indicated by longer chair ride times with INSCOP administration than with placebo, and efficacy increases with dose. Similar results were seen using another motion sickness simulator, the motion simulator dome, at the Naval Aerospace Medical Research Laboratory, with significantly increased time in the dome in motion-susceptible subjects when using INSCOP compared to untreated controls. Conclusion: Higher bioavailability, linear pharmacokinetics, a low incidence of side effects, and a favorable efficacy profile make INSCOP a desirable formulation for prophylactic and rescue treatment of astronauts in space and military personnel on duty.

A survey study comparing young adults with MS and healthy controls on self-esteem, self-efficacy, mood and quality of life.

PubMed

Messmer Uccelli, Michele; Traversa, Silvia; Ponzio, Michela

2016-09-15

Studies have shown that people with multiple sclerosis (MS) report low levels of self-efficacy and self-esteem, high levels of anxiety and depression and reduced quality of life. The study aims to assess self-esteem, self-efficacy, mood and quality of life in young adults with MS and to compare them to a healthy control group. The age range for inclusion in the study was between 18 and 35years of age for both groups. Subjects with MS were recruited through the Italian MS Society. Healthy controls were recruited through social media and from a university undergraduate program. Subjects completed an anonymous online questionnaire combining various scales. Group differences on demographic data were assessed using parametric and non-parametric tests. Analyses of covariance (ANCOVA) were performed to evaluate differences between the two groups on scales of self-perception, mood and quality of life, adjusting for potentially confounding factors. Eighty-nine subjects with MS and 109 HC were included in the analysis. ANCOVA failed to demonstrate statistically significant differences between groups on self-esteem (F=0.11, p=0.743), self-efficacy (F=2.22, p=0.138), mood (anxiety F=0.03, p=0.855; depression F=0.06, p=0.812) and quality of life (F=0.08, p=0.772). This study demonstrated that young adults with MS and healthy controls have similar levels of self-esteem and self-efficacy and that they do not differ significantly on measures of mood and quality of life, as previously reported. Copyright © 2016. Published by Elsevier B.V.

Cadexomer iodine provides superior efficacy against bacterial wound biofilms in vitro and in vivo.

PubMed

Fitzgerald, Daniel J; Renick, Paul J; Forrest, Emma C; Tetens, Shannon P; Earnest, David N; McMillan, Jillian; Kiedaisch, Brett M; Shi, Lei; Roche, Eric D

2017-01-01

Examination of clinical samples indicates bacterial biofilms are present in the majority of chronic wounds, and substantial evidence suggests biofilms contribute significantly to delayed healing. Bacteria in biofilms are highly tolerant of antimicrobials, and little data exist to guide the choice of anti-biofilm wound therapy. Cadexomer iodine (CI) was recently reported to have superior efficacy compared to diverse wound dressings against Pseudomonas aeruginosa biofilms in an ex vivo model. In the current study, the strong performance of CI vs. P. aeruginosa biofilm was confirmed using colony and colony drip-flow in vitro wound biofilm models. Similar in vitro efficacy of CI was also demonstrated against mature Staphylococcus aureus biofilms using the same models. Additionally, the rapid kill of mature S. aureus and P. aeruginosa colony biofilms was visualized by confocal microscopy using Live/Dead fluorescent stains. Superior in vitro efficacy of CI vs. staphylococcal biofilms was further demonstrated against methicillin-resistant S. aureus (MRSA) using multiple biofilm models with log reduction, Live/Dead, and metabolic endpoints. Comparator antimicrobial dressings, including silver-based dressings used throughout and other active agents used in individual models, elucidated only limited effects against the mature biofilms. Given the promising in vitro activity, CI was tested in an established mouse model of MRSA wound biofilm. CI had significantly greater impact on MRSA biofilm in mouse wounds than silver dressings or mupirocin based on Gram-stained histology sections and quantitative microbiology from biopsy samples (>4 log reduction in CFU/g vs. 0.7-1.6, p < 0.0001). The superior efficacy for CI in these in vitro and in vivo models suggests CI topical products may represent a better choice to address established bacterial biofilm in chronic wounds. © 2016 by the Wound Healing Society.

Best methods for evaluating educational impact: a comparison of the efficacy of commonly used measures of library instruction

PubMed Central

Schilling, Katherine; Applegate, Rachel

2012-01-01

Objectives and Background: Libraries are increasingly called upon to demonstrate student learning outcomes and the tangible benefits of library educational programs. This study reviewed and compared the efficacy of traditionally used measures for assessing library instruction, examining the benefits and drawbacks of assessment measures and exploring the extent to which knowledge, attitudes, and behaviors actually paralleled demonstrated skill levels. Methods: An overview of recent literature on the evaluation of information literacy education addressed these questions: (1) What evaluation measures are commonly used for evaluating library instruction? (2) What are the pros and cons of popular evaluation measures? (3) What are the relationships between measures of skills versus measures of attitudes and behavior? Research outcomes were used to identify relationships between measures of attitudes, behaviors, and skills, which are typically gathered via attitudinal surveys, written skills tests, or graded exercises. Results and Conclusions: Results provide useful information about the efficacy of instructional evaluation methods, including showing significant disparities between attitudes, skills, and information usage behaviors. This information can be used by librarians to implement the most appropriate evaluation methods for measuring important variables that accurately demonstrate students' attitudes, behaviors, or skills. PMID:23133325

Best methods for evaluating educational impact: a comparison of the efficacy of commonly used measures of library instruction.

PubMed

Schilling, Katherine; Applegate, Rachel

2012-10-01

Libraries are increasingly called upon to demonstrate student learning outcomes and the tangible benefits of library educational programs. This study reviewed and compared the efficacy of traditionally used measures for assessing library instruction, examining the benefits and drawbacks of assessment measures and exploring the extent to which knowledge, attitudes, and behaviors actually paralleled demonstrated skill levels. An overview of recent literature on the evaluation of information literacy education addressed these questions: (1) What evaluation measures are commonly used for evaluating library instruction? (2) What are the pros and cons of popular evaluation measures? (3) What are the relationships between measures of skills versus measures of attitudes and behavior? Research outcomes were used to identify relationships between measures of attitudes, behaviors, and skills, which are typically gathered via attitudinal surveys, written skills tests, or graded exercises. Results provide useful information about the efficacy of instructional evaluation methods, including showing significant disparities between attitudes, skills, and information usage behaviors. This information can be used by librarians to implement the most appropriate evaluation methods for measuring important variables that accurately demonstrate students' attitudes, behaviors, or skills.

Efficacy of Four Solanum spp. Extracts in an Animal Model of Cutaneous Leishmaniasis.

PubMed

Cos, Paul; Janssens, Jo; Piñón, Abel; Cuesta-Rubio, Osmany; Yglesias-Rivera, Arianna; Díaz-García, Alexis; Vilegas, Wagner; Monzote, Lianet

2018-06-05

Background: Leishmaniasis is a complex protozoa disease caused by Leishmania genus (Trypanosomatidae family). Currently, there have been renewed interests worldwide in plants as pharmaceutical agents. In this study, the in vivo efficacy of Solanum spp. is assessed in an L. amazonensis BALB/c mice model for experimental cutaneous leishmaniasis. Methods: Animals were infected with 5 × 10⁶ metacyclic promastigotes and 30-day post-infection, a treatment with 30 mg/kg of Solanum extracts or Glucantime ® (GTM) was applied intralesionally every four days to complete 5 doses. Results: Neither death nor loss of weight higher than 10% was observed. All the tested extracts were able to control the infection, compared with the infected and untreated group. Solanum havanense Jacq. extract showed the highest efficacy and was superior ( p < 0.05) to GTM. Solanum myriacanthum Dunal., S. nudum Dunal. and S. seaforthianum Andr. extracts demonstrated a similar effect ( p > 0.05) to GTM. An increase of IFN-γ ( p < 0.05) was displayed only by animals treated with S. nudum compared to the group treated with a vehicle, while no differences ( p > 0.05) were observed for IL-12. Conclusions: In vivo effects of Solanum extracts were demonstrated, suggesting that this genus could be further explored as a new antileishmanial alternative.

The Bruton Tyrosine Kinase (BTK) Inhibitor Acalabrutinib Demonstrates Potent On-Target Effects and Efficacy in Two Mouse Models of Chronic Lymphocytic Leukemia.

PubMed

Herman, Sarah E M; Montraveta, Arnau; Niemann, Carsten U; Mora-Jensen, Helena; Gulrajani, Michael; Krantz, Fanny; Mantel, Rose; Smith, Lisa L; McClanahan, Fabienne; Harrington, Bonnie K; Colomer, Dolors; Covey, Todd; Byrd, John C; Izumi, Raquel; Kaptein, Allard; Ulrich, Roger; Johnson, Amy J; Lannutti, Brian J; Wiestner, Adrian; Woyach, Jennifer A

2017-06-01

Purpose: Acalabrutinib (ACP-196) is a novel, potent, and highly selective Bruton tyrosine kinase (BTK) inhibitor, which binds covalently to Cys481 in the ATP-binding pocket of BTK. We sought to evaluate the antitumor effects of acalabrutinib treatment in two established mouse models of chronic lymphocytic leukemia (CLL). Experimental Design: Two distinct mouse models were used, the TCL1 adoptive transfer model where leukemic cells from Eμ-TCL1 transgenic mice are transplanted into C57BL/6 mice, and the human NSG primary CLL xenograft model. Mice received either vehicle or acalabrutinib formulated into the drinking water. Results: Utilizing biochemical assays, we demonstrate that acalabrutinib is a highly selective BTK inhibitor as compared with ibrutinib. In the human CLL NSG xenograft model, treatment with acalabrutinib demonstrated on-target effects, including decreased phosphorylation of PLCγ2, ERK, and significant inhibition of CLL cell proliferation. Furthermore, tumor burden in the spleen of the mice treated with acalabrutinib was significantly decreased compared with vehicle-treated mice. Similarly, in the TCL1 adoptive transfer model, decreased phosphorylation of BTK, PLCγ2, and S6 was observed. Most notably, treatment with acalabrutinib resulted in a significant increase in survival compared with mice receiving vehicle. Conclusions: Treatment with acalabrutinib potently inhibits BTK in vivo , leading to on-target decreases in the activation of key signaling molecules (including BTK, PLCγ2, S6, and ERK). In two complementary mouse models of CLL, acalabrutinib significantly reduced tumor burden and increased survival compared with vehicle treatment. Overall, acalabrutinib showed increased BTK selectivity compared with ibrutinib while demonstrating significant antitumor efficacy in vivo on par with ibrutinib. Clin Cancer Res; 23(11); 2831-41. ©2016 AACR . ©2016 American Association for Cancer Research.

The Bruton’s tyrosine kinase (BTK) inhibitor acalabrutinib demonstrates potent on-target effects and efficacy in two mouse models of chronic lymphocytic leukemia

PubMed Central

Herman, Sarah E. M.; Montraveta, Arnau; Niemann, Carsten U.; Mora-Jensen, Helena; Gulrajani, Michael; Krantz, Fanny; Mantel, Rose; Smith, Lisa L.; McClanahan, Fabienne; Harrington, Bonnie K.; Colomer, Dolors; Covey, Todd; Byrd, John C.; Izumi, Raquel; Kaptein, Allard; Ulrich, Roger; Johnson, Amy J.; Lannutti, Brian J.; Wiestner, Adrian; Woyach, Jennifer A.

2017-01-01

Purpose Acalabrutinib (ACP-196) is a novel, potent, and highly selective BTK inhibitor, which binds covalently to Cys481 in the ATP-binding pocket of BTK. We sought to evaluate the anti-tumor effects of acalabrutinib treatment in two established mouse models of chronic lymphocytic leukemia (CLL). Experimental Design Two distinct mouse models were used, the TCL1 adoptive transfer model where leukemic cells from Eμ-TCL1 transgenic mice are transplanted into C57BL/6 mice, and the human NSG primary CLL xenograft model. Mice received either vehicle or acalabrutinib formulated into the drinking water. Results Utilizing biochemical assays we demonstrate that acalabrutinib is a highly selective BTK inhibitor as compared to ibrutinib. In the human CLL NSG xenograft model, treatment with acalabrutinib demonstrated on-target effects including decreased phosphorylation of PLCγ2, ERK and significant inhibition of CLL cell proliferation. Further, tumor burden in the spleen of the mice treated with acalabrutinib was significantly decreased compared to vehicle treated mice. Similarly, in the TCL1 adoptive transfer model, decreased phosphorylation of BTK, PLCγ2 and S6 was observed. Most notably, treatment with acalabrutinib resulted in a significant increase in survival compared to mice receiving vehicle. Conclusions Treatment with acalabrutinib potently inhibits BTK in vivo, leading to on-target decreases in the activation of key signaling molecules (including BTK, PLCγ2, S6 and ERK). In two complementary mouse models of CLL acalabrutinib significantly reduced tumor burden and increased survival compared to vehicle treatment. Overall, acalabrutinib showed increased BTK selectivity compared to ibrutinib while demonstrating significant anti-tumor efficacy in vivo on par with ibrutinib. PMID:27903679

Acceptance and commitment therapy - Do we know enough? Cumulative and sequential meta-analyses of randomized controlled trials.

PubMed

Hacker, Thomas; Stone, Paul; MacBeth, Angus

2016-01-15

Acceptance and Commitment Therapy (ACT) has accrued a substantial evidence base. Recent systematic and meta-analytic reviews suggest that ACT is effective compared to control conditions. However, these reviews appraise the efficacy of ACT across a broad range of presenting problems, rather than addressing specific common mental health difficulties. Focussing on depression and anxiety we performed a meta-analysis of trials of ACT. We incorporated sequential meta-analysis (SMA) techniques to critically appraise the sufficiency of the existing evidence base. Findings suggest that ACT demonstrates at least moderate group and pre-post effects for symptom reductions for both anxiety and depression. However using SMA findings are more qualified. There is currently insufficient evidence to confidently conclude that ACT for anxiety is efficacious when compared to active control conditions or as primary treatment for anxiety. Similarly, using SMA, there is currently insufficient evidence to suggest a moderate efficacy of ACT for depression compared to active control conditions. To stimulate further research we offer specific estimates of additional numbers of participants required to reach sufficiency to help inform future studies. We also discuss the appropriate strategies for future research into ACT for anxiety given the current evidence suggests no differential efficacy of ACT in the treatment of anxiety compared to active control conditions. Copyright © 2015 Elsevier B.V. All rights reserved.

Type D Personality, Self-Efficacy, and Medication Adherence in Patients with Heart Failure

PubMed Central

Wu, Jia-Rong; Song, Eun Kyeung; Moser, Debra K.

2015-01-01

Background Type D personality is a known predictor of non-adherence to prescribed medication regimens among patients with heart failure (HF). Both Type D personality and non-adherence are independent predictors of poor health outcomes among HF patients. Self-efficacy, which is modifiable, is also associated with medication adherence. Objectives To determine the relationships among Type D personality, medication self-efficacy, and medication adherence in 84 patients with HF. Methods Medication self-efficacy, Type D personality, medication adherence, demographic and clinical data were collected. Hierarchical linear regression and mediation analyses were used. Results Type D patients were more likely to have lower medication self-efficacy (p = .023) and poorer medication adherence (p = .027) compared with non-Type D patients. Low medication self-efficacy was associated with poor medication adherence (p < .001). Type D did not predict (p = .422) medication adherence after entering medication self-efficacy in the model demonstrating that medication self-efficacy was a mediator of the relationship between Type D and medication adherence. Conclusions Medication self-efficacy mediates the relationship between Type D personality and medication adherence. Developing and applying interventions to enhance medication self-efficacy for Type D patients may help to sever the link between Type D personality and poor outcomes. PMID:25979573

Comparative Efficacy and Acceptability of Anti-Diabetic Agents for Alzheimer's Disease and Mild Cognitive Impairment: A Systematic Review and Network Meta-analysis.

PubMed

Cao, Bing; Rosenblat, Joshua D; Brietzke, Elisa; Park, Caroline; Lee, Yena; Musial, Natalie; Pan, Zihang; Mansur, Rodrigo B; McIntyre, Roger S

2018-05-23

The current meta-analysis compares the efficacy (i.e., pro-cognitive effects) and acceptability of anti-diabetic agents for Alzheimer's disease (AD) and mild cognitive impairment (MCI). Cochrane Library (CENTRAL), PubMed/MEDLINE, EMBASE and PsycINFO were searched from inception to January 15, 2018 for randomized controlled trials (RCTs) comparing anti-diabetic agents with placebo and/or another active anti-diabetic agent for the treatment of AD or MCI. Nineteen eligible studies (n = 4,855) evaluating the effects of six different anti-diabetic drugs (i.e., intranasal insulin, pioglitazone, rosiglitazone, metformin, sitagliptin and liraglutide) were included. The results of 29 pairwise comparisons indicated that cognition was significantly improved in subjects treated with anti-diabetic agents compared to placebo. Pioglitazone 15-30 mg demonstrated the greatest efficacy compared to placebo in network meta-analysis. No significant differences in acceptability were identified when comparing agents with each other and with placebo. The current findings indicate a pro-cognitive class effect of anti-diabetic agents in AD/MCI. Other anti-diabetic agents should also be investigated in future studies. This study is registered with PROSPERO (CRD42018085967). This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

What is the role of combination drug therapy in the treatment of overactive bladder? ICI-RS 2014.

PubMed

Visco, Anthony G; Fraser, Matthew O; Newgreen, Donald; Oelke, Matthias; Cardozo, Linda

2016-02-01

The role of combination therapy using oral antimuscarinic medications for the treatment of overactive bladder was proposed at the 2014 International Consultation on Incontinence-Research Society in Bristol, UK to identify key factors to consider when making clinical decisions and to guide future research design. Combination therapy is justified if monotherapy is associated with suboptimal efficacy or bothersome side effects. Combination therapy has the potential to improve efficacy with fewer side effects than monotherapy. Two Phase 2 studies comparing combination therapy that included an antimuscarinic demonstrated improvement in mean voided volume, the primary outcome chosen, with some combinations showing improved micturition frequency and quality of life. The two studies found no evidence of an increased safety risk with combination therapy compared to monotherapy. Future studies should use clinically meaningful or patient reported outcomes such as incontinence episodes when comparing efficacy. If surrogate measures are used, a clear justification should be provided. Cost analyses should be planned for clinical research trials evaluating combination drug therapy. Combination therapy is reasonable when monotherapy has suboptimal efficacy or bothersome side effects. Future research studies evaluating combination therapy for urgency urinary incontinence should ideally(1) be performed as part of a randomized clinical trial,(2) evaluate non-responders to monotherapy,(3) evaluate combination therapy using medications with different mechanisms of action,(4) include clinically meaningful and patient reported outcomes when evaluating efficacy, and(5) include cost-effectiveness analyses to justify any increased cost by showing improvement in efficacy or reduction in side effects. © 2016 Wiley Periodicals, Inc.

Sex Differences in Varenicline Efficacy for Smoking Cessation: A Meta-Analysis

PubMed Central

Smith, Philip H.; Kaufman, Mira; Mazure, Carolyn M.; Weinberger, Andrea H.

2016-01-01

Abstract Introduction: Women have lower rates of quitting than men with both bupropion and nicotine replacement. It is unknown whether varenicline demonstrates differential efficacy for men and women. The purpose of this study was to conduct the first comprehensive meta-analysis of clinical trial data examining sex differences in the efficacy of varenicline for smoking cessation. Methods: Searching MEDLINE, EMBASE, and PsychINFO, 17 of 43 clinical trials of varenicline for smoking cessation published through December 31, 2014 were low-bias randomized double-blind placebo-controlled trials. Data ( n = 6710 smokers, 34% female, n = 16 studies, 96% of available data) was analyzed with Metafor program in R. Outcome endpoints were 7-day point-prevalence (PP) and continuous-abstinence (CA) at week 12 (end of treatment), week 24 (6-month follow-up), and week 52 (12-month follow-up). Results: Using placebo, women were less likely than men to quit (PP-12, CA-24; P < .05 for sex). Using varenicline, similar rates of abstinence for men and women were demonstrated for all six outcomes (eg, PP-12 abstinence rates were 53% in both women and men). Varenicline versus placebo outcomes demonstrated that varenicline was more effective for women for short and intermediate outcomes (PP-12, CA-12, CA-24; P < .05 sex × medication interaction). For end-of-treatment PP, varenicline was 46% more effective for women. For continuous abstinence, varenicline was 34% (CA-12) and 31% (CA-24) more effective for women. Conclusions: Unlike other smoking cessation medications, varenicline demonstrated greater efficacy among women smokers for short and immediate-term outcomes and equal efficacy for 1-year outcomes. Varenicline may be particularly useful for reducing the sex disparity typically seen in rates of smoking cessation. Implications: Varenicline is currently the most effective FDA-approved smoking cessation medication and this is the first demonstration that women compared with men have a preferred therapeutic response for a smoking cessation medication when considering short-term outcomes. Importantly, this is also the first demonstration that women have similar rates of quitting to men when considering longer-term, 1-year outcomes. PMID:26446070

Attention and interpretation bias modification treatment for social anxiety disorder: A randomized clinical trial of efficacy and synergy.

PubMed

Naim, Reut; Kivity, Yogev; Bar-Haim, Yair; Huppert, Jonathan D

2018-06-01

Attention bias modification treatment (ABMT) and cognitive bias modification of interpretation (CBM-I) both have demonstrated efficacy in alleviating social anxiety, but how they compare with each other, their combination, and with a combined control condition has not been studied. We examined their relative and combined efficacy compared to control conditions in a randomized controlled trial (RCT). Ninety-five adults diagnosed with social anxiety disorder (SAD), were randomly allocated to 4 groups: ABMT + CBM-I control (hereafter ABMT; n = 23), CBM-I + ABMT control (hereafter CBM-I; n = 24), combined ABMT + CBM-I (n = 23), and combined control (n = 25). Treatment included eight sessions over four weeks. Clinician-rated and self-reported measures of social anxiety symptoms, functional impairment, and threat-related attention and interpretive biases were evaluated at baseline, post-treatment, and 3-month follow-up. ABMT yielded greater symptom reduction as measured by both clinician-ratings (Cohen's ds = 0.57-0.70) and self-reports (ds = 0.70-0.85) compared with the CBM-I, the combined ABMT + CBM-I, and the combined control conditions. Neither of the other conditions demonstrated superior symptom change compared to the control condition. No group differences were found for functioning or cognitive biases measures. Limitations mainly include the mix of active and control treatments applied across the different groups. Therefore, the net effect of each of the treatments by itself could not be clearly tested. Results suggest superiority of ABMT compared to CBM-I and their combination in terms of symptom reduction. Possible interpretations and methodological issues underlying the observed findings are discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

A pilot study of the comparative efficacy of 100 Hz magnetic seizure therapy and electroconvulsive therapy in persistent depression.

PubMed

Fitzgerald, Paul B; Hoy, Kate E; Elliot, David; McQueen, Susan; Wambeek, Lenore E; Chen, Leo; Clinton, Anne Maree; Downey, Glenn; Daskalakis, Zafiris J

2018-05-01

Magnetic seizure therapy (MST) is a novel brain stimulation technique that uses a high-powered transcranial magnetic stimulation device to produce therapeutic seizures. Preliminary MST studies have found antidepressant effects in the absence of cognitive side effects but its efficacy compared to electroconvulsive therapy (ECT) remains unclear. The aim of this study was to investigate the therapeutic efficacy and cognitive profile of MST compared to standard right unilateral ECT treatment. Thirty-seven patients completed a course of at least nine ECT or MST treatments in a randomized double-blind protocol. Assessments of depression severity and cognition were performed before and after treatment. No difference in the antidepressant effectiveness between the treatments was seen across any of the clinical outcome measures, although the overall response rates in both groups were quite low. In regards to cognition, following MST there were significant improvements in tests of psychomotor speed, verbal memory, and cognitive inhibition, with no reductions in cognitive performance. Following ECT there was significant improvement in only one of the cognitive inhibition tasks. With respect to the between-group comparisons, the MST group showed a significantly greater improvement on psychomotor speed than ECT. MST showed similar efficacy to right unilateral ECT in patients with treatment-resistant depression without cognitive side effects but in a sample that was only of sufficient size to demonstrate relatively large differences in response between the two groups. Future research should aim to optimize the methods of MST administration and compare its efficacy to ECT in large randomized controlled trials. © 2018 Wiley Periodicals, Inc.

A method to rapidly and accurately compare relative efficacies of non-invasive imaging reporter genes in a mouse model, and its application to luciferase reporters

PubMed Central

Gil, Jose S.; Machado, Hidevaldo B.; Herschman, Harvey R.

2013-01-01

Purpose Our goal is to develop a simple, quantitative, robust method to compare the efficacy of imaging reporter genes in culture and in vivo. We describe an adenoviral vector-liver transduction procedure, and compare the luciferase reporter efficacies. Procedures Alternative reporter genes are expressed in a common adenoviral vector. Vector amounts used in vivo are based on cell culture titrations, ensuring the same transduction efficacy is used for each vector. After imaging, in vivo and in vitro values are normalized to hepatic vector transduction using quantitative real-time PCR. Results We assayed standard firefly luciferase (FLuc), enhanced firefly luciferase (EFLuc), luciferase 2 (Luc2), humanized Renilla luciferase (hRLuc), Renilla luciferase 8.6-535 (RLuc8.6), and a membrane-bound Gaussia luciferase variant (extGLuc) in cell culture and in vivo. We observed a greater that 100-fold increase in bioluminescent signal for both EFLuc and Luc2 when compared to FLuc, and a greater than 106-fold increase for RLuc8.6 when compared to hRLuc. ExtGLuc was not detectable in liver. Conclusions Our findings contrast, in some cases, with conclusions drawn in prior comparisons of these reporter genes, and demonstrate the need for a standardized method to evaluate alternative reporter genes in vivo. Our procedure can be adapted for reporter genes that utilize alternative imaging modalities (fluorescence, bioluminescence, MRI, SPECT, PET). PMID:21850545

The Relationship between Falls Efficacy and Improvement in Fall Risk Factors Following an Exercise Plus Educational Intervention for Older Adults with Hip Osteoarthritis.

PubMed

Arnold, C M; Faulkner, R A; Gyurcsik, N C

2011-01-01

Older adults with decreased confidence in their ability to prevent a fall may benefit from an exercise programme that includes self-efficacy-enhancing education. The objectives of this study were to explore differences in fall-risk outcomes in older adults with higher vs. lower levels of falls efficacy and to evaluate the relationship between baseline falls-efficacy status and changes in fall risk factors following two interventions. Fifty-four older adults with hip osteoarthritis and at least one risk factor for falls received aquatic exercise twice weekly plus education once weekly (EE) or aquatic exercise only, twice weekly (EO), for 11 weeks. EE participants with low baseline falls efficacy demonstrated significantly (p<0.05) greater improvement in balance and falls efficacy compared to EE participants with high baseline falls efficacy. In the EE group only, baseline falls-efficacy status (low vs. high median split on the Activities-specific Balance Confidence Scale) was significantly (p<0.05) correlated with positive balance and falls-efficacy change scores (Spearman rank r=0.45 and 0.63 respectively). Individuals with one or more fall-risk factors and low falls efficacy may benefit from receiving an intervention that combines exercise with self-efficacy-enhancing education. Falls-efficacy screening may be important for decisions regarding referral to fall-prevention programmes.

The Relationship between Falls Efficacy and Improvement in Fall Risk Factors Following an Exercise Plus Educational Intervention for Older Adults with Hip Osteoarthritis

PubMed Central

Faulkner, R.A.; Gyurcsik, N.C.

2011-01-01

ABSTRACT Purpose: Older adults with decreased confidence in their ability to prevent a fall may benefit from an exercise programme that includes self-efficacy-enhancing education. The objectives of this study were to explore differences in fall-risk outcomes in older adults with higher vs. lower levels of falls efficacy and to evaluate the relationship between baseline falls-efficacy status and changes in fall risk factors following two interventions. Method: Fifty-four older adults with hip osteoarthritis and at least one risk factor for falls received aquatic exercise twice weekly plus education once weekly (EE) or aquatic exercise only, twice weekly (EO), for 11 weeks. Results: EE participants with low baseline falls efficacy demonstrated significantly (p<0.05) greater improvement in balance and falls efficacy compared to EE participants with high baseline falls efficacy. In the EE group only, baseline falls-efficacy status (low vs. high median split on the Activities-specific Balance Confidence Scale) was significantly (p<0.05) correlated with positive balance and falls-efficacy change scores (Spearman rank r=0.45 and 0.63 respectively). Conclusions: Individuals with one or more fall-risk factors and low falls efficacy may benefit from receiving an intervention that combines exercise with self-efficacy-enhancing education. Falls-efficacy screening may be important for decisions regarding referral to fall-prevention programmes. PMID:22942514

A Model for Evaluating Topical Antimicrobial Efficacy against Methicillin-Resistant Staphylococcus aureus Biofilms in Superficial Murine Wounds

PubMed Central

Renick, Paul J.; Tetens, Shannon P.; Carson, Dennis L.

2012-01-01

A wound biofilm model was created by adapting a superficial infection model. Partial-thickness murine wounds were inoculated with methicillin-resistant Staphylococcus aureus (MRSA). Dense biofilm communities developed at the wound surface after 24 h as demonstrated by microscopy and quantitative microbiology. Common topical antimicrobial agents had reduced efficacy when treatment was initiated 24 h after inoculation compared to 4 h after inoculation. This model provides a rapid in vivo test for new agents to treat wound biofilm infections. PMID:22644024

Update on tolterodine extended-release for treatment of overactive bladder

PubMed Central

Omotosho, Tola; Chen, Chi Chiung Grace

2010-01-01

Overactive bladder is a prevalent condition which negatively impacts quality of life and puts a significant economical burden on society. First-line therapy often includes pharmacotherapy with antimuscarinic medications, and numerous research studies have demonstrated that tolterodine extended-release (ER) is an efficacious and tolerable formulation of this class of medication. This review provides an update on the clinical use of tolterodine ER, detailing the current literature on its efficacy, tolerability, adverse effects, and comparability with other commonly prescribed medications for the treatment of overactive bladder. PMID:24198627

Vitamin D and Depression: A Systematic Review and Meta-Analysis Comparing Studies with and without Biological Flaws

PubMed Central

Spedding, Simon

2014-01-01

Efficacy of Vitamin D supplements in depression is controversial, awaiting further literature analysis. Biological flaws in primary studies is a possible reason meta-analyses of Vitamin D have failed to demonstrate efficacy. This systematic review and meta-analysis of Vitamin D and depression compared studies with and without biological flaws. The systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The literature search was undertaken through four databases for randomized controlled trials (RCTs). Studies were critically appraised for methodological quality and biological flaws, in relation to the hypothesis and study design. Meta-analyses were performed for studies according to the presence of biological flaws. The 15 RCTs identified provide a more comprehensive evidence-base than previous systematic reviews; methodological quality of studies was generally good and methodology was diverse. A meta-analysis of all studies without flaws demonstrated a statistically significant improvement in depression with Vitamin D supplements (+0.78 CI +0.24, +1.27). Studies with biological flaws were mainly inconclusive, with the meta-analysis demonstrating a statistically significant worsening in depression by taking Vitamin D supplements (−1.1 CI −0.7, −1.5). Vitamin D supplementation (≥800 I.U. daily) was somewhat favorable in the management of depression in studies that demonstrate a change in vitamin levels, and the effect size was comparable to that of anti-depressant medication. PMID:24732019

Preclinical safety and efficacy of a new recombinant FIX drug product for treatment of hemophilia B.

PubMed

Dietrich, Barbara; Schiviz, Alexandra; Hoellriegl, Werner; Horling, Frank; Benamara, Karima; Rottensteiner, Hanspeter; Turecek, Peter L; Schwarz, Hans Peter; Scheiflinger, Friedrich; Muchitsch, Eva-Maria

2013-11-01

Baxter has developed a new recombinant factor IX (rFIX) drug product (BAX326) for treating patients with hemophilia B, or congenital FIX deficiency. An extensive preclinical program evaluated the pharmacokinetics, efficacy, and safety of BAX326 in different species. The efficacy of BAX326 was tested in three mouse models of primary pharmacodynamics: tail-tip bleeding, carotid occlusion, and thrombelastography. The pharmacokinetics was evaluated after a single intravenous bolus injection in mice, rats, and macaques. Toxicity was assessed in rats and macaques, safety pharmacology in rabbits and macaques, and immunogenicity in mice. BAX326 was shown to be efficacious in all three primary pharmacodynamic studies (P ≤ 0.0076). Hemostatic efficacy was dose related and similar for the three lots tested. Pharmacokinetic results showed that rFIX activity and rFIX antigen concentrations declined in a bi-phasic manner, similar to a previously licensed rFIX product. BAX326 was well tolerated in rabbits and macaques at all dose levels; no thrombogenic events and no adverse clinical, respiratory, or cardiovascular effects occurred. BAX326 was also shown to have a similar immunogenicity profile to the comparator rFIX product in mice. These results demonstrate that BAX326 has a favorable preclinical safety and efficacy profile, predictive of a comparable effect to that of the previously licensed rFIX in humans.

An evaluation of varying protocols for high-level disinfection of flexible fiberoptic laryngoscopes.

PubMed

Liming, Bryan; Funnell, Ian; Jones, Anthony; Demons, Samandra; Marshall, Kathryn; Harsha, Wayne

2014-11-01

The use of flexible fiberoptic laryngoscopes (FFLs) is ubiquitous in otolaryngology practices. As with any medical device, there exists a small risk for transmission of pathogenic microorganisms between patients, necessitating high-level decontamination between uses. Most of the literature to date has studied channeled scopes such as those used in esophagogastroduodenoscopy and colonoscopy. A recent study of nonchanneled flexible laryngoscopes suggested that current high-level decontamination practices in use at some institutions, including ours, may be overly aggressive. We sought to evaluate and compare the efficacy of varying techniques of high-level disinfection of FFLs. FFLs were used in routine clinical encounters and then disinfected with a variety of techniques. The FFLs were then cultured for bacteria and fungi, and the rates of positive cultures were compared between the techniques and the controls. In this study, we took FFLs following use in routine clinical practice and disinfected them using one of eight decontamination protocols. We compared the bacterial and fungal culture results to positive and negative controls. We demonstrated that each of the eight cleaning protocols was statistically efficacious at removing bacterial contamination. Our results for fungal cultures did not reach statistical significance. Using in vitro inoculation of FFLs, this study demonstrated that quicker and more cost-effective practices are equally efficacious to more time-consuming and expensive techniques with regard to bacterial contamination of FFLs. NA © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

In vivo cleansing efficacy of biodegradable exfoliating beads assessed by skin bioengineering techniques.

PubMed

Kitsongsermthon, J; Duangweang, K; Kreepoke, J; Tansirikongkol, A

2017-11-01

The plastic microbeads, used in many cleansers, will be banned in cosmetic and personal care products within 2017 since they are non-degradable and can disturb the living organisms in water reservoirs. Various choices of biodegradable beads are commercially available, but their efficacy has not been proven yet. This study aimed to compare the cleansing efficacy in dirt and sebum removal aspects of three types of exfoliating beads. The gel scrubs with polyethylene (PE) beads, mannan beads or wax beads, were formulated and evaluated for their stability. The in vivo evaluation was done in 38 healthy volunteers and the skin irritation, efficacy for dirt and sebum removal were measured by Mexameter ® , Colorimeter ® , and Sebumeter ® , respectively. The selected gel scrubs did not cause an irritation in any volunteers. The differences in dirt residues between before and after scrubbing were not statistically significant among three gel scrubs and the similar result was also reported in the sebum removal study. All gel scrubs demonstrated the comparable cleansing efficacy in term of dirt and sebum removal. Thus, mannan beads and wax beads may be replaced non-biodegradable PE beads to achieve the similar cleansing effect. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Efficacy and safety of rasagiline as an adjunct to levodopa treatment in Chinese patients with Parkinson's disease: a randomized, double-blind, parallel-controlled, multi-centre trial.

PubMed

Zhang, Lina; Zhang, Zhiqin; Chen, Yangmei; Qin, Xinyue; Zhou, Huadong; Zhang, Chaodong; Sun, Hongbin; Tang, Ronghua; Zheng, Jinou; Yi, Lin; Deng, Liying; Li, Jinfang

2013-08-01

Rasagiline mesylate is a highly potent, selective and irreversible monoamine oxidase type B (MAOB) inhibitor and is effective as monotherapy or adjunct to levodopa for patients with Parkinson's disease (PD). However, few studies have evaluated the efficacy and safety of rasagiline in the Chinese population. This study was designed to investigate the safety and efficacy of rasagiline as adjunctive therapy to levodopa treatment in Chinese PD patients. This was a randomized, double-blind, placebo-controlled, parallel-group, multi-centre trial conducted over a 12-wk period that enrolled 244 PD patients with motor fluctuations. Participants were randomly assigned to oral rasagiline mesylate (1 mg) or placebo, once daily. Altogether, 219 patients completed the trial. Rasagiline showed significantly greater efficacy compared with placebo. During the treatment period, the primary efficacy variable--mean adjusted total daily off time--decreased from baseline by 1.7 h in patients treated with 1.0 mg/d rasagiline compared to placebo (p < 0.05). Scores using the Unified Parkinson's Disease Rating Scale also improved during rasagiline treatment. Rasagiline was well tolerated. This study demonstrated that rasagiline mesylate is effective and well tolerated as an adjunct to levodopa treatment in Chinese PD patients with fluctuations.

Antibiotic Treatment of Experimental Pneumonic Plague in Mice

PubMed Central

Byrne, William R.; Welkos, Susan L.; Pitt, M. Louise; Davis, Kelly J.; Brueckner, Ralf P.; Ezzell, John W.; Nelson, Gene O.; Vaccaro, Joseph R.; Battersby, Luann C.; Friedlander, Arthur M.

1998-01-01

A mouse model was developed to evaluate the efficacy of antibiotic treatment of pneumonic plague; streptomycin was compared to antibiotics with which there is little or no clinical experience. Infection was induced by inhalation of aerosolized Yersinia pestis organisms. Antibiotics were administered by intraperitoneal injection every 6 hours for 5 days, at doses that produced levels of drug in serum comparable to those observed in humans treated for other serious infections. These studies compared in vitro to in vivo activity and evaluated the efficacy of antibiotics started at different times after exposure. Early treatment (started 24 h after challenge, when 0 of 10 mice tested had positive blood cultures) with netilmicin, ciprofloxacin, ofloxacin, ceftriaxone, ceftazidime, aztreonam, ampicillin, and rifampin (but not cefazolin, cefotetan, or ceftizoxime) demonstrated efficacy comparable to streptomycin. Late treatment (started 42 h after exposure, when five of five mice tested had positive blood cultures) with netilmicin, ciprofloxacin, ofloxacin, and a high dose (20 mg/kg of body weight every 6 h) of gentamicin produced survival rates comparable to that with streptomycin, while all of the beta-lactam antibiotics (cefazolin, cefotetan, ceftriaxone, ceftazidime, aztreonam, and ampicillin) and rifampin were significantly inferior to streptomycin. In fact, all groups of mice treated late with beta-lactam antibiotics experienced accelerated mortality rates compared to normal-saline-treated control mice. These studies indicate that netilmicin, gentamicin, ciprofloxacin, and ofloxacin may be alternatives for the treatment of pneumonic plague in humans. However, the beta-lactam antibiotics are not recommended, based upon poor efficacy in this mouse model of pneumonic plague, particularly when pneumonic plague may be associated with bacteremia. PMID:9517950

Retrospective Comparison of Single-Port Sleeve Gastrectomy Versus Three-Port Laparoscopic Sleeve Gastrectomy: a Propensity Score Adjustment Analysis.

PubMed

Mauriello, Claudio; Chouillard, Elie; d'alessandro, Antonio; Marte, Gianpaolo; Papadimitriou, Argyri; Chahine, Elias; Kassir, Radwan

2018-04-16

Evaluate the efficacy of single-port sleeve gastrectomy (SPSG) and then compare it to a less-invasive sleeve approach (three-port) (3PSG) according to a propensity score (PS) matching analysis. We analyzed all patients who underwent SG through a three-port or a single-port laparoscopic approach. After 2 years, the follow-up was completed in 84% patients treated with 3PSG and 95% patients of the SPSG group. Excess weight loss (EWL) was comparable for the first year of follow-up within the two groups except for the controls at 3 months in which the SPSG group showed a higher EWL (p = 0.0243). We demonstrated the efficacy of SPSG in bariatric surgery even compared to another, less invasive, laparoscopic SG approach (three-port).

Comparison of oral robenacoxib and ketoprofen for the treatment of acute pain and inflammation associated with musculoskeletal disorders in cats: a randomised clinical trial.

PubMed

Sano, Tadashi; King, Jonathan N; Seewald, Wolfgang; Sakakibara, Nobuhiro; Okumura, Masahiro

2012-08-01

The objective of the study was to evaluate the efficacy and tolerability of robenacoxib, a selective cyclooxygenase-2 inhibitor, for the treatment of acute pain and inflammation associated with musculoskeletal disorders in cats. The study was a prospective, multi-centre, randomised, blinded, non-inferiority design clinical trial comparing robenacoxib to ketoprofen. A total of 68 cats presenting with pain and inflammation associated with acute musculoskeletal disorders were recruited and allocated randomly to receive, orally once daily for 5-6 days, either 1.0-2.4 mg/kg robenacoxib (n=47) or 1mg/kg ketoprofen (n=21). The primary efficacy endpoint was the total clinician score, which was the sum of clinician numerical rating scale scores for pain, inflammation and mobility. Assessments were made at baseline, on day 2, and day 4 or 5. For the total clinician score, non-inferior efficacy of robenacoxib was demonstrated with a relative efficacy of 1.151 (95% confidence interval 0.872-1.494). Non-inferior efficacy of robenacoxib was also demonstrated for the secondary endpoint of the total owner score. Robenacoxib was superior (P<0.05) to ketoprofen for the owner's assessment of activity and human/animal relationship. The tolerability of both treatments was good as assessed by monitoring adverse events, clinical signs and haematology and serum biochemistry variables. Copyright © 2012. Published by Elsevier Ltd.

Curcumin-polymeric nanoparticles against colon-26 tumor-bearing mice: cytotoxicity, pharmacokinetic and anticancer efficacy studies.

PubMed

Chaurasia, Sundeep; Chaubey, Pramila; Patel, Ravi R; Kumar, Nagendra; Mishra, Brahmeshwar

2016-01-01

Curcumin (CUR), can inhibit proliferation and induce apoptosis of tumor cells, its extreme insolubility and limited bioavailability restricted its clinical application. An innovative polymeric nanoparticle of CUR has been developed to enhance the bioavailability and anti-cancer efficacy of CUR, in vitro and in vivo. Cationic copolymer Eudragit E 100 was selected as carrier, which can enhance properties of poor bioavailable chemotherapeutic drugs (CUR). The CUR-loaded Eudragit E 100 nanoparticles (CENPs) were prepared by emulsification-diffusion-evaporation method. The in vitro cytotoxicity study of CENPs was carried out using sulphorhodamine B assay. Pharmacokinetic and anti-cancer efficacy of CENPs was investigated in Wister rats as well as colon-26 tumor-bearing mice after oral administration. CENPs showed acceptable particle size and percent entrapment efficiency. In vitro cytotoxicity studies in terms of 50% cell growth inhibition values demonstrated ∼19-fold reduction when treated with CENPs as compared to pure CUR. ∼91-fold increase in Cmax and ∼95-fold increase in AUC0-12h were observed indicating a significant enhancement in the oral bioavailability of CUR when orally administered as CENPs compared to pure CUR. The in vivo anti-cancer study performed with CENPs showed a significant increase in efficacy compared with pure CUR, as observed by tumor volume, body weight and survival rate. The results clearly indicate that the developed polymeric nanoparticles offer a great potential to improve bioavailability and anticancer efficacy of hydrophobic chemotherapeutic drug.

Quaternization enhances the transgene expression efficacy of aminoglycoside-derived polymers.

PubMed

Miryala, Bhavani; Feng, Yunpeng; Omer, Ala; Potta, Thrimoorthy; Rege, Kaushal

2015-07-15

The objective of the present study was to synthesize and investigate the transgene expression efficacy of quaternized derivatives of aminoglycoside polymers in different cancer cell lines. A series of glycidyltrimethylammonium chloride (GTMAC) derivatives of aminoglycoside polymers (GTMAC-AM polymers), containing varying degrees of quaternization (13-45%), were synthesized. The structures and properties of GTMAC-AM polymers were investigated using FT-IR and (1)H NMR spectroscopy. Physicochemical factors that influence transgene expression efficacy including DNA binding, hydrodynamic size, zeta potential and cytotoxicity, were determined. Formation of polymer-plasmid DNA complexes was also visualized using atomic force microscopy. GTMAC-AM polymers demonstrated higher transgene expression efficacies compared to their parent polymers, 25 kDa poly(ethyleneimine), as well as Lipofectamine-3000. Our results indicate that quaternization enhances the transgene expression efficacy and reduces the cytotoxicity of aminoglycoside-derived polymers, making it an attractive strategy for nucleic acid delivery with these new materials. Copyright © 2015 Elsevier B.V. All rights reserved.

Self-Explanation and Explanatory Feedback in Games: Individual Differences, Gameplay, and Learning

ERIC Educational Resources Information Center

Killingsworth, Stephen S.; Clark, Douglas B.; Adams, Deanne M.

2015-01-01

Previous research has demonstrated the efficacy of two explanation-based approaches for increasing learning in educational games. The first involves asking students to explain their answers (self-explanation) and the second involves providing correct explanations (explanatory feedback). This study (1) compared self-explanation and explanatory…

Efficacy of sodium dodecyl sulphate and natural extracts against E. coli biofilm.

PubMed

Fink, Rok; Kulaš, Stefan; Oder, Martina

2018-05-02

The aim of this study was to determine and compare the efficacy of a standard cleaning agent, sodium dodecyl sulphate, and natural extracts from pomegranate peel grape skin and bay laurel leaf against E. coli biofilm. The biofilm was exposed for 10 minutes to three different concentrations of each tested compound. The results show that bay laurel leaf extract is the most efficient with 43% biofilm biomass reduction, followed by pomegranate peel extract (35%); sodium dodecyl sulphate and grape skin extract each have 30% efficacy. Our study demonstrated that natural extracts from selected plants have the same or even better efficacy against E. coli biofilm removal from surfaces than the tested classical cleaning agent do. All this indicates that natural plant extracts, which are acceptable from the health and environment points of view, can be potential substitutes for classical cleaning agents.

Enhanced bioavailability and bioefficacy of an amorphous solid dispersion of curcumin.

PubMed

Chuah, Ai Mey; Jacob, Bindya; Jie, Zhang; Ramesh, Subbarayan; Mandal, Shibajee; Puthan, Jithesh K; Deshpande, Parag; Vaidyanathan, Vadakkanchery V; Gelling, Richard W; Patel, Gaurav; Das, Tapas; Shreeram, Sathyavageeswaran

2014-08-01

Curcumin has been shown to have a wide variety of biological activities for various human diseases including inflammation, diabetes and cancer. However, the poor oral bioavailability of curcumin poses a significant pharmacological barrier to its use therapeutically and/or as a functional food. Here we report the evaluation of the bioavailability and bio-efficacy of curcumin as an amorphous solid dispersion (ASD) in a matrix consisting of hydroxypropyl methyl cellulose (HPMC), lecithin and isomalt using hot melt extrusion for application in food products. Oral pharmacokinetic studies in rats showed that ASD curcumin was ∼13-fold more bioavailable compared to unformulated curcumin. Evaluation of the anti-inflammatory activity of ASD curcumin in vivo demonstrated enhanced bio-efficacy compared to unformulated curcumin at 10-fold lower dose. Thus ASD curcumin provides a more potent and efficacious formulation of curcumin which may also help in masking the colour, taste and smell which currently limit its application as a functional food ingredient. Copyright © 2014 Elsevier Ltd. All rights reserved.

Deltamethrin resistance in Aedes aegypti results in treatment failure in Merida, Mexico.

PubMed

Vazquez-Prokopec, Gonzalo M; Medina-Barreiro, Anuar; Che-Mendoza, Azael; Dzul-Manzanilla, Felipe; Correa-Morales, Fabian; Guillermo-May, Guillermo; Bibiano-Marín, Wilbert; Uc-Puc, Valentín; Geded-Moreno, Eduardo; Vadillo-Sánchez, José; Palacio-Vargas, Jorge; Ritchie, Scott A; Lenhart, Audrey; Manrique-Saide, Pablo

2017-06-01

The operational impact of deltamethrin resistance on the efficacy of indoor insecticide applications to control Aedes aegypti was evaluated in Merida, Mexico. A randomized controlled trial quantified the efficacy of indoor residual spraying (IRS) against adult Ae. aegypti in houses treated with either deltamethrin (to which local Ae. aegypti expressed a high degree of resistance) or bendiocarb (to which local Ae. aegypti were fully susceptible) as compared to untreated control houses. All adult Ae. aegypti infestation indices during 3 months post-spraying were significantly lower in houses treated with bendiocarb compared to untreated houses (odds ratio <0.75; incidence rate ratio < 0.65) whereas no statistically significant difference was detected between the untreated and the deltamethrin-treated houses. On average, bendiocarb spraying reduced Ae. aegypti abundance by 60% during a 3-month period. Results demonstrate that vector control efficacy can be significantly compromised when the insecticide resistance status of Ae. aegypti populations is not taken into consideration.

Epithelial V-Like Antigen Mediates Efficacy of Anti-Alpha4 Integrin Treatment in a Mouse Model of Multiple Sclerosis

PubMed Central

Wright, Erik; Rahgozar, Kusha; Hallworth, Nicholas; Lanker, Stefan; Carrithers, Michael D.

2013-01-01

Natalizumab inhibits the transmigration of activated T lymphocytes into the brain and is highly efficacious in multiple sclerosis (MS). However, from a pharmacogenomic perspective, its efficacy and safety in specific patients remain unclear. Here our goal was to analyze the effects of epithelial V-like antigen (EVA) on anti-alpha4 integrin (VLA4) efficacy in a mouse model of MS, experimental autoimmune encephalomyelitis (EAE). EVA has been previously characterized in human CD4 T lymphocytes, mouse thymic development, and choroid plexus epithelial cells. Further analysis here demonstrated expression in B lymphocytes and an increase in EVA+ lymphocytes following immunization. Following active induction of EAE using the MOG35–55 active immunization model, EVA deficient mice developed more severe EAE and white matter tissue injury as compared to wild type controls. This severe EAE phenotype did not respond to anti-VLA4 treatment. In both the control antibody and anti-VLA4 conditions, these mice demonstrated persistent CNS invasion of mature B lymphocyte (CD19+, CD21+, sIgG+), increased serum autoantibody levels, and extensive complement and IgG deposition within lesions containing CD5+IgG+ cells. Wild type mice treated with control antibody also demonstrated the presence of CD19+, CD21+, sIgG+ cells within the CNS during peak EAE disease severity and detectable serum autoantibody. In contrast, wild type mice treated with anti-VLA4 demonstrated reduced serum autoantibody levels as compared to wild type controls and EVA-knockout mice. As expected, anti-VLA4 treatment in wild type mice reduced the total numbers of all CNS mononuclear cells and markedly decreased CD4 T lymphocyte invasion. Treatment also reduced the frequency of CD19+, CD21+, sIgG+ cells in the CNS. These results suggest that anti-VLA4 treatment may reduce B lymphocyte associated autoimmunity in some individuals and that EVA expression is necessary for an optimal therapeutic response. We postulate that these findings could optimize the selection of treatment responders. PMID:23951051

Clinical, double-blind, placebo-controlled study investigating the combination of acetylsalicylic acid and pseudoephedrine for the symptomatic treatment of nasal congestion associated with common cold.

PubMed

Loose, Irene; Winkel, Matthias

2004-01-01

It was the aim of this clinical study to demonstrate the efficacy of 1000 mg acetylsalicylic acid (ASA, CAS 50-78-2) in combination with 60 mg pseudoephedrine (PSE, CAS 90-82-4), compared with placebo, in the symptomatic treatment of nasal congestion associated with the common cold. A further aim was to demonstrate the efficacy of 500 mg ASA + 30 mg PSE and of 1000 mg paracetamol (CAS 103-90-2) + 60 mg PSE (active control) in the symptomatic treatment of nasal congestion. The study was designed as a randomized, two-center, double-blind, double-dummy, placebo-controlled, parallel-group, single-dose efficacy and safety trial over 6 h and was carried out in the USA. In total, at two centers, 643 patients who had a history and diagnosis of acute upper respiratory tract infection (URTI), were included; they showed symptoms such as nasal congestion, scratchy/sore throat, headache, generalized muscle ache, earache, runny nose, fever, sneezing etc. The investigational drugs ASA and PSE were both provided as granules in sachets and the granules were dissolved in water before administration; the combined preparation of paracetamol + PSE was administered as commercially available tablets encapsulated for blinding. For all preparations, matching placebos were provided. The primary efficacy variable was the area under the curve for differences from baseline on a nasal congestion scale in the first 2 h after treatment. To be eligible for the study, otherwise healthy volunteers were to present with nasal stuffiness of recent onset that reached a score of at least 6 on the 11-point scale for nasal congestion (0 = not stuffy, 10 = very stuffy). The primary analysis of the primary efficacy variable was calculated by analysis of variance including treatment group, severity (moderate/severe) and center as main strata. The analysis was performed using the intent-to-treat population. All active treatments proved to be statistically significantly superior to placebo with regard to the primary efficacy variable. Significant superiority of active treatment compared with placebo could also be demonstrated for an interval of up to 6 h after intake of the drug and for the relief of nasal congestion. The lower dose did not reveal significant different results compared with placebo for relief of nasal congestion in patients with a severe nasal congestion score at baseline. As well in patients with moderate nasal congestion score (NCS) at start of the study the difference from baseline in the NCS compared with placebo was not statistically significant. Thus a trend towards better efficacy in the higher dose could be assumed. No difference was found between 1000 mg ASA + 60 mg PSE and the active control. There were no differences between the two centers. The treatment proved to be safe and well tolerated, without relevant differences between the four treatment groups. Main adverse events were found to be related to the upper respiratory tract infection or were of gastrointestinal nature. In conclusion, the combination of ASA with PSE can be considered as an effective and safe remedial for the symptomatic treatment of the nasal congestion during URTI.

Meta-analysis Exploring the Effectiveness of S-1-Based Chemotherapy for Advanced Non-Small Cell Lung Cancer.

PubMed

Sun, Xin; Sun, Li; Zhang, Shu-Ling; Xiong, Zhi-Cheng; Ma, Jie-Tao; Han, Cheng-Bo

2017-01-01

S-1 is a new oral fluoropyrimidine formulation that comprises tegafur, 5-chloro-2,4-dihydroxypyridine, and potassium oxonate. S-1 is designed to enhance antitumor activity and to reduce gastrointestinal toxicity. Several studies have demonstrated that both S-1 monotherapy and S-1 combination regimens showed encouraging efficacies and mild toxicities in the treatment of lung squamous cell carcinoma and adenocarcinoma. However, it is unclear whether S-1 can be used as standard care in advanced non-small cell lung cancer (NSCLC). The purpose of this meta-analysis was to assess the efficacy and safety of S-1-based chemotherapy, compared with standard chemotherapy, in patients with locally advanced or metastatic NSCLC. Thirteen randomized controlled trials (RCTs) involving 2,134 patients with a similar ratio of different pathological types were included. In first-line or second-line chemotherapy, compared with standard chemotherapy, S-1-based chemotherapy showed similar efficacy in terms of median overall survival (mOS), median progression free survival (mPFS), and objective response rate (ORR) (all P > 0.1), and significantly reduced the incidence of grade ≥ 3 hematological toxicities. In patients with locally advanced NSCLC receiving concurrent chemoradiotherapy, compared with standard chemoradiotherapy, significantly improved survival in the S-1-based chemotherapy was noted in terms of mOS and mPFS (risk radio [RR] = 1.289, P = 0.009; RR = 1.289, P = 0.000, respectively) with lower incidence of grade ≥ 3 neutropenia (RR = 0.453, P = 0.000). The present meta-analysis demonstrates that S-1-based chemotherapy shows similar benefits in advanced NSCLC and improves survival in locally advanced NSCLC, compared with standard treatment.

Therapeutic Efficacy of Autologous Non-Mobilized Enriched Circulating Endothelial Progenitors in Patients With Critical Limb Ischemia　- The SCELTA Trial.

PubMed

Liotta, Francesco; Annunziato, Francesco; Castellani, Sergio; Boddi, Maria; Alterini, Brunetto; Castellini, Giovanni; Mazzanti, Benedetta; Cosmi, Lorenzo; Acquafresca, Manlio; Bartalesi, Filippo; Dilaghi, Beatrice; Dorigo, Walter; Graziani, Gabriele; Bartolozzi, Benedetta; Bellandi, Guido; Carli, Giulia; Bartoloni, Alessandro; Fargion, Aaron; Fassio, Filippo; Fontanari, Paolo; Landini, Giancarlo; Lucente, Eleonora A M; Michelagnoli, Stefano; Orsi Battaglini, Carolina; Panigada, Grazia; Pigozzi, Clara; Querci, Valentina; Santarlasci, Veronica; Parronchi, Paola; Troisi, Nicola; Baggiore, Cristiana; Romagnani, Paola; Mannucci, Edoardo; Saccardi, Riccardo; Pratesi, Carlo; Gensini, Gianfranco; Romagnani, Sergio; Maggi, Enrico

2018-05-25

The therapeutic efficacy of bone marrow mononuclear cells (BM-MNC) autotransplantation in critical limb ischemia (CLI) has been reported. Variable proportions of circulating monocytes express low levels of CD34 (CD14 + CD34 low cells) and behave in vitro as endothelial progenitor cells (EPCs). The aim of the present randomized clinical trial was to compare the safety and therapeutic effects of enriched circulating EPCs (ECEPCs) with BM-MNC administration.Methods and Results:ECEPCs (obtained from non-mobilized peripheral blood by immunomagnetic selection of CD14 + and CD34 + cells) or BM-MNC were injected into the gastrocnemius of the affected limb in 23 and 17 patients, respectively. After a mean of 25.2±18.6-month follow-up, both groups showed significant and progressive improvement in muscle perfusion (primary endpoint), rest pain, consumption of analgesics, pain-free walking distance, wound healing, quality of life, ankle-brachial index, toe-brachial index, and transcutaneous PO 2 . In ECEPC-treated patients, there was a positive correlation between injected CD14 + CD34 low cell counts and the increase in muscle perfusion. The safety profile was comparable between the ECEPC and BM-MNC treatment arms. In both groups, the number of deaths and major amputations was lower compared with eligible untreated patients and historical reference patients. This study supports previous trials showing the efficacy of BM-MNC autotransplantation in CLI patients and demonstrates comparable therapeutic efficacy between BM-MNC and EPEPCs.

Efficacy and safety of prophylactic levetiracetam in supratentorial brain tumour surgery: a systematic review and meta‐analysis

PubMed Central

Tsaousi, Georgia; Apostolidou, Eirini; Karakoulas, Konstantinos; Kouvelas, Dimitrios; Amaniti, Ekaterini

2016-01-01

Aims The aim of this study was to perform an up‐to‐date systematic review and meta‐analysis on the efficacy and safety of prophylactic administration of levetiracetam in brain tumour patients. Method A systematic review of studies published until April 2015 was conducted using Scopus/Elsevier, EMBASE and MEDLINE. The search was limited to articles reporting results from adult patients, suffering from brain tumour, undergoing supratentorial craniotomy for tumour resection or biopsy and administered levetiracetam in the perioperative period for seizure prophylaxis. Outcomes included the efficacy and safety of levetiracetam, as well as the tolerability of the specific regimen, defined by the discontinuation of the treatment due to side effects. Results The systematic review included 1148 patients from 12 studies comparing levetiracetam with no treatment, phenytoin and valproate, while only 243 patients from three studies, comparing levetiracetam vs phenytoin efficacy and safety, were included in the meta‐analysis. The combined results from the meta‐analysis showed that levetiracetam administration was followed by significantly fewer seizures than treatment with phenytoin (OR = 0.12 [0.03–0.42]: χ2 = 1.76: I2 = 0%). Analysis also showed significantly fewer side effects in patients receiving levetiracetam, compared to other groups (P < 0.05). The combined results showed fewer side effects in the levetiracetam group compared to the phenytoin group (OR = 0.65 [0.14–2.99]: χ2 = 8.79: I2 = 77%). Conclusions The efficacy of prophylaxis with levetiracetam seems to be superior to that with phenytoin and valproate administration. Moreover, levetiracetam use demonstrates fewer side effects in brain tumour patients. Nevertheless, high risk of bias and moderate methodological quality must be taken into account when considering these results. PMID:26945547

Are there any differences in the efficacy and safety of different formulations of Oral 5-ASA used for induction and maintenance of remission in ulcerative colitis? evidence from cochrane reviews.

PubMed

Feagan, Brian G; Chande, Nilesh; MacDonald, John K

2013-08-01

We systematically reviewed and compared the efficacy and safety of oral mesalamine formulations (sustained release, delayed release, and prodrugs) used for induction and maintenance of remission in ulcerative colitis. The main objective of this review was to determine if there are any differences in efficacy or safety among the oral 5-ASA drugs. A literature search in February 2013 identified all applicable randomized trials. Study quality was evaluated using the Cochrane risk of bias tool. The Grading of Recommendations Assessment, Development and Evaluation criteria were used to assess the overall quality of the evidence. Studies were subgrouped by common mesalamine comparators for meta-analysis. Studies were pooled for analysis if they compared equimolar doses of oral 5-ASA. Seventeen studies that evaluated 2925 patients were identified. The risk of bias was low for most factors, although 1 study was single blind and 3 were open label. No difference was observed between oral 5-ASA and comparator 5-ASA formulations in the proportion of patients with clinical remission (relative risk, 0.94; 95% confidence interval, 0.86-1.02), clinical improvement (relative risk, 0.89; 95% confidence interval, 0.77-1.01), or relapse at 12 months (relative risk, 1.01; 95% confidence interval, 0.80-1.28). Subgroup analyses showed no important differences in efficacy. No significant difference was demonstrated in rates of adverse events or withdrawal due to adverse events. There does not seem to be any difference in efficacy or safety among the various formulations of oral 5-ASA. Oral mesalamine is an effective and safe treatment of mild-to-moderate or quiescent ulcerative colitis regardless of the chosen formulation.

In vitro thrombolytic efficacy of echogenic liposomes loaded with tissue plasminogen activator and octafluoropropane gas

NASA Astrophysics Data System (ADS)

Shekhar, Himanshu; Bader, Kenneth B.; Huang, Shenwen; Peng, Tao; Huang, Shaoling; McPherson, David D.; Holland, Christy K.

2017-01-01

Echogenic liposomes loaded with the thrombolytic recombinant tissue-type plasminogen activator (rt-PA) are under development for the treatment of ischemic stroke. These agents are designed to co-encapsulate cavitation nuclei to promote bubble activity in response to ultrasound exposure, and to enable localized delivery of thrombolytic. Stable cavitation improves the efficacy of the thrombolytic through enhanced fluid mixing. Echogenic liposomes that encapsulate air-filled microbubbles nucleate scant stable cavitation activity in response to 120 kHz intermittent ultrasound exposure, and have demonstrated thrombolytic efficacy equivalent to rt-PA alone. It was hypothesized that encapsulating octafluoropropane (OFP) gas within rt-PA-loaded liposomes instead of air will enhance ultrasound-mediated stable cavitation activity and increase thrombolytic efficacy compared to previous studies. The thrombolytic efficacy and cavitation activity nucleated from liposomes that encapsulate OFP microbubbles and rt-PA (OFP t-ELIP) was evaluated in vitro. Human whole blood clots were exposed to human fresh-frozen plasma alone, rt-PA (0, 0.32, 1.58, and 3.15 µg ml-1), or OFP t-ELIP at equivalent enzymatic activity, with and without exposure to intermittent ultrasound. Further, numerical simulations were performed to gain insight into the mechanisms of cavitation nucleation. Sustained ultraharmonic activity was nucleated from OFP t-ELIP when exposed to ultrasound. Furthermore, the thrombolytic efficacy was enhanced compared to rt-PA alone at concentrations of 1.58 µg ml-1 and 3.15 µg ml-1 (p  <  0.05). These results indicate that OFP t-ELIP can nucleate sustained stable cavitation activity and enhance the efficacy of thrombolysis.

Therapeutic management of premenstrual syndrome.

PubMed

Freeman, Ellen W

2010-12-01

Premenstrual syndrome (PMS) is among the most common health problems reported by reproductive-age women. Estimates indicate that up to 25% of women may warrant treatment for the distress or impaired functioning associated with the symptoms. The primary focus of this review is the clinical condition of PMS and randomized, placebo-controlled trials of PMS treatment. A literature search in PubMed was conducted for these topics. The most recent reports of specific treatments in controlled treatment studies and all meta-analyses were selected. Reports consistently indicate that serotonergic antidepressants reduce PMS symptoms compared to a placebo. Hormonal treatments are the most widely prescribed medical treatment. Some oral contraceptives and gonadotropin-releasing hormone analogs have demonstrated efficacy, particularly for women who want contraception and PMS symptom control. Numerous non-pharmacologic treatments are utilized, but efficacy is reported only for calcium supplements, Vitex agnus castus (chasteberry), and cognitive-behavioral therapies. Further research to develop new therapies for the 40% of women with PMS who do not respond to the currently available treatments is needed. There are treatments with demonstrated efficacy for PMS, and the majority of women can be helped.

In vivo investigation of hybrid Paclitaxel nanocrystals with dual fluorescent probes for cancer theranostics.

PubMed

Hollis, Christin P; Weiss, Heidi L; Evers, B Mark; Gemeinhart, Richard A; Li, Tonglei

2014-06-01

To develop novel hybrid paclitaxel (PTX) nanocrystals, in which bioactivatable (MMPSense® 750 FAST) and near infrared (Flamma Fluor® FPR-648) fluorophores are physically incorporated, and to evaluate their anticancer efficacy and diagnostic properties in breast cancer xenograft murine model. The pure and hybrid paclitaxel nanocrystals were prepared by an anti-solvent method, and their physical properties were characterized. The tumor volume change and body weight change were evaluated to assess the treatment efficacy and toxicity. Bioimaging of treated mice was obtained non-invasively in vivo. The released MMPSense molecules from the hybrid nanocrystals were activated by matrix metalloproteinases (MMPs) in vivo, similarly to the free MMPSense, demonstrating its ability to monitor cancer progression. Concurrently, the entrapped FPR-648 was imaged at a different wavelength. Furthermore, when administered at 20 mg/kg, the nanocrystal formulations exerted comparable efficacy as Taxol®, but with decreased toxicity. Hybrid nanocrystals that physically integrated two fluorophores were successfully prepared from solution. Hybrid nanocrystals were shown not only exerting antitumor activity, but also demonstrating the potential of multi-modular bioimaging for diagnostics.

Topical intra-articular compared with intravenous tranexamic acid to reduce blood loss in primary total knee replacement: a double-blind, randomized, controlled, noninferiority clinical trial.

PubMed

Gomez-Barrena, Enrique; Ortega-Andreu, Miguel; Padilla-Eguiluz, Norma G; Pérez-Chrzanowska, Hanna; Figueredo-Zalve, Reyes

2014-12-03

Abundant literature regarding the use of intravenous tranexamic acid (TXA) in primary total knee replacement is available. Randomized controlled trials have confirmed the efficacy of topical TXA compared with placebo, but the comparison between topical and intravenous TXA is unclear. The present study was designed to verify noninferior efficacy and safety of topical intra-articular TXA compared with intravenous TXA in primary total knee replacement with cemented implants. A Phase-III, single-center, double-blind, randomized, controlled clinical trial was performed to compare topical intra-articular TXA (3 g of TXA in 100 mL of physiological saline solution) with two intravenous doses of TXA (15 mg/kg in 100 mL of physiological saline solution, one dose before tourniquet release and another three hours after surgery) in a multimodal protocol for blood loss prevention. The primary outcome was the blood transfusion rate, and the secondary outcomes included visible blood loss (as measured in the drain) at twenty-four hours postoperatively and invisible blood loss (as estimated from the Nadler formula) at forty-eight hours postoperatively. The sample size of seventy-eight patients was calculated to give a statistical power of 99% for demonstrating noninferiority. Thirty-nine patients each were allocated to receive topical intra-articular TXA (the experimental group) and intravenous TXA (the control group); there were no significant differences in demographics or preoperative laboratory values between the groups. Noninferiority was estimated by comparing the confidence intervals with a delta of 10%. Student t and Mann-Whitney tests were used to assess the significance of any differences. The transfusion rate was zero in both groups; thus, noninferiority was demonstrated for the primary efficacy end point, suggesting equivalence. Noninferiority was also demonstrated for the secondary efficacy end points. Drain blood loss at twenty-four hours was 315.6 mL (95% confidence interval [CI], 248.5 to 382.7 mL) in the experimental group and 308.1 mL (95% CI, 247.6 to 368.5 mL) in the control group (p = 0.948, Mann-Whitney). Also, estimated blood loss at forty-eight hours was 1259.0 mL (95% CI, 1115.6 to 1402.3 mL) in the experimental group and 1317.9 mL (95% CI, 1175.4 to 1460.4 mL) in the control group (p = 0.837, Mann-Whitney). No significant safety differences were seen between groups. Topical administration of TXA according to the described protocol demonstrated noninferiority compared with intravenous TXA, with no safety concerns. This randomized controlled trial supports the topical intra-articular administration of TXA in primary total knee replacement with cemented implants. Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence. Copyright © 2014 by The Journal of Bone and Joint Surgery, Incorporated.

Self-efficacy and self-esteem in third-year pharmacy students.

PubMed

Yorra, Mark L

2014-09-15

To identify the experiential and demographic factors affecting the self-efficacy and self-esteem of third-year pharmacy (P3) students. A 25-item survey that included the Rosenberg Self-Esteem Scale and the General Self-Efficacy Scale, as well as types and length of pharmacy practice experiences and demographic information was administered to doctor of pharmacy (PharmD) students from 5 schools of pharmacy in New England at the completion of their P3 year. The survey response rate was approximately 50% of the total target population (399/820). Students with a grade point average (GPA)≥3.0 demonstrated a higher significant effect from unpaid introductory pharmacy practice experiences (IPPEs) on their self-efficacy scores (p<0.05) compared to students with lower GPAs. Students who had completed more than the required amount of pharmacy experiences had higher levels of self-efficacy and self-esteem (p<0.05). Ethnicity also was related to students' levels of self-efficacy and self-esteem. Self-efficacy and self-esteem are two important factors in pharmacy practice. Colleges and schools of pharmacy should ensure that students complete enough practice experiences, beyond the minimum of 300 IPPE hours, as one way to improve their self-efficacy and self-esteem.

Self-Efficacy and Self-Esteem in Third-Year Pharmacy Students

PubMed Central

2014-01-01

Objective. To identify the experiential and demographic factors affecting the self-efficacy and self-esteem of third-year pharmacy (P3) students. Methods. A 25-item survey that included the Rosenberg Self-Esteem Scale and the General Self-Efficacy Scale, as well as types and length of pharmacy practice experiences and demographic information was administered to doctor of pharmacy (PharmD) students from 5 schools of pharmacy in New England at the completion of their P3 year. Results. The survey response rate was approximately 50% of the total target population (399/820). Students with a grade point average (GPA)≥3.0 demonstrated a higher significant effect from unpaid introductory pharmacy practice experiences (IPPEs) on their self-efficacy scores (p<0.05) compared to students with lower GPAs. Students who had completed more than the required amount of pharmacy experiences had higher levels of self-efficacy and self-esteem (p<0.05). Ethnicity also was related to students’ levels of self-efficacy and self-esteem. Conclusion. Self-efficacy and self-esteem are two important factors in pharmacy practice. Colleges and schools of pharmacy should ensure that students complete enough practice experiences, beyond the minimum of 300 IPPE hours, as one way to improve their self-efficacy and self-esteem. PMID:25258439

A comparative study of enzyme immobilization strategies for multi-walled carbon nanotube glucose biosensors

NASA Astrophysics Data System (ADS)

Shi, Jin; Claussen, Jonathan C.; McLamore, Eric S.; Haque, Aeraj ul; Jaroch, David; Diggs, Alfred R.; Calvo-Marzal, Percy; Rickus, Jenna L.; Porterfield, D. Marshall

2011-09-01

This work addresses the comparison of different strategies for improving biosensor performance using nanomaterials. Glucose biosensors based on commonly applied enzyme immobilization approaches, including sol-gel encapsulation approaches and glutaraldehyde cross-linking strategies, were studied in the presence and absence of multi-walled carbon nanotubes (MWNTs). Although direct comparison of design parameters such as linear range and sensitivity is intuitive, this comparison alone is not an accurate indicator of biosensor efficacy, due to the wide range of electrodes and nanomaterials available for use in current biosensor designs. We proposed a comparative protocol which considers both the active area available for transduction following nanomaterial deposition and the sensitivity. Based on the protocol, when no nanomaterials were involved, TEOS/GOx biosensors exhibited the highest efficacy, followed by BSA/GA/GOx and TMOS/GOx biosensors. A novel biosensor containing carboxylated MWNTs modified with glucose oxidase and an overlying TMOS layer demonstrated optimum efficacy in terms of enhanced current density (18.3 ± 0.5 µA mM - 1 cm - 2), linear range (0.0037-12 mM), detection limit (3.7 µM), coefficient of variation (2%), response time (less than 8 s), and stability/selectivity/reproducibility. H2O2 response tests demonstrated that the most possible reason for the performance enhancement was an increased enzyme loading. This design is an excellent platform for versatile biosensing applications.

Improvement of a PCR test to diagnose infection by Mansonella ozzardi.

PubMed

Vera, Luana Janaína Souza; Basano, Sergio de Almeida; Camargo, Juliana de Souza Almeida Aranha; França, Andonai Krauze de; Ferreira, Ricardo de Godoi Mattos; Casseb, Almeida Andrade; Medeiros, Jansen Fernandes; Fontes, Gilberto; Camargo, Luís Marcelo Aranha

2011-01-01

Mansonelliasis is caused by Mansonella ozzardi. It is widespread in the Amazon region, with a high prevalence. The common exam of thick blood smears stained with Giemsa shows low efficacy levels and has been an obstacle to diagnosing individuals with low blood parasitemia. In order to increase diagnosis efficacy, the PCR technique was improved. PCR demonstrated the best performance, with sensitivity and negative predictive values (NPV) of 100%, followed by blood filtration through membrane filters, which showed a sensitivity of 88.9% and a NPV of 84.6%, when compared to thick blood smears.

New scanner fiber optic delivery system for laser phototherapy in the treatment of neonatal jaundice

NASA Astrophysics Data System (ADS)

Hamza, Mostafa; Hamza, Mohammad S. E.

1995-05-01

The authors have introduced laser phototherapy for the treatment of neonatal jaundice. Clinical trials have demonstrated its high efficacy compared to the conventionally used fluorescent phototherapy. In this paper a new modification to laser irradiation in phototherapy can be achieved by scanning the laser output beam in the selected wavelength of irradiation (488 nm) through a fiberoptic bundle which irradiate the skin of the baby. Scanning of the laser beam provides intermittent irradiation at high frequency, which can provide the same therapeutic efficacy with almost half the power of laser irradiation.

Synthesis of Nanodiamond-Daunorubicin Conjugates to Overcome Multidrug Chemoresistance in Leukemia

PubMed Central

Man, Han B.; Kim, Hansung; Kim, Ho-Joong; Robinson, Erik; Liu, Wing Kam; Chow, Edward Kai-Hua; Ho, Dean

2013-01-01

Nanodiamonds (NDs) are promising candidates in nanomedicine, demonstrating significant potential as gene/drug delivery platforms for cancer therapy. We have synthesized ND vectors capable of chemotherapeutic loading and delivery with applications towards chemoresistant leukemia. The loading of Daunorubicin (DNR) onto NDs was optimized by adjusting reaction parameters such as acidity and concentration. The resulting conjugate, a novel therapeutic payload for NDs, was characterized extensively for size, surface charge, and loading efficiency. A K562 human myelogenous leukemia cell line, with multidrug resistance conferred by incremental DNR exposure, was used to demonstrate the efficacy enhancement resulting from ND-based delivery. While resistant K562 cells were able to overcome treatment from DNR alone, as compared with non-resistant K562 cells, NDs were able to improve DNR delivery into resistant K562 cells. By overcoming efflux mechanisms present in this resistant leukemia line, ND-enabled therapeutics have demonstrated the potential to improve cancer treatment efficacy, especially towards resistant strains. PMID:23916889

Nabumetone in the treatment of skin and soft tissue injury.

PubMed

Jenner, P N

1987-10-30

Nabumetone, a new nonsteroidal anti-inflammatory agent, has been evaluated for the treatment of skin and soft tissue injury, including sports injury, in clinical trials involving nearly 1,000 patients. Its efficacy, safety, and tolerance in these patients is reviewed. The efficacy of nabumetone in the treatment of soft tissue injury has been demonstrated to be similar to that of soluble aspirin, ibuprofen, and naproxen. It was not possible in these studies to demonstrate a definite advantage over placebo, and the reasons for this are discussed along with some suggestions for future studies. There were no serious adverse experiences reported, and nabumetone was well tolerated and compared favorably with the other agents used, including placebo. It caused significantly fewer gastrointestinal side effects than soluble aspirin. Nabumetone is an appropriate choice of nonsteroidal anti-inflammatory drug for the treatment of sports injury.

Assessment of in vitro inhibitory activity of hydrogen peroxide on the growth of Malassezia pachydermatis and to compare its efficacy with commercial ear cleaners.

PubMed

Marrero, Edrei Javier; Silva, Freddy Alejandro; Rosario, Inmaculada; Déniz, Soraya; Real, Fernando; Padilla, Daniel; Díaz, Esther Licia; Acosta-Hernández, Begoña

2017-10-01

Otitis caused by Malassezia pachydermatis is generally a common and recurrent disease in canine clinical pathology. The increased incidence of fungal resistant to antifungal in both humans and pets is a cause for concern and is associated with the indiscriminate use of antifungals. Finding the most effective disinfectants and antifungals has become essential. To evaluate the in vitro inhibitory activity of hydrogen peroxide on the growth of M. pachydermatis and compare its efficacy with commercial ear cleaners. The test for sensitivity to antimicrobials was carried out following the indications of the CLSI document M44-A2. The comparative results demonstrated that hydrogen peroxide 1.5% showed excellent results for growth inhibition of M. pachydermatis, followed by Epiotic ® and MalAcetic ® , the lowest result was for Otoclean ® . © 2017 Blackwell Verlag GmbH.

Increasing efficacy and reducing systemic absorption of brimonidine tartrate ophthalmic gels in rabbits.

PubMed

Pang, Xiaochen; Li, Jiawei; Pi, Jiaxin; Qi, Dongli; Guo, Pan; Li, Nan; Wu, Yumei; Liu, Zhidong

2018-03-01

Systemic absorption of ocularly administered Brimonidine Tartrate has been reported to give rise to several side-effects. Hence, it has become crucial to develop a delivery system that could increase efficacy and reduce systemic absorption. Therefore, the present work aims to develop Brimonidine Tartrate gels with different concentrations (0.05%, 0.1%, and 0.2% w/v, respectively) using Carbopol 974 P and HPMC E4M, and compare the therapeutic efficacy and systemic absorption with that of eye drop (0.2%, w/v) by UPLC-MS/MS. The result of histological analysis did not show any morphological or structural changes after the administration of formulations. In vitro residence time studies demonstrated that the gels exhibited a better precorneal residence time as compared with the eye drop. The gels with lower concentrations of the drug (0.05% and 0.1%, w/v) could significantly decrease intraocular pressure (IOP) in both normal and water-loaded rabbits as compared to the eye drop. Finally, the values of the ratio of AUC (0→∞) in comparison to eye drop showed the gels with lower concentrations of Brimonidine Tartrate could decrease the systemic absorption. From the result, it can be concluded the 0.1% ophthalmic gel has a potential to improve therapeutic efficacy and reduce the potential toxicity caused by systemic absorption.

Knock-down and speed of kill of a combination of fipronil and permethrin for the prevention of Ctenocephalides felis flea infestation in dogs.

PubMed

Halos, Lénaïg; Fourie, Josephus J; Fankhauser, Becky; Beugnet, Frederic

2016-02-02

A topical combination of fipronil + permethrin (Frontline Tri-Act/Frontect, Merial) has recently been developed to control fleas, ticks, mosquitoes, sandflies and stable flies on dogs. Two studies were conducted to assess its speed of kill and knock-down effect on Ctenocephalides felis fleas. The combination was compared to either fipronil alone or to a combination of permethrin, dinotefuran, and pyriproxyfen, In each study, 18 dogs were randomly allocated to one of three groups: (Group 1: untreated dog; Group 2: treated once on D0 with the combination of fipronil and permethrin; Group 3: treated once on D0 either with fipronil alone (study 1) or with a combination of permethrin, dinetofuran and pyriproxyfen (study 2)). Each dog was infested with 100 unfed adult C. felis fleas on Days 2 (study 2), 7, 14, 21 and 28. Fleas were collected from dogs at 1 h and 12 h post- infestations (PI) (study 1) or at 2 h and 6 h PI (study 2) to assess efficacy and from collection pans underneath cages 1 h (study 1) or 5 min (study 2) PI to assess knock-down effect. All treated dogs had significantly (p ≤ 0.01) lower flea counts than untreated dogs at every time point in both studies. For a whole month, a significant knock-down effect against infesting fleas is obtained in five minutes PI with the combination of permethrin and fipronil. Complete efficacy (>95%) was achieved in 1 h (study 1) or 2 h (study 2) PI for 14 days and by 6 h PI for all challenges conducted throughout the month. Efficacy remains >85% at 2 h PI for the whole month. A significantly higher efficacy of the fipronil + permethrin combination compared to other treatments was demonstrated at the earliest time points for the month (1 h knock-down effect and insecticidal efficacy compared to fipronil alone; 5 min knock-down effect compared to the combination of permethrin + dinetofuran + pyriproxyfen). The rapid flea knock-down effect and speed of kill demonstrated by the spot on combination of fipronil + permethrin provide a reliable strategy against flea infestations in dogs.

Management of Powdery Mildew in Squash by Plant and Alga Extract Biopesticides

PubMed Central

Zhang, Shouan; Mersha, Zelalem; Vallad, Gary E.; Huang, Cheng-Hua

2016-01-01

Although many fungicides are registered for use to control powdery mildew on cucurbits, management of resistance to fungicides in pathogen populations still remains a major challenge. Two biopesticides Regalia SC and HMO 736 were evaluated in the greenhouse and field for their efficacy against powdery mildew in squash. In greenhouses, Regalia SC alone significantly (P < 0.05) reduced powdery mildew compared to the nontreated control, and was as effective as the chemical standard Procure 480SC (triflumizole). In alternation with Procure 480SC, Regalia SC demonstrated greater or equivalent effects on reducing the disease. HMO 736 alone showed varying levels of disease control, but alternating with Procure 480SC significantly improved control efficacy. In addition, application of Regalia SC or HMO 736 each in alternation with Procure 480SC significantly increased the chlorophyll content in leaves and the total fresh weight of squash plants, when compared with the water control, Regalia SC and HMO 736 alone. In field trials, application of Regalia SC and HMO 736 each alone significantly reduced disease severity in one of two field trials during the early stage of disease development, but not during later stages when disease pressure became high. Both Regalia SC and HMO 736 each applied in alternation with Procure 480SC significantly improved the control efficacy compared to Procure 480SC alone. Results from this study demonstrated that an integrated management program can be developed for powdery mildew in squash by integrating the biopesticides Regalia SC, HMO 736 with the chemical fungicide Procure 480SC. PMID:27904459

Management of Powdery Mildew in Squash by Plant and Alga Extract Biopesticides.

PubMed

Zhang, Shouan; Mersha, Zelalem; Vallad, Gary E; Huang, Cheng-Hua

2016-12-01

Although many fungicides are registered for use to control powdery mildew on cucurbits, management of resistance to fungicides in pathogen populations still remains a major challenge. Two biopesticides Regalia SC and HMO 736 were evaluated in the greenhouse and field for their efficacy against powdery mildew in squash. In greenhouses, Regalia SC alone significantly ( P < 0.05) reduced powdery mildew compared to the nontreated control, and was as effective as the chemical standard Procure 480SC (triflumizole). In alternation with Procure 480SC, Regalia SC demonstrated greater or equivalent effects on reducing the disease. HMO 736 alone showed varying levels of disease control, but alternating with Procure 480SC significantly improved control efficacy. In addition, application of Regalia SC or HMO 736 each in alternation with Procure 480SC significantly increased the chlorophyll content in leaves and the total fresh weight of squash plants, when compared with the water control, Regalia SC and HMO 736 alone. In field trials, application of Regalia SC and HMO 736 each alone significantly reduced disease severity in one of two field trials during the early stage of disease development, but not during later stages when disease pressure became high. Both Regalia SC and HMO 736 each applied in alternation with Procure 480SC significantly improved the control efficacy compared to Procure 480SC alone. Results from this study demonstrated that an integrated management program can be developed for powdery mildew in squash by integrating the biopesticides Regalia SC, HMO 736 with the chemical fungicide Procure 480SC.

A review of telavancin activity in in vitro biofilms and animal models of biofilm-associated infections.

PubMed

Chan, Cynthia; Hardin, Thomas C; Smart, Jennifer I

2015-01-01

Tissue- and device-associated biofilm infections are important medical problems. These infections are difficult to treat due to a high-level of tolerance to antibiotics. Telavancin has been studied in several in vitro biofilm models and has demonstrated efficacy against staphylococcal and enterococcal-associated biofilm infections, including those formed by methicillin-resistant Staphylococcus aureus. Telavancin was effective against the difficult-to-treat vancomycin- and glycopeptide-intermediate strains of S. aureus in these models. Furthermore, the efficacy of telavancin has been evaluated in several biofilm-related in vivo models, including osteomyelitis, endocarditis and device-associated infections in rabbits. Overall, telavancin exhibited similar or greater efficacy than vancomycin and other comparators in these animal models and maintained activity against vancomycin-intermediate and daptomycin nonsusceptible strains of S. aureus.

Behavior Therapy for Pediatric Trichotillomania: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Franklin, Martin E.; Edson, Aubrey L.; Ledley, Deborah A.; Cahill, Shawn P.

2011-01-01

Objective: To examine the efficacy and durability of a behavioral therapy (BT) protocol for pediatric TTM compared with a minimal attention control (MAC) condition. It was hypothesized that the BT condition would be superior to MAC at the end of acute treatment, and would also demonstrate durability of gains through the maintenance treatment…

A meta-analytic review of the relationship of cancer coping self-efficacy with distress and quality of life

PubMed Central

Chirico, Andrea; Lucidi, Fabio; Merluzzi, Thomas; Alivernini, Fabio; De Laurentiis, Michelino; Botti, Gerardo; Giordano, Antonio

2017-01-01

Self-efficacy for coping with cancer is a specific construct that refers to behaviors that occur in the course of dealing with a cancer diagnosis, cancer treatments, and transitioning to survivorship. One of the more widely used measures of self-efficacy for coping strategies with cancer is the Cancer Behavior Inventory. The following general questions provide a framework for this research: 1. Is self-efficacy for coping with cancer related to distress and quality of life of a cancer patient?. 2. Do self-efficacy for coping with cancer and the target psychological outcomes (i.e., distress and quality of life) change in longitudinal studies, with or without intervention? One-hundred eighty studies cited the different versions of the Cancer Behavior Inventory and 47 used the scale. Result showed an inverse relationship between self-efficacy for coping with cancer and distress, and a positive relationship between self-efficacy for coping with cancer and Quality of Life, both with a large effect size. The strong relationship of self-efficacy and outcomes, resulted of the specificity of the instrument, which targets specific coping strategies that are closely aligned with positive outcomes in adjusting to cancer. However, the results are consistent with the theory, which states that compared to those with low efficacy, highly efficacious people demonstrate less anxiety and better adjustment in stressful situations and consistent with prior results in which self-efficacy is positively related to quality of life. PMID:28404938

Effects of omeprazole in improving concurrent chemoradiotherapy efficacy in rectal cancer.

PubMed

Zhang, Jin-Liang; Liu, Min; Yang, Qing; Lin, Shi-Yong; Shan, Hong-Bo; Wang, Hui-Yun; Xu, Guo-Liang

2017-04-14

To explore the effects of omeprazole on chemoradiotherapy efficacy and tumor recurrence in rectal cancer. The medical data of 125 rectal cancer patients who received the same neoadjuvant chemoradiotherapy (CRT) followed by surgery were retrospectively collected. Patients who received omeprazole (OME) orally at a dose of 20 mg at least once daily for six days and/or intravenously at 40 mg a day were recognized as eligible OME users (EOU). Otherwise, patients were regarded as non-eligible OME users (non-EOU). Moreover, a preferred OME dose cut-off of 200 mg on tumor recurrence was obtained by receiver operating characteristic (ROC) curves. Patients were divided into two groups: the effective OME group (EOG, OME ≥ 200 mg) and the non-effective OME group (non-EOG, OME < 200 mg). The good response rate of CRT efficacy (50.8%) in EOU was significantly increased compared with non-EOU (30.6%) ( P = 0.02). The recurrence rate in the EOG was 10.3%, which was significantly lower compared with 31.3% in non-EOG ( P = 0.025). The good response rate of CRT efficacy in EOG was 55.2%, which was obviously higher compared with 36.5% in non-EOG, with a significant difference ( P = 0.072). Multivariate Cox analysis demonstrated that OME (non-EOG and EOG) was an independent and significant impact factor for DFS ( P = 0.048, HR = 0.30, 95%CI: 0.09-0.99). When applied as an adjuvant drug in cancer treatment for relieving common side effects of chemotherapy, omeprazole has a synergetic effect in improving CRT efficacy and decreasing rectal cancer recurrence.

Estrogenic agonist activity of ICI 182,780 (Faslodex) in hippocampal neurons: implications for basic science understanding of estrogen signaling and development of estrogen modulators with a dual therapeutic profile.

PubMed

Zhao, Liqin; O'Neill, Kathleen; Brinton, Roberta Diaz

2006-12-01

The present study sought to determine the characteristics of ICI 182,780 (Faslodex) action in rat primary hippocampal neurons. We first investigated the neuroprotective efficacy of ICI 182,780 against neurodegenerative insults associated with Alzheimer's disease and related disorders. Dose-response analyses revealed that ICI 182,780, in a concentration-dependent manner, significantly promoted neuron survival following exposure to either excitotoxic glutamate (200 muM)- or beta-amyloid(1-42) (1.5 muM)-induced neurodegeneration of hippocampal neurons. At a clinically relevant concentration of 50 ng/ml, ICI 182,780 exerted nearly maximal neuroprotection against both insults with efficacy comparable with that induced by the endogenous estrogen 17beta-estradiol. Thereafter, we investigated the impact of 50 ng/ml ICI 182,780 on mechanisms of 17beta-estradiol-inducible neuronal plasticity and neuroprotection. Results of these analyses demonstrated that ICI 182,780 directly induced a series of rapid intracellular Ca(2+) concentration ([Ca(2+)](i)) oscillations in a pattern comparable with that of 17beta-estradiol. In addition, ICI 182,780 exerted dual regulation of the glutamate-induced rise in [Ca(2+)](i) identical to that induced by 17beta-estradiol. Further analyses demonstrated that ICI 182,780 induced significant activation of extracellular signal-regulated kinase 1/2 and Akt (protein kinase B) and significantly increased expression of spinophilin and Bcl-2, with efficacy comparable with neurons treated with 17beta-estradiol. Taken together, results of these in vitro analyses of ICI 182,780 provide direct evidence of an estrogenic agonist profile of ICI 182,780 action in rat hippocampal neurons. Therapeutic development of neuroselective estrogen receptor modulators that mimic ICI 182,780 is discussed with respect to the potential of safe and efficacious alternatives to estrogen therapy for the prevention of postmenopausal cognitive decline and late-onset Alzheimer's disease.

Pharmacokinetics, safety, and efficacy of a liposome encapsulated thymidylate synthase inhibitor, OSI-7904L [(S)-2-[5-[(1,2-dihydro-3-methyl-1-oxobenzo[f]quinazolin-9-yl)methyl]amino-1-oxo-2-isoindolynl]-glutaric acid] in mice.

PubMed

Desjardins, John; Emerson, David L; Colagiovanni, Dorothy B; Abbott, Elizabeth; Brown, Eric N; Drolet, Daniel W

2004-06-01

OSI-7904L [(S)-2-[5-[(1,2-dihydro-3-methyl-1-oxobenzo[f]quinazolin-9-yl)methyl]amino-1-oxo-2-isoindolynl]-glutaric acid] is a liposomal formulation of the highly specific, noncompetitive, thymidylate synthase inhibitor OSI-7904 (also known as GW1843, 1843U89, and GS7904). The liposome formulation was developed to enhance the therapeutic index and dose schedule convenience of this potent antifolate compound. The studies presented here were conducted to determine the antitumor efficacy, distribution, pharmacokinetics, and safety of OSI-7904L in mice. In a human colon adenocarcinoma xenograft model in mice, OSI-7904L demonstrated superior antitumor efficacy compared with OSI-7904 or 5-fluorouracil. Furthermore, OSI-7904L could be administered less frequently than OSI-7904 although still generating greater tumor growth inhibition. Distribution studies confirmed that OSI-7904L-treated animals had much greater plasma, tissue, and tumor exposure than did OSI-7904-treated animals. Tumor exposures, based on area under the curve, in OSI-7904L-treated mice were increased over 100-fold compared with tumor exposures in OSI-7904-treated mice. Plasma exposures following OSI-7904L administration were greater than dose proportional consistent with saturation of plasma clearance mechanisms. OSI-7904L was much more toxic than OSI-7904 in the mouse with primary toxicities to the intestines, bone marrow, and thymus. Minimal toxicity to the lungs and liver was noted. These data clearly demonstrated that in mice, OSI-7904L has an increased plasma residence time as well as increased tissue and tumor exposure compared with OSI-7904, thus resulting in increased potency and toxicity. Potential benefits of OSI-7904L include improved efficacy and a more convenient schedule of administration.

A Randomized Trial of a Web-based Intervention to Improve Migraine Self-Management and Coping

PubMed Central

Bromberg, Jonas; Wood, Mollie E.; Black, Ryan A.; Surette, Daniel A.; Zacharoff, Kevin L.; Chiauzzi, Emil J.

2011-01-01

Objective Test the clinical efficacy of a web-based intervention designed to increase patient self-efficacy to perform headache self-management activities and symptom management strategies; and reduce migraine-related psychological distress. Background In spite of their demonstrated efficacy, behavioral interventions are used infrequently as an adjunct in medical treatment of migraine. Little clinical attention is paid to the behavioral factors that can help manage migraine more effectively, improve the quality of care, and improve quality of life. Access to evidenced-based, tailored, behavioral treatment is limited for many people with migraine. Design The study is a parallel group design with two conditions, (1) an experimental group exposed to the web intervention, and (2) a no-treatment control group that was not exposed to the intervention. Assessments for both groups were conducted at baseline (T1), 1-month (T2), 3-months (T3), and 6-months (T4). Results Compared to controls, participants in the experimental group reported significantly: increased headache self-efficacy, increased use of relaxation, increased use of social support, decreased pain catastrophizing, decreased depression, and decreased stress. The hypothesis that the intervention would reduce pain could not be tested. Conclusions Demonstrated increases in self-efficacy to perform headache self-management, increased use of positive symptom management strategies, and reported decreased migraine-related depression and stress, suggest that the intervention may be a useful behavioral adjunct to a comprehensive medical approach to managing migraine. PMID:22413151

Performance of the plant-based repellent TT-4302 against mosquitoes in the laboratory and field and comparative efficacy to 16 mosquito repellents against Aedes aegypti (Diptera: Culicidae).

PubMed

Bissinger, B W; Schmidt, J P; Owens, J J; Mitchell, S M; Kennedy, M K

2014-03-01

Repellent efficacy of the plant-based repellent, TT-4302 (5% geraniol), was compared with 16 other products in laboratory arm-in-cage trials against Aedes aegypti (L). Eight repellents (Badger, BioUD, Burt's bees, California Baby, Cutter Natural, EcoSMART, Herbal Armor, and SkinSmart) exhibited a mean repellency below 90% to Ae. aegypti at 0.5 h after application. Three repellents (Buzz Away Extreme, Cutter Advanced, and OFF! Botanicals lotion) fell below 90% repellency 1.5 h after application. TT-4302 exhibited 94.7% repellency 5 h posttreatment, which was a longer duration than any of the other repellents tested. The positive control, 15% DEET (OFF! Active), was repellent for 3 h before activity dropped below 90%. Additional arm-in-cage trials comparing TT-4302 with 15% DEET were carried out against Anopheles quadrimaculatus Say. At 6 h after treatment, TT-4302 provided 95.2% repellency while DEET exhibited 72.2%. In North Carolina field trials, TT-4302 provided 100% repellency 5 h after application against Aedes albopictus Skuse while DEET provided 77.6% repellency. These results demonstrate that TT-4302 is an efficacious plant-based repellent that provides an extended duration of protection compared with many other commercially available products.

The Comparative Efficacy of Lifestyle Intervention and Metformin by Educational Attainment in the Diabetes Prevention Program

PubMed Central

O’Brien, Matthew J.; Whitaker, Robert C.; Yu, Daohai; Ackermann, Ronald T.

2015-01-01

Objective Educational attainment is inversely associated with type 2 diabetes risk, but it is unknown whether education impacts individuals’ diabetes prevention efforts. We examined the comparative efficacy of intensive lifestyle intervention and metformin by educational attainment among participants in the Diabetes Prevention Program (DPP), an ongoing U.S. multi-site trial beginning in 1996. Methods We studied 2,910 DPP participants randomized to receive lifestyle intervention, metformin, or placebo. Stratifying by educational attainment, diabetes incidence and relative risk reductions by treatment assignment were estimated using Cox proportional hazards regression. Results 47% of participants had completed college and 53% had not. Compared to placebo, lifestyle participants who had completed college demonstrated a 68% reduction in diabetes incidence (95% CI=56, 77), whereas those with less education experienced a 47% risk reduction (95% CI=29, 61). For metformin participants, college graduates experienced a 49% relative risk reduction (95% CI=33, 62), compared to 23% (95% CI=1, 41) among those with lower educational attainment. There was a statistically significant education-by-treatment interaction with incident diabetes (p=0.03). Conclusions Intensive lifestyle intervention and metformin have greater efficacy among highly educated individuals. Future efforts to deliver these treatments and study their dissemination may be more effective if tailored to individuals’ educational background. PMID:26024851

The comparative efficacy of lifestyle intervention and metformin by educational attainment in the Diabetes Prevention Program.

PubMed

O'Brien, Matthew J; Whitaker, Robert C; Yu, Daohai; Ackermann, Ronald T

2015-08-01

Educational attainment is inversely associated with type 2 diabetes risk, but it is unknown whether education impacts individuals' diabetes prevention efforts. We examined the comparative efficacy of intensive lifestyle intervention and metformin by educational attainment among participants in the Diabetes Prevention Program (DPP), an ongoing U.S. multi-site trial beginning in 1996. We studied 2,910 DPP participants randomized to receive lifestyle intervention, metformin, or placebo. Stratifying by educational attainment, diabetes incidence and relative risk reductions by treatment assignment were estimated using Cox proportional hazards regression. 47% of participants had completed college and 53% had not. Compared to placebo, lifestyle participants who had completed college demonstrated a 68% reduction in diabetes incidence (95% CI=56, 77), whereas those with less education experienced a 47% risk reduction (95% CI=29, 61). For metformin participants, college graduates experienced a 49% relative risk reduction (95% CI=33, 62), compared to 23% (95% CI=1, 41) among those with lower educational attainment. There was a statistically significant education-by-treatment interaction with incident diabetes (p=0.03). Intensive lifestyle intervention and metformin have greater efficacy among highly educated individuals. Future efforts to deliver these treatments and study their dissemination may be more effective if tailored to individuals' educational background. Copyright © 2015 Elsevier Inc. All rights reserved.

In vivo pharmacological evaluation and efficacy study of methotrexate-encapsulated polymer-coated layered double hydroxide nanoparticles for possible application in the treatment of osteosarcoma.

PubMed

Ray, Sayantan; Saha, Suman; Sa, Biswanath; Chakraborty, Jui

2017-04-01

Considering the existing drawbacks of methotrexate (MTX) with respect to its solubility and toxicity, we incorporated it in a nanoceramic matrix, Mg-Al-layered double hydroxide (LDH) to form LDH-MTX nanoparticles, and the same was in turn encapsulated in a nontoxic and biodegradable polymer, poly (D,L-lactide-co-glycolide) (PLGA), to arrest the initial burst release and dose-dumping-related toxicity, already reported by our group. Our present study was designed to evaluate the pharmacokinetics, tissue distribution, survival rate of the test animals, and antitumor efficacy of the PLGA-LDH-MTX nanoparticles and its counterpart without LDH, PLGA-MTX nanoparticles compared with bare MTX. The median lethal dose (LD 50 ) of the former was higher, compared with bare MTX, using Balb/c nude mice, indicating it to be completely safe for use. Also, a comparative pharmacokinetic and antitumour efficacy study using MTX, PLGA-MTX, and PLGA-LDH-MTX nanoparticles in osteosarcoma-induced Balb/c nude mice in vivo demonstrated superiority of PLGA-LDH-MTX as compared to PLGA-MTX and bare MTX. The results suggest that PLGA-LDH-MTX nanoparticles might exhibit potential advantages over the present-day chemotherapy over bare MTX, for the possibility of treatment of osteosarcoma.

Efficacy of tulathromycin compared with tilmicosin and florfenicol for the control of respiratory disease in cattle at high risk of developing bovine respiratory disease.

PubMed

Rooney, Kathleen A; Nutsch, Robert G; Skogerboe, Terry L; Weigel, Daniel J; Gajewski, Kimberly; Kilgore, W Randal

2005-01-01

Three studies conducted at feedlots in Colorado, Idaho, and Texas examined the comparative efficacy of tulathromycin injectable solution for the treatment of cattle at high risk of developing undifferentiated bovine respiratory disease (BRD). Each study randomly allocated 250 calves to receive tulathromycin at 2.5 mg/kg and 250 calves to receive either tilmicosin at 10 mg/kg (Colorado site) or florfenicol at 40 mg/kg (Idaho and Texas sites) on arrival at the feedlot. Calves were housed by treatment group in pens with 50 calves/pen. Beginning 3 days after antimicrobial treatment, cattle were observed for signs of BRD daily until harvest. In all three studies, the treatment success rates at 28 days after treatment and at harvest were significantly higher (P < or = .013) for cattle treated with tulathromycin than for cattle treated with either tilmicosin or florfenicol. Fewer tulathromycin-treated cattle were removed from the group as "chronics" or "mortalities" at 28 days posttreatment (P < or = .014) in all three studies. Tulathromycin demonstrated superior efficacy compared with tilmicosin and florfenicol when treating groups of high-risk cattle before the onset of signs of BRD.

An evaluation of analgesic regimens for abdominal surgery in mice.

PubMed

Hayes, K E; Raucci, J A; Gades, N M; Toth, L A

2000-11-01

This study was designed to evaluate the efficacy of several analgesic regimens for use after intraperitoneal implantation of telemetry transmitters in mice. The lengths of time required for postoperative recovery of food and water intake, locomotor activity, and core temperature of mice that did not receive postsurgical analgesic medication were compared to those of mice that were given either an analgesic in the drinking water or buprenorphine injections. Many measured variables were not substantially altered by analgesic medications. However, ibuprofen-treated mice demonstrated significantly greater locomotor activity on days 2 through 5 after surgery and a more rapid return to stable postsurgical levels of activity and water intake as compared to those in untreated mice. These changes are consistent with potential analgesic efficacy of the ibuprofen treatment regimen. Buprenorphine injections elicited hyperactivity, hyperthermia, and reduced food and water intake during both the immediate postsurgical recovery period and after apparent recuperation from surgery, as compared to effects observed in saline-treated mice. Evaluating the effect of analgesic regimens on postsurgical changes in physiologic and behavioral variables can be useful in assessing the efficacy of analgesic treatments, but some changes may indicate pharmacologic effects that do not reflect pain relief.

Comparable efficacy and safety of various topical formulations of terbinafine in tinea pedis irrespective of the treatment regimen: results of a meta-analysis.

PubMed

Korting, Hans Christian; Kiencke, Peter; Nelles, Sandra; Rychlik, Reinhard

2007-01-01

Terbinafine has been widely used with major success as a topical antifungal therapy for tinea pedis (athlete's foot). Its efficacy and safety have been validated in several clinical trials, which have demonstrated clinical efficacy for the drug after only 1 week of treatment when applied once daily, a reflection of the high fungicidal potency of the drug and its ability to form a depot in the upper skin layer. To improve patients' compliance further, a terbinafine-containing film-forming solution has been developed for single-dose therapy of athlete's foot. This novel formulation delivers terbinafine in high amounts and for a prolonged period of time into the skin, making one-shot treatment feasible. Over the past years there have been a variety of trials evaluating use of topical terbinafine addressing different pharmaceutical formulations, treatment durations, and application frequencies, but a detailed meta-analysis of these trials has not been conducted to date. The present study is the first meta-analytic evaluation of the available data on the efficacy (clinical and mycologic cure rates) and safety (adverse events) of all topical forms of terbinafine for the treatment of tinea pedis. An international, systematic literature search of 12 electronic databases (including MEDLINE, EMBASE, and Cochrane databases) using a pre-specified search strategy was conducted in March 2006. This meta-analysis included only randomized controlled trials in which terbinafine had been used for topical treatment of tinea pedis in comparison with placebo or an active control. Studies of all available topical formulations of terbinafine, frequencies of application, and durations of treatment were included. Of 100 identified articles published between 1990 and 2006, 19 met the criteria for analysis. These 19 studies involved 2899 patients with clinical and mycologic diagnoses of tinea pedis (nine placebo-controlled trials and ten active-controlled trials). Efficacy analysis demonstrated that the mycologic cure rate was significantly superior with terbinafine compared with placebo (relative risk [RR] 3.17; p < 0.001). No significant differences in efficacy were found amongst different formulations of terbinafine, treatment durations, or frequencies of application. Comparable results were obtained with respect to clinical cure rate for terbinafine compared with placebo (RR 2.75; p < 0.001). Comparison of the efficacy of terbinafine versus active control indicated a nonsignificant difference in favor of terbinafine with regard to mycologic cure rate (RR 1.03; p = 0.423) and clinical cure rate (RR 1.09; p = 0.11). The median duration of treatment was also shorter with terbinafine (1 week) compared with active controls (2 weeks). Analysis of the placebo-controlled studies showed that there was no significant difference in the risk of adverse events with terbinafine compared with placebo (RR 1.34; p = 0.34). Likewise, no significant differences in adverse events were found between terbinafine and active controls (RR 1.08; p = 0.72). Terbinafine is very well tolerated in any topical pharmaceutical formulation and also has high efficacy as a cure for tinea pedis, irrespective of type of pharmaceutical formulation, treatment duration, and frequency of application, including the recently established one-shot regimen. In addition, terbinafine has an apparently unique advantage over other antifungal agents with respect to the required duration of treatment for tinea pedis.

Short communication: Efficacy of copper sulfate hoof baths against digital dermatitis--Where is the evidence?

PubMed

Thomsen, Peter T

2015-04-01

Digital dermatitis is a major problem in modern dairy production because of decreased animal welfare and financial losses. Individual cow treatments are often seen as too time consuming by farmers, and walk-through hoof baths have therefore been used extensively to control digital dermatitis. For decades, copper sulfate hoof baths have been used to treat and prevent digital dermatitis. Copper sulfate has been referred to as the industry gold standard when it comes to hoof-bath chemicals. In several scientific studies testing the efficacy of other hoof-care products, copper sulfate has been used as a positive control, thereby indicating that copper sulfate has a known positive effect. However, this may not be the case. A dilemma may exist between (1) copper sulfate generally being perceived as being effective against digital dermatitis and (2) a possible lack of well-documented scientific evidence of this effect. The objective of this study was to evaluate the existing scientific literature to determine whether the efficacy of copper sulfate used in hoof baths against digital dermatitis has in fact been demonstrated scientifically. A systematic literature search identified 7 peer-reviewed journal articles describing the efficacy of copper sulfate in hoof baths as treatment or prevention of bovine digital dermatitis. Only 2 of the 7 studies compared copper sulfate to a negative control; most studies were relatively small, and often no clear positive effect of copper sulfate was demonstrated. In conclusion, the frequent claim that copper sulfate is widely reported to be effective is supported by little scientific evidence. Well-designed clinical trials evaluating the effect of copper sulfate against digital dermatitis compared with a negative control are needed. Until such studies have been made, the efficacy of copper sulfate in hoof baths against digital dermatitis remains largely unproven. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

In Vivo Cardiac Cellular Reprogramming Efficacy Is Enhanced by Angiogenic Preconditioning of the Infarcted Myocardium With Vascular Endothelial Growth Factor

PubMed Central

Mathison, Megumi; P. Gersch, Robert; Nasser, Ahmed; Lilo, Sarit; Korman, Mallory; Fourman, Mitchell; Hackett, Neil; Shroyer, Kenneth; Yang, Jianchang; Ma, Yupo; Crystal, Ronald G.; Rosengart, Todd K.

2012-01-01

Background In situ cellular reprogramming offers the possibility of regenerating functional cardiomyocytes directly from scar fibroblasts, obviating the challenges of cell implantation. We hypothesized that pretreating scar with gene transfer of the angiogenic vascular endothelial growth factor (VEGF) would enhance the efficacy of this strategy. Methods and Results Gata4, Mef2c, and Tbx5 (GMT) administration via lentiviral transduction was demonstrated to transdifferentiate rat fibroblasts into (induced) cardiomyocytes in vitro by cardiomyocyte marker studies. Fisher 344 rats underwent coronary ligation and intramyocardial administration of an adenovirus encoding all 3 major isoforms of VEGF (AdVEGF‐All6A+) or an AdNull control vector (n=12/group). Lentivirus encoding GMT or a GFP control was administered to each animal 3 weeks later, followed by histologic and echocardiographic analyses. GMT administration reduced the extent of fibrosis by half compared with GFP controls (12±2% vs 24±3%, P<0.01) and reduced the number of myofibroblasts detected in the infarct zone by 4‐fold. GMT‐treated animals also demonstrated greater density of cardiomyocyte‐specific marker beta myosin heavy chain 7+ cells compared with animals receiving GFP with or without VEGF (P<0.01). Ejection fraction was significantly improved after GMT vs GFP administration (12±3% vs −7±3%, P<0.01). Eight (73%) GFP animals but no GMT animals demonstrated decreased ejection fraction during this interval (P<0.01). Also, improvement in ejection fraction was 4‐fold greater in GMT/VEGF vs GMT/null animals (17±2% vs 4±1%, P<0.05). Conclusions VEGF administration to infarcted myocardium enhances the efficacy of GMT‐mediated cellular reprogramming in improving myocardial function and reducing the extent of myocardial fibrosis compared with the use of GMT or VEGF alone. PMID:23316332

A comparative study of matrix metalloproteinase and aggrecanase mediated release of latent cytokines at arthritic joints.

PubMed

Mullen, Lisa; Adams, Gill; Foster, Julie; Vessillier, Sandrine; Köster, Mario; Hauser, Hansjörg; Layward, Lorna; Gould, David; Chernajovsky, Yuti

2014-09-01

Latent cytokines are engineered by fusing the latency associated peptide (LAP) derived from transforming growth factor-β (TGF-β) with the therapeutic cytokine, in this case interferon-β (IFN-β), via an inflammation-specific matrix metalloproteinase (MMP) cleavage site. To demonstrate latency and specific delivery in vivo and to compare therapeutic efficacy of aggrecanase-mediated release of latent IFN-β in arthritic joints to the original MMP-specific release. Recombinant fusion proteins with MMP, aggrecanase or devoid of cleavage site were expressed in CHO cells, purified and characterised in vitro by Western blotting and anti-viral protection assays. Therapeutic efficacy and half-life were assessed in vivo using the mouse collagen-induced arthritis model (CIA) of rheumatoid arthritis and a model of acute paw inflammation, respectively. Transgenic mice with an IFN-regulated luciferase gene were used to assess latency in vivo and targeted delivery to sites of disease. Efficient localised delivery of IFN-β to inflamed paws, with low levels of systemic delivery, was demonstrated in transgenic mice using latent IFN-β. Engineering of latent IFN-β with an aggrecanase-sensitive cleavage site resulted in efficient cleavage by ADAMTS-4, ADAMTS-5 and synovial fluid from arthritic patients, with an extended half-life similar to the MMP-specific molecule and greater therapeutic efficacy in the CIA model. Latent cytokines require cleavage in vivo for therapeutic efficacy, and they are delivered in a dose dependent fashion only to arthritic joints. The aggrecanase-specific cleavage site is a viable alternative to the MMP cleavage site for the targeting of latent cytokines to arthritic joints. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Antimicrobial efficacy of eucalyptus oil and 1,8-cineole alone and in combination with chlorhexidine digluconate against microorganisms grown in planktonic and biofilm cultures.

PubMed

Hendry, E R; Worthington, T; Conway, B R; Lambert, P A

2009-12-01

Effective disinfection and antisepsis is pivotal in preventing infections within the healthcare setting. Chlorhexidine digluconate (CHG) is a widely used disinfectant/antiseptic possessing broad-spectrum antimicrobial activity; however, its penetration into bacterial biofilms and human skin is poor. The aim of this study was to investigate the antimicrobial efficacy of crude eucalyptus oil (EO) and its main component 1,8-cineole (a recognized permeation enhancer), alone and in combination with CHG, against a panel of clinically relevant microorganisms grown in planktonic and biofilm cultures. MICs and minimum bactericidal/fungicidal concentrations were determined for each microorganism grown in suspension and biofilm using microbroth dilution and ATP bioluminescence, respectively. Chequerboard assays were used to determine synergistic, indifferent or antagonistic interactions between CHG and EO or 1,8-cineole. Antimicrobial activity was demonstrated by CHG, EO and 1,8-cineole; however, CHG was significantly more active against microorganisms in both planktonic and biofilm modes of growth (P < 0.05). Crude EO was significantly more efficacious against microorganisms grown in suspension compared with 1,8-cineole (P < 0.05). Synergistic activity was demonstrated between CHG and both EO and 1,8-cineole against suspensions of Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Escherichia coli and Candida albicans, and biofilm cultures of MRSA and Pseudomonas aeruginosa. In conclusion, CHG may be combined with either crude EO or its major component 1,8-cineole for enhanced, synergistic antimicrobial activity against a wide range of microorganisms in planktonic and biofilm modes of growth; however, the superior antimicrobial efficacy associated with crude EO alone, compared with 1,8-cineole, favours its combination with CHG.

Anti-vascular endothelial growth factor for neovascular age-related macular degeneration: a meta-analysis of randomized controlled trials.

PubMed

Nguyen, Chu Luan; Oh, Lawrence J; Wong, Eugene; Wei, Joe; Chilov, Michael

2018-05-30

To evaluate the relative efficacy and safety of anti-vascular endothelial growth factor (anti-VEGF) agents for the treatment of neovascular age-related macular degeneration (AMD). Systematic literature review identifying RCTs comparing anti-VEGF agents to another treatment published before June 2016. Efficacy assessed by mean change in best corrected visual acuity (BCVA) and central macular thickness (CMT) from baseline at up to 2 years followup. Safety assessed by proportions of patients with death, arteriothrombotic and venous thrombotic events, and at least one serious systemic adverse event at up to 2 years of followup. Fifteen RCTs selected for meta-analysis (8320 patients). Two trials compared pegaptanib, and three trials compared ranibizumab versus control. Eight trials compared bevacizumab with ranibizumab. Two trials compared aflibercept with ranibizumab. There were no significant differences between bevacizumab and ranibizumab for BCVA at 1 or 2 years (weighted mean difference = - 0.57, 95% CI - 1.55 to 0.41, P = 0.25 and weighted mean difference = - 0.76, 95% CI - 2.25 to 0.73, P = 0.32, respectively). Ranibizumab was more effective in reducing CMT at 1 year (weighted mean difference = 4.49, 95% CI 1.13 to 7.84, P = 0.009). Risk ratios comparing rates of serious systemic adverse events at 1 and 2 years were slightly out of favour for bevacizumab. Aflibercept compared with ranibizumab demonstrated similar mean change in BCVA, reduction in CMT, and safety at 1 year. Bevacizumab and ranibizumab had equivalent efficacy for BCVA, while ranibizumab had greater reduction in CMT and less rate of serious systemic adverse events. Aflibercept and ranibizumab had comparable efficacy for BCVA and CMT. This provides information to balance comparable effects on vision and risk of adverse events between anti-VEGF agents.

Programs for the Prevention of Youth Depression: Evaluation of Efficacy, Effectiveness, and Readiness for Dissemination

PubMed Central

Brunwasser, Steven M.; Garber, Judy

2015-01-01

Objective To evaluate the current state of evidence of the effectiveness of depression prevention programs for youth, assess the degree to which current evidence supports broad implementation, and outline additional steps needed to close the gap between effectiveness and dissemination. Method We used the Society for Prevention Research’s Standards of Evidence (Flay et al., 2005) to evaluate the degree to which existing depression prevention programs have established intervention efficacy, effectiveness, and readiness for dissemination. We reviewed all depression prevention programs for youth that have been evaluated in at least two published, randomized controlled trials in which the intervention was compared to a no-intervention control group. A total of 37 studies evaluating 11 different programs were reviewed with regard to depressive symptoms and diagnoses post intervention and at follow-up (at least 6 months). Results Eight programs demonstrated significant main effects on depressive symptoms relative to controls in multiple RCTs; five programs had at least one trial with significant main effects present at least one year post-intervention. Two programs demonstrated efficacy for both depressive symptoms and depressive episodes across multiple independent trials. Regarding effectiveness, six programs had at least one study showing significant effects when delivered by endogenous service providers; four programs had significant effects in studies conducted independently of the program developers. Conclusions Several programs have demonstrated promise in terms of efficacy, but no depression prevention program for children or adolescents as yet has garnered sufficient evidence of effectiveness under real-world conditions to warrant widespread dissemination at this time. PMID:25933173

Novel Method to Assess Arterial Insufficiency in Rodent Hindlimb

PubMed Central

Ziegler, Matthew A.; DiStasi, Matthew R.; Miller, Steven J.; Dalsing, Michael C.; Unthank, Joseph L.

2015-01-01

Background Lack of techniques to assess maximal blood flow capacity thwarts the use of rodent models of arterial insufficiency to evaluate therapies for intermittent claudication. We evaluated femoral vein outflow (VO) in combination with stimulated muscle contraction as a potential method to assess functional hindlimb arterial reserve and therapeutic efficacy in a rodent model of subcritical limb ischemia. Materials and methods VO was measured with perivascular flow probes at rest and during stimulated calf muscle contraction in young healthy rats (Wistar Kyoto, WKY; lean Zucker, LZR) and rats with cardiovascular risk factors (Spontaneously Hypertensive, SHR; Obese Zucker, OZR) with acute and/or chronic femoral arterial occlusion. Therapeutic efficacy was assessed by administration of Ramipril or Losartan to SHR after femoral artery excision. Results VO measurement in WKY demonstrated the utility of this method to assess hindlimb perfusion at rest and during calf muscle contraction. While application to diseased models (OZR, SHR) demonstrated normal resting perfusion compared to contralateral limbs, a significant reduction in reserve capacity was uncovered with muscle stimulation. Administration of Ramipril and Losartan demonstrated significant improvement in functional arterial reserve. Conclusion The results demonstrate that this novel method to assess distal limb perfusion in small rodents with subcritical limb ischemia is sufficient to unmask perfusion deficits not apparent at rest, detect impaired compensation in diseased animal models with risk factors, and assess therapeutic efficacy. The approach provides a significant advance in methods to investigate potential mechanisms and novel therapies for subcritical limb ischemia in pre-clinical rodent models. PMID:26850199

Effects of a Structured Discharge Planning Program on Perceived Functional Status, Cardiac Self-efficacy, Patient Satisfaction, and Unexpected Hospital Revisits Among Filipino Cardiac Patients: A Randomized Controlled Study.

PubMed

Cajanding, Ruff Joseph

Cardiovascular diseases remain the leading cause of morbidity and mortality among Filipinos and are responsible for a very large number of hospital readmissions. Comprehensive discharge planning programs have demonstrated positive benefits among various populations of patients with cardiovascular disease, but the clinical and psychosocial effects of such intervention among Filipino patients with acute myocardial infarction (AMI) have not been studied. In this study we aimed to determine the effectiveness of a nurse-led structured discharge planning program on perceived functional status, cardiac self-efficacy, patient satisfaction, and unexpected hospital revisits among Filipino patients with AMI. A true experimental (randomized control) 2-group design with repeated measures and data collected before and after intervention and at 1-month follow-up was used in this study. Participants were assigned to either the control (n = 68) or the intervention group (n = 75). Intervention participants underwent a 3-day structured discharge planning program implemented by a cardiovascular nurse practitioner, which is comprised of a series of individualized lecture-discussion, provision of feedback, integrative problem solving, goal setting, and action planning. Control participants received standard routine care. Measures of functional status, cardiac self-efficacy, and patient satisfaction were measured at baseline; cardiac self-efficacy and patient satisfaction scores were measured prior to discharge, and perceived functional status and number of revisits were measured 1 month after discharge. Participants in the intervention group had significant improvement in functional status, cardiac self-efficacy, and patient satisfaction scores at baseline and at follow-up compared with the control participants. Furthermore, participants in the intervention group had significantly fewer hospital revisits compared with those who received only standard care. The results demonstrate that a nurse-led structured discharge planning program is an effective intervention in improving perceived functional health status, cardiac self-efficacy, and patient satisfaction, while reducing the number of unexpected hospital revisits, among Filipino patients with AMI. It is recommended that this intervention be incorporated in the optimal care of patients being discharged with an AMI.

Dronedarone: a promising alternative for the management of atrial fibrillation.

PubMed

Yalta, Kenan; Turgut, Okan Onur; Yilmaz, Mehmet Birhan; Yilmaz, Ahmet; Tandogan, Izzet

2009-10-01

Atrial fibrillation (AF) is the most frequently encountered chronic arrhythmia associated with significant morbidity. It is generally encountered in the elderly, and will presumably become more prevalent in the future due to the increasing proportion of the elderly in the population. Major studies on AF have demonstrated no significant difference between rhythm and rate control in terms of mortality. However, young population with new-onset or lone AF, or patients in whom the maintenance of sinus rhythm is a must (due to recurrent thromboembolic events etc.) still gives rise to significant concerns related to the obligatory long-term prophylaxis. The long-term administration of the currently available conventional agents (amiodarone, dofetilide, sotalol, propafenone,flecainide etc.) is considered as a 'double edged sword' due to the presence of life-threatening adverse effects including pro-arrhythmia and organ toxicity associated with these agents. Several molecules are being developed for the management of AF. However, only a few novel agents confer promising results with respect to safety and efficacy issues in the major studies. Dronedarone is an amiodarone analogue without iodine moiety in its structure, and is similar to amiodarone with regard to its structural and electrophysiological properties. Dronedarone is largely denuded of the potentially life-threatening adverse effects of anti-arrhythmics. Major clinical studies have demonstrated both rhythm and rate-controlling efficacy of dronedarone compared to placebo without any serious adverse effects in patients with AF. However, the ANDROMEDA trial, a large scale study including patients hospitalized for symptomatic congestive heart failure (with severely depressed left ventricular systolic functions) was prematurely terminated due to the increased mortality in the dronedarone arm compared to placebo indicating a lack of safety in this group of patients. Conversely, the recently published ATHENA study (including more than 4,600 high risk patients, but excluding those with severe heart failure) demonstrated a significant reduction in cardiovascular hospitalizations and cardiovascular mortality with dronedarone compared to placebo. In contrast, the DIONYSOS study, comparing dronedarone with amiodarone, demonstrated better safety, but lower efficacy of dronedarone for the maintenance of sinus rhythm in patients with AF. Further clinical trials (including head to head comparison with other conventional anti-arrhythmics) are still required to determine the place of dronedarone in the management of AF. The present review focuses on basic and clinical aspects of dronedarone, a novel agent for the management of AF.

Reconceptualizing Efficacy in Substance Use Prevention Research: Refusal Response Efficacy and Drug Resistance Self-Efficacy in Adolescent Substance Use

PubMed Central

Choi, Hye Jeong; Krieger, Janice L.; Hecht, Michael L.

2014-01-01

The purpose of this study is to utilize the Extended Parallel Process Model (EPPM) to expand the construct of efficacy in the adolescent substance use context. Using survey data collected from 2,129 seventh-grade students in 39 rural schools, we examined the construct of drug refusal efficacy and demonstrated relationships among response efficacy (RE), self-efficacy (SE), and adolescent drug use. Consistent with the hypotheses, confirmatory factor analyses of a 12-item scale yielded a three-factor solution: refusal RE, alcohol-resistance self-efficacy (ASE), and marijuana-resistance self-efficacy (MSE). Refusal RE and ASE/MSE were negatively related to alcohol use and marijuana use, whereas MSE was positively associated with alcohol use. These data demonstrate that efficacy is a broader construct than typically considered in drug prevention. Prevention programs should reinforce both refusal RE and substance-specific resistance SE. PMID:23330857

PI3K/mTOR Dual Inhibitor, LY3023414, Demonstrates Potent Antitumor Efficacy Against Esophageal Adenocarcinoma in a Rat Model.

PubMed

Zaidi, Ali H; Kosovec, Juliann E; Matsui, Daisuke; Omstead, Ashten N; Raj, Moses; Rao, Rohit R; Biederman, Robert W W; Finley, Gene G; Landreneau, Rodney J; Kelly, Ronan J; Jobe, Blair A

2017-07-01

The purpose of the current study is to determine the efficacy of a PI3K/mTOR dual inhibitor, LY3023414, on established EAC in an in vivo model. Esophageal adenocarcinoma (EAC) is a highly lethal cancer with limited treatment options. The PI3K/mTOR pathway is upregulated in EAC and may be a target for novel therapies. Esophagojejunostomy was performed on Sprague-Dawley rats to induce carcinogenesis, and LY3023414 was cyclically administered intraperitoneally between 32 and 40 weeks postsurgery to treatment animals. Magnetic resonance imaging (MRI) and histology were used to determine clinical response. Immunohistochemistry, immunofluorescence, and Western blot were used to validate apoptosis by cleaved caspase-3, proliferation by Ki67, and pathway inhibition, respectively. Mean MRI tumor volume increased by 109.2% in controls (n = 32) and decreased by 56.8% in treatment animals (n=17) (P < 0.01). Treatment with LY3023414 demonstrated tumor volume increase in 0% (control = 46.4%) (P < 0.01), decrease in 58.8% (control = 7.1%) (P < 0.01), and stable volume in 41.2% (control = 46.4%) (P = 0.77). EAC prevalence in controls increased by 25%; whereas, prevalence in treatment animals decreased by 29.4% (P < 0.01). Approximately, 75% of treatment animals presenting with residual masses on MRI had a histological response >50%. Increased apoptosis by cleaved caspase-3 (P = 0.03) and decreased proliferation by Ki67 (P < 0.01) were demonstrated in the treatment arm, when compared with the control arm. On Western blot analysis of pathway checkpoints, p-mTOR (p=0.03) and PI3K-α (P = 0.04) were downregulated in treatment responsive residual tumors, when compared with controls. LY3023414 demonstrates efficacy against EAC in a preclinical model, establishing the rationale for clinical testing.

Pathogen-Specific T Cell Polyfunctionality Is a Correlate of T Cell Efficacy and Immune Protection

PubMed Central

Boyd, Anders; Almeida, Jorge R.; Darrah, Patricia A.; Sauce, Delphine; Seder, Robert A.; Appay, Victor; Gorochov, Guy; Larsen, Martin

2015-01-01

Introduction Understanding the factors that delineate the efficacy of T cell responses towards pathogens is crucial for our ability to develop potent therapies against infectious diseases. Multidimensional evaluation of T cell functionality at the single-cell level enables exhaustive analysis of combinatorial functional properties, hence polyfunctionality. We have recently invented an algorithm that quantifies polyfunctionality, the Polyfunctionality Index (Larsen et al. PLoS One 2012). Here we demonstrate that quantitative assessment of T cell polyfunctionality correlates with T cell efficacy measured as the capacity to kill target cells in vitro and control infection in vivo. Methods We employed the polyfunctionality index on two datasets selected for their unique ability to evaluate the polyfunctional imprint on T cell efficacy. 1) HIV-specific CD8+ T cells and 2) Leishmania major-specific CD4+ T cells were analysed for their capacity to secrete multiple effector molecules, kill target cells and control infection. Briefly, employing the Polyfunctionality Index algorithm we determined the parameter estimates resulting in optimal correlation between T cell polyfunctionality and T cell efficacy. Results T cell polyfunctionality is correlated with T cell efficacy measured as 1) target killing (r=0.807, P<0.0001) and 2) lesion size upon challenge with Leishmania major (r=-0.50, P=0.004). Contrary to an approach relying on the Polyfunctionality Index algorithm, quantitative evaluation of T cell polyfunctionality traditionally ignores the gradual contribution of more or less polyfunctional T cells. Indeed, comparing both approaches we show that optimal description of T cell efficacy is obtained when gradually integrating all levels of polyfunctionality in accordance with the Polyfunctionality Index. Conclusions Our study presents a generalizable methodology to objectively evaluate the impact of polyfunctionality on T cell efficacy. We show that T cell polyfunctionality is a superior correlate of T cell efficacy both in vitro and in vivo as compared with response size. Therefore, future immunotherapies should aim to increase T cell polyfunctionality. PMID:26046523

Efficacy and safety of prophylaxis with once-weekly BAY 79-4980 compared with thrice-weekly rFVIII-FS in haemophilia A patients. A randomised, active-controlled, double-blind study.

PubMed

Powell, Jerry; Martinowitz, Uri; Windyga, Jerzy; Di Minno, Giovanni; Hellmann, Andrzej; Pabinger, Ingrid; Maas Enriquez, Monika; Schwartz, Lawrence; Ingerslev, Jørgen

2012-11-01

The benefits of prophylaxis of haemophilia A patients regarding joint health and quality-of-life are well established. However, adherence to an up to every-other-day infusion regimen is a barrier to widespread adoption of prophylaxis. BAY 79-4980 is an investigational drug consisting of rFVIII-FS (sucrose-formulated recombinant FVIII) reconstituted with liposome solvent. Previous clinical studies showed extended protection from bleeding after a single injection of BAY 79-4980 (13.3 ± 6.2 days) compared with rFVIII-FS (7.2 ± 1.7 days). The effect of once-a-week prophylaxis with BAY 79-4980 (35 IU/kg) compared with three times-per-week rFVIII-FS (25 IU/kg) in previously treated, severe haemophilia A patients was evaluated in a 52-week, double-blind, two-arm, randomised, controlled study. The primary and secondary endpoints were protection from total bleeds and joint bleeds, respectively. Short- and long-term safety and tolerability of BAY 79-4980 including effects on lipid levels were assessed. A total of 139 and 131 subjects were evaluable for safety and efficacy analyses, respectively. A large difference in efficacy between treatment groups was observed with 72.1% (49/68) in the rFVIII-FS control group demonstrating <9 bleeds/year compared with 38.1% (24/63) of BAY 79-4980-treated subjects. A similar difference was seen in annualised joint bleeds, with 43 subjects (63.2%) in the control group demonstrating <5 joint bleeds/year compared with 24 subjects (38.1%) treated with BAY 79-4980. The distribution of bleeds seven days post-prophylactic treatment with BAY 79-4980 showed that 61% of bleeds occurred after day 4 post dosing. There were no safety concerns identified. The investigational treatment arm was prematurely discontinued due to failure to achieve the primary endpoint.

Randomized, double-blind, comparative study of levofloxacin and ofloxacin in the treatment of complicated urinary tract infections.

PubMed

Peng, M Y

1999-03-01

Levofloxacin, the optical S-(-) isomer of ofloxacin, was compared with ofloxacin in the treatment of complicated urinary tract infections (UTIs). Patients eligible for the trial were randomly assigned to either a daily 300 mg of levofloxacin or 600 mg of ofloxacin for 10 consecutive days. The double blind design was achieved by a double-dummy technique utilizing placebo of both test drugs. Efficacy variables measured were: urine white blood cell counts for the effects on pyuria, urine cultures for effects on bacteriuria, subjective symptoms, and overall clinical efficacy which combined results from effects on bacteriuria, pyuria and subjective symptoms. Safety endpoints were the incidence of adverse events and laboratory test monitoring after a 10-day treatment. A total of 104 patients were enrolled into this trial and 46 patients were evaluable for efficacy endpoints. Most patients with culture-negative (48 cases), mixed flora (5 cases), and less than 10,000 colony forming units/mL of bacteria (3 cases) were excluded from analyses. None of the demographic and baseline characteristics were significantly different between treatments (p > 0.05). Therapeutic effects upon bacteriuria for both treatment groups were similar with a response rate of 90.0% for levofloacin and 88.5% for ofloxacin. Efficacy on the subjective symptoms revealed response rates of 90.0% in the levofloxacin group and 80.7% in the ofloxacin group, with the overall clinical efficacy of 90% in the levofloxacin and 84.6% in the ofloxacin groups. All the efficacy variables measured between treatments were not statistically different which indicated an equivalent efficacy in the treatment of complicated UTIs (p > 0.05). Of the 104 patients exposed to the test medications, only three having adverse effects. One developed epigastralgia in the levofloxacin group, and 2 developed a headache in the ofloxacin treatment. All events were moderate in severity and were resolved quickly after medication. Four laboratory data abnormalities were observed (defined by 25% as exceeding the normal range), and were considered to not be related to the test medications. Both antibiotics were efficacious in the treatment of complicated UTIs (response rates ranging from 80 to 90%) and were well tolerated. Levofloxacin demonstrated comparable antibacterial effects and safety profiles with double potency dosage, compared to the ofloxacin.

Using a Human Challenge Model of Infection to Measure Vaccine Efficacy: A Randomised, Controlled Trial Comparing the Typhoid Vaccines M01ZH09 with Placebo and Ty21a.

PubMed

Darton, Thomas C; Jones, Claire; Blohmke, Christoph J; Waddington, Claire S; Zhou, Liqing; Peters, Anna; Haworth, Kathryn; Sie, Rebecca; Green, Christopher A; Jeppesen, Catherine A; Moore, Maria; Thompson, Ben A V; John, Tessa; Kingsley, Robert A; Yu, Ly-Mee; Voysey, Merryn; Hindle, Zoe; Lockhart, Stephen; Sztein, Marcelo B; Dougan, Gordon; Angus, Brian; Levine, Myron M; Pollard, Andrew J

2016-08-01

Typhoid persists as a major cause of global morbidity. While several licensed vaccines to prevent typhoid are available, they are of only moderate efficacy and unsuitable for use in children less than two years of age. Development of new efficacious vaccines is complicated by the human host-restriction of Salmonella enterica serovar Typhi (S. Typhi) and lack of clear correlates of protection. In this study, we aimed to evaluate the protective efficacy of a single dose of the oral vaccine candidate, M01ZH09, in susceptible volunteers by direct typhoid challenge. We performed a randomised, double-blind, placebo-controlled trial in healthy adult participants at a single centre in Oxford (UK). Participants were allocated to receive one dose of double-blinded M01ZH09 or placebo or 3-doses of open-label Ty21a. Twenty-eight days after vaccination, participants were challenged with 104CFU S. Typhi Quailes strain. The efficacy of M01ZH09 compared with placebo (primary outcome) was assessed as the percentage of participants reaching pre-defined endpoints constituting typhoid diagnosis (fever and/or bacteraemia) during the 14 days after challenge. Ninety-nine participants were randomised to receive M01ZH09 (n = 33), placebo (n = 33) or 3-doses of Ty21a (n = 33). After challenge, typhoid was diagnosed in 18/31 (58.1% [95% CI 39.1 to 75.5]) M01ZH09, 20/30 (66.7% [47.2 to 87.2]) placebo, and 13/30 (43.3% [25.5 to 62.6]) Ty21a vaccine recipients. Vaccine efficacy (VE) for one dose of M01ZH09 was 13% [95% CI -29 to 41] and 35% [-5 to 60] for 3-doses of Ty21a. Retrospective multivariable analyses demonstrated that pre-existing anti-Vi antibody significantly reduced susceptibility to infection after challenge; a 1 log increase in anti-Vi IgG resulting in a 71% decrease in the hazard ratio of typhoid diagnosis ([95% CI 30 to 88%], p = 0.006) during the 14 day challenge period. Limitations to the study included the requirement to limit the challenge period prior to treatment to 2 weeks, the intensity of the study procedures and the high challenge dose used resulting in a stringent model. Despite successfully demonstrating the use of a human challenge study to directly evaluate vaccine efficacy, a single-dose M01ZH09 failed to demonstrate significant protection after challenge with virulent Salmonella Typhi in this model. Anti-Vi antibody detected prior to vaccination played a major role in outcome after challenge. ClinicalTrials.gov (NCT01405521) and EudraCT (number 2011-000381-35).

A Phase 3, Randomized, Double-Blind, Multicenter Study to Evaluate the Safety and Efficacy of Intravenous Iclaprim Vs Vancomycin for the Treatment of Acute Bacterial Skin and Skin Structure Infections Suspected or Confirmed to be Due to Gram-Positive Pathogens: REVIVE-1.

PubMed

Huang, David B; O'Riordan, William; Overcash, J Scott; Heller, Barry; Amin, Faisal; File, Thomas M; Wilcox, Mark H; Torres, Antoni; Dryden, Matthew; Holland, Thomas L; McLeroth, Patrick; Shukla, Rajesh; Corey, G Ralph

2018-04-03

Our objective in this study was to demonstrate the safety and efficacy of iclaprim compared with vancomycin for the treatment of patients with acute bacterial skin and skin structure infections (ABSSSIs). REVIVE-1 was a phase 3, 600-patient, double-blinded, randomized (1:1), active-controlled trial among patients with ABSSSI that compared the safety and efficacy of iclaprim 80 mg fixed dose with vancomycin 15 mg/kg, both administered intravenously every 12 hours for 5-14 days. The primary endpoint of this study was a ≥20% reduction in lesion size (early clinical response [ECR]) compared with baseline among patients randomized to iclaprim or vancomycin at the early time point (ETP), 48 to 72 hours after the start of administration of study drug in the intent-to-treat population. ECR among patients who received iclaprim and vancomycin at the ETP was 80.9% (241 of 298) of patients receiving iclaprim compared with 81.0% (243 of 300) of those receiving vancomycin (treatment difference, -0.13%; 95% confidence interval, -6.42%-6.17%). Iclaprim was well tolerated in the study, with most adverse events categorized as mild. Iclaprim achieved noninferiority (10% margin) at ETP compared with vancomycin and was well tolerated in this phase 3 clinical trial for the treatment of ABSSSI. Based on these results, iclaprim appears to be an efficacious and safe treatment for ABSSSI suspected or confirmed to be due to gram-positive pathogens. NCT02600611.

Comparing Linguistic Complexity and Efficiency in Conversations from Stimulation and Conversation Therapy in Aphasia

ERIC Educational Resources Information Center

Savage, Meghan C.; Donovan, Neila J.

2017-01-01

Background: Efficacy studies have demonstrated the benefit of group conversation therapy for a person with aphasia (PWA). However, a PWA typically participates in individual therapy prior to group therapy. Stimulation therapy (ST) is the most common type of individual aphasia therapy. Ultimately, the outcome of therapy is to enable the PWA to…

Career Decision Making in the Shadow of Economic Downturn: A Study of Cape Breton High School Students.

ERIC Educational Resources Information Center

Chisholm, Joe; Edmunds, Alan

2001-01-01

Examines differences in levels of career decision-making self-efficacy in Cape Breton high school students who lived in communities with recent closures of mining and steel industries compared to students from communities with no such closures. Students demonstrated considerable confidence in their career decision-making abilities implying that…

An Analysis on the Effect of Computer Self-Efficacy over Scientific Research Self-Efficacy and Information Literacy Self-Efficacy

ERIC Educational Resources Information Center

Tuncer, Murat

2013-01-01

Present research investigates reciprocal relations amidst computer self-efficacy, scientific research and information literacy self-efficacy. Research findings have demonstrated that according to standardized regression coefficients, computer self-efficacy has a positive effect on information literacy self-efficacy. Likewise it has been detected…

Identifying configurations of behavior change techniques in effective medication adherence interventions: a qualitative comparative analysis.

PubMed

Kahwati, Leila; Viswanathan, Meera; Golin, Carol E; Kane, Heather; Lewis, Megan; Jacobs, Sara

2016-05-04

Interventions to improve medication adherence are diverse and complex. Consequently, synthesizing this evidence is challenging. We aimed to extend the results from an existing systematic review of interventions to improve medication adherence by using qualitative comparative analysis (QCA) to identify necessary or sufficient configurations of behavior change techniques among effective interventions. We used data from 60 studies in a completed systematic review to examine the combinations of nine behavior change techniques (increasing knowledge, increasing awareness, changing attitude, increasing self-efficacy, increasing intention formation, increasing action control, facilitation, increasing maintenance support, and motivational interviewing) among studies demonstrating improvements in adherence. Among the 60 studies, 34 demonstrated improved medication adherence. Among effective studies, increasing patient knowledge was a necessary but not sufficient technique. We identified seven configurations of behavior change techniques sufficient for improving adherence, which together accounted for 26 (76 %) of the effective studies. The intervention configuration that included increasing knowledge and self-efficacy was the most empirically relevant, accounting for 17 studies (50 %) and uniquely accounting for 15 (44 %). This analysis extends the completed review findings by identifying multiple combinations of behavior change techniques that improve adherence. Our findings offer direction for policy makers, practitioners, and future comparative effectiveness research on improving adherence.

Antimotion-sickness efficacy of scopolamine 12 and 72 hours after transdermal administration

NASA Technical Reports Server (NTRS)

Graybiel, A.; Cramer, D. B.; Wood, C. D.

1982-01-01

The antimotion sickness remedy, transdermal therapeutic system-scopolamine, administered in this experiment was scheduled to deliver 1.0 mg of scopolamine over a period of 3 d, and this paper compares its efficacy 12 and 72 h after administration. In a double-blind study, six male college students were individually exposed to a standardized provocative test in a slow rotation room after six apparently identical treatments comprising four placebos and two medications. Efficacy was categorized as beneficial, inconsequential, or detrimental. None of the responses was detrimental. Following the first administration of the therapeutic system, there were four beneficial responses after 12 h but none was beneficial after 72 h. Following the second treatment regimen, there were four beneficial responses after 12 h and three beneficial responses after 72 h. Great individual differences were demonstrated, two subjects accounting for six beneficial responses and two accounting for only one beneficial response. The difference in efficacy after 12 and 72 h has practical and theoretical significance.

Antivenom therapy for snakebites in children: is there evidence?

PubMed

Schmidt, James M

2005-04-01

A new Fab fragment antivenom (CroFab) for the treatment of crotaline envenomation, the predominant venomous snakebite in the United States, has drastically changed snakebite management since its release in December 2000. This review examines the evidence supporting the use of CroFab, with particular attention on the pediatric population. The published experience with CroFab in humans consists of six studies and some case reports. These publications demonstrate that CroFab is highly efficacious in treating both the local and systemic toxic effects of crotaline envenomation. They identify an important phenomenon of recurrent or delayed toxicity in some patients. The studies report a very low incidence of acute or delayed hypersensitivity reactions to the antivenom. They suggest comparable efficacy and safety of CroFab in the pediatric population as in adults. Based on limited data, CroFab has been shown to be a safe and efficacious antivenom for use in children as well as adults. Further studies are needed to refine our understanding of its efficacy, safety, indications, and dosing.

Buprenorphine: revisiting the efficacy of transdermal delivery system.

PubMed

Kitzmiller, Joseph P; Barnett, Christopher J; Steiner, Nathan S; Stoicea, Nicoleta; Kamar, Nawal; Luzum, Jasmine A; Mikulik, Eduard; Bergese, Sergio D

2015-01-01

Buprenorphine is a lipid-soluble pharmaceutic used in the management of chronic pain. It is a partial agonist at μ-opioid receptors, an antagonist at κ-opioid receptors, an agonist at δ-opioid receptors and a partial agonist at ORL-1 (nociceptin) receptors. An extensive literature search, including Google Scholar and Pubmed database, was conducted. Terms including and associated to 'efficacy of transdermal buprenorphine' were utilized to procure contemporary research articles in order to evaluate and compare the transdermal buprenorphine patch to commonly used traditional pain management medications. Transdermal buprenorphine has demonstrated better efficacy than conventional pain management pharmacotherapies. Side effects were similar to those associated with other opioids and included headache, dizziness, somnolence, constipation, dry mouth, nausea, vomiting, pruritus and erythema. Similar to transdermal delivery systems used with other medication, transdermal buprenorphine was associated with application-site pruritus and application-site reactions. Transdermal buprenorphine has significant potential for managing chronic pain. In addition to increased convenience and efficacy, advantages of transdermal buprenorphine include decreased tolerance and decreased withdrawal.

How Placebo Needles Differ From Placebo Pills?

PubMed Central

Chae, Younbyoung; Lee, Ye-Seul; Enck, Paul

2018-01-01

Because acupuncture treatment is defined by the process of needles penetrating the body, placebo needles were originally developed with non-penetrating mechanisms. However, whether placebo needles are valid controls in acupuncture research is subject of an ongoing debate. The present review provides an overview of the characteristics of placebo needles and how they differ from placebo pills in two aspects: (1) physiological response and (2) blinding efficacy. We argue that placebo needles elicit physiological responses similar to real acupuncture and therefore provide similar clinical efficacy. We also demonstrate that this efficacy is further supported by ineffective blinding (even in acupuncture-naïve patients) which may lead to opposite guesses that will further enhances efficacy, as compared to no-treatment, e.g., with waiting list controls. Additionally, the manner in which placebo needles can exhibit therapeutic effects relative to placebo pills include enhanced touch sensations, direct stimulation of the somatosensory system and activation of multiple brain systems. We finally discuss alternative control strategies for the placebo effects in acupuncture therapy.

Dienogest in the treatment of endometriosis.

PubMed

Bizzarri, Nicolò; Remorgida, Valentino; Leone Roberti Maggiore, Umberto; Scala, Carolina; Tafi, Emanuela; Ghirardi, Valentina; Salvatore, Stefano; Candiani, Massimo; Venturini, Pier Luigi; Ferrero, Simone

2014-09-01

Dienogest (DNG) is an oral progestin, derivative of 19-nortestosterone, that has recently been introduced for the treatment of endometriosis. This review examines the clinical efficacy, safety and tolerability of DNG in the treatment of endometriosis. The material included in the current manuscript was searched and obtained via Medline, Pubmed and EMBASE, from inception until February 2014. The term 'dienogest' was associated with the following search terms: 'endometriosis', 'pharmacokinetics', 'safety' and 'efficacy'. Several trials demonstrated the clinical efficacy, safety and tolerability of DNG. However the use of DNG is associated with some limitations. So far, no study investigated the potential of contraceptive effect of this treatment and therefore, it should be recommended with other methods of contraception (e.g., barrier methods). A further limitation of the use of DNG as daily therapy in the long term is that the cost of the therapy is higher than other progestins available on the market and combined oral contraceptives. Therefore, future studies should be designed to compare the efficacy and safety of DNG with other progestins.

Phase I/II adaptive design for drug combination oncology trials

PubMed Central

Wages, Nolan A.; Conaway, Mark R.

2014-01-01

Existing statistical methodology on dose finding for combination chemotherapies has focused on toxicity considerations alone in finding a maximum tolerated dose combination to recommend for further testing of efficacy in a phase II setting. Recently, there has been increasing interest in integrating phase I and phase II trials in order to facilitate drug development. In this article, we propose a new adaptive phase I/II method for dual-agent combinations that takes into account both toxicity and efficacy after each cohort inclusion. The primary objective, both within and at the conclusion of the trial, becomes finding a single dose combination with an acceptable level of toxicity that maximizes efficacious response. We assume that there exist monotone dose–toxicity and dose–efficacy relationships among doses of one agent when the dose of other agent is fixed. We perform extensive simulation studies that demonstrate the operating characteristics of our proposed approach, and we compare simulated results to existing methodology in phase I/II design for combinations of agents. PMID:24470329

Folate receptor-targeted nanoparticle delivery of HuR-RNAi suppresses lung cancer cell proliferation and migration.

PubMed

Muralidharan, Ranganayaki; Babu, Anish; Amreddy, Narsireddy; Basalingappa, Kanthesh; Mehta, Meghna; Chen, Allshine; Zhao, Yan Daniel; Kompella, Uday B; Munshi, Anupama; Ramesh, Rajagopal

2016-06-21

Human antigen R (HuR) is an RNA binding protein that is overexpressed in many human cancers, including lung cancer, and has been shown to regulate the expression of several oncoproteins. Further, HuR overexpression in cancer cells has been associated with poor-prognosis and therapy resistance. Therefore, we hypothesized that targeted inhibition of HuR in cancer cells should suppress several HuR-regulated oncoproteins resulting in an effective anticancer efficacy. To test our hypothesis, in the present study we investigated the efficacy of folate receptor-α (FRA)-targeted DOTAP:Cholesterol lipid nanoparticles carrying HuR siRNA (HuR-FNP) against human lung cancer cells. The therapeutic efficacy of HuR-FNP was tested in FRA overexpressing human H1299 lung cancer cell line and compared to normal lung fibroblast (CCD16) cells that had low to no FRA expression. Physico-chemical characterization studies showed HuR-FNP particle size was 303.3 nm in diameter and had a positive surface charge (+4.3 mV). Gel retardation and serum stability assays showed that the FNPs were efficiently protected siRNA from rapid degradation. FNP uptake was significantly higher in H1299 cells compared to CCD16 cells indicating a receptor-dose effect. The results of competitive inhibition studies in H1299 cells demonstrated that HuR-FNPs were efficiently internalized via FRA-mediated endocytosis. Biologic studies demonstrated HuR-FNP but not C-FNP (control siRNA) induced G1 phase cell-cycle arrest and apoptosis in H1299 cells resulting in significant growth inhibition. Further, HuR-FNP exhibited significantly higher cytotoxicity against H1299 cells than it did against CCD16 cells. The reduction in H1299 cell viability was correlated with a marked decrease in HuR mRNA and protein expression. Further, reduced expression of HuR-regulated oncoproteins (cyclin D1, cyclin E, and Bcl-2) and increased p27 tumor suppressor protein were observed in HuR-FNP-treated H1299 cells but not in C-FNP-treated cells. Finally, cell migration was significantly inhibited in HuR-FNP-treated H1299 cells compared to C-FNP. Our results demonstrate that HuR is a molecular target for lung cancer therapy and its suppression using HuR-FNP produced significant therapeutic efficacy in vitro.

Online instructional anatomy videos: Student usage, self-efficacy, and performance in upper limb regional anatomy assessment.

PubMed

Langfield, Tracey; Colthorpe, Kay; Ainscough, Louise

2017-12-04

Allied health professionals concur that a sound knowledge of practical gross anatomy is vital for the clinician, however, human anatomy courses in allied health programs have been identified as high-risk for attrition and failure. While anatomists and clinicians agree that learning anatomy via human cadaveric instruction is the preferred method, students vary in their reaction to the cadaveric learning experience and have differing levels of anatomy self-efficacy. This study investigated whether student self-efficacy had an effect on student usage of supplemental instructional videos and whether the use of videos had an impact on student self-efficacy and/or learning. Anatomy self-efficacy differed based on gender and prior performance. Student usage of the videos varied widely and students with lower self-efficacy were more inclined to use the resources. The provision of the videos did not improve overall cohort performance as compared to a historical cohort, however, those students that accessed all video sets experienced a greater normalized learning gain compared to students that used none or one of the four sets of videos. Student reports and usage patterns indicate that the videos were primarily used for practical class preparation and revision. Potentially, the videos represent a passive mode of teaching whereas active learning has been demonstrated to result in greater learning gains. Adapting the videos into interactive tutorials which will provide opportunity for feedback and the development of students' self-evaluation may be more appropriate. Anat Sci Educ. © 2017 American Association of Anatomists. © 2017 American Association of Anatomists.

Augmenting the efficacy of anti-cocaine catalytic antibodies through chimeric hapten design and combinatorial vaccination.

PubMed

Wenthur, Cody J; Cai, Xiaoqing; Ellis, Beverly A; Janda, Kim D

2017-08-15

Given the need for further improvements in anti-cocaine vaccination strategies, a chimeric hapten (GNET) was developed that combines chemically-stable structural features from steady-state haptens with the hydrolytic functionality present in transition-state mimetic haptens. Additionally, as a further investigation into the generation of an improved bifunctional antibody pool, sequential vaccination with steady-state and transition-state mimetic haptens was undertaken. While GNET induced the formation of catalytically-active antibodies, it did not improve overall behavioral efficacy. In contrast, the resulting pool of antibodies from GNE/GNT co-administration demonstrated intermediate efficacy as compared to antibodies developed from either hapten alone. Overall, improved antibody catalytic efficiency appears necessary to achieve the synergistic benefits of combining cocaine hydrolysis with peripheral sequestration. Copyright © 2017 Elsevier Ltd. All rights reserved.

Efficacy of budesonide in collagenous colitis Evaluation of: Miehlke S, Madisch A, Kupcinskas L, et al. Budesonide is more effective than mesalamine or placebo in short-term treatment of collagenous colitis. Gastroenterology 2014;146(5):1222-1230 e1222.

PubMed

Drug, Vasile L; Antoniu, Sabina A

2014-10-01

Collagenous colitis (CC) is a less common colonic disease with variable prevalence and undulating course. Among the available therapies, budesonide was demonstrated to induce a rapid and sustained remission in many cases, but little is known about the comparative efficacy of other treatments, such as mesalamine. Evaluation of a randomized study assessing the efficacy and safety of budesonide over mesalamine in patients with CC. Data from the study showed that budesonide was significantly superior to placebo and to mesalamine and further supports the recommendation of the current guidelines on the use of budesonide in CC. However, other forms of mesalamine may further be evaluated for this disease.

Comparing Safety and Efficacy of "Third-Generation" Antiepileptic Drugs: Long-Term Extension and Post-marketing Treatment.

PubMed

Kwok, Charlotte S; Johnson, Emily L; Krauss, Gregory L

2017-11-01

Four "third-generation" antiepileptic drugs (AEDs) were approved for adjunctive treatment of refractory focal onset seizures during the past 10 years. Long-term efficacy and safety of the drugs were demonstrated in large extension studies and in reports of subgroups of patients not studied in pivotal trials. Reviewing extension study and post-marketing outcome series for the four newer AEDs-lacosamide, perampanel, eslicarbazepine acetate and brivaracetam-can guide clinicians in treating and monitoring patients. AED extension studies evaluate treatment retention, drug tolerability, and drug safety during individualized treatment with flexible dosing and thus provide information not available in rigid pivotal trials. Patient retention in the studies ranged from 75 to 80% at 1 year and from 36 to 68% at 2-year treatment intervals. Safety findings were generally similar to those of pivotal trials, with no major safety risks identified and with several specific adverse drug effects, such as hyponatremia, reported. The third-generation AEDs, some through new mechanisms and others with improved tolerability compared to related AEDs, provide new options in efficacy and tolerability.

Experience and challenges presented by a multicenter crossover study of combination analgesic therapy for the treatment of painful HIV-associated polyneuropathies.

PubMed

Harrison, Taylor; Miyahara, Sachiko; Lee, Anthony; Evans, Scott; Bastow, Barbara; Simpson, David; Gilron, Ian; Dworkin, Robert; Daar, Eric S; Wieclaw, Linda; Clifford, David B

2013-07-01

There is limited evidence for efficacy of analgesics as monotherapy for neuropathic pain associated with HIV-associated polyneuropathies, in spite of demonstrated efficacy in other neuropathic pain conditions. We evaluated the tolerability and analgesic efficacy of duloxetine, methadone, and the combination of duloxetine-methadone compared with placebo. This study was a phase II, randomized, double-blind, placebo-controlled, four-period crossover multicenter study of analgesic therapy for patients with at least moderate neuropathic pain due to HIV-associated polyneuropathy. Duloxetine, methadone, combination duloxetine-methadone, and placebo were administered in four different possible sequences. The primary outcome measure was mean pain intensity (MPI) measured daily in a study-supplied pain diary. A total of 15 patients were enrolled from eight study sites and eight patients completed the entire trial. Study treatments failed to show statistically significant change in MPI compared with placebo. Adverse events were frequent and associated with high rates of drug discontinuation and study dropout. Challenges with participant recruitment and poor retention precluded trial completion to its planned targets, limiting our evaluation of the analgesic efficacy of the study treatments. Challenges to successful completion of this study and lessons learned are discussed. Wiley Periodicals, Inc.

Experience and challenges presented by a multicenter crossover study of combination analgesic therapy for the treatment of painful HIV-associated polyneuropathies

PubMed Central

Harrison, Taylor; Miyahara, Sachiko; Lee, Anthony; Evans, Scott; Bastow, Barbara; Simpson, David; Gilron, Ian; Dworkin, Robert; Daar, Eric S.; Wieclaw, Linda; Clifford, David B.

2014-01-01

Objective There is limited evidence for efficacy of analgesics as monotherapy for neuropathic pain associated with HIV-associated polyneuropathies, in spite of demonstrated efficacy in other neuropathic pain conditions. We evaluated the tolerability and analgesic efficacy of duloxetine, methadone, and the combination of duloxetine-methadone compared to placebo. Design This study was a phase II, randomized, double blind, placebo-controlled, four-period crossover multi-center study of analgesic therapy for patients with at least moderate neuropathic pain due to HIV-associated polyneuropathy. Duloxetine, methadone, combination duloxetine-methadone, and placebo were administered in four different possible sequences. The primary outcome measure was mean pain intensity (MPI) measured daily in a study-supplied pain diary. Results A total of 15 patients were enrolled from 8 study sites and 8 patients completed the entire trial. Study treatments failed to show statistically significant change in MPI compared to placebo. Adverse events were frequent and associated with high rates of drug discontinuation and study drop-out. Conclusions Challenges with participant recruitment and poor retention precluded trial completion to its planned targets, limiting our evaluation of the analgesic efficacy of the study treatments. Challenges to successful completion of this study and lessons learned are discussed. PMID:23565581

Clinical efficacy and safety of imepitoin in comparison with phenobarbital for the control of idiopathic epilepsy in dogs.

PubMed

Tipold, A; Keefe, T J; Löscher, W; Rundfeldt, C; de Vries, F

2015-04-01

The anticonvulsant activity and safety of imepitoin, a novel antiepileptic drug licensed in the European Union, were evaluated in a multicentre field efficacy study as well as in a safety study under laboratory conditions. Efficacy of imepitoin was compared with phenobarbital in 226 client-owned dogs in a blinded parallel group design. The administration of imepitoin twice daily in incremental doses of 10, 20 or 30 mg/kg demonstrated comparable efficacy to phenobarbital in controlling seizures in dogs. The frequency of adverse events including somnolence/sedation, polydipsia and increased appetite was significantly higher in the phenobarbital group. In phenobarbital-treated dogs, significantly increased levels of alkaline phosphatase, gamma-glutamyl-transferase and other liver enzymes occurred, while no such effect was observed in the imepitoin group. In a safety study under laboratory conditions, healthy beagle dogs were administered 0, 30, 90 or 150 mg/kg imepitoin twice daily for 26 weeks. A complete safety evaluation including histopathology was included in the study. A no-observed-adverse-event level of 90 mg/kg twice daily was determined. These results indicate that imepitoin is a potent and safe antiepileptic drug for dogs. © 2014 The Authors. Journal of Veterinary Pharmacology and Therapeutics Published by John Wiley & Sons Ltd.

The efficacy of intra-articular sodium hyaluronate in patients with reducing displaced disc of the temporomandibular joint.

PubMed

Hepguler, S; Akkoc, Y S; Pehlivan, M; Ozturk, C; Celebi, G; Saracoglu, A; Ozpinar, B

2002-01-01

In this clinical trial, we examined the efficacy of intra-articular hyaluronic acid (HA) treatment in 38 patients with reducing displaced disc of the temporomandibular joint (TMJ). Subjects received two unilateral upper space injections of HA or physiological saline solution with 1 week apart. Efficacy was based on the following measurements: pain and sound intensity of the joint measured by visual analogue scale (VAS), modified Helkimo's clinical dysfunction index and the intensity of joint vibration during opening and closing the mouth measured by accelerometers. These measurements were performed before the first injection and 1 and 6 months after the last injection. In the treatment group (n=19), all measurements improved significantly at month 1 and at month 6 compared with the baseline (P < 0.01). The same measurements, in the placebo group (n=19), did not show any change, except for the pain intensity which improved at month 1 and month 6 (P < 0.05). The change in baseline measurements of all of the efficacy criteria at month 1 and at month 6 in the treatment group was significantly better compared with the change obtained with placebo at the same time intervals. This study demonstrates that intra-articular sodium hyaluronate (Orthovisc) injection into the TMJ is an effective treatment for a reducing displaced disc.

Inorganic Nanovehicle Targets Tumor in an Orthotopic Breast Cancer Model

NASA Astrophysics Data System (ADS)

Choi, Goeun; Kwon, Oh-Joon; Oh, Yeonji; Yun, Chae-Ok; Choy, Jin-Ho

2014-03-01

The clinical efficacy of conventional chemotherapeutic agent, methotrexate (MTX), can be limited by its very short plasma half-life, the drug resistance, and the high dosage required for cancer cell suppression. In this study, a new drug delivery system is proposed to overcome such limitations. To realize such a system, MTX was intercalated into layered double hydroxides (LDHs), inorganic drug delivery vehicle, through a co-precipitation route to produce a MTX-LDH nanohybrid with an average particle size of approximately 130 nm. Biodistribution studies in mice bearing orthotopic human breast tumors revealed that the tumor-to-liver ratio of MTX in the MTX-LDH-treated-group was 6-fold higher than that of MTX-treated-one after drug treatment for 2 hr. Moreover, MTX-LDH exhibited superior targeting effect resulting in high antitumor efficacy inducing a 74.3% reduction in tumor volume compared to MTX alone, and as a consequence, significant survival benefits. Annexin-V and propidium iodine dual staining and TUNEL analysis showed that MTX-LDH induced a greater degree of apoptosis than free MTX. Taken together, our data demonstrate that a new MTX-LDH nanohybrid exhibits a superior efficacy profile and improved distribution compared to MTX alone and has the potential to enhance therapeutic efficacy via inhibition of tumor proliferation and induction of apoptosis.

Inorganic nanovehicle targets tumor in an orthotopic breast cancer model.

PubMed

Choi, Goeun; Kwon, Oh-Joon; Oh, Yeonji; Yun, Chae-Ok; Choy, Jin-Ho

2014-03-21

The clinical efficacy of conventional chemotherapeutic agent, methotrexate (MTX), can be limited by its very short plasma half-life, the drug resistance, and the high dosage required for cancer cell suppression. In this study, a new drug delivery system is proposed to overcome such limitations. To realize such a system, MTX was intercalated into layered double hydroxides (LDHs), inorganic drug delivery vehicle, through a co-precipitation route to produce a MTX-LDH nanohybrid with an average particle size of approximately 130 nm. Biodistribution studies in mice bearing orthotopic human breast tumors revealed that the tumor-to-liver ratio of MTX in the MTX-LDH-treated-group was 6-fold higher than that of MTX-treated-one after drug treatment for 2 hr. Moreover, MTX-LDH exhibited superior targeting effect resulting in high antitumor efficacy inducing a 74.3% reduction in tumor volume compared to MTX alone, and as a consequence, significant survival benefits. Annexin-V and propidium iodine dual staining and TUNEL analysis showed that MTX-LDH induced a greater degree of apoptosis than free MTX. Taken together, our data demonstrate that a new MTX-LDH nanohybrid exhibits a superior efficacy profile and improved distribution compared to MTX alone and has the potential to enhance therapeutic efficacy via inhibition of tumor proliferation and induction of apoptosis.

Comparative efficacy and safety of mavacoxib and carprofen in the treatment of canine osteoarthritis

PubMed Central

Payne-Johnson, M; Becskei, C; Chaudhry, Y; Stegemann, M R

2015-01-01

A multi-site, masked, randomised parallel group study employing a double dummy treatment design was performed in canine veterinary patients to determine the comparative efficacy and safety of mavacoxib and carprofen in the treatment of pain and inflammation associated with osteoarthritis for a period of 134 days. Treatments were administered according to their respective summaries of product characteristics. Of 139 dogs screened, 124 were suitable for study participation: 62 of which were dosed with mavacoxib and 62 with carprofen. Both treatments resulted in a very similar pattern of considerable improvement as indicated in all parameters assessed by both owner and veterinarian. The primary efficacy endpoint ‘overall improvement’ was a composite score of owner assessments after approximately six weeks of treatment. Both drugs were remarkably effective, with 57/61 (93.4 per cent) of mavacoxib-treated dogs and 49/55 (89.1 per cent) of carprofen-treated dogs demonstrating overall improvement and with mavacoxib's efficacy being non-inferior to carprofen. The treatments had a similar safety profile as evidenced by documented adverse events and summaries of clinical pathology parameters. The positive clinical response to treatment along with the safety and dosing regimen of mavacoxib makes it an attractive therapy for canine osteoarthritis. PMID:25433056

Comparative efficacy and safety of mavacoxib and carprofen in the treatment of canine osteoarthritis.

PubMed

Payne-Johnson, M; Becskei, C; Chaudhry, Y; Stegemann, M R

2015-03-14

A multi-site, masked, randomised parallel group study employing a double dummy treatment design was performed in canine veterinary patients to determine the comparative efficacy and safety of mavacoxib and carprofen in the treatment of pain and inflammation associated with osteoarthritis for a period of 134 days. Treatments were administered according to their respective summaries of product characteristics. Of 139 dogs screened, 124 were suitable for study participation: 62 of which were dosed with mavacoxib and 62 with carprofen. Both treatments resulted in a very similar pattern of considerable improvement as indicated in all parameters assessed by both owner and veterinarian. The primary efficacy endpoint 'overall improvement' was a composite score of owner assessments after approximately six weeks of treatment. Both drugs were remarkably effective, with 57/61 (93.4 per cent) of mavacoxib-treated dogs and 49/55 (89.1 per cent) of carprofen-treated dogs demonstrating overall improvement and with mavacoxib's efficacy being non-inferior to carprofen. The treatments had a similar safety profile as evidenced by documented adverse events and summaries of clinical pathology parameters. The positive clinical response to treatment along with the safety and dosing regimen of mavacoxib makes it an attractive therapy for canine osteoarthritis. British Veterinary Association.

Field note: comparative efficacy of a woody evapotranspiration landfill cover following the removal of aboveground biomass.

PubMed

Schnabel, William; Munk, Jens; Byrd, Amanda

2015-01-01

Woody vegetation cultivated for moisture management on evapotranspiration (ET) landfill covers could potentially serve a secondary function as a biomass crop. However, research is required to evaluate the extent to which trees could be harvested from ET covers without significantly impacting their moisture management function. This study investigated the drainage through a six-year-old, primarily poplar/cottonwood ET test cover for a period of one year following the harvest of all woody biomass exceeding a height of 30 cm above ground surface. Results were compared to previously reported drainage observed during the years leading up to the coppice event. In the first year following coppice, the ET cover was found to be 93% effective at redirecting moisture during the spring/summer season, and 95% effective during the subsequent fall/winter season. This was slightly lower than the 95% and 100% efficacy observed in the spring/summer and fall/winter seasons, respectively, during the final measured year prior to coppice. However, the post-coppice efficacy was higher than the efficacy observed during the first three years following establishment of the cover. While additional longer-term studies are recommended, this project demonstrated that woody ET covers could potentially produce harvestable biomass while still effectively managing aerial moisture.

Agonist contraction during intermittent theta burst stimulation enhances motor cortical plasticity of the wrist flexors.

PubMed

Mirdamadi, J L; Suzuki, L Y; Meehan, S K

2015-03-30

Differences in cortical control across the different muscles of the upper limb may mitigate the efficacy of TMS interventions targeting a specific muscle. The current study sought to determine whether weak concurrent contraction during TMS could enhance the efficacy of intermittent theta burst stimulation (iTBS) in the forearm flexors. Motor evoked potentials (MEP) were elicited from the flexor (FCR) and extensor carpi radialis (ECR) motor cortical hotspots before and after iTBS over the FCR cortical hotspot. During iTBS the FCR was either relaxed (iTBS-Relax) or tonically contracted to 10% of maximum voluntary force (iTBS-Contract). iTBS-Relax failed to produce consistent potentiation of MEPFCR amplitude. Individuals with a relatively lower RMTFCR compared RMTECR demonstrated MEPFCR facilitation post-iTBS-Relax. Individuals with relatively higher RMTFCR demonstrated less facilitation and even suppression of MEPFCR amplitude. iTBS-Contract facilitated MEPFCR amplitude but only for MEPFCR evoked from the ECR hotspot. Interactions between overlapping cortical representations determine the efficacy of iTBS. Tonic contraction increases the efficacy of iTBS by enhancing the volume of the cortical representation. However, metaplastic effects may attenuate the enhancement of MEP gain at the motor cortical hotspot. The use of TMS as an adjunct to physical therapy should account for inter-muscle interactions when targeting muscles of the forearm. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Safety and efficacy of antioxidants-loaded nanoparticles for an anti-aging application.

PubMed

Felippi, Cândice C; Oliveira, Dileusa; Ströher, Alessandra; Carvalho, Anderson R; Van Etten, Eliana A M Aquino; Bruschi, Márcia; Raffin, Renata P

2012-04-01

The aim of this work was to perform a pilot study on the safety and efficacy of nanoparticle formulation for cosmetic application. The encapsulated actives in the nanoparticles were a blend of coenzyme Q10, retinyl palmitate, tocopheryl acetate, grape seed oil and linseed oil. The nanoparticle suspension was characterized in terms of pH and particle size. For the safety assessment, alternative methods as cytotoxicity and HET CAM were used. The clinical skin compatibility tests were also performed. The efficacy was evaluated in healthy volunteers presenting different degrees of periorbital wrinkles. Skin hydration was performed by corneometry. The nanoparticles presented narrow size around 140 nm and pH close to neutral and were suitable to cutaneous application. The alternative tests demonstrated that the nanoparticles did not present potential to induce skin irritant effects, cytotoxicity or generate oxidative stress. The clinical assays confirmed the in vitro results, demonstrating the safety of the nanoparticles, which were not irritant, sensitizing and comedogenic. Furthermore, the exposure to UVA light did not cause photoxicity. Regarding the efficacy, nanoparticles presented significant reduction in wrinkle degree after 21 days of application compared to the control. The volunteers could differentiate the nanoparticles and the control product by means of subjective analyses. In conclusion, the nanoparticles containing antioxidant actives were safe for topical use and presented anti-aging activity in vivo and are suitable to be used as cosmetic ingredient.

Characterization of a novel novobiocin analogue as a putative C-terminal inhibitor of heat shock protein 90 in prostate cancer cells.

PubMed

Matthews, Shawna B; Vielhauer, George A; Manthe, Craig A; Chaguturu, Vamsee K; Szabla, Kristen; Matts, Robert L; Donnelly, Alison C; Blagg, Brian S J; Holzbeierlein, Jeffrey M

2010-01-01

Hsp90 is important in the folding, maturation and stabilization of pro-tumorigenic client proteins and represents a viable drug target for the design of chemotherapies. Previously, we reported the development of novobiocin analogues designed to inhibit the C-terminal portion of Hsp90, which demonstrated the ability to decrease client protein expression. We now report the characterization of the novel novobiocin analogue, F-4, which demonstrates improved cytotoxicity in prostate cancer cell lines compared to the N-terminal inhibitor, 17-AAG. LNCaP and PC-3 cells were treated with 17-AAG or F-4 in anti-proliferative, apoptosis, cell cycle and cytotoxicity assays. Western blot and prostate specific antigen (PSA) ELISAs were used to determine client protein degradation, induction of Hsp90 and to assess the functional status of the androgen receptor (AR) in response to F-4 treatment. Surface plasmon resonance (SPR) was also used to determine the binding properties of F-4 to Hsp90. F-4 demonstrated improved potency and efficacy compared to novobiocin in anti-proliferative assays and decreased expression of client proteins. PSA secretion was inhibited in a dose-dependent manner that paralleled a decrease in AR expression. The binding of F-4 to Hsp90 was determined to be saturable with a binding affinity (K(d)) of 100 microM. In addition, superior efficacy was demonstrated by F-4 compared to 17-AAG in experiments measuring cytotoxicity and apoptosis. These data reveal distinct modes of action for N-terminal and C-terminal Hsp90 inhibitors, which may offer unique therapeutic benefits for the treatment of prostate cancer.

Characterization of a novel novobiocin analogue as a putative C-terminal inhibitor of heat shock protein 90 in prostate cancer cells

PubMed Central

Shawna, B. Comer; George, A. Vielhauer; Craig, A. Manthe; Vamsee, K. Chaguturu; Kristen, Szabla; Robert, L. Matts; Alison, C. Donnelly; Brian, S. J. Blagg; Jeffrey, M. Holzbeierlein

2009-01-01

Purpose Hsp90 is important in the folding, maturation and stabilization of pro-tumorigenic client proteins and represents a viable drug target for the design of chemotherapies. Previously, we reported the development of novobiocin analogues designed to inhibit the C-terminal portion of Hsp90, which demonstrated the ability to decrease client protein expression. We now report the characterization of the novel novobiocin analogue, F-4, which demonstrates improved cytotoxicity in prostate cancer cell lines compared to the N-terminal inhibitor, 17-AAG. Materials and Methods LNCaP and PC-3 cells were treated with 17-AAG or F-4 in anti-proliferative, apoptosis, cell cycle and cytotoxicity assays. Western blot and prostate specific antigen (PSA) ELISAs were used to determine client protein degradation, induction of Hsp90 and to assess the functional status of the androgen receptor (AR) in response to F-4 treatment. Surface Plasmon Resonance (SPR) was also used to determine the binding properties of F-4 to Hsp90. Results F-4 demonstrated improved potency and efficacy compared to novobiocin in anti-proliferative assays and decreased expression of client proteins. PSA secretion was inhibited in a dose-dependent manner that paralleled a decrease in AR expression. The binding of F-4 to Hsp90 was determined to be saturable with a binding affinity (Kd) of 100 µM. In addition, superior efficacy was demonstrated by F-4 compared to 17-AAG in experiments measuring cytotoxicity and apoptosis Conclusions These data reveal distinct modes of action for N-terminal and C-terminal Hsp90 inhibitors, which may offer unique therapeutic benefits for the treatment of prostate cancer. PMID:19739131

Preapproval and postapproval availability of published comparative efficacy research on biological agents.

PubMed

Thomas, Rachel Hutchins; Freeman, Maisha Kelly; Hughes, Peter J

2013-07-15

Preapproval and postapproval availability of published comparative efficacy studies on biological agents approved between 2000 and 2010 was investigated. Approval packages published on the Food and Drug Administration (FDA) website were examined for all biological agents approved between 2000 and 2010 to determine if comparative efficacy studies were available at the time of FDA approval. The availability of comparative efficacy studies published subsequent to approval was determined by searching PubMed for randomized, active-controlled experimental or observational study designs that measured efficacy as the primary endpoint and were relevant to the original FDA-approved indication. From 2000 to 2010, 107 biological agents were approved by FDA. Of the biological agents with alternative treatments, 54.6% had comparative efficacy data available at the time of approval. Although standard-reviewed biological agents were more likely to have comparative efficacy trials included in the FDA approval packages than priority-reviewed biological agents, statistically significant differences are unlikely. Subsequent to approval, 58.1% of biological agents had at least one published comparative efficacy trial, representing a 3.5% absolute increase in the availability of comparative efficacy studies since the time of approval. Vaccines and biological agents in the hematologic diseases, oncology, and miscellaneous diseases classes had fewer published postapproval comparative efficacy studies per agent compared with the overall group of biological agents. Nearly half of all biological agents approved for marketing between 2000 and 2010 lacked publicly accessible, active-controlled efficacy studies at the time of drug approval; a slightly greater proportion of biological agents had comparative efficacy data published subsequent to their approval.

Safety, efficacy, actions, and patient acceptability of drospirenone/ethinyl estradiol contraceptive pills in the treatment of premenstrual dysphoric disorder.

PubMed

Breech, Lesley L; Braverman, Paula K

2010-08-09

Premenstrual dysphoric disorder (PMDD) is estimated to affect 3%-8% of reproductive age women. Multiple therapeutic modalities have been evaluated with varying efficacy for the associated somatic and mood symptoms. The majority of older studies had shown that oral contraceptive pills (OCs) were most effective for the physical symptoms. However, newer OCs containing a novel progestin, drospirenone, have shown promise in alleviating both the somatic and affective/behavioral symptoms. This progestin, which is a derivative of spironolactone, has both antimineralocorticoid and antiandrogenic activity. A 24/4 formulation containing 20 μg of ethinyl estradiol has been found effective in randomized double-blind placebo-controlled trials utilizing established scales documenting symptoms associated with PMDD. Multiple studies have shown that drospirenone-containing OCs are safe without evidence of clinically adverse effects on carbohydrate metabolism, lipids, blood pressure, weight, serum potassium or increased thrombotic events compared to other low dose OCs. In addition, significant improvements have been demonstrated in acne, hirsutism, and fluid retention symptoms. Several open label studies demonstrated good patient compliance and reported satisfaction with the method. Because of the significant placebo effect demonstrated in the blinded placebo-controlled trials, additional large randomized placebo-controlled trials are needed to confirm the efficacy of the drospirenone OCs in the treatment of PMDD. However, this OC formulation appears to be a promising therapeutic modality.

Safety, efficacy, actions, and patient acceptability of drospirenone/ethinyl estradiol contraceptive pills in the treatment of premenstrual dysphoric disorder

PubMed Central

Breech, Lesley L; Braverman, Paula K

2010-01-01

Premenstrual dysphoric disorder (PMDD) is estimated to affect 3%–8% of reproductive age women. Multiple therapeutic modalities have been evaluated with varying efficacy for the associated somatic and mood symptoms. The majority of older studies had shown that oral contraceptive pills (OCs) were most effective for the physical symptoms. However, newer OCs containing a novel progestin, drospirenone, have shown promise in alleviating both the somatic and affective/behavioral symptoms. This progestin, which is a derivative of spironolactone, has both antimineralocorticoid and antiandrogenic activity. A 24/4 formulation containing 20 μg of ethinyl estradiol has been found effective in randomized double-blind placebo-controlled trials utilizing established scales documenting symptoms associated with PMDD. Multiple studies have shown that drospirenone-containing OCs are safe without evidence of clinically adverse effects on carbohydrate metabolism, lipids, blood pressure, weight, serum potassium or increased thrombotic events compared to other low dose OCs. In addition, significant improvements have been demonstrated in acne, hirsutism, and fluid retention symptoms. Several open label studies demonstrated good patient compliance and reported satisfaction with the method. Because of the significant placebo effect demonstrated in the blinded placebo-controlled trials, additional large randomized placebo-controlled trials are needed to confirm the efficacy of the drospirenone OCs in the treatment of PMDD. However, this OC formulation appears to be a promising therapeutic modality. PMID:21072278

Advancing career counseling and employment support for survivors: an intervention evaluation.

PubMed

Davidson, M Meghan; Nitzel, Camie; Duke, Alysondra; Baker, Cynthia M; Bovaird, James A

2012-04-01

The purpose of this research was to conduct a replication-based and extension study examining the effectiveness of a 5-week career group counseling intervention, Advancing Career Counseling and Employment Support for Survivors (ACCESS; Chronister, 2008). The present study was conducted in a markedly different geographic region within a larger community as compared with the original investigation conducted by Chronister and McWhirter (2006). Women survivors of intimate partner violence (N = 73) participated in ACCESS, with career-search self-efficacy, perceived career barriers, perceived career supports, anxiety, and depression assessed at preintervention, postintervention, and 8-week follow-up. Women survivors demonstrated significant improvements in career-search self-efficacy and perceived career barriers at postintervention. Moreover, these same improvements were maintained at the 8-week follow-up assessment with the addition of significant improvements in perceived future financial supports, anxiety, and depression compared with preintervention scores. This work replicates the initial findings regarding the effectiveness of ACCESS with respect to career-search self-efficacy (Chronister & McWhirter, 2006) as well as extends the initial research to include improvements in perceived career barriers and perceived career supports. Moreover, the present study extends the work to include the mental health outcomes of anxiety and depression; results demonstrated improvements in these areas at 8-week follow-up. This investigation begins to fill a critical need for evaluated career-focused interventions for the underserved population of women survivors of intimate partner violence.

In vitro antifungal efficacy of ciclopirox olamine alone and associated with zinc pyrithione compared to ketoconazole against Malassezia globosa and Malassezia restricta reference strains.

PubMed

Roques, Christine; Brousse, Sabine; Panizzutti, Cédric

2006-12-01

The aim of this study was to determine the in vitro fungicidal and growth inhibitory activity of ciclopirox olamine alone (1% and 1.5%) or in association with 1% zinc pyrithione compared to 2% ketoconazole, against Malassezia species particularly involved in the pathogenesis of seborrheic dermatitis. Experiments were performed on Malassezia globosa IP 2387.96 and M. restricta IP 2392.96 strains. Growth inhibitory activity of the active compounds in solution was evaluated by measuring minimal inhibitory concentrations using a broth micro-method and their fungicidal activity by a filtration method after contact times between solutions and yeasts ranging from 3-5 to 30 min. Concerning the determination of minimal inhibitory concentration of ciclopirox olamine/zinc pyrithione, it revealed the marked synergistic inhibitory effect of the association, leading to a higher efficacy compared to ketoconazole. As to the fungicidal activity of ciclopirox olamine, it significantly increased with the contact time. After 15-30 min of contact between 1.5% ciclopirox olamine and Malassezia strains, a 2-log reduction of Malassezia counts was observed. The 1.5% ciclopirox olamine/1% zinc pyrithione association was characterized by a steady fungicidal efficacy whereas the 2% ketoconazole solution did not express any fungicidal effect. In conclusion, this study demonstrates the in vitro inhibitory and fungicidal efficacy of the ciclopirox olamine/zinc pyrithione association against Malassezia species and underscores its potential interest in the treatment of seborrheic dermatitis.

Hypofractionated radiation therapy for prostate cancer: biologic and technical considerations

PubMed Central

Sanfilippo, Nicholas J; Cooper, Benjamin T

2014-01-01

The optimal radiation schedule for the curative treatment of prostate cancer is not known. The dose-response of tumors and normal tissues to fractionated irradiation can be described according to a parameter called the alpha-beta ratio (α/β). In the past several years numerous reports have been published that suggest that the alpha-beta ratio for prostate cancer may be quite low; between 1 and 3. If this hypothesis is true, then a radiation therapy schedule that employs less frequent and larger fractions, termed hypofractionation, may be more efficacious. Multiple randomized trials have been conducted comparing moderate (less than 5 Gy/day) hypofractionated radiation therapy and standard radiation therapy in men with prostate cancer. In the majority of these studies the moderate hypofractionated arm had equivalent efficacy with a similar or improved side effect profile. One area to use caution may be in patients with compromised (IPSS > 12) urinary function at baseline due to an increase in urinary toxicity observed in patients treated with hypofractionated radiation in one study. Extreme hypofractionation (greater than or equal to 5 Gy/day), is currently being compared in a randomized trial. Early prospectively collected data from multiple institutions demonstrates efficacy and toxicity that compares favorably with historical controls. The cost savings from hypofractionation could be profound on a national level and only increases the necessity of testing hypofractionated treatment schedules. Long term data and future trials will help radiation oncologists determine the ideal fractionation scheme based on cost, efficacy, and toxicity. PMID:25606574

Efficacy of protracted temozolomide dosing is limited in MGMT unmethylated GBM xenograft models.

PubMed

Cen, Ling; Carlson, Brett L; Pokorny, Jenny L; Mladek, Ann C; Grogan, Patrick T; Schroeder, Mark A; Decker, Paul A; Anderson, S Keith; Giannini, Caterina; Wu, Wenting; Ballman, Karla V; Kitange, Gaspar J; Sarkaria, Jann N

2013-06-01

Temozolomide (TMZ) is important chemotherapy for glioblastoma multiforme (GBM), but the optimal dosing schedule is unclear. The efficacies of different clinically relevant dosing regimens were compared in a panel of 7 primary GBM xenografts in an intracranial therapy evaluation model. Protracted TMZ therapy (TMZ daily M-F, 3 wk every 4) provided superior survival to a placebo-treated group in 1 of 4 O(6)-DNA methylguanine-methyltransferase (MGMT) promoter hypermethylated lines (GBM12) and none of the 3 MGMT unmethylated lines, while standard therapy (TMZ daily M-F, 1 wk every 4) provided superior survival to the placebo-treated group in 2 of 3 MGMT unmethylated lines (GBM14 and GBM43) and none of the methylated lines. In comparing GBM12, GBM14, and GBM43 intracranial specimens, both GBM14 and GBM43 mice treated with protracted TMZ had a significant elevation in MGMT levels compared with placebo. Similarly, high MGMT was found in a second model of acquired TMZ resistance in GBM14 flank xenografts, and resistance was reversed in vitro by treatment with the MGMT inhibitor O(6)-benzylguanine, demonstrating a mechanistic link between MGMT overexpression and TMZ resistance in this line. Additionally, in an analysis of gene expression data, comparison of parental and TMZ-resistant GBM14 demonstrated enrichment of functional ontologies for cell cycle control within the S, G2, and M phases of the cell cycle and DNA damage checkpoints. Across the 7 tumor models studied, there was no consistent difference between protracted and standard TMZ regimens. The efficacy of protracted TMZ regimens may be limited in a subset of MGMT unmethylated tumors by induction of MGMT expression.

Efficacy and safety of febuxostat for prevention of tumor lysis syndrome in patients with malignant tumors receiving chemotherapy: a phase III, randomized, multi-center trial comparing febuxostat and allopurinol.

PubMed

Tamura, Kazuo; Kawai, Yasukazu; Kiguchi, Toru; Okamoto, Masataka; Kaneko, Masahiko; Maemondo, Makoto; Gemba, Kenichi; Fujimaki, Katsumichi; Kirito, Keita; Goto, Tetsuya; Fujisaki, Tomoaki; Takeda, Kenji; Nakajima, Akihiro; Ueda, Takanori

2016-10-01

Control of serum uric acid (sUA) levels is very important during chemotherapy in patients with malignant tumors, as the risks of tumor lysis syndrome (TLS) and renal events are increased with increasing levels of sUA. We investigated the efficacy and safety of febuxostat, a potent non-purine xanthine oxidase inhibitor, compared with allopurinol for prevention of hyperuricemia in patients with malignant tumors, including solid tumors, receiving chemotherapy in Japan. An allopurinol-controlled multicenter, open-label, randomized, parallel-group comparative study was carried out. Patients with malignant tumors receiving chemotherapy, who had an intermediate risk of TLS or a high risk of TLS and were not scheduled to be treated with rasburicase, were enrolled and then randomized to febuxostat (60 mg/day) or allopurinol (300 or 200 mg/day). All patients started to take the study drug 24 h before chemotherapy. The primary objective was to confirm the non-inferiority of febuxostat to allopurinol based on the area under the curve (AUC) of sUA for a 6-day treatment period. Forty-nine and 51 patients took febuxostat and allopurinol, respectively. sUA decreased over time after initiation of study treatment. The least squares mean difference of the AUC of sUA between the treatment groups was -33.61 mg h/dL, and the 95 % confidence interval was -70.67 to 3.45, demonstrating the non-inferiority of febuxostat to allopurinol. No differences were noted in safety outcomes between the treatment groups. Febuxostat demonstrated an efficacy and safety similar to allopurinol in patients with malignant tumors receiving chemotherapy. http://www.clinicaltrials.jp ; Identifier: JapicCTI-132398.

A randomized, open-label, standard controlled, parallel group study of efficacy and safety of baclofen, and chlordiazepoxide in uncomplicated alcohol withdrawal syndrome.

PubMed

Girish, K; Vikram Reddy, K; Pandit, Lakshmi V; Pundarikaksha, H P; Vijendra, R; Vasundara, K; Manjunatha, R; Nagraj, Moulya; Shruthi, R

2016-02-01

Alcohol withdrawal syndrome (AWS) is a distressing condition, generally controlled by benzodiazepines (BZD's). Baclofen, a gamma-aminobutyric acid-B (GABAB) agonist, has also shown promising results in controlling AWS. As there are few studies comparing the efficacy and tolerability of chlordiazepoxide with baclofen, the present study was taken up. The objective of this study was to compare efficacy and tolerability of baclofen with chlordiazepoxide in uncomplicated AWS. Sixty subjects with uncomplicated AWS were randomized into two groups of 30 each, to receive baclofen (30 mg) or chlordiazepoxide (75 mg) in decremented fixed dose regime for 9 days. Clinical efficacy was assessed by Clinical Institute Withdrawal Assessment for Alcohol-Revised Scale (CIWA-Ar) and tolerability by the nature and severity of adverse events. Lorazepam was used as rescue medication. Secondary efficacy parameters were Clinical Global Impression scores, symptom-free days, and subject satisfaction as assessed by visual analog scale. This study was registered with Clinical Trial Registry-India (CTRI/2013/04/003588), also subsequently registered with WHO's ICTRP clinical trial portal. Both baclofen and chlordiazepoxide showed a consistent reduction in the total CIWA-Ar scores. However, chlordiazepoxide showed a faster and a more effective control of anxiety and agitation requiring lesser lorazepam supplementation, and also showed a better subject satisfaction compared to baclofen. Both the drugs showed good tolerability with mild self-limiting adverse events. The present study demonstrates that baclofen is not as good as chlordiazepoxide in the treatment of uncomplicated AWS. However, baclofen might be considered as an alternative. Copyright © 2016 Chang Gung University. Published by Elsevier B.V. All rights reserved.

The Efficacy of Internet-based Cognitive Behavioral Therapy on the Anxiety Disorders among Adolescent Girls.

PubMed

Karbasi, Afsaneh; Haratian, Azadeh

2018-01-01

The prevalence of anxiety disorders among children and adolescents are found to be approximately between 8-12 and 5-10, respectively, and the long-lasting effects of such disorders can expose the sufferers to impairment and dysfunction in several areas of life the examples of which are poor educational performance, low self-esteem, and depression. The present study aims to evaluate the efficacy of internet-based, cognitive-behavioral therapy (ICBT) in treating the anxiety disorders among adolescent females. The sample included thirty girls aged between 10 and 18 years suffering from a variety of anxiety disorders, under pharmaceutical therapy and referred to clinics of child and adolescent psychiatry specialists in Isfahan. The sample was selected through diagnostic interviews by psychiatrists based on the Diagnostic and Statistical Manual of Mental Disorders, 4 th Edition, Text Revision; afterward, they were randomly assigned to either the experimental or the control groups. To evaluate the efficacy of an ICBT in reducing anxiety disorder symptoms, Screen for Child Anxiety Related Emotional Disorders questionnaire was administered among the patients both before and 4 weeks after the treatment. The covariance analysis results aimed to compare the anxiety disorder score variations between the two groups which demonstrate the fact that anxiety disorder scores in these two groups differ from one another ( P < 0.001). This study is comprised of two Conclusions.the significant reduction in the mean of anxiety disorders scores in the experimental group compared to those in control group can be indicative of the efficacy of ICBT. In addition the significant reduction in the average of anxiety disorders symptoms' scores according to the type of anxiety disorders in the experimental group, compared to those in control group, can be indicative of the efficacy of ICBT.

Expanding the Evidence Base: Comparing Randomized Controlled Trials and Observational Studies of Statins.

PubMed

Atar, Dan; Ong, Seleen; Lansberg, Peter J

2015-01-01

It is widely accepted that randomized controlled trials (RCTs) are the gold standard for demonstrating the efficacy of a given therapy (results under ideal conditions). Observational studies, on the other hand, can complement this by demonstrating effectiveness (results under real-world conditions). To examine the role that observational studies can play in complementing data from RCTs, we reviewed published studies for statins, a class of drugs that have been widely used to reduce the risk of cardiovascular (CV) events by lowering low-density lipoprotein cholesterol levels. RCTs have consistently demonstrated the benefits of statin treatment in terms of CV risk reduction and have demonstrated that more intensive statin therapy has incremental benefits over less intensive treatment. Observational studies of statin use in 'real-world' populations have served to augment the evidence base generated from statin RCTs in preselected populations of patients who are often at high CV risk and have led to similar safety and efficacy findings. They have also raised questions about factors affecting medication adherence, under-treatment, switching between statins, and failure to reach low-density lipoprotein cholesterol target levels, questions for which the answers could lead to improved patient care.

[The HMPC monograph on Hypericum: Background, development, contents].

PubMed

Länger, Reinhard

2010-12-01

The adoption of the EU community monograph on Hypericum constitutes a milestone in the process of harmonisation of herbal medicinal products within the European Community. The assessment of the published clinical data revealed that for two types of extracts the evidence of the efficacy in mild to moderate depressive episodes compared to placebo or standard medication was found to be acceptable. Additionally, a sufficient efficacy in relapse prophylaxis could be demonstrated for these two herbal preparations. For some other dry extracts, the efficacy in the short-term treatment of symptoms in mild depressive disorders was found to be substantiated. Short-term treatment with preparations containing low amounts of hyperforin did not increase cytochrome P450 enzyme activity. Therefore the oral administration of traditional herbal preparations is restricted to two weeks. In the case that an applicant demonstrates that the daily intake of hyperforin is below 1 mg the warnings on interactions may be omitted in traditional herbal medicinal products. Additionally the cutaneous administration of traditional liquid herbal preparations for the traditional use in symptomatic treatment of minor inflammations of the skin and as an aid in healing minor wounds was included in the monograph.

Pharmacologic therapies for severe steroid refractory hospitalized ulcerative colitis: A network meta-analysis.

PubMed

Komaki, Yuga; Komaki, Fukiko; Micic, Dejan; Yamada, Akihiro; Suzuki, Yasuo; Sakuraba, Atsushi

2017-06-01

A limited option of therapies is available for hospitalized patients with severe steroid refractory ulcerative colitis (UC). Furthermore, there exists a paucity of direct comparisons between them. To provide a comparative evaluation of the efficacy and safety of pharmacologic therapies, we conducted a network meta-analysis combined with a benefit-risk analysis of randomized controlled trials (RCTs) performed in hospitalized patients with severe steroid refractory UC. Electronic databases were searched through November 2015 for RCTs evaluating the efficacy of therapies for severe steroid refractory hospitalized UC. The outcomes were clinical response, colectomy free rate, and severe adverse events leading to discontinuation of therapy. The primary endpoints were the rank of therapies based on network meta-analysis combined with benefit-risk analysis between clinical response and severe adverse events as well as colectomy free rate and severe adverse events. Eight RCTs of 421 patients were identified. Cyclosporine, infliximab, and tacrolimus as well as placebo were included in our analysis. Network meta-analysis with benefit-risk analysis simultaneously assessing clinical response and severe adverse events demonstrated the rank order of efficacy as infliximab, cyclosporine, tacrolimus, and placebo. Similar analysis for colectomy-free rate and severe adverse events demonstrated the same rank order of efficacy. The differences among infliximab, cyclosporine, and tacrolimus were small in all analyses. The results of the present comprehensive benefit-risk assessment using network meta-analysis provide RCT-based evidence on efficacy and safety of infliximab, cyclosporine, and tacrolimus for hospitalized patients with severe steroid refractory UC. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Dexamethasone nanowafer as an effective therapy for dry eye disease.

PubMed

Coursey, Terry G; Henriksson, Johanna Tukler; Marcano, Daniela C; Shin, Crystal S; Isenhart, Lucas C; Ahmed, Faheem; De Paiva, Cintia S; Pflugfelder, Stephen C; Acharya, Ghanashyam

2015-09-10

Dry eye disease is a major public health problem that affects millions of people worldwide. It is presently treated with artificial tear and anti-inflammatory eye drops that are generally administered several times a day and may have limited therapeutic efficacy. To improve convenience and efficacy, a dexamethasone (Dex) loaded nanowafer (Dex-NW) has been developed that can release the drug on the ocular surface for a longer duration of time than drops, during which it slowly dissolves. The Dex-NW was fabricated using carboxymethyl cellulose polymer and contains arrays of 500 nm square drug reservoirs filled with Dex. The in vivo efficacy of the Dex-NW was evaluated using an experimental mouse dry eye model. These studies demonstrated that once a day Dex-NW treatment on alternate days during a five-day treatment period was able to restore a healthy ocular surface and corneal barrier function with comparable efficacy to twice a day topically applied dexamethasone eye drop treatment. The Dex-NW was also very effective in down regulating expression of inflammatory cytokines (TNF-α, and IFN-γ), chemokines (CXCL-10 and CCL-5), and MMP-3, that are stimulated by dry eye. Despite less frequent dosing, the Dex-NW has comparable therapeutic efficacy to topically applied Dex eye drops in experimental mouse dry eye model, and these results provide a strong rationale for translation to human clinical trials for dry eye. Copyright © 2015 Elsevier B.V. All rights reserved.

Mental Health Does Not Moderate Compensatory Cognitive Training Efficacy for Veterans With a History of Mild Traumatic Brain Injury.

PubMed

Pagulayan, Kathleen F; O'Neil, Maya; Williams, Rhonda M; Turner, Aaron P; Golshan, Shahrokh; Roost, Mai S; Laman-Maharg, Benjamin; Huckans, Marilyn; Storzbach, Daniel; Twamley, Elizabeth W

2017-09-01

To examine the potential moderating effects of mental health symptoms on the efficacy of compensatory cognitive training (CCT) for Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn veterans with a history of mild traumatic brain injury (mTBI). Secondary analysis of a randomized controlled trial of CCT. Posttraumatic stress disorder, depression, and substance dependence symptom severity were examined as potential moderators of CCT efficacy for subjective cognitive complaints, use of cognitive strategies, and objective neurocognitive performance. Three Veterans Affairs medical centers. Participants included veterans with history of mTBI (N=119): 50 participated in CCT and 69 received usual care (UC). CCT is a 10-week group-based (90 minutes per session) manualized cognitive rehabilitation intervention. Objective (neuropsychological functioning) and subjective (self-report) cognitive functioning and use of cognitive strategies. Baseline mental health symptoms did not moderate CCT efficacy: veterans who received CCT reported significantly greater improvement in cognitive difficulties and use of cognitive strategies compared with the UC group, regardless of baseline mental health symptom severity. The CCT group also demonstrated significant improvements on neuropsychological measures of attention, learning, and executive functioning compared with the UC group, regardless of baseline mental health symptom severity. CCT is efficacious for improving objective cognitive functioning and compensatory strategy use for veterans with a history of mTBI, regardless of the severity of comorbid psychiatric symptoms. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Exploring photoinactivation of microbial biofilms using laser scanning microscopy and confined two-photon excitation.

PubMed

Thomsen, Hanna; Graf, Fabrice E; Farewell, Anne; Ericson, Marica B

2018-05-21

One pertinent complication in bacterial infection is the growth of biofilms, i.e., communities of surface-adhered bacteria resilient to antibiotics. Photodynamic inactivation has been proposed as an alternative to antibiotic treatment; however, novel techniques complementing standard efficacy measures are required. Herein, we present an approach employing multiphoton microscopy complemented with Airyscan super-resolution microscopy, to visualize the distribution of curcumin in Staphylococcus epidermidis biofilms. The effects of complexation of curcumin with hydroxypropyl-γ-cyclodextrin (HPγCD) were studied. It was shown that HPγCD-curcumin demonstrated higher bioavailability in the biofilms compared to curcumin, without affecting the subcellular uptake. Spectral quantification following photodynamic inactivation demonstrates a method for monitoring elimination of biofilms in real time using noninvasive 3D imaging. Additionally, spatially confined two-photon inactivation was demonstrated for the first time in biofilms. These results support the feasibility of advanced optical microscopy as a sensitive tool for evaluating treatment efficacy in biofilms towards improved mechanistic studies of photodynamic inactivation. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Anti-MRSA beta-lactams in development, with a focus on ceftobiprole: the first anti-MRSA beta-lactam to demonstrate clinical efficacy.

PubMed

Bush, Karen; Heep, Markus; Macielag, Mark J; Noel, Gary J

2007-04-01

Ceftobiprole is the first of the investigational beta-lactam antibiotics with in vitro activity against methicillin-resistant staphylococci to reach and complete Phase III therapeutic trials. Its antibacterial spectrum includes methicillin-resistant Staphylococcus aureus (MRSA), Enterococcus faecalis, penicillin-resistant streptococci and many Gram-negative pathogens. It has demonstrated in vivo activity against many experimental infections caused by these pathogens. Ceftobiprole has completed Phase III clinical trials for complicated skin and skin structure infections, is being studied in Phase III pneumonia trials and has demonstrated non-inferiority compared with vancomycin in a Phase III complicated skin and skin structure infections trial, resulting in > 90% clinical cures of infections caused by MRSA. Other anti-MRSA beta-lactams in therapeutic clinical trials include the carbapenem CS-023/RO-4908463 and the cephalosporin ceftaroline (PPI-0903). The future of all of these agents will depend on their clinical efficacy, safety and their ability to be accepted as beta-lactams for the reliable treatment of a broad spectrum of infections, including those caused by MRSA.

Assessing Academic Self-Efficacy, Knowledge, and Attitudes in Undergraduate Physiology Students

PubMed Central

Woolcock, Andrew D.; Creevy, Kate E.; Coleman, Amanda E.; Moore, James N.; Brown, Scott A.

2016-01-01

Academic self-efficacy affects the success of students in the sciences. Our goals were to develop an instrument to assess the self-efficacy and attitudes toward science of students in an undergraduate physiology course. We hypothesized 1) that our instrument would demonstrate that students taking this course would exhibit greater self-efficacy and more positive attitudes toward science than students in a non-science undergraduate course, and 2) that the physiology students’ self-efficacy and attitudes would improve after completing the course. A 25-question survey instrument was developed with items investigating demographic information, self-efficacy, content knowledge, confidence, and attitudes regarding science. Students in either an undergraduate physiology course (Group P) or a history course (Group H) completed the survey. Forty-eight students in Group P completed both PRE- and POST-class surveys, while 50 students in Group H completed the pre-class survey. The academic self-efficacy of Group P as assessed by the PRE-survey was significantly higher than Group H (p=0.0003). Interestingly, there was no significant difference between groups in content knowledge in the PRE-survey. The self-efficacy of Group P was significantly higher as assessed by the POST-survey, when compared to the PRE-survey (p<0.0001) coincident with an improvement (p<0.001) in content knowledge for Group P in the POST-survey. This study established a survey instrument with utility in assessing self-efficacy, attitudes, and content knowledge. Our approach has applicability to studies designed to determine the impact of instructional variables on academic self-efficacy, attitudes, and confidence of students in the sciences. PMID:27713903

Efficacy, safety, and improved tolerability of travoprost BAK-free ophthalmic solution compared with prior prostaglandin therapy

PubMed Central

Henry, J Charles; Peace, James H; Stewart, Jeanette A; Stewart, William C

2008-01-01

Purpose To evaluate the efficacy, safety and tolerability of changing to travoprost BAK-free from prior prostaglandin therapy in patients with primary open-angle glaucoma or ocular hypertension. Design Prospective, multi-center, historical control study. Methods Patients treated with latanoprost or bimatoprost who needed alternative therapy due to tolerability issues were enrolled. Patients were surveyed using the Ocular Surface Disease Index (OSDI) to evaluate OSD symptoms prior to changing to travoprost BAK-free dosed once every evening. Patients were re-evaluated 3 months later. Results In 691 patients, travoprost BAK-free demonstrated improved mean OSDI scores compared to either latanoprost or bimatoprost (p < 0.0001). Patients having any baseline OSD symptoms (n = 235) demonstrated significant improvement after switching to travoprost BAK-free (p < 0.0001). In 70.2% of these patients, symptoms were reduced in severity by at least 1 level. After changing medications to travoprost BAK-free, mean intraocular pressure (IOP) was significantly decreased (p < 0.0001). Overall, 72.4% preferred travoprost BAK-free (p < 0.0001, travoprost BAK-free vs prior therapy). Travoprost BAK-free demonstrated less conjunctival hyperemia than either prior therapy (p < 0.0001). Conclusions Patients previously treated with a BAK-preserved prostaglandin analog who are changed to travoprost BAK-free have clinically and statistically significant improvement in their OSD symptoms, decreased hyperemia, and equal or better IOP control. PMID:19668762

The Effects of an Education Program on Home Renovation for Fall Prevention of Korean Older People

ERIC Educational Resources Information Center

Jang, Miseon; Lee, Yeunsook

2015-01-01

This study aims to verify the effects of an education program on home renovation for fall prevention among older people, more specifically fall efficacy and home renovation intentions. A quasiexperimental study with nonequivalent control and comparative groups was conducted to demonstrate the effects of the education. A total of 51 older people…

A Comparison of Cognitive Bias Modification for Interpretation and Computerized Cognitive Behavior Therapy: Effects on Anxiety, Depression, Attentional Control, and Interpretive Bias

ERIC Educational Resources Information Center

Bowler, Jennifer O.; Mackintosh, Bundy; Dunn, Barnaby D.; Mathews, Andrew; Dalgleish, Tim; Hoppitt, Laura

2012-01-01

Objective: Computerized cognitive behavioral therapy (cCBT) and cognitive bias modification for interpretation (CBM-I) both have demonstrated efficacy in alleviating social anxiety, but how they compare with each other has not been investigated. The present study tested the prediction that both interventions would reduce anxiety relative to a…

Increasing daily water intake and fluid adherence in children receiving treatment for retentive encopresis.

PubMed

Kuhl, Elizabeth S; Hoodin, Flora; Rice, Jennifer; Felt, Barbara T; Rausch, Joseph R; Patton, Susana R

2010-11-01

To examine the efficacy of an enhanced intervention (EI) compared to standard care (SC) in increasing daily water intake and fluid goal adherence in children seeking treatment for retentive encopresis. Changes in beverage intake patterns and fluid adherence were examined by comparing 7-week diet diary data collected during participation in the EI to achieved data for families who had previously completed the SC. Compared to children in SC (n = 19), children in the EI (n = 18) demonstrated a significantly greater increase in daily water intake from baseline to the conclusion of treatment ( p ≤ .001), and were four and six times more likely to meet fluid targets in Phases 1 (Weeks 3-4) and 2 (Weeks 5-6) of fluid intervention, respectively (both p ≤ .001). Enhanced education and behavioral strategies were efficacious in increasing children's intake of water and improving fluid adherence. Future research should replicate the findings in a prospective randomized clinical trial to discern their effectiveness.

Use of customised pressure-guided elastic bandages to improve efficacy of compression bandaging for venous ulcers.

PubMed

Sermsathanasawadi, Nuttawut; Chatjaturapat, Choedpong; Pianchareonsin, Rattana; Puangpunngam, Nattawut; Wongwanit, Chumpol; Chinsakchai, Khamin; Ruangsetakit, Chanean; Mutirangura, Pramook

2017-08-01

Compression bandaging is a major treatment of chronic venous ulcers. Its efficacy depends on the applied pressure, which is dependent on the skill of the individual applying the bandage. To improve the quality of bandaging by reducing the variability in compression bandage interface pressures, we changed elastic bandages into a customised version by marking them with circular ink stamps, applied when the stretch achieves an interface pressure between 35 and 45 mmHg. Repeated applications by 20 residents of the customised bandage and non-marked bandage to one smaller and one larger leg were evaluated by measuring the sub-bandage pressure. The results demonstrated that the target pressure range is more often attained with the customised bandage compared with the non-marked bandage. The customised bandage improved the efficacy of compression bandaging for venous ulcers, with optimal sub-bandage pressure. © 2016 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Pharmacologic treatments for the behavioral symptoms associated with autism spectrum disorders across the lifespan

PubMed Central

Doyle, Carolyn A.; McDougle, Christopher J.

2012-01-01

This review outlines pharmacologic treatments for the behavioral symptoms associated with autism spectrum disorders (ASDs) in children, adolescents, and adults. Symptom domains include repetitive and stereotyped behaviors, irritability and aggression, hyperactivity and inattention, and social impairment. Medications covered include serotonin reuptake inhibitors (SRIs), mirtazapine, antipsychotics, psychostimulants, atomoxetine, α-2 agonists, D-cycloserine, and memantine. Overall, SRIs are less efficacious and more poorly tolerated in children with ASDs than in adults. Antipsychotics are the most efficacious drugs for the treatment of irritability in ASDs, and may be useful in the treatment of other symptoms. Psychostimulants demonstrate some benefit for the treatment of hyperactivity and inattention in individuals with ASDs, but are less efficacious and associated with more adverse effects compared with individuals with ADHD. D-cycloserine and memantine appear helpful in the treatment of social impairment, although further research is needed. PMID:23226952

Is the LINX reflux management system an effective treatment for gastro-oesophageal reflux disease?

PubMed

Loh, Yiwen; McGlone, Emma Rose; Reddy, Marcus; Khan, Omar A

2014-01-01

A best evidence topic in surgery was written according to a structured protocol. The question addressed whether LINX™ Reflux management system is an efficacious treatment for patients with symptoms of gastro-oesophageal reflux disease (GORD) not controlled by proton pump inhibitors (PPI). Forty-eight LINX-related papers were identified using the reported search, of which three represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group, study type, relevant outcomes and results of these papers are tabulated. All three studies were prospective case studies. They demonstrated that LINX is an efficacious treatment for GORD patients with good short and medium term outcomes and an acceptable safety profile. Further studies are required to determine its long term outcomes and its relative efficacy as compared to other established treatments. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Antimicrobial efficacy of 0·05% cetylpyridinium chloride mouthrinses.

PubMed

Sreenivasan, P K; Haraszthy, V I; Zambon, J J

2013-01-01

This study evaluated the antimicrobial activity of two commercially available 0·05% cetylpyridinium chloride (CPC) mouthrinses with or without alcohol and examined its antimicrobial activity on oral bacterial species including fresh clinical isolates compared to a chlorhexidine mouthrinse and a control fluoride mouthrinse without CPC. Two different approaches were used to evaluate antimicrobial activity. First, the minimum inhibitory concentration (MIC) was determined for each mouthrinse against a panel of 25 micro-organisms including species associated with dental caries, gingivitis and periodontitis. Second, supragingival dental plaque obtained from 15 adults was incubated with the four mouthrinses to evaluate antimicrobial activity on micro-organisms in oral biofilms. Both CPC mouthrinses exhibited lower MIC's, that is, greater antimicrobial activity, against oral Gram-negative bacteria especially periodontal pathogens and species implicated in halitosis such as Aggregatibacter actinomycemcomitans, Campylobacter rectus, Eikenella corrodens, Porphyromonas gingivalis, Prevotella intermedia and Solobacterium moorei than the control mouthrinse. Ex-vivo tests on supragingival plaque micro-organisms demonstrated significantly greater antimicrobial activity by the CPC mouthrinses (>90% killing, P < 0·001) and the chlorhexidine rinse (>98% killing, P < 0·05) compared to the control fluoride mouthrinse. Whilst the chlorhexidine mouthrinse was most effective, mouthrinses containing 0·05% CPC formulated with or without alcohol demonstrated broad-spectrum antimicrobial activity against both laboratory strains and supragingival plaque bacteria compared to a control mouthrinse without CPC. These in vitro and ex-vivo studies provide a biological rationale for previous clinical studies demonstrating the efficacy of CPC mouthrinses in reducing supragingival plaque and plaque-associated gingivitis. © 2012 The Society for Applied Microbiology.

High-dose versus low-dose local anaesthetic for transversus abdominis plane block post-Caesarean delivery analgesia: a meta-analysis.

PubMed

Ng, S C; Habib, A S; Sodha, S; Carvalho, B; Sultan, P

2018-02-01

The optimal local-anaesthetic (LA) dose for transversus-abdominis-plane (TAP) block is unclear. In this meta-analysis, we aimed to determine whether TAP blocks for Caesarean delivery (CD) with low-dose (LD) LA demonstrated non-inferiority in terms of analgesic efficacy, compared with high-dose (HD) LA. A literature search was performed for randomised controlled trials examining the analgesic efficacy of TAP blocks vs control after CD. The different dosing used in these studies was classified as HD or LD (bupivacaine equivalents >50 or ≤50 mg per block side, respectively). The pooled results of each dose group vs control were indirectly compared using the Q test. The primary outcome was 24 h opioid consumption. Secondary outcomes included 6 and 24 h postoperative pain scores, time to first analgesia, 6 h opioid consumption, opioid-related side-effects, and maternal satisfaction. Fourteen studies consisting of 770 women (389 TAP and 381 control) were included. Compared with controls, the 24 h opioid consumption (milligram morphine equivalents) was lower in HD [mean difference (MD) 95% confidence interval (CI) -22.41 (-38.56, -6.26); P=0.007; I 2 =93%] and LD [MD 95% CI -16.29 (-29.74, -2.84); P=0.02; I 2 =98%] TAP groups. However, no differences were demonstrated between the HD and LD groups (P=0.57). There were also no differences between the HD and LD groups for the 6 h opioid consumption, time to first analgesia, 6 and 24 h pain scores, postoperative nausea and vomiting, pruritus, and maternal satisfaction. Low-dose TAP blocks for Caesarean delivery provide analgesia and opioid-sparing effects comparable with the high-dose blocks. This suggests that lower doses can be used to reduce local anaesthetic toxicity risk without compromising the analgesic efficacy. Copyright © 2017 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

Comparing The Efficacy of Hematoxylin and Eosin, Periodic Acid Schiff and Fluorescent Periodic Acid Schiff-Acriflavine Techniques for Demonstration of Basement Membrane in Oral Lichen Planus: A Histochemical Study

PubMed Central

Pujar, Ashwini; Pereira, Treville; Tamgadge, Avinash; Bhalerao, Sudhir; Tamgadge, Sandhya

2015-01-01

Background: Basement membrane (BM) is a thick sheet of extracellular matrix molecules, upon which epithelial cells attach. Various immunohistochemical studies in the past have been carried out but these advanced staining techniques are expensive and not feasible in routine laboratories. Although hematoxylin and eosin (H-E) is very popular among pathologists for looking at biopsies, the method has some limitations. This is where special stains come handy. Aims and Objectives: The aim of the present study was to demonstrate and compare the efficacy of H-E, periodic acid Schiff (PAS) and fluorescent periodic acid–acriflavine staining techniques for the basement membrane and to establish a histochemical stain which could be cost effective, less time consuming, and unambiguous for observation of the basement membrane zone. Materials and Methods: A total number of 40 paraffin-embedded tissue sections of known basement membrane containing tissues including 10 – Normal oral mucosa (NOM) and 30 – oral lichen planus (OLP) were considered in the study. Four-micron-thick sections of each block were cut and stained with H-E stain, PAS and fluorescent periodic acid–acriflavine stain. Sections were evaluated by three oral pathologists independently for continuity, contrast and pattern. Results: Though all the three stains showed favorable features at different levels, acriflavine stain was better than the other stains in demonstrating BM continuity, contrast and also the pattern followed by PAS stain. Acriflavine stain was the better in demonstrating a fibrillar pattern of a BM. Acriflavine stains a BM distinctly and is less time consuming and easy to carry out using readily available dyes as compared to other stains. Conclusion: The continuity and contrast along with the homogenous pattern and the afibrillar pattern of the BM was better demonstrated by acriflavine followed by the PAS stain. PMID:26538690

Efficacy of a standardized herbal preparation (Roidosanal®) in the treatment of hemorrhoids: A randomized, controlled, open-label multicentre study

PubMed Central

Aggrawal, Kapil; Satija, Naveen; Dasgupta, Gita; Dasgupta, Partha; Nain, Parul; Sahu, Aditya R.

2014-01-01

Background: Catechins and epicatechins are monomers of naturally occurring proanthocyanidins, which have been reported with free radical scavenging, antioxidant, antiinflammatory, antiallergic, and vasodilatory properties. Plant parts rich in proanthocyanidins have been used for years in treatment of various ano-rectal diseases. This study compares the efficacy of two herbal preparations, Daflon® 500 mg and Roidosanal®, in ameliorating the signs and symptoms associated with hemorrhoids. Objective: To evaluate the safety and to compare the efficacy of a herbal preparation, Roidosanal® versus Daflon® 500 mg, on signs and symptoms of hemorrhoidal disease. Materials and Methods: In this pilot, active controlled, open-labeled multicentre study, 73 patients with proctoscopy proven hemorrhoids (Grade I to III) were randomly assigned to receive either Roidosanal® (Gr R; n = 37) or Daflon® 500 mg (Gr D; n = 36), for 15 days, at three centers in India. Assessment of hemorrhoidal symptoms was carried out in all patients at different time points. Intent-to-treat analysis was performed for both primary and secondary endpoints. Results: Baseline characteristics were comparable between the two groups. Both products were found to be equally effective in improving the ano-rectal conditions in Grade I and Grade II hemorrhoids; however, Roidosanal® demonstrated better efficacy in patients with Grade III hemorrhoids. Hemorrhoids associated symptoms like bleeding, pain, etc., improved in both groups, although intergroup comparisons were comparable. Conclusion: Both Roidosanal® and Daflon® 500 mg were equally effective in resolving signs and symptoms of hemorrhoids. Roidosanal® can be tried as a safe and effective treatment option for treatment of hemorrhoids. Further randomized, double-blind and large multicentre studies are recommended. PMID:24948863

Fenoterol hydrobromide delivered via HFA-MDI or CFC-MDI in patients with asthma: a safety and efficacy comparison.

PubMed

Goldberg, J; Böhning, W; Schmidt, P; Freund, E

2000-10-01

The main objective of the study was to compare the long-term safety and tolerability of fenoterol hydrobromide delivered using a metered-dose inhaler formulated with the alternative propellant, hydrofluoroalkane 134a (HFA-MDI), with delivery using the currently available chlorofluorocarbon MDI (CFC-MDI; Berotec 100). A further objective was to compare the efficacy of fenoterol HFA-MDI with fenoterol CFC-MDI, using the pulmonary function parameters of forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC) and peak expiratory flow (PEF). Following a 2-week run-in phase, a 12-week, double-blind parallel group comparison was undertaken in 290 patients randomized on a 2:1 basis to two puffs of 100 microg fenoterol four times a day (HFA-MDI=197 patients; CFC-MDI=93 patients). A total of 236 patients in this multi-centre study completed the trial as planned. The overall incidence of adverse events (AEs) was similar in both groups (29.9% of HFA-MDI patients and 28% of CFC-MDI patients). Reports of respiratory disorder AEs were also comparable (21.8% HFA-MDI; 22.6% CFCMDI). End of study laboratory tests, ECG, pulse, blood pressure and physical examination showed no significant differences from pre-study baselines in either group and both treatments appeared to be well tolerated. Pre-dose FEV1 measurements taken at the three clinic visits were constant and increase in FEV1 at 5 and 30 min post-dose demonstrated equivalent efficacy for the two formulations. No difference between the two groups was observed in PEF or in the use of rescue medication. We conclude from these findings that the long-term safety and efficacy profile of fenoterol HFA-MDI is comparable to that of the fenoterol CFC-MDI.

Level of response and safety of pharmacological monotherapy in the treatment of acute bipolar I disorder phases: a systematic review and meta-analysis

PubMed Central

Tamayo, Jorge M.; Zarate, Carlos A.; Vieta, Eduard; Vázquez, Gustavo; Tohen, Mauricio

2010-01-01

In recent years, combinations of pharmacological treatments have become common for the treatment of bipolar disorder type I (BP I); however, this practice is usually not evidence-based and rarely considers monotherapy drug regimen (MDR) as an option in the treatment of acute phases of BP I. Therefore, we evaluated comparative data of commonly prescribed MDRs for both manic and depressive phases of BP I. Medline, PsycINFO, EMBASE, the Cochrane Library, the ClinicalStudyResults.org and other data sources were searched from 1949 to March 2009 for placebo and active controlled randomized clinical trials (RCTs). Risk ratios (RRs) for response, remission, and discontinuation rates due to adverse events (AEs), lack of efficacy, or discontinuation due to any cause, and the number needed to treat or harm (NNT or NNH) were calculated for each medication individually and for all evaluable trials combined. The authors included 31 RCTs in the analyses comparing a MDR with placebo or with active treatment for acute mania, and 9 RCTs comparing a MDR with placebo or with active treatment for bipolar depression. According to the collected evidence, most of the MDRs when compared to placebo showed significant response and remission rates in acute mania. In the case of bipolar depression only quetiapine and, to a lesser extent, olanzapine showed efficacy as MDR. Overall, MDRs were well tolerated with low discontinuation rates due to any cause or AE, although AE profiles differed among treatments. We concluded that most MDRs were efficacious and safe in the treatment of manic episodes, but very few MDRs have demonstrated being efficacious for bipolar depressive episodes. PMID:20128953

Zwitterionic Nanocages Overcome the Efficacy Loss of Biologic Drugs.

PubMed

Li, Bowen; Yuan, Zhefan; Zhang, Peng; Sinclair, Andrew; Jain, Priyesh; Wu, Kan; Tsao, Caroline; Xie, Jingyi; Hung, Hsiang-Chieh; Lin, Xiaojie; Bai, Tao; Jiang, Shaoyi

2018-04-01

For biotherapeutics that require multiple administrations to fully cure diseases, the induction of undesirable immune response is one common cause for the failure of their treatment. Covalent binding of hydrophilic polymers to proteins is commonly employed to mitigate potential immune responses. However, while this technique is proved to partially reduce the antibodies (Abs) reactive to proteins, it may induce Abs toward their associated polymers and thus result in the loss of efficacy. Zwitterionic poly(carboxybetaine) (PCB) is recently shown to improve the immunologic properties of proteins without inducing any antipolymer Abs against itself. However, it is unclear if the improved immunologic profiles can translate to better clinical outcomes since improved immunogenicity cannot directly reflect amelioration in efficacy. Here, a PCB nanocage (PCB NC) is developed, which can physically encase proteins while keeping their structure intact. PCB NC encapsulation of uricase, a highly immunogenic enzyme, is demonstrated to eradicate all the immune responses. To bridge the gap between immunogenicity and efficacy studies, the therapeutic performance of PCB NC uricase is evaluated and compared with its PEGylated counterpart in a clinical-mimicking gouty rat model to determine any loss of efficacy evoked after five administrations. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Head lice and the use of spinosad.

PubMed

Villegas, Susan C; Breitzka, Robin L

2012-01-01

Head lice infestations are responsible for social and economic distress. Despite a reported increase in resistance, permethrin 1% is still the first-line treatment of head lice. Alternative topical pediculicidal agents include malathion and benzyl alcohol, but resistance is of growing concern. In 2011, a new pediculicide, spinosad, was introduced. Our aim was to review the clinical pharmacology, efficacy, tolerability, and current place in therapy of spinosad for the treatment of head lice. Pertinent articles and abstracts were identified through searches of MEDLINE/Ebsco and MEDLINE/Ovid from 1948 to September 2011 and International Pharmaceutical Abstracts from 1966 to September 2011. Two reports described 3 trials of spinosad used for the treatment of head lice. One study (n = 120) demonstrated efficacy of both spinosad 0.5% and spinosad 1% compared with placebo, with 82.5% and 86.1% of patients free of live lice 14 days after treatment, respectively, compared with 25.6% in the placebo group (P < 0.001 for each treatment). The difference between the spinosad 0.5% and 1% treatment groups was not significant. Two trials (n = 1038) comparing spinosad 0.9% with permethrin 1% reported greater efficacy for spinosad with absence of live lice 14 days after 1 or 2 treatments for 84.6% and 86.7%, respectively, of primary cases compared with 44.9% and 42.9% with permethrin (P < 0.001 for both studies). The most common reported adverse events were eye and scalp irritation, but they were not statistically significant (P = 0.329 and P = 0.395, respectively). Only application-site erythema reactions showed statistical significance, with 6.8% in the permethrin group versus 3.1% in the spinosad group (P = 0.007). Although limited, the available literature suggests that spinosad is an effective and well-tolerated agent for the treatment of head lice. In a time of increasing resistance, spinosad has demonstrated superior performance compared with permethrin. A review of the literature did not identify any studies comparing spinosad to benzyl alcohol 5% or malathion 0.5%. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

Affective symptoms and change in diabetes self-efficacy and glycaemic control

PubMed Central

Robertson, S. M.; Amspoker, A. B.; Cully, J. A.; Ross, E. L.; Naik, A. D.

2013-01-01

Aims To examine the role of baseline depression, anxiety and stress symptoms on post-intervention diabetes self-efficacy and glycaemic control (HbA1c). Methods The current study analysed data from patients (n = 85) with treated but uncontrolled Type 2 diabetes who participated in a comparative effectiveness study of two diabetes self-management interventions. Hierarchical linear regression was used to examine the relationships between baseline affective symptoms and post-intervention diabetes self-efficacy and the moderating effects of baseline affective symptoms on the relationship between changes in diabetes self-efficacy and post-intervention HbA1c. Results Baseline depression was inversely associated with post-intervention diabetes self-efficacy (P = 0.0001) after adjusting for baseline characteristics including diabetes self-efficacy. In contrast, normal–mild levels of stress were associated with higher post-intervention diabetes self-efficacy (P = 0.04). Anxiety and stress symptoms significantly and independently moderated the relationship between changes in diabetes self-efficacy and post-intervention HbA1c (P = 0.02 and P = 0.03, respectively). Further evaluation of these interactions demonstrated that changes in diabetes self-efficacy were associated with lower post-intervention HbA1c, but only among those with higher baseline affective symptoms. Conclusions We found a moderating effect across affective symptoms on the relationship between diabetes self-efficacy changes and post-intervention HbA1c in the context of a self-management intervention. Results suggest that patients with poorly controlled diabetes who have higher levels of depression, anxiety and stress symptoms may derive greater benefits from self-management interventions known to improve diabetes self-efficacy. PMID:23350920

Can we well assess the relative efficacy and tolerability of a new drug versus others at the time of marketing authorization using mixed treatment comparisons? A detailed illustration with escitalopram.

PubMed

Llorca, Pierre-Michel; Lançon, Christophe; Brignone, Mélanie; Painchault, Caroline; Rive, Benoit; Toumi, Mondher; François, Clément

2015-01-01

To assess the variation of relative efficacy and tolerability of an antidepressant versus others based on both pre-marketing (registration studies) and post-marketing studies versus pre-marketing studies only in patients with major depressive disorder. The relative efficacy and tolerability of antidepressants was assessed by mixed treatment comparisons (MTCs) using data acquired over two time periods: before registration of the reference drug escitalopram (1989-2002) and up to 5 years later (1989-2007). Ranking probability outputs were presented for efficacy, using change from baseline to 8 weeks on Montgomery-Åsberg Depression Rating Scale total score, and tolerability, using withdrawals due to adverse events. The relative efficacy and tolerability of some selected antidepressants, including escitalopram, varied considerably over the two time periods. The improved relative efficacy and tolerability of escitalopram over time, compared with citalopram, was demonstrated by greater separation of ranking probability curves for efficacy and tolerability. In 2002, escitalopram ranked low with 13.9% and 5.1% probability of being in the top four antidepressants' relative efficacy and tolerability, respectively. In 2007, ranking probabilities for relative efficacy and tolerability of escitalopram increased to 52.5% and 82.1%, respectively. Time of marketing authorization may not be the most appropriate time to evaluate the relative efficacy and tolerability of a new antidepressant based on MTC approach due to the asymmetry of information between new and older compounds. However, the first evaluation of relative effect of a new drug for health technology assessment recommendations is commonly done at this time. Re-evaluation of a drug several years after its launch is likely to provide a more accurate indication of its relative efficacy and tolerability.

Network meta-analysis of migraine disorder treatment by NSAIDs and triptans.

PubMed

Xu, Haiyang; Han, Wei; Wang, Jinghua; Li, Mingxian

2016-12-01

Migraine is a neurological disorder resulting in large socioeconomic burden. This network meta-analysis (NMA) is designed to compare the relative efficacy and tolerability of non-steroidal anti-inflammatory agents (NSAIDs) and triptans. We conducted systematic searches in database PubMed and Embase. Treatment effectiveness was compared by synthesizing direct and indirect evidences using NMA. The surface under curve ranking area (SUCRA) was created to rank those interventions. Eletriptan and rizatriptan are superior to sumatriptan, zolmitriptan, almotriptan, ibuprofen and aspirin with respect to pain-relief. When analyzing 2 h-nausea-absence, rizatriptan has a better efficacy than sumatriptan, while other treatments indicate no distinctive difference compared with placebo. Furthermore, sumatriptan demonstrates a higher incidence of all-adverse-event compared with diclofenac-potassium, ibuprofen and almotriptan. This study suggests that eletriptan may be the most suitable therapy for migraine from a comprehensive point of view. In the meantime ibuprofen may also be a good choice for its excellent tolerability. Multi-component medication also attracts attention and may be a promising avenue for the next generation of migraine treatment.

The effects of radiation on antitumor efficacy of an oncolytic adenovirus vector in the Syrian hamster model

PubMed Central

Young, Brittany A.; Spencer, Jacqueline F.; Ying, Baoling; Toth, Karoly; Wold, William S. M.

2013-01-01

We report that radiation enhances the antitumor efficacy of the oncolytic adenovirus vector VRX-007 in Syrian hamster tumors. We used tumor-specific irradiation of subcutaneous tumors and compared treatment options of radiation alone or combined with VRX-007 and cyclophosphamide (CP). Radiation therapy further augmented the VRX-007-mediated inhibition of tumor growth, in both CP-treated and non-CP-treated hamsters, even though radiation did not lead to increased viral replication in tumors when compared to those treated with VRX-007 alone. Moreover, tumor growth inhibition was similar in tumors irradiated either one week before or after injection with VRX-007, which suggests that radiation exerts its antitumor effect independently from vector therapy. Thus, our results demonstrate that these two therapies do not have to be provided simultaneously to enhance their combined effectiveness against subcutaneous hamster tumors. PMID:23928730

The effects of radiation on antitumor efficacy of an oncolytic adenovirus vector in the Syrian hamster model.

PubMed

Young, B A; Spencer, J F; Ying, B; Toth, K; Wold, W S M

2013-09-01

We report that radiation enhances the antitumor efficacy of the oncolytic adenovirus vector VRX-007 in Syrian hamster tumors. We used tumor-specific irradiation of subcutaneous tumors and compared treatment options of radiation alone or combined with VRX-007 and cyclophosphamide (CP). Radiation therapy further augmented the VRX-007-mediated inhibition of tumor growth, in both CP-treated and non-CP-treated hamsters, even though radiation did not lead to increased viral replication in tumors when compared with those treated with VRX-007 alone. Moreover, tumor growth inhibition was similar in tumors irradiated either 1 week before or after injection with VRX-007, which suggests that radiation exerts its antitumor effect independently from vector therapy. Thus, our results demonstrate that these two therapies do not have to be provided simultaneously to enhance their combined effectiveness against subcutaneous hamster tumors.

A randomized, double-blind study comparing the efficacy of selenium sulfide shampoo 1% and ciclopirox shampoo 1% as adjunctive treatments for tinea capitis in children.

PubMed

Chen, Catherine; Koch, Laine H; Dice, James E; Dempsey, Kimberly K; Moskowitz, Alan B; Barnes-Eley, Myra L; Hubbard, Thomas W; Williams, Judith V

2010-01-01

Our objective was to compare the efficacy of selenium sulfide shampoo 1% and ciclopirox shampoo 1% as adjunctive treatments for tinea capitis in children. Forty children aged 1-11 years with clinically diagnosed tinea capitis were randomized to receive selenium sulfide shampoo 1% or ciclopirox shampoo 1% twice a week as adjuncts to an 8-week course of ultramicronized griseofulvin dosed at 10-12 mg/kg/day. At weeks 2, 4, and 8, subjects returned to the clinic for evaluation and scalp cultures. Subjects then returned for follow-up visits 4 weeks after completing treatment. Overall, by 8 weeks, 30 of 33 (90.9%) treated children demonstrated mycological cure. Selenium sulfide shampoo 1% and ciclopirox shampoo 1% were equally effective as adjunctive treatments for tinea capitis in children in our study. © 2010 Wiley Periodicals, Inc.

Understanding exercise self-efficacy and barriers to leisure-time physical activity among postnatal women.

PubMed

Cramp, Anita G; Bray, Steven R

2011-07-01

Studies have demonstrated that postnatal women are at high risk for physical inactivity and generally show lower levels of leisure-time physical activity (LTPA) compared to prepregnancy. The overall purpose of the current study was to investigate social cognitive correlates of LTPA among postnatal women during a 6-month period following childbirth. A total of 230 women (mean age = 30.9) provided descriptive data regarding barriers to LTPA and completed measures of LTPA and self-efficacy (exercise and barrier) for at least one of the study data collection periods. A total of 1,520 barriers were content analyzed. Both exercise and barrier self-efficacy were positively associated with subsequent LTPA. Exercise self-efficacy at postnatal week 12 predicted LTPA from postnatal weeks 12 to 18 (β = .40, R (2) = .18) and exercise self-efficacy at postnatal week 24 predicted LTPA during weeks 24-30 (β = .49, R (2) = .30). Barrier self-efficacy at week 18 predicted LTPA from weeks 18 to 24 (β = .33, R (2) = .13). The results of the study identify a number of barriers to LTPA at multiple time points closely following childbirth which may hinder initiation, resumption or maintenance of LTPA. The results also suggest that higher levels of exercise and barrier self-efficacy are prospectively associated with higher levels of LTPA in the early postnatal period. Future interventions should be designed to investigate causal effects of developing participants' exercise and barrier self-efficacy for promoting and maintaining LTPA during the postnatal period.

Improved therapy for neuroblastoma using a combination approach: superior efficacy with vismodegib and topotecan

PubMed Central

Chaturvedi, Nagendra K.; McGuire, Timothy R.; Coulter, Don W.; Shukla, Ashima; McIntyre, Erin M.; Sharp, John Graham; Joshi, Shantaram S.

2016-01-01

Aberrant activation/expression of pathways/molecules including NF-kB, mTOR, hedgehog and polo-like-kinase-1 (PLK1) are correlated with poor-prognosis neuroblastoma. Therefore, to identify a most efficacious treatment for neuroblastoma, we investigated the efficacy of NF-kB/mTOR dual-inhibitor 13-197, hedgehog inhibitor vismodegib and PLK1 inhibitor BI2536 alone or combined with topotecan against high-risk neuroblastoma. The in vitro efficacy of the inhibitors alone or combined with topotecan on cell growth/apoptosis and molecular mechanism(s) were investigated. Results showed that as single agents 13-197, BI2536 and vismodegib significantly decreased neuroblastoma cell growth and induced apoptosis by targeting associated pathways/molecules. In combination with topotecan, 13-197 did not show significant additive/synergistic effects against neuroblastoma. However, BI2536 or vismodegib further significantly decreased neuroblastoma cell growth/survival. These results clearly showed that vismodegib combination with topotecan was synergistic and more efficacious compared with BI2536 in combination. Together, in vitro data demonstrated that vismodegib was most efficacious in potentiating topotecan-induced antineuroblastoma effects. Therefore, we tested the combined efficacy of vismodegib and topotecan against neuroblastoma in vivo using NSG mice. This resulted in significantly (p<0.001) reduced tumor growth and increased survival of mice. Together, the combination of vismodegib and topotecan showed a significant enhanced antineuroblastoma efficacy by targeting associated pathways/molecules which warrants further preclinical evaluation for translation to the clinic. PMID:26934655

Pharmacological treatments for alleviating agitation in dementia: a systematic review and network meta-analysis.

PubMed

Kongpakwattana, Khachen; Sawangjit, Ratree; Tawankanjanachot, Itthipol; Bell, J Simon; Hilmer, Sarah N; Chaiyakunapruk, Nathorn

2018-04-10

To determine the most efficacious and acceptable treatments of agitation in dementia. MEDLINE, EMBASE, PsycINFO, CENTRAL and clinicaltrials.gov were searched up to 7 February 2017. Two independent reviewers selected randomized controlled trials (RCTs) of treatments to alleviate agitation in people with all-types dementia. Data were extracted using standardized forms and study quality was assessed using the revised Cochrane Risk of Bias Tool for RCTs. Data were pooled using meta-analysis. The primary outcome, efficacy, was 8-week response rates defined as a 50% reduction in baseline agitation score. The secondary outcome was treatment acceptability defined as treatment continuation for 8 weeks. Thirty-six RCTs comprising 5585 participants (30.9% male; mean ± standard deviation age, 81.8 ± 4.9 years) were included. Dextromethorphan/quinidine [odds ratio (OR) 3.04; 95% confidence interval (CI), 1.63-5.66], risperidone (OR 1.96; 95% CI, 1.49-2.59) and selective serotonin reuptake inhibitors as a class (OR 1.61; 95% CI, 1.02-2.53) were found to be significantly more efficacious than placebo. Haloperidol appeared less efficacious than nearly all comparators. Most treatments had noninferior treatment continuation compared to placebo, except oxcarbazepine, which was inferior. Findings were supported by subgroup and sensitivity analyses. Risperidone, serotonin reuptake inhibitors as a class and dextromethorphan/quinidine demonstrated evidence of efficacy for agitation in dementia, although findings for dextromethorphan/quinidine were based on a single RCT. Our findings do not support prescribing haloperidol due to lack of efficacy, or oxcarbazepine due to lack of acceptability. The decision to prescribe should be based on comprehensive consideration of the benefits and risks, including those not evaluated in this meta-analysis. © 2018 The British Pharmacological Society.

Efficacy of dosing and re-dosing of two oral fixed combinations of indomethacin, prochlorperazine and caffeine compared with oral sumatriptan in the acute treatment of multiple migraine attacks: a double-blind, double-dummy, randomised, parallel group, multicentre study

PubMed Central

Sandrini, G; Cerbo, R; Del Bene, E; Ferrari, A; Genco, S; Grazioli, I; Martelletti, P; Nappi, G; Pinessi, L; Sarchielli, P; Tamburro, P; Uslenghi, C; Zanchin, G

2007-01-01

Aims and methods: In this double-blind, double-dummy, randomised, parallel group, multicentre study, the efficacy of dosing and re-dosing of a fixed combination of indomethacin, prochlorperazine and caffeine (Indoprocaf) was compared with encapsulated sumatriptan in the acute treatment of two migraine attacks. Additionally, in the group taking Indoprocaf, two different oral formulations were tested: effervescent tablets and encapsulated coated tablets. Results: Of 297 patients randomised (150 assigned to Indoprocaf and 147 to sumatriptan), 281 were included in the intention-to-treat efficacy analysis. The initial dosing of Indoprocaf and sumatriptan was similarly effective with pain-free rates higher than 30% (95% CI of odds-ratio: 0.57–1.28) and headache relief rates of about 60% (95% CI of odds-ratio: 0.82–1.84) with both the drugs. The efficacy of re-dosing of Indoprocaf as rescue medication was more effective than that of sumatriptan with pain-free values of 47% vs. 27% in the total attacks with a statistically significant difference in the first migraine attack in favour of Indoprocaf. The efficacy of re-dosing to treat a recurrence/relapse was very high without differences between the drugs (pain-free: 60% with Indoprocaf and 50% with sumatriptan in the total attacks). Indoprocaf and sumatriptan were well-tolerated. Conclusion: The study demonstrated that the efficacy of the initial dosing of Indoprocaf was not higher than that of sumatriptan, but that the strategy to use the lowest effective dose as soon as the headache occurred, followed by a second dose if the headache has not relieved or to treat a relapse, was very effective, especially with Indoprocaf. PMID:17627707

High Versus Low Theoretical Fidelity Pedometer Intervention Using Social-Cognitive Theory on Steps and Self-Efficacy.

PubMed

Raedeke, Thomas D; Dlugonski, Deirdre

2017-12-01

This study was designed to compare a low versus high theoretical fidelity pedometer intervention applying social-cognitive theory on step counts and self-efficacy. Fifty-six public university employees participated in a 10-week randomized controlled trial with 2 conditions that varied in theoretical fidelity. Participants in the high theoretical fidelity condition wore a pedometer and participated in a weekly group walk followed by a meeting to discuss cognitive-behavioral strategies targeting self-efficacy. Participants in the low theoretical fidelity condition met for a group walk and also used a pedometer as a motivational tool and to monitor steps. Step counts were assessed throughout the 10-week intervention and after a no-treatment follow-up (20 weeks and 30 weeks). Self-efficacy was measured preintervention and postintervention. Participants in the high theoretical fidelity condition increased daily steps by 2,283 from preintervention to postintervention, whereas participants in the low fidelity condition demonstrated minimal change during the same time period (p = .002). Individuals attending at least 80% of the sessions in the high theoretical fidelity condition showed an increase of 3,217 daily steps (d = 1.03), whereas low attenders increased by 925 (d = 0.40). Attendance had minimal impact in the low theoretical fidelity condition. Follow-up data revealed that step counts were at least somewhat maintained. For self-efficacy, participants in the high, compared with those in the low, theoretical fidelity condition showed greater improvements. Findings highlight the importance of basing activity promotion efforts on theory. The high theoretical fidelity intervention that included cognitive-behavioral strategies targeting self-efficacy was more effective than the low theoretical fidelity intervention, especially for those with high attendance.

Microbiologic evaluation of microfiber mops for surface disinfection.

PubMed

Rutala, William A; Gergen, Maria F; Weber, David J

2007-11-01

Recently, health care facilities have started to use a microfiber mopping technique rather than a conventional, cotton string mop to clean floors. The effectiveness of microfiber mops to reduce microbial levels on floors was investigated. We compared the efficacy of microfiber mops with that of conventional, cotton string mops in 3 test conditions (cotton mop and standard wringer bucket, microfiber mop and standard wringer bucket, microfiber system). Twenty-four rooms were evaluated for each test condition. RODAC plates containing D/E Neutralizing Agar were used to assess "precleaning" and "postcleaning" microbial levels. The microfiber system demonstrated superior microbial removal compared with cotton string mops when used with a detergent cleaner (95% vs 68%, respectively). The use of a disinfectant did not improve the microbial elimination demonstrated by the microfiber system (95% vs 95%, respectively). However, use of disinfectant did significantly improve microbial removal when a cotton string mop was used (95% vs 68%, respectively). The microfiber system demonstrated superior microbial removal compared with cotton string mops when used with a detergent cleaner. The use of a disinfectant did not improve the microbial elimination demonstrated by the microfiber system.

Single-session motivational interviewing for drug detoxification inpatients: effects on self-efficacy, stages of change and substance use.

PubMed

Berman, Anne H; Forsberg, Lars; Durbeej, Natalie; Källmén, Håkan; Hermansson, Ulric

2010-02-01

Thirty-five inpatients at a Stockholm hospital drug user detoxification unit received single-session Motivational Interviewing (MI) between 2006 and 2008. At baseline and after 3 months, they were compared to a semi-randomized control group of 52 patients with treatment as usual. In the MI group, self-efficacy increased regarding abstention in connection with positive feelings, appreciation of positive drug effects increased, and participants tended to transition toward preparation/action stages of change. Despite implementation challenges, the study demonstrates the feasibility and effectiveness of single-session MI delivery in the inpatient drug detoxification setting and suggests paths for future research on delivery of single-session MI.

Comparative efficacy and safety of oxcarbazepine versus divalproex sodium in the treatment of acute mania: a pilot study.

PubMed

Kakkar, Ashish Kumar; Rehan, H S; Unni, K E S; Gupta, Neeraj Kumar; Chopra, Deepti; Kataria, Dinesh

2009-04-01

This study compared the efficacy and safety of oxcarbazepine and divalproex sodium in acute mania patients. In this 12 week, randomized, double-blind pilot study, 60 patients diagnosed with acute mania (DSM-IV) and a baseline Young Mania Rating Scale (YMRS) score of 20 or more received flexibly dosed oxcarbazepine (1,000-2,400 mg/day) or divalproex (750-2,000 mg/day). The mean decrease in the YMRS score from baseline was used as the main outcome measure of response to treatment. A priori protocol-defined threshold scores were or=15 for relapse. Number of patients showing adequate response and the time taken to achieve improvement was compared. Adverse events were systematically recorded throughout the study. Over 12 weeks, mean improvement in YMRS scores was comparable for both the groups including the mean total scores as well as percentage fall from baseline. There were no significant differences between treatments in the rates of symptomatic mania remission (90% in divalproex and 80% in oxcarbazepine group) and subsequent relapse. Median time taken to symptomatic remission was 56 days in divalproex group while it was 70 days in the oxcarbazepine group (p=0.123). A significantly greater number of patients in divalproex group experienced one or more adverse drug events as compared to patients in the oxcarbazepine group (66.7% versus 30%, p<0.01). Oxcarbazepine demonstrated comparable efficacy to divalproex sodium in the management of acute mania. Also the overall adverse event profile was found to be superior for oxcarbazepine.

Greenhouse and field-based studies on the distribution of dimethoate in cotton and its effect on Tetranychus urticae by drip irrigation.

PubMed

He, Jiangtao; Zhou, Lijuan; Yao, Qiang; Liu, Bo; Xu, Hanhong; Huang, Jiguang

2018-01-01

The two-spotted spider mite, Tetranychus urticae Koch is an important pest of cotton. We investigated the efficacy of dimethoate in controlling T. urticae by drip irrigation. Greenhouse and field experiments were carried out to determine the efficacy of dimethoate to T. urticae and the absorption and distribution of dimethoate in cotton. Greenhouse results showed that cotton leaves received higher amounts of dimethoate compared with cotton roots and stems, with higher amounts in young leaves compared with old leaves and cotyledon having the lowest amounts among leaves. Field results showed the efficacy of dimethoate to T. urticae by drip irrigation varied by volume of dripping water, soil pH and dimethoate dosage. Dimethoate applied at 3.00 kg ha -1 with 200 m 3  ha -1 water at weak acidic soil pH (5.70-6.70) through drip irrigation can obtain satisfactory control efficacy (81.49%, 7 days) to T. urticae, without negatively impacting on its natural enemy Neoseiulus cucumeris. The residue of dimethoate in all cotton seed samples were not detectable. These results demonstrate the effectiveness of applying dimethoate by drip irrigation for control of T. urticae on cotton. This knowledge could aid in the applicability of dimethoate by drip irrigation for field management of T. urticae populations. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Efficacy of prokinetics with a split-dose of polyethylene glycol in bowel preparation for morning colonoscopy: a randomized controlled trial.

PubMed

Kim, Hyoung Jun; Kim, Tae Oh; Shin, Bong Chul; Woo, Jae Gon; Seo, Eun Hee; Joo, Hee Rin; Heo, Nae-Yun; Park, Jongha; Park, Seung Ha; Yang, Sung Yeon; Moon, Young Soo; Shin, Jin-Yong; Lee, Nae Young

2012-01-01

Currently, a split-dose of polyethylene glycol (PEG) is the mainstay of bowel preparation due to its tolerability, bowel-cleansing action, and safety. However, bowel preparation with PEG is suboptimal because residual fluid reduces the polyp detection rate and requires a more thorough colon inspection. The aim of our study was to demonstrate the efficacy of a sufficient dose of prokinetics on bowel cleansing together with split-dose PEG. A prospective endoscopist-blinded study was conducted. Patients were randomly allocated to two groups: prokinetic with split-dose PEG or split-dose PEG alone. A prokinetic [100 mg itopride (Itomed)], was administered twice simultaneously with each split-dose of PEG. Bowel-cleansing efficacy was measured by endoscopists using the Ottawa scale and the segmental fluidity scale score. Each participant completed a bowel preparation survey. Mean scores from the Ottawa scale, segmental fluid scale, and rate of poor preparation were compared between both groups. Patients in the prokinetics with split-dose PEG group showed significantly lower total Ottawa and segmental fluid scores compared with patients in the split-dose of PEG alone group. A sufficient dose of prokinetics with a split-dose of PEG showed efficacy in bowel cleansing for morning colonoscopy, largely due to the reduction in colonic fluid. Copyright © 2012 S. Karger AG, Basel.

High drug payload curcumin nanosuspensions stabilized by mPEG-DSPE and SPC: in vitro and in vivo evaluation.

PubMed

Hong, Jingyi; Liu, Yingying; Xiao, Yao; Yang, Xiaofeng; Su, Wenjing; Zhang, Mingzhu; Liao, Yonghong; Kuang, Haixue; Wang, Xiangtao

2017-11-01

Curcumin (CUR) is a promising drug candidate based on its broad bioactivities and good antitumor effect, but the application of CUR is potentially restricted because of its poor solubility and bioavailability. This study aims at developing a simple and effective drug delivery system for CUR to enhance its solubility and bioavailability thus to improve its antitumor efficacy. Curcumin nanosuspensions (CUR-NSps) were prepared by precipitation-ultrasonication method using mPEG2000-DSPE and soybean lecithin as a combined stabilizer. CUR-NSps with a high drug payload of 67.07% were successfully prepared. The resultant CUR-NSps had a mean particle size of 186.33 ± 2.73 nm with a zeta potential of -19.00 ± 1.31 mV. In vitro cytotoxicity assay showed that CUR-NSps exhibited enhanced cytotoxicity compared to CUR solution. The pharmacokinetics results demonstrated that CUR-NSps exhibited a significantly greater AUC 0-24 and prolonged MRT compared to CUR injections after intravenous administration. In the biodistribution study, CUR-NSps demonstrated enhanced biodistribution compared with CUR injections in liver, spleen, kidney, brain, and tumor. The CUR-NSps also showed improved antitumor therapeutic efficacy over the injections (70.34% versus 40.03%, p < 0.01). These results suggest that CUR-NSps might represent a promising drug formulation for intravenous administration of CUR for the treatment of cancer.

Attenuation and protection efficacy of ORF C gene-deleted recombinant of infectious laryngotracheitis virus.

PubMed

Garcia, Maricarmen; Spatz, S J; Cheng, Y; Riblet, S M; Volkening, J D; Schneiders, G H

2016-09-01

Infectious laryngotracheitis (ILT) is a highly contagious respiratory disease of chickens caused by infectious laryngotracheitis virus (ILTV). The disease is controlled by the use of live-attenuated vaccines. Previously we reported the complete nucleotide sequence of the ILTV vaccine strain (TCO) and identified a nonsense mutation in the gene encoding the ORF C protein. This suggested that the ORF C protein might be associated with viral virulence. To investigate this, an ILTV recombinant with a deletion in the gene encoding ORF C was constructed using the genome of the virulent United States Department of Agriculture (USDA) challenge strain (USDAch). Compared to the parental virus, the ΔORF C recombinant replicated in chicken kidney (CK) cells with similar kinetics and generated similar titres. This demonstrated that the ORF C deletion had no deleterious effects on replication efficacy in vitro. In chickens, the recombinant induced only minor microscopic tracheal lesions when inoculated via the intra-tracheal/ocular route, while the parental strain induced moderate to severe microscopic tracheal lesions, even though virus load in the tracheas were comparable. Groups of chickens vaccinated via eye-drop with the ∆ORFC-ILTV were protected to levels comparable to those elicited by TCO vaccination. To our knowledge, this is the first report that demonstrates the suitability of ∆ORFC as a live-attenuated vaccine to prevent the losses caused by ILTV.

Using a Human Challenge Model of Infection to Measure Vaccine Efficacy: A Randomised, Controlled Trial Comparing the Typhoid Vaccines M01ZH09 with Placebo and Ty21a

PubMed Central

Jones, Claire; Blohmke, Christoph J.; Waddington, Claire S.; Zhou, Liqing; Peters, Anna; Haworth, Kathryn; Sie, Rebecca; Green, Christopher A.; Jeppesen, Catherine A.; Moore, Maria; Thompson, Ben A. V.; John, Tessa; Kingsley, Robert A.; Yu, Ly-Mee; Voysey, Merryn; Hindle, Zoe; Lockhart, Stephen; Sztein, Marcelo B.; Dougan, Gordon; Angus, Brian; Levine, Myron M.; Pollard, Andrew J.

2016-01-01

Background Typhoid persists as a major cause of global morbidity. While several licensed vaccines to prevent typhoid are available, they are of only moderate efficacy and unsuitable for use in children less than two years of age. Development of new efficacious vaccines is complicated by the human host-restriction of Salmonella enterica serovar Typhi (S. Typhi) and lack of clear correlates of protection. In this study, we aimed to evaluate the protective efficacy of a single dose of the oral vaccine candidate, M01ZH09, in susceptible volunteers by direct typhoid challenge. Methods and Findings We performed a randomised, double-blind, placebo-controlled trial in healthy adult participants at a single centre in Oxford (UK). Participants were allocated to receive one dose of double-blinded M01ZH09 or placebo or 3-doses of open-label Ty21a. Twenty-eight days after vaccination, participants were challenged with 104CFU S. Typhi Quailes strain. The efficacy of M01ZH09 compared with placebo (primary outcome) was assessed as the percentage of participants reaching pre-defined endpoints constituting typhoid diagnosis (fever and/or bacteraemia) during the 14 days after challenge. Ninety-nine participants were randomised to receive M01ZH09 (n = 33), placebo (n = 33) or 3-doses of Ty21a (n = 33). After challenge, typhoid was diagnosed in 18/31 (58.1% [95% CI 39.1 to 75.5]) M01ZH09, 20/30 (66.7% [47.2 to 87.2]) placebo, and 13/30 (43.3% [25.5 to 62.6]) Ty21a vaccine recipients. Vaccine efficacy (VE) for one dose of M01ZH09 was 13% [95% CI -29 to 41] and 35% [-5 to 60] for 3-doses of Ty21a. Retrospective multivariable analyses demonstrated that pre-existing anti-Vi antibody significantly reduced susceptibility to infection after challenge; a 1 log increase in anti-Vi IgG resulting in a 71% decrease in the hazard ratio of typhoid diagnosis ([95% CI 30 to 88%], p = 0.006) during the 14 day challenge period. Limitations to the study included the requirement to limit the challenge period prior to treatment to 2 weeks, the intensity of the study procedures and the high challenge dose used resulting in a stringent model. Conclusions Despite successfully demonstrating the use of a human challenge study to directly evaluate vaccine efficacy, a single-dose M01ZH09 failed to demonstrate significant protection after challenge with virulent Salmonella Typhi in this model. Anti-Vi antibody detected prior to vaccination played a major role in outcome after challenge. Trial registration ClinicalTrials.gov (NCT01405521) and EudraCT (number 2011-000381-35). PMID:27533046

Desvenlafaxine Versus Placebo in a Fluoxetine-Referenced Study of Children and Adolescents with Major Depressive Disorder

PubMed Central

Murphy, William; Abbas, Richat; Chiles, Deborah; England, Richard D.; Ramaker, Sara; Wajsbrot, Dalia B.

2018-01-01

Abstract Objectives: To evaluate the short-term efficacy and safety of desvenlafaxine (25–50 mg/d) compared with placebo in children and adolescents with major depressive disorder (MDD). Methods: Outpatient children (7–11 years) and adolescents (12–17 years) who met DSM-IV-TR criteria for MDD and had screening and baseline Children's Depression Rating Scale–Revised (CDRS-R) total scores >40 were randomly assigned to 8-week treatment with placebo, desvenlafaxine (25, 35, or 50 mg/d based on baseline weight), or fluoxetine (20 mg/d). The primary efficacy endpoint was change from baseline in CDRS-R total score at week 8, analyzed using a mixed-effects model for repeated measures. Secondary efficacy endpoints included week 8 Clinical Global Impressions–Severity, Clinical Global Impressions–Improvement (CGI-I), and response (CGI-I ≤ 2). Safety assessments included adverse events, physical and vital sign measurements, laboratory evaluations, electrocardiogram, and the Columbia-Suicide Severity Rating Scale. Results: The safety population included 339 patients (children, n = 130; adolescents, n = 209). The primary endpoint, change from baseline in CDRS-R total score at week 8, did not statistically separate from placebo, for either desvenlafaxine (adjusted mean [standard error] change, −22.6 [1.17]) or fluoxetine (−24.8 [1.17]; placebo, −23.1 [1.18]). Week 8 CGI-I response rates were significantly greater for fluoxetine (78.2%; p = 0.017) than for placebo (62.6%); desvenlafaxine (68.7%) did not differ from placebo. Other secondary outcomes were consistent with those obtained with CDRS-R. Rates of treatment-emergent adverse events were comparable among treatment groups (desvenlafaxine, 60.0%; placebo, 70.5%; and fluoxetine, 64.3%). Conclusion: Desvenlafaxine did not demonstrate efficacy for treating MDD in children and adolescents in this trial. Because neither desvenlafaxine nor the reference medication, fluoxetine, demonstrated a statistically significant difference from placebo on the primary endpoint, this was considered a failed trial and no efficacy conclusions can be drawn. Desvenlafaxine 25–50 mg/d was generally safe and well tolerated in children and adolescents in this study. PMID:29189044

Efficacy and Safety of Doxepin 1 mg, 3 mg, and 6 mg in Adults with Primary Insomnia

PubMed Central

Roth, Thomas; Rogowski, Roberta; Hull, Steven; Schwartz, Howard; Koshorek, Gail; Corser, Bruce; Seiden, David; Lankford, Alan

2007-01-01

Study Objectives: To evaluate the efficacy and safety of doxepin 1, 3, and 6 mg in insomnia patients. Design: Adults (18-64 y) with chronic primary insomnia (DSM-IV) were randomly assigned to one of four sequences of 1 mg, 3 mg, and 6 mg of doxepin, and placebo in a crossover study. Treatment periods consisted of 2 polysomnographic assessment nights with a 5-day or 12-day drug-free interval between periods. Efficacy was assessed using polysomnography (PSG) and patient-reported measures. Safety analyses included measures of residual sedation and adverse events. Measurements and Results: Sixty-seven patients were randomized. Wake time during sleep, the a priori defined primary endpoint, was statistically significantly improved at the doxepin 3 mg and 6 mg doses versus placebo. All three doses had statistically significant improvements versus placebo for PSG-defined wake after sleep onset, total sleep time, and overall sleep efficiency (SE). SE in the final third-of-the-night also demonstrated statistically significant improvement at all doses. The doxepin 6 mg dose significantly reduced subjective latency to sleep onset. All three doxepin doses had a safety profile comparable to placebo. There were no statistically significant differences in next-day residual sedation, and sleep architecture was generally clinically preserved. Conclusions: In adults with primary insomnia, doxepin 1 mg, 3 mg, and 6 mg was well-tolerated and produced improvement in objective and subjective sleep maintenance and duration endpoints that persisted into the final hour of the night. The side-effect profile was comparable to placebo, with no reported anticholinergic effects, no memory impairment, and no significant hangover/next-day residual effects. These data demonstrate that doxepin 1 mg, 3 mg, and 6 mg is efficacious in improving the sleep of patients with chronic primary insomnia. Citation: Roth T; Rogowski R; Hull S; Schwartz H; Koshorek G; Corser B; Seiden D. Efficacy and safety of doxepin 1 mg, 3 mg, and 6 mg in adults with primary insomnia. SLEEP 2007;30(11):1555-1561. PMID:18041488

Efficacy, pharmacokinetics, and biodistribution of thermosensitive chitosan/β-glycerophosphate hydrogel loaded with docetaxel.

PubMed

Li, Cuiyun; Ren, Shuangxia; Dai, Yu; Tian, Fengjie; Wang, Xin; Zhou, Sufeng; Deng, Shuhua; Liu, Qi; Zhao, Jie; Chen, Xijing

2014-04-01

Docetaxel (DTX) is a widely used anticancer drug for various solid tumors. However, its poor solubility in water and lack of specification are two limitations for clinical use. The aim of the study was to develop a thermosensitive chitosan/β-glycerophosphate (C/GP) hydrogel loaded with DTX for intratumoral delivery. The in vitro release profiles, in vivo antitumor efficacy, pharmacokinetics, and biodistribution of DTX-loaded C/GP hydrogel (DTX-C/GP) were evaluated. The results of in vitro release study demonstrated that DTX-C/GP had the property of controlled delivery for a reasonable time span of 3 weeks and the release period was substantially affected by initial DTX strength. The antitumor efficacy of DTX-C/GP was observed at 20 mg/kg in H22 tumor-bearing mice. It was found that the tumor volume was definitely minimized by intratumoral injection of DTX-C/GP. Compared with saline group, the tumor inhibition rate of blank gel, intravenous DTX solution, intratumoral DTX solution, and DTX-C/GP was 2.3%, 29.8%, 41.9%, and 58.1%, respectively. Further, the in vivo pharmacokinetic characteristics of DTX-C/GP correlated well with the in vitro release. DTX-C/GP significantly prolonged the DTX retention and maintained a high DTX concentration in tumor. The amount of DTX distributed to the normal tissues was minimized so that the toxicity was effectively reduced. In conclusion, DTX-C/GP demonstrated controlled release and significant efficacy and exhibited potential for further clinical development.

LASIK versus photorefractive keratectomy for high myopic (> 3 diopter) astigmatism.

PubMed

Katz, Toam; Wagenfeld, Lars; Galambos, Peter; Darrelmann, Benedikt Große; Richard, Gisbert; Linke, Stephan Johannes

2013-12-01

To compare the efficacy, safety, predictability, and vector analysis indices of LASIK and photorefractive keratectomy (PRK) for correction of high cylinder of greater than 3 diopters (D) in myopic eyes. The efficacy, safety, and predictability of LASIK or PRK performed in 114 consecutive randomly selected myopic eyes with an astigmatism of greater than 3 D were retrospectively analyzed at the 2- to 6-month follow-up visits. Vector analysis of the cylindrical correction was compared between the treatment groups. A total of 57 eyes receiving PRK and 57 eyes receiving LASIK of 114 refractive surgery candidates were enrolled in the study. No statistically significant difference in efficacy [efficacy index = 0.76 (±0.32) for PRK vs 0.74 (±0.19) for LASIK (P = .82)], safety [safety index = 1.10 (±0.26) for PRK vs 1.01 (±0.17) for LASIK (P = .121)], or predictability [achieved astigmatism < 1 D in 39% of PRK- and 54% of LASIK-treated eyes, and < 2 D in 88% of PRK- and 89% of LASIK-treated eyes (P = .218)] was demonstrated. Using Alpins vector analysis, the surgically induced astigmatism and difference vector were not significantly different between the surgery methods, whereas the correction index showed a slight and significant advantage of LASIK over PRK (1.25 for PRK and 1.06 for LASIK, P < .001). LASIK and PRK are comparably safe, effective, and predictable procedures for excimer laser correction of high astigmatism of greater than 3 D in myopic eyes. Predictability of the correction of the cylindrical component is lower than that of the spherical equivalent. Copyright 2013, SLACK Incorporated.

A phase III, randomized, non-inferiority study comparing the efficacy and safety of biosimilar filgrastim versus originator filgrastim for chemotherapy-induced neutropenia in breast cancer patients

PubMed Central

Hegg, Roberto; Mattar, André; de Matos, João Nunes; Pedrini, José Luiz; Aleixo, Sabina Bandeira; Rocha, Roberto Odebrecht; Cramer, Renato Peixoto; van-Eyll-Rocha, Sylvie

2016-01-01

OBJECTIVES: To compare the efficacy and safety of two filgrastim formulations for controlling chemotherapy-induced neutropenia and to evaluate the non-inferiority of the test drug relative to the originator. METHODS: This phase III non-inferiority study had a randomized, multicenter, and open-label design. The patients were randomized at a ratio of 1:1 with a follow-up period of 6 weeks for each patient. In both study arms, filgrastim was administered subcutaneously at a daily dose of 5 mg/kg body weight. The primary endpoint was the rate of grade 4 neutropenia in the first treatment cycle. The secondary endpoints were the duration of grade 4 neutropenia, the generation of anti-filgrastim antibodies, and the rates of adverse events, laboratory abnormalities, febrile neutropenia, and neutropenia of any grade. RESULTS: The primary efficacy analysis demonstrated the non-inferiority of the test drug compared with the originator drug; the upper limit of the 90% confidence interval (CI) for the rate of neutropenia between the two groups (12.61%) was lower than the established margin of non-inferiority. The two treatments were similar with respect to the secondary endpoints and safety. CONCLUSION: The efficacy and safety profile of the test drug were similar to those of the originator product based on the rate of grade 4 neutropenia in the first treatment cycle. This study supports Anvisa's approval of the first biosimilar drug manufactured by the Brazilian industry (Fiprima®). PMID:27759847

Blockade of protease-activated receptor-4 (PAR4) provides robust antithrombotic activity with low bleeding.

PubMed

Wong, Pancras C; Seiffert, Dietmar; Bird, J Eileen; Watson, Carol A; Bostwick, Jeffrey S; Giancarli, Mary; Allegretto, Nick; Hua, Ji; Harden, David; Guay, Jocelyne; Callejo, Mario; Miller, Michael M; Lawrence, R Michael; Banville, Jacques; Guy, Julia; Maxwell, Brad D; Priestley, E Scott; Marinier, Anne; Wexler, Ruth R; Bouvier, Michel; Gordon, David A; Schumacher, William A; Yang, Jing

2017-01-04

Antiplatelet agents are proven efficacious treatments for cardiovascular and cerebrovascular diseases. However, the existing drugs are compromised by unwanted and sometimes life-threatening bleeding that limits drug usage or dosage. There is a substantial unmet medical need for an antiplatelet drug with strong efficacy and low bleeding risk. Thrombin is a potent platelet agonist that directly induces platelet activation via the G protein (heterotrimeric guanine nucleotide-binding protein)-coupled protease-activated receptors PAR1 and PAR4. A PAR1 antagonist is approved for clinical use, but its use is limited by a substantial bleeding risk. Conversely, the potential of PAR4 as an antiplatelet target has not been well characterized. Using anti-PAR4 antibodies, we demonstrated a low bleeding risk and an effective antithrombotic profile with PAR4 inhibition in guinea pigs. Subsequently, high-throughput screening and an extensive medicinal chemistry effort resulted in the discovery of BMS-986120, an orally active, selective, and reversible PAR4 antagonist. In a cynomolgus monkey arterial thrombosis model, BMS-986120 demonstrated potent and highly efficacious antithrombotic activity. BMS-986120 also exhibited a low bleeding liability and a markedly wider therapeutic window compared to the standard antiplatelet agent clopidogrel tested in the same nonhuman primate model. These preclinical findings define the biological role of PAR4 in mediating platelet aggregation. In addition, they indicate that targeting PAR4 is an attractive antiplatelet strategy with the potential to treat patients at a high risk of atherothrombosis with superior safety compared with the current standard of care. Copyright © 2017, American Association for the Advancement of Science.

The low FODMAP diet: recent advances in understanding its mechanisms and efficacy in IBS.

PubMed

Staudacher, Heidi M; Whelan, Kevin

2017-08-01

There is an intensifying interest in the interaction between diet and the functional GI symptoms experienced in IBS. Recent studies have used MRI to demonstrate that short-chain fermentable carbohydrates increase small intestinal water volume and colonic gas production that, in those with visceral hypersensitivity, induces functional GI symptoms. Dietary restriction of short-chain fermentable carbohydrates (the low fermentable oligosaccharide, disaccharide, monosaccharide and polyol (FODMAP) diet) is now increasingly used in the clinical setting. Initial research evaluating the efficacy of the low FODMAP diet was limited by retrospective study design and lack of comparator groups, but more recently well-designed clinical trials have been published. There are currently at least 10 randomised controlled trials or randomised comparative trials showing the low FODMAP diet leads to clinical response in 50%-80% of patients with IBS, in particular with improvements in bloating, flatulence, diarrhoea and global symptoms. However, in conjunction with the beneficial clinical impact, recent studies have also demonstrated that the low FODMAP diet leads to profound changes in the microbiota and metabolome, the duration and clinical relevance of which are as yet unknown. This review aims to present recent advances in the understanding of the mechanisms by which the low FODMAP diet impacts on symptoms in IBS, recent evidence for its efficacy, current findings regarding the consequences of the diet on the microbiome and recommendations for areas for future research. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Influence of an apical negative pressure irrigation system on bacterial elimination during endodontic therapy: a prospective randomized clinical study.

PubMed

Pawar, Rekha; Alqaied, Abdullah; Safavi, Kamran; Boyko, Jennifer; Kaufman, Blythe

2012-09-01

Recent in vitro studies that use an apical negative pressure irrigation system, EndoVac, have demonstrated promising results in the production of debris-free root canals, while also preventing potential extrusion of irrigants into the periapical region. We conducted a randomized, controlled, prospective clinical study to determine whether the use of EndoVac irrigation (EndoVac group) was more efficient compared with standard needle irrigation (control group) in obtaining canals from which microbes could not be cultivated. Routine endodontic therapy was performed in 48 patients with necrotic, single-rooted, single-canal teeth. The patients were randomly assigned to either the EndoVac group (n = 25) or control group (n = 23). Irrigation with either method was carried out with 0.5% sodium hypochlorite. After surface disinfection, before instrumentation and on completion of chemomechanical preparation, intracanal microbial samples were obtained and cultured under anaerobic conditions. The frequency of microbial cultivability by using either irrigation system was analyzed. The frequency of obtaining culture-negative root canals was 90.9% and 82.6% for the control group and EndoVac group, respectively. There was no significant difference in the antimicrobial efficacy of either control group or EndoVac group (Fisher exact test, P = .665). Furthermore, no significant association between study variables and the irrigation systems' antimicrobial efficacy was found (P > .05). The results of this prospective in vivo study demonstrate that the antimicrobial efficacy of EndoVac irrigation is comparable to that of standard irrigation. Copyright © 2012 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Motivational Interviewing with Parents of Overweight Children: Study Design and Methods for the NOURISH+MI Study

PubMed Central

Bean, Melanie K.; Jeffers, Amy J.; Tully, Carrie B.; Thornton, Laura M.; Mazzeo, Suzanne E.

2014-01-01

There is an urgent need for innovative approaches to pediatric obesity treatment. There is also a demand for targeted strategies that reduce attrition and improve treatment adherence. Intervening exclusively with parents of overweight children is a novel approach with demonstrated efficacy in reducing child body mass index (BMI) percentile. Motivational interviewing (MI), a brief communication style for exploring and resolving ambivalence about behavior change, might enhance treatment engagement when implemented as part of obesity interventions. The aim of this report is to provide the rationale and methods for a novel study of MI with parents in the treatment of their children’s overweight. We designed and are currently implementing NOURISH+MI, a randomized controlled trial examining the feasibility and efficacy of an adjunct values-based MI intervention, implemented within a culturally-tailored parent intervention for overweight children ages 5-11 years, NOURISH+ (Nourishing Our Understanding of Role modeling to Improve Support and Health). Specifically, we are randomly assigning 60 parents to this adjunctive treatment, and investigating if adding two MI sessions prior to the NOURISH+ group intervention will enhance treatment effects. We will be able to compare NOURISH+MI participants with those from the two NOURISH+ treatment conditions (NOURISH+ and control). We hypothesize that children whose parents participate in NOURISH+MI will demonstrate lower attrition and greater adherence with NOURISH+, ultimately leading to greater treatment effects, compared with children whose parents are randomized to NOURISH+ or a control group. Findings will contribute to the emerging literature examining the efficacy of MI within pediatric obesity interventions. PMID:24530488

Less than 3 doses of the HPV vaccine – Review of efficacy against virological and disease end points

PubMed Central

Basu, Partha; Bhatla, Neerja; Ngoma, Twalib; Sankaranarayanan, Rengaswamy

2016-01-01

ABSTRACT World Health Organization (WHO) recommended 2 doses of the Human Papillomavirus (HPV) vaccine for girls below 15 y on the basis of the immune-bridging studies demonstrating non-inferior immune response of 2 doses in the adolescent girls compared to 3 doses in the young adult women in whom the efficacy against disease is established. The biological nature of the antigens (virus-like particles) constituting the HPV vaccine is responsible for the vigorous antibody response that may make the third dose redundant. The protection offered by 2 doses has been demonstrated in non-randomized clinical trials to be comparable to that offered by 3 doses against incident and persistent infections of vaccine targeted HPV types. However, results emerging from the ecological and nested case-control studies embedded in the population based screening programs of different countries indicate reduced efficacy of 2 doses against virological and disease end points. Some recent studies observed the protective effect of single dose of the vaccine against incident and persistent infections of the vaccine targeted HPV types to be similar to 3 doses in spite of immunological inferiority. The sample size, duration of follow-ups and number of events were limited in these studies. Longer follow ups of the less than 3 doses cohorts in the ongoing studies as well as appropriately designed and ethically justifiable randomized studies are needed to establish the protection offered by the alternative schedules at least beyond 10 y of vaccination. PMID:26933961

Highly selective peroxisome proliferator-activated receptor δ (PPARδ) modulator demonstrates improved safety profile compared to GW501516.

PubMed

Lagu, Bharat; Kluge, Arthur F; Goddeeris, Matthew M; Tozzo, Effie; Fredenburg, Ross A; Chellur, Shekar; Senaiar, Ramesh S; Jaleel, Mahaboobi; Babu, D Ravi Krishna; Tiwari, Nirbhay K; Takahashi, Taisuke; Patane, Michael A

2017-11-04

Compound 1 regulates significantly fewer genes than the PPARδ modulator, GW501516. Both compounds are efficacious in a thermal injury model of muscle regeneration. The restricted gene profile of 1 relative to GW501516 suggests that 1 may be pharmacoequivalent to GW501516 with fewer PPAR-related safety concerns. Copyright © 2017 Elsevier Ltd. All rights reserved.

Metacognitive Strategy Training in Self-Questioning: The Strengths of Multimethod Investigations of the Comparative Effects of Two Instructional Approaches on Self-Efficacy and Achievement.

ERIC Educational Resources Information Center

McInerney, Valentina; McInerney, Dennis M.

This paper presents a model of how multimethod approaches to research can be used to understand and measure individual diversity in learning, cognitions, and affect. The paper demonstrates the value of gathering qualitative data to supplement quantitative findings from quasi-experimental research in relation to achievement outcomes, acquiring a…

Meaning-making intervention during breast or colorectal cancer treatment improves self-esteem, optimism, and self-efficacy.

PubMed

Lee, Virginia; Robin Cohen, S; Edgar, Linda; Laizner, Andrea M; Gagnon, Anita J

2006-06-01

Existential issues often accompany a diagnosis of cancer and remain one aspect of psychosocial oncology care for which there is a need for focused, empirically tested interventions. This study examined the efficacy of a novel psychological intervention specifically designed to address existential issues through the use of meaning-making coping strategies on psychological adjustment to cancer. Eighty-two breast or colorectal cancer patients were randomly chosen to receive routine care (control group) or up to four sessions that explored the meaning of the emotional responses and cognitive appraisals of each individual's cancer experience within the context of past life events and future goals (experimental group). This paper reports the results from 74 patients who completed and returned pre- and post-test measures for self-esteem, optimism, and self-efficacy. After controlling for baseline scores, the experimental group participants demonstrated significantly higher levels of self-esteem, optimism, and self-efficacy compared to the control group. The results are discussed in light of the theoretical and clinical implications of meaning-making coping in the context of stress and illness.

Efficacy of Topical Therapy with Newly Developed Terbinafine and Econazole Formulations in the Treatment of Dermatophytosis in Cats.

PubMed

Ivaskiene, M; Matusevicius, A P; Grigonis, A; Zamokas, G; Babickaite, L

2016-09-01

In the field of veterinary dermatology dermatophytosis is one of the most frequently occurring infectious diseases, therefore its treatment should be effective, convenient, safe and inexpensive. The aim of this study was to evaluate the efficacy of newly developed topical formulations in the treatment of cats with dermatophytosis. Evaluation of clinical efficacy and safety of terbinafine and econazole formulations administered topically twice a day was performed in 40 cats. Cats, suffering from the most widely spread Microsporum canis-induced dermatophytosis and treated with terbinafine hydrochloride 1% cream, recovered within 20.3±0.88 days; whereas when treated with econazole nitrate 1% cream, they recovered within 28.4±1.14 days. A positive therapeutic effect was yielded by combined treatment with local application of creams and whole coat spray with enilconazole 0.2% emulsion "Imaverol". Most cats treated with econazole cream revealed redness and irritation of the skin at the site of application. This study demonstrates that terbinafine tended to have superior clinical efficacy (p<0.001) in the treatment of dermatophytosis in cats compared to the azole tested.

Efficacy of PARP inhibitor rucaparib in orthotopic glioblastoma xenografts is limited by ineffective drug penetration into the central nervous system

PubMed Central

Parrish, Karen E.; Cen, Ling; Murray, James; Calligaris, David; Kizilbash, Sani; Mittapalli, Rajendar K.; Carlson, Brett L.; Schroeder, Mark A.; Sludden, Julieann; Boddy, Alan V.; Agar, Nathalie Y.R.; Curtin, Nicola J.; Elmquist, William F.; Sarkaria, Jann N.

2015-01-01

Poly (ADP-ribose) polymerase (PARP) inhibition can enhance the efficacy of temozolomide (TMZ) and prolong survival in orthotopic glioblastoma (GBM) xenografts. The aim of this study was to evaluate the combination of the PARP inhibitor rucaparib with TMZ and to correlate pharmacokinetic and pharmacodynamic studies with efficacy in patient-derived GBM xenograft models. The combination of rucaparib with TMZ was highly effective in vitro in short-term explant cultures derived from GBM12, and similarly, the combination of rucaparib and TMZ (dosed for 5 days every 28 days × 3 cycles) significantly prolonged the time to tumor regrowth by 40% in heterotopic xenografts. In contrast, the addition of rucaparib had no impact on the efficacy of TMZ in GBM12 or GBM39 orthotopic models. Using Madin-Darby canine kidney (MDCK) II cells stably expressing murine BCRP1 or human MDR1, cell accumulation studies demonstrated that rucaparib is transported by both transporters. Consistent with the influence of these efflux pumps on central nervous system drug distribution, Mdr1a/b−/−Bcrp1−/− knockout mice had a significantly higher brain to plasma ratio for rucaparib (1.61 ± 0.25) than wild-type mice (0.11 ± 0.08). A pharmacokinetic and pharmacodynamic evaluation after a single dose confirmed limited accumulation of rucaparib in the brain associated with substantial residual PARP enzymatic activity. Similarly, matrix-assisted laser desorption/ionization mass spectrometric imaging demonstrated significantly enhanced accumulation of drug in flank tumor compared to normal brain or orthotopic tumors. Collectively, these results suggest that limited drug delivery into brain tumors may significantly limit the efficacy of rucaparib combined with TMZ in GBM. PMID:26438157

Efficacy of PARP Inhibitor Rucaparib in Orthotopic Glioblastoma Xenografts Is Limited by Ineffective Drug Penetration into the Central Nervous System.

PubMed

Parrish, Karen E; Cen, Ling; Murray, James; Calligaris, David; Kizilbash, Sani; Mittapalli, Rajendar K; Carlson, Brett L; Schroeder, Mark A; Sludden, Julieann; Boddy, Alan V; Agar, Nathalie Y R; Curtin, Nicola J; Elmquist, William F; Sarkaria, Jann N

2015-12-01

PARP inhibition can enhance the efficacy of temozolomide and prolong survival in orthotopic glioblastoma (GBM) xenografts. The aim of this study was to evaluate the combination of the PARP inhibitor rucaparib with temozolomide and to correlate pharmacokinetic and pharmacodynamic studies with efficacy in patient-derived GBM xenograft models. The combination of rucaparib with temozolomide was highly effective in vitro in short-term explant cultures derived from GBM12, and, similarly, the combination of rucaparib and temozolomide (dosed for 5 days every 28 days for 3 cycles) significantly prolonged the time to tumor regrowth by 40% in heterotopic xenografts. In contrast, the addition of rucaparib had no impact on the efficacy of temozolomide in GBM12 or GBM39 orthotopic models. Using Madin-Darby canine kidney (MDCK) II cells stably expressing murine BCRP1 or human MDR1, cell accumulation studies demonstrated that rucaparib is transported by both transporters. Consistent with the influence of these efflux pumps on central nervous system drug distribution, Mdr1a/b(-/-)Bcrp1(-/-) knockout mice had a significantly higher brain to plasma ratio for rucaparib (1.61 ± 0.25) than wild-type mice (0.11 ± 0.08). A pharmacokinetic and pharmacodynamic evaluation after a single dose confirmed limited accumulation of rucaparib in the brain is associated with substantial residual PARP enzymatic activity. Similarly, matrix-assisted laser desorption/ionization mass spectrometric imaging demonstrated significantly enhanced accumulation of drug in flank tumor compared with normal brain or orthotopic tumors. Collectively, these results suggest that limited drug delivery into brain tumors may significantly limit the efficacy of rucaparib combined with temozolomide in GBM. ©2015 American Association for Cancer Research.

Anti-tumor efficacy study of the Bruton's tyrosine kinase (BTK) inhibitor, ONO/GS-4059, in combination with the glycoengineered type II anti-CD20 monoclonal antibody obinutuzumab (GA101) demonstrates superior in vivo efficacy compared to ONO/GS-4059 in combination with rituximab.

PubMed

Yasuhiro, Tomoko; Sawada, Wako; Klein, Christian; Kozaki, Ryohei; Hotta, Shingo; Yoshizawa, Toshio

2017-03-01

The activated B-cell diffuse large B-cell-like lymphoma (ABC-DLBCL) correlates with poor prognosis. The B-cell receptor signaling pathway is known to be dysregulated in NHL/CLL and given BTK is a downstream mediator of BCR signaling, BTK constitutes an interesting and obvious therapeutic target. Given the high potency and selectivity of the BTK inhibitor, ONO/GS-4059, it was hypothesized that, the anti-tumor activity of ONO/GS-4059 could be further enhanced by combining it with the anti-CD20 Abs, rituximab (RTX) or obinutuzumab (GA101). ONO/GS-4059 combined with GA101 or RTX was significantly better than the respective monotherapy with tumor growth inhibition (TGI) of 90% for the GA101 combination and 86% for the RTX combination. In contrast, ibrutinib (PCI-32765) combined with RTX did not result in improved efficacy compared with respective monotherapy. Taken together these data indicate that the combination of ONO/GS-4059 with rituximab and particularly obinutuzumab may be an effective treatment for ABC-DLBCL.

Atorvastatin calcium encapsulated eudragit nanoparticles with enhanced oral bioavailability, safety and efficacy profile.

PubMed

Kumar, Nagendra; Chaurasia, Sundeep; Patel, Ravi R; Khan, Gayasuddin; Kumar, Vikas; Mishra, Brahmeshwar

2017-03-01

Atorvastatin calcium (ATR), a second generation statin drug, was encapsulated in eudragit RSPO-based polymeric nanoparticles. The effect of independent variables (polymer content, stabilizer concentration, volume of chloroform and homogenization speed) on response variables (mean diameter particle size and entrapment efficiency) were investigated by employing central composite experimental design. All the independent variables were found to be significant for determining the response variables. Solid-state characterization study indicated the absence of physicochemical interaction between drug and polymer in formulation. Morphological study exhibited homogenous spherical shape of formulated nanoparticles. In vitro release study in phosphate buffer (pH 7.4) demonstrated sustained release profile over 24 h. Pharmacokinetic study in Charles Foster rats showed significant enhancement in oral bioavailability as compared to pure drug suspension. Efficacy study (lipid profile and blood glucose level) significantly justified the effectiveness of formulation having 50% less dose of ATR as compared to pure drug suspension. The effectiveness of formulation was further justified with an improved plasma safety profile of treated rats. Hence, ATR encapsulated eudragit RSPO nanoparticles can serve as potential drug delivery approach to enhance drug bioavailability, efficacy and safety profiles to alter existing marketed drug products.

Meta-analysis of randomized, controlled trials comparing griseofulvin and terbinafine in the treatment of tinea capitis.

PubMed

Tey, Hong Liang; Tan, Andy Soon Leong; Chan, Yuin Chew

2011-04-01

Griseofulvin has been the standard treatment for tinea capitis but newer antifungal agents, particularly terbinafine, are increasingly being used because of their shorter duration of treatment and more consistent absorption rates. We sought to compare the efficacy of oral griseofulvin and oral terbinafine in the treatment of tinea capitis. A search of MEDLINE, EMBASE, Cochrane Central Register of Clinical Trials, and the Cochrane Skin Group Ongoing Skin Trials Register was performed up to January 2010 for randomized controlled trials comparing griseofulvin and terbinafine in the treatment of tinea capitis in immunocompetent patients. The primary outcome measure was the complete cure rate. The mycological and clinical cure rates and adverse effects were secondary outcome measures. Pooling of treatment effect was accomplished using a random effects model and the I(2) test was used to check for heterogeneity among the studies. Seven studies involving 2163 subjects were included. There was no significant difference in efficacy between griseofulvin (mean duration of treatment 8 weeks, range 6-12 weeks) and terbinafine (mean duration of treatment 4 weeks, range 2-6 weeks); odds ratio = 1.22 favoring terbinafine (95% confidence interval [CI] = 0.785-1.919; P = .37). In the pooled analysis of 5 studies in which Trichophyton species were the predominant (≥65%) pathogenic dermatophyte, terbinafine showed a trend toward greater efficacy (odds ratio 1.49; 95% CI = 0.975-2.277; P = .065). Subgroup analysis revealed that terbinafine was more efficacious than griseofulvin in treating Trichophyton species (1.616; 95% CI = 1.274-2.051; P < .001) and griseofulvin was more efficacious than terbinafine in treating Microsporum species (0.408; 95% CI = 0.254-0.656; P < .001). Both griseofulvin and terbinafine demonstrated good safety profiles in the studies. Data on efficacy of griseofulvin and terbinafine for separate groups of Trichophyton and Microsporum species were not available from every study. In the subgroup analysis of Microsporum species, data from only 3 studies were available. This meta-analysis suggests that terbinafine is more efficacious than griseofulvin in treating tinea capitis caused by Trichophyton species, whereas griseofulvin is more efficacious than terbinafine in treating tinea capitis caused by Microsporum species. Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Comparison of Efficacy Between Endoscopic Cyclophotocoagulation and Alternative Surgeries in Refractory Glaucoma

PubMed Central

Yang, Yangfan; Zhong, Jing; Dun, Zhongjun; Liu, Xiao-an; Yu, Minbin

2015-01-01

Abstract Refractory glaucoma refers to uncontrolled intraocular pressure (IOP) despite anti-glaucoma medication and surgical treatment, which remains a challenge to be treated. The objective of this study is to evaluate and statistically compare the clinical efficacy between endoscopic cyclophotocoagulation (ECP) and alternative surgical techniques in the treatment of refractory glaucoma in this article, as a meta-analysis. Data sources are China Biomedical Database (Sinomed, online version), China National Knowledge Infrastructure (CNKI), Cqvip, Wanfang database, and PubMed. The randomized controlled trial (RCT) and case–control study literatures evaluating the clinical efficacy between ECP and other surgical techniques were searched electronically from public databases. The methodology quality of the retrieved articles was evaluated according to the RCT or case–control study criteria. The success rate of treatment, intraocular pressure (IOP) and visual acuity were statistically compared. RevMan 5.3 software was used for the meta-analysis. In total, 6 relevant control studies were selected in this study with a total sampling of 429 cases (429 eyes), including 204 eyes in the ECP group and 225 in the non-ECP group. Meta-analysis demonstrated that the clinical efficacy did not significantly differ between 2 groups (P > 0.05). Postoperative IOP was dramatically reduced in both groups. However, it was difficult to evaluate the combined influence of ECP and non-ECP therapies upon IOP reduction. In conclusion, ECP and non-ECP treatment yielded almost equivalent clinical efficacy in treating refractory glaucoma. The IOP-lowering degree, safety, and incidence of complications remain to be further elucidated by RCTs with a larger sample size. PMID:26426659

Strengths, weaknesses and future challenges of biosimilars' development. An opinion on how to improve the knowledge and use of biosimilars in clinical practice.

PubMed

Scavone, Cristina; Rafaniello, Concetta; Berrino, Liberato; Rossi, Francesco; Capuano, Annalisa

2017-12-01

Biosimilars started receiving the marketing authorization by European Medicine Agency since 2006. The development of biosimilars follows a well-defined step-wise approach, the so-called comparability exercise, which aims to compare non-clinical (mainly quality features and biological activity) and clinical (efficacy and safety profiles) features of new biosimilars with their respective reference products. Despite the undeniable advantages of such procedure, some concerns (such as the absence of switching studies or the evaluation of efficacy and safety in all therapeutic indications) still exist about its. In particular, the European regulatory framework on biosimilars approval does not include the conduction of switching studies demonstrating the interchangeability to be carried out before marketing authorization. This is one of the main aspects that negatively affects healthcare professionals' clinical decisions on switch. In order to achieve a better knowledge on safety and efficacy of biosimilar drugs, real world data should be collected and post-marketing efficacy and safety clinical studies (including those evaluating specific endpoints, therapeutic regimens and patients population), should be planned. also the conduction of well-designed switching studies is highly advisable, especially in the case of biosimilar drugs used in oncology settings. Lastly, considering the critical role of antidrug antibodies on efficacy/safety profile of biologic drugs, studies based on therapeutic drug monitoring would be useful in order to achieve treatment optimization. Implementing the above strategies could be helpful to fill the gap in knowledge observed in the present European biosimilar regulatory framework. Copyright © 2017 Elsevier Ltd. All rights reserved.

Combination of glycolic acid peel and topical 20% azelaic acid cream in melasma patients: efficacy and improvement in quality of life.

PubMed

Dayal, Surabhi; Sahu, Priyadarshini; Dua, Ruchika

2017-03-01

Glycolic acid (GA) peel is one of the most versatile agents in the treatment of melasma. GA peeling alone or in combination with topical hypopigmenting agents has shown encouraging results. However, there is paucity of controlled trial demonstrating the efficacy of glycolic peel in conjunction with topical azelaic acid (AA). We therefore sought to highlight the efficacy and safety of this combination in melasma. To assess the clinical efficacy, safety and reduction in melasma quality of life (MELASQOL) scores on combining serial GA peels with topical 20% AA cream in epidermal melasma. Sixty patients of epidermal melasma were enrolled for 24 weeks. Patients were divided into two groups: (1) Study group received serial GA peel every 3 weeks with twice daily 20% AA cream, and (2) control group received only 20% AA cream. Clinical improvement was assessed objectively using Melasma Area Severity Index (MASI). Melasma-related quality of life was measured by MELASQOL scale in both groups. Side effects were observed at each visit. The improvement in MASI and percentage decrease in MASI scoring were statistically significant 12 weeks onwards in study group as compared to control group. There was also a significant reduction in MELASQOL scores in study group as compared to control group after treatment. Minor reversible side effects were observed in both groups, which did not require cessation of therapy. GA peel enhances therapeutic efficacy of topical AA cream for treatment of melasma, with improvement in quality of life without serious side effects. © 2016 Wiley Periodicals, Inc.

The Confounded Self-Efficacy Construct: Review, Conceptual Analysis, and Recommendations for Future Research

PubMed Central

Williams, David; Rhodes, Ryan E.

2014-01-01

Self-efficacy is central to health behaviour theories due to its robust predictive capabilities. In this paper we present and review evidence for a self-efficacy-as-motivation argument in which standard self-efficacy questionnaires—i.e., ratings of whether participants “can do” the target behaviour—reflect motivation rather than perceived capability. The potential implication is that associations between self-efficacy ratings (particularly those that employ a “can do” operationalization) and health-related behaviours simply indicate that people are likely to do what they are motivated to do. There is some empirical evidence for the self-efficacy-as-motivation argument, with three studies demonstrating causal effects of outcome expectancy on subsequent self-efficacy ratings. Three additional studies show that—consistent with the self-efficacy-as-motivation argument—controlling for motivation by adding the phrase “if you wanted to” to the end of self-efficacy items decreases associations between self-efficacy ratings and motivation. Likewise, a qualitative study using a thought-listing procedure demonstrates that self-efficacy ratings have motivational antecedents. The available evidence suggests that the self-efficacy-as-motivation argument is viable, although more research is needed. Meanwhile, we recommend that researchers look beyond self-efficacy to identify the many and diverse sources of motivation for health-related behaviours. PMID:25117692

The confounded self-efficacy construct: conceptual analysis and recommendations for future research.

PubMed

Williams, David M; Rhodes, Ryan E

2016-06-01

Self-efficacy is central to health behaviour theories due to its robust predictive capabilities. In this paper, we present and review evidence for a self-efficacy-as-motivation argument in which standard self-efficacy questionnaires - i.e., ratings of whether participants 'can do' the target behaviour - reflect motivation rather than perceived capability. The potential implication is that associations between self-efficacy ratings (particularly those that employ a 'can do' operationalisation) and health-related behaviours simply indicate that people are likely to do what they are motivated to do. There is some empirical evidence for the self-efficacy-as-motivation argument, with three studies demonstrating causal effects of outcome expectancy on subsequent self-efficacy ratings. Three additional studies show that - consistent with the self-efficacy-as-motivation argument - controlling for motivation by adding the phrase 'if you wanted to' to the end of self-efficacy items decreases associations between self-efficacy ratings and motivation. Likewise, a qualitative study using a thought-listing procedure demonstrates that self-efficacy ratings have motivational antecedents. The available evidence suggests that the self-efficacy-as-motivation argument is viable, although more research is needed. Meanwhile, we recommend that researchers look beyond self-efficacy to identify the many and diverse sources of motivation for health-related behaviours.

Using Virtual Reality in the Inference-Based Treatment of Compulsive Hoarding

PubMed Central

St-Pierre-Delorme, Marie-Eve; O’Connor, Kieron

2016-01-01

The present study evaluated the efficacy of adding a virtual reality (VR) component to the treatment of compulsive hoarding (CH), following inference-based therapy (IBT). Participants were randomly assigned to either an experimental or a control condition. Seven participants received the experimental and seven received the control condition. Five sessions of 1 h were administered weekly. A significant difference indicated that the level of clutter in the bedroom tended to diminish more in the experimental group as compared to the control group F(2,24) = 2.28, p = 0.10. In addition, the results demonstrated that both groups were immersed and present in the environment. The results on posttreatment measures of CH (Saving Inventory revised, Saving Cognition Inventory and Clutter Image Rating scale) demonstrate the efficacy of IBT in terms of symptom reduction. Overall, these results suggest that the creation of a virtual environment may be effective in the treatment of CH by helping the compulsive hoarders take action over their clutter. PMID:27486574

Enhanced performance of macrophage-encapsulated nanoparticle albumin-bound-paclitaxel in hypo-perfused cancer lesions

NASA Astrophysics Data System (ADS)

Leonard, Fransisca; Curtis, Louis T.; Yesantharao, Pooja; Tanei, Tomonori; Alexander, Jenolyn F.; Wu, Min; Lowengrub, John; Liu, Xuewu; Ferrari, Mauro; Yokoi, Kenji; Frieboes, Hermann B.; Godin, Biana

2016-06-01

Hypovascularization in tumors such as liver metastases originating from breast and other organs correlates with poor chemotherapeutic response and higher mortality. Poor prognosis is linked to impaired transport of both low- and high-molecular weight drugs into the lesions and to high washout rate. Nanoparticle albumin-bound-paclitaxel (nAb-PTX) has demonstrated benefits in clinical trials when compared to paclitaxel and docetaxel. However, its therapeutic efficacy for breast cancer liver metastasis is disappointing. As macrophages are the most abundant cells in the liver tumor microenvironment, we design a multistage system employing macrophages to deliver drugs into hypovascularized metastatic lesions, and perform in vitro, in vivo, and in silico evaluation. The system encapsulates nAb-PTX into nanoporous biocompatible and biodegradable multistage vectors (MSV), thus promoting nAb-PTX retention in macrophages. We develop a 3D in vitro model to simulate clinically observed hypo-perfused tumor lesions surrounded by macrophages. This model enables evaluation of nAb-PTX and MSV-nab PTX efficacy as a function of transport barriers. Addition of macrophages to this system significantly increases MSV-nAb-PTX efficacy, revealing the role of macrophages in drug transport. In the in vivo model, a significant increase in macrophage number, as compared to unaffected liver, is observed in mice, confirming the in vitro findings. Further, a mathematical model linking drug release and retention from macrophages is implemented to project MSV-nAb-PTX efficacy in a clinical setting. Based on macrophage presence detected via liver tumor imaging and biopsy, the proposed experimental/computational approach could enable prediction of MSV-nab PTX performance to treat metastatic cancer in the liver.Hypovascularization in tumors such as liver metastases originating from breast and other organs correlates with poor chemotherapeutic response and higher mortality. Poor prognosis is linked to impaired transport of both low- and high-molecular weight drugs into the lesions and to high washout rate. Nanoparticle albumin-bound-paclitaxel (nAb-PTX) has demonstrated benefits in clinical trials when compared to paclitaxel and docetaxel. However, its therapeutic efficacy for breast cancer liver metastasis is disappointing. As macrophages are the most abundant cells in the liver tumor microenvironment, we design a multistage system employing macrophages to deliver drugs into hypovascularized metastatic lesions, and perform in vitro, in vivo, and in silico evaluation. The system encapsulates nAb-PTX into nanoporous biocompatible and biodegradable multistage vectors (MSV), thus promoting nAb-PTX retention in macrophages. We develop a 3D in vitro model to simulate clinically observed hypo-perfused tumor lesions surrounded by macrophages. This model enables evaluation of nAb-PTX and MSV-nab PTX efficacy as a function of transport barriers. Addition of macrophages to this system significantly increases MSV-nAb-PTX efficacy, revealing the role of macrophages in drug transport. In the in vivo model, a significant increase in macrophage number, as compared to unaffected liver, is observed in mice, confirming the in vitro findings. Further, a mathematical model linking drug release and retention from macrophages is implemented to project MSV-nAb-PTX efficacy in a clinical setting. Based on macrophage presence detected via liver tumor imaging and biopsy, the proposed experimental/computational approach could enable prediction of MSV-nab PTX performance to treat metastatic cancer in the liver. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr07796f

Efficacy and safety of TMC278 in antiretroviral-naive HIV-1 patients: week 96 results of a phase IIb randomized trial.

PubMed

Pozniak, Anton L; Morales-Ramirez, Javier; Katabira, Elly; Steyn, Dewald; Lupo, Sergio H; Santoscoy, Mario; Grinsztejn, Beatriz; Ruxrungtham, Kiat; Rimsky, Laurence T; Vanveggel, Simon; Boven, Katia

2010-01-02

TMC278 is a next-generation nonnucleoside reverse transcriptase inhibitor highly active against wild-type and nonnucleoside reverse transcriptase inhibitor-resistant HIV-1 in vitro. The week 96 analysis of TMC278-C204, a large dose-ranging study of TMC278 in treatment-naive HIV-1-infected patients, is presented. Phase IIb randomized trial. Three hundred sixty-eight patients were randomized and treated with three blinded once-daily TMC278 doses 25, 75 or 150 mg, or an open-label, active control, efavirenz 600 mg once daily, all with two nucleoside reverse transcriptase inhibitors. The primary analysis was at week 48. No TMC278 dose-response relationship for efficacy and safety was observed. TMC278 demonstrated potent antiviral efficacy comparable with efavirenz over 48 weeks that was sustained to week 96 (76.9-80.0% and 71.4-76.3% of TMC278-treated patients with confirmed viral load <50 copies/ml, respectively; time-to-loss of virological-response algorithm). Median increases from baseline in CD4 cell count with TMC278 at week 96 (138.0-149.0 cells/microl) were higher than at week 48 (108.0-123.0 cells/microl). All TMC278 doses were well tolerated. The incidences of the most commonly reported grade 2-4 adverse events at least possibly related to study medication, including nausea, dizziness, abnormal dreams/nightmare, dyspepsia, asthenia, rash, somnolence and vertigo, were low and lower with TMC278 than with efavirenz. Incidences of serious adverse events, grade 3 or 4 adverse events and discontinuations due to adverse events were similar among groups. All TMC278 doses demonstrated potent and sustained efficacy comparable with efavirenz in treatment-naive patients over 96 weeks. TMC278 was well tolerated with lower incidences of neurological and psychiatric adverse events, rash and lower lipid elevations than those with efavirenz. TMC278 25 mg once daily was selected for further clinical development.

Efficacy of Duloxetine for the Treatment of Generalized Anxiety Disorder: Implications for Primary Care Physicians

PubMed Central

Koponen, Hannu; Allgulander, Christer; Erickson, Janelle; Dunayevich, Eduardo; Pritchett, Yili; Detke, Michael J.; Ball, Susan G.; Russell, James M.

2007-01-01

Objective: This study examined the efficacy and tolerability of duloxetine, a dual reuptake inhibitor of serotonin and norepinephrine, for the treatment of patients with generalized anxiety disorder (GAD). Method: Patients were ≥ 18 years old and recruited from 5 European countries, the United States, and South Africa. The study had a 9-week, multicenter, randomized, double-blind, fixed-dose, placebo-controlled, parallel-group design. A total of 513 patients (mean age = 43.8 years; 67.8% female) with a DSM-IV–defined GAD diagnosis received treatment with duloxetine 60 mg/day (N = 168), duloxetine 120 mg/day (N = 170), or placebo (N = 175). The primary efficacy measure was the Hamilton Rating Scale for Anxiety (HAM-A) total score. Secondary measures included the Sheehan Disability Scale, HAM-A psychic and somatic anxiety factor scores, and HAM-A response, remission, and sustained improvement rates. The study was conducted from July 2004 to September 2005. Results: Both groups of duloxetine-treated patients demonstrated significantly greater improvements in anxiety symptom severity compared with placebo-treated patients as measured by HAM-A total score and HAM-A psychic and somatic anxiety factor scores (p values ranged from ≤ .01 to ≤ .001). Duloxetine-treated patients had greater functional improvements in Sheehan Disability Scale global and specific domain scores (p ≤ .001) than placebo-treated patients. Both duloxetine doses also resulted in significantly greater HAM-A response, remission, and sustained improvement rates compared with placebo (p values ranged from ≤ .01 to ≤ .001). The rate of study discontinuation due to adverse events was 11.3% for duloxetine 60 mg and 15.3% for duloxetine 120 mg versus 2.3% for placebo (p ≤ .001). Conclusion: The results of this study demonstrate that duloxetine 60 mg/day and 120 mg/day were efficacious and well tolerated and thus may provide primary care physicians with a useful pharmacologic intervention for GAD. Clinical Trials Registration: ClinicalTrials.gov identifier NCT00122824. PMID:17607331

Mode-of-action, efficacy, and safety of a homologous multi-epitope vaccine in a murine model for adjuvant treatment of renal cell carcinoma.

PubMed

Doehn, Christian; Esser, Norbert; Pauels, Hans-Gerd; Kiessig, Stephan T; Stelljes, Matthias; Grossmann, Armin; Jocham, Dieter; Drevs, Joachim

2009-07-01

In a phase-III trial it was recently shown that an adjuvant renal cell carcinoma (RCC) vaccine (Reniale) reduces the risk of tumour progression following nephrectomy. This clinical trial focused on efficacy and did not investigate end-points relating to mode-of-action of the vaccine. In a murine model we investigated mode-of-action, efficacy, and safety of a homologous RENCA cell-based vaccine. Six groups with 12 BALB/c mice per group received five vaccinations (lysate of 1x10(6)-1x10(7) RENCA cells, manufactured with or without prior IFN-gamma incubation) at 3-wk intervals before tumour transplantation and one vaccination 14 d afterwards. Controls (12 mice) received only solvent. All mice were sacrificed 21 d after tumour transplantation. Animal welfare, tumour growth, number of metastases, and the presence of cytotoxic T-lymphocytes as determined by a (51)chromium-release assay. Adoptive immune transfer experiments (vaccination of nine mice with the RENCA vaccine or saline and transfer of serum, spleen cells, and CD4 and/or CD8 depleted spleen cells into five recipient mice each) were carried out to demonstrate involvement of different immune mechanisms. All controls developed a renal tumour, compared to 7/72 animals (9.7%) in the vaccine groups. The mean number of lung metastases was 100 (range 3-750) in controls and 4 (range 0-196) in the vaccine groups, respectively. Tumour uptake and number of metastases were not related to the vaccine dose. The (51)chromium-release assay confirmed a significant tumour-specific cytolytic activity and marginally increased NK activity of splenocytes from vaccinated mice against RENCA cells compared to controls. Adoptive immune transfer experiments showed that the antitumoural effective immune mechanisms are cell-based. We could demonstrate the mode-of-action, efficacy, and safety of a homologous tumour vaccine in a RENCA model. These findings support the positive results from a phase-III trial with Reniale.

Improved Tumor Penetration and Single-Cell Targeting of Antibody-Drug Conjugates Increases Anticancer Efficacy and Host Survival.

PubMed

Cilliers, Cornelius; Menezes, Bruna; Nessler, Ian; Linderman, Jennifer; Thurber, Greg M

2018-02-01

Current antibody-drug conjugates (ADC) have made advances in engineering the antibody, linker, conjugation site, small-molecule payload, and drug-to-antibody ratio (DAR). However, the relationship between heterogeneous intratumoral distribution and efficacy of ADCs is poorly understood. Here, we compared trastuzumab and ado-trastuzumab emtansine (T-DM1) to study the impact of ADC tumor distribution on efficacy. In a mouse xenograft model insensitive to trastuzumab, coadministration of trastuzumab with a fixed dose of T-DM1 at 3:1 and 8:1 ratios dramatically improved ADC tumor penetration and resulted in twice the improvement in median survival compared with T-DM1 alone. In this setting, the effective DAR was lowered, decreasing the amount of payload delivered to each targeted cell but increasing the number of cells that received payload. This result is counterintuitive because trastuzumab acts as an antagonist in vitro and has no single-agent efficacy in vivo , yet improves the effectiveness of T-DM1 in vivo Novel dual-channel fluorescence ratios quantified single-cell ADC uptake and metabolism and confirmed that the in vivo cellular dose of T-DM1 alone exceeded the minimum required for efficacy in this model. In addition, this technique characterized cellular pharmacokinetics with heterogeneous delivery after 1 day, degradation and payload release by 2 days, and in vitro cell killing and in vivo tumor shrinkage 2 to 3 days later. This work demonstrates that the intratumoral distribution of ADC, independent of payload dose or plasma clearance, plays a major role in ADC efficacy. Significance: This study shows how lowering the drug-to-antibody ratio during treatment can improve the intratumoral distribution of a antibody-drug conjugate, with implications for improving the efficacy of this class of cancer drugs. Cancer Res; 78(3); 758-68. ©2017 AACR . ©2017 American Association for Cancer Research.

Clinical efficacy and safety of mesenchymal stem cell transplantation for osteoarthritis treatment: A meta-analysis

PubMed Central

Li, Li; Tao, Sun; Bo, Lin; Lin, Chen

2017-01-01

Purpose The aim of this study was to evaluate the therapeutic efficacy and safety of mesenchymal stem cells (MSCs) for the treatment of patients with knee osteoarthritis (OA). Materials We performed a meta-analysis of relevant published clinical studies. An electronic search was conducted for randomized controlled trials (RCTs) of MSC-based therapy in knee OA. The visual analogue scale (VAS), International Knee Documentation Committee (IKDC) form, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Lequesne algofunctional indices (Lequesne), Lysholm knee scale (Lysholm), Tegner activity scale (Tegner) and adverse events (AEs) were evaluated. Results Eleven eligible trials with 582 knee OA patients were included in the present meta-analysis. We demonstrated that MSC treatment could significantly decrease VAS and increase IKDC scoresafter a 24-month follow-up compared with controls (P<0.05). MSC therapy also showed significant decreases in WOMAC and Lequesne scores after the 12-month follow-up (P<0.01). Analysis of Lysholm (24-month) and Tegner (12- and 24-month) scores also demonstrated favorable results for MSC treatment (P<0.05). Conclusion Overall, MSC transplantation treatment was shown to be safe and has great potential as an efficacious clinical therapy for patients with knee OA. PMID:28448518

A comparative, randomized, controlled study on clinical efficacy and dental staining reduction of a mouthwash containing Chlorhexidine 0.20% and Anti Discoloration System (ADS).

PubMed

Marrelli, Massimo; Amantea, Massimiliano; Tatullo, Marco

2015-01-01

A good control of bacterial plaque is an essential factor for the success of periodontal therapy, therefore it is the main objective that the clinician together with the patient must get to have a healthy periodontium. The plaque control with mouthwashes is the most important home therapy as it helps to reduce the formation of plaque between the mechanical removal with a toothbrush. Authors analyzed the clinical data from a trial carried out with 3 different mouthwashes containing 0.2% Chlorhexidine (CHX). In addition, the ADS (Anti Discoloration System - Curaden Healthcare) was tested in comparison with the other mouthwashes without this system. We tested antiplaque activity showed by 3 of the most commercialized mouthwashes, moreover, we tested the ability in reducing the dental staining related to the oral assumption of Chlorhexidine. Our results demonstrated the clinical efficacy of the 3 mouthwashes with CHX. Particularly performing was the anti discoloration system (Curaden Healthcare), with a clinical detection of dental stainings significantly less than the others tested. This study demonstrated the clinical efficacy of ADS system in the reduction of tooth staining, without a loss of antiplaque activity with respect to the competing mouthwashes containing CHX.

Age of drinking onset as a moderator of the efficacy of parent-based, brief motivational, and combined intervention approaches to reduce drinking and consequences among college students.

PubMed

Mallett, Kimberly A; Ray, Anne E; Turrisi, Rob; Belden, Calum; Bachrach, Rachel L; Larimer, Mary E

2010-07-01

The current study tested age of onset as a moderator of intervention efficacy on drinking and consequence outcomes among a high-risk population of college students (i.e., former high school athletes). Students were randomized to one of four conditions: assessment only control, combined parent-based intervention (PBI) and brief motivational intervention (BMI), PBI alone, and BMI alone. Participants (n = 1,275) completed web-administered measures at baseline (summer before starting college) and 10-month follow-up. Overall, the combined intervention demonstrated the strongest and most consistent reductions across all outcomes, particularly with the youngest initiators. Participants who initiated drinking at the youngest ages had significantly lower peak drinking, typical weekly drinking, and reported consequences at follow-up when they received the combined intervention when compared to the control group. The BMI and PBI groups, when examined independently, demonstrated significant effects across outcomes but were inconsistent across the different age groups. Results suggest the combination of a PBI and a peer-delivered BMI is an appropriate and efficacious way to reduce drinking and related consequences among individuals who initiated drinking earlier in adolescence and are at an increased risk of experiencing alcohol problems.

Efficacy Study of Novel Diamidine Compounds in a Trypanosoma evansi Goat Model

PubMed Central

Gillingwater, Kirsten; Gutierrez, Carlos; Bridges, Arlene; Wu, Huali; Deborggraeve, Stijn; Ali Ekangu, Rosine; Kumar, Arvind; Ismail, Mohamed; Boykin, David; Brun, Reto

2011-01-01

Three diamidines (DB 75, DB 867 and DB 1192) were selected and their ability to cure T. evansi experimentally infected goats was investigated. A toxicity assessment and pharmacokinetic analysis of these compounds were additionally carried out. Goats demonstrated no signs of acute toxicity, when treated with four doses of 1 mg/kg/day (total dose 4 mg/kg). Complete curative efficacy of experimentally infected goats was seen in the positive control group treated with diminazene at 5 mg/kg and in the DB 75 and DB 867 groups treated at 2.5 mg/kg. Drug treatment was administered once every second day for a total of seven days. Complete cure was also seen in the group of goats treated with DB 75 at 1.25 mg/kg. DB 1192 was incapable of curing goats at either four-times 2.5 mg/kg or 1.25 mg/kg. Pharmacokinetic analysis clearly demonstrated that the treatment failures of DB 1192 were due to sub-therapeutic compound levels in goat plasma, whilst compound levels for DB 75 and DB 867 remained well within the therapeutic window. In conclusion, two diamidine compounds (DB 75 and DB 867) presented comparable efficacy at lower doses than the standard drug diminazene and could be considered as potential clinical candidates against T. evansi infection. PMID:21698106

Efficacy study of novel diamidine compounds in a Trypanosoma evansi goat model.

PubMed

Gillingwater, Kirsten; Gutierrez, Carlos; Bridges, Arlene; Wu, Huali; Deborggraeve, Stijn; Ekangu, Rosine Ali; Kumar, Arvind; Ismail, Mohamed; Boykin, David; Brun, Reto

2011-01-01

Three diamidines (DB 75, DB 867 and DB 1192) were selected and their ability to cure T. evansi experimentally infected goats was investigated. A toxicity assessment and pharmacokinetic analysis of these compounds were additionally carried out. Goats demonstrated no signs of acute toxicity, when treated with four doses of 1 mg/kg/day (total dose 4 mg/kg). Complete curative efficacy of experimentally infected goats was seen in the positive control group treated with diminazene at 5 mg/kg and in the DB 75 and DB 867 groups treated at 2.5 mg/kg. Drug treatment was administered once every second day for a total of seven days. Complete cure was also seen in the group of goats treated with DB 75 at 1.25 mg/kg. DB 1192 was incapable of curing goats at either four-times 2.5 mg/kg or 1.25 mg/kg. Pharmacokinetic analysis clearly demonstrated that the treatment failures of DB 1192 were due to sub-therapeutic compound levels in goat plasma, whilst compound levels for DB 75 and DB 867 remained well within the therapeutic window. In conclusion, two diamidine compounds (DB 75 and DB 867) presented comparable efficacy at lower doses than the standard drug diminazene and could be considered as potential clinical candidates against T. evansi infection.

Sustained Release of an Anti-Glaucoma Drug: Demonstration of Efficacy of a Liposomal Formulation in the Rabbit Eye

PubMed Central

Ang, Marcus; Darwitan, Anastasia; Foo, Selin; Zhen, Ma; Koo, Magdalene; Wong, Tina T.; Venkatraman, Subbu S.

2011-01-01

Topical medication remains the first line treatment of glaucoma; however, sustained ocular drug delivery via topical administration is difficult to achieve. Most drugs have poor penetration due to the multiple physiological barriers of the eye and are rapidly cleared if applied topically. Currently, daily topical administration for lowering the intra-ocular pressure (IOP), has many limitations, such as poor patient compliance and ocular allergy from repeated drug administration. Poor compliance leads to suboptimal control of IOP and disease progression with eventual blindness. The delivery of drugs in a sustained manner could provide the patient with a more attractive alternative by providing optimal therapeutic dosing, with minimal local toxicity and inconvenience. To investigate this, we incorporated latanoprost into LUVs (large unilamellar vesicles) derived from the liposome of DPPC (di-palmitoyl-phosphatidyl-choline) by the film hydration technique. Relatively high amounts of drug could be incorporated into this vesicle, and the drug resides predominantly in the bilayer. Vesicle stability monitored by size measurement and DSC (differential scanning calorimetry) analysis showed that formulations with a drug/lipid mole ratio of about 10% have good physical stability during storage and release. This formulation demonstrated sustained release of latanoprost in vitro, and then tested for efficacy in 23 rabbits. Subconjunctival injection and topical eye drop administration of the latanoprost/liposomal formulation were compared with conventional daily administration of latanoprost eye drops. The IOP lowering effect with a single subconjunctival injection was shown to be sustained for up to 50 days, and the extent of IOP lowering was comparable to daily eye drop administration. Toxicity and localized inflammation were not observed in any treatment groups. We believe that this is the first demonstration, in vivo, of sustained delivery to the anterior segment of the eye that is safe and efficacious for 50 days. PMID:21931735

Preclinical Evaluation of Promitil, a Radiation-Responsive Liposomal Formulation of Mitomycin C Prodrug, in Chemoradiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tian, Xi; Warner, Samuel B.; Wagner, Kyle T.

Purpose: To examine the effect of radiation on in vitro drug activation and release of Promitil, a pegylated liposomal formulation of a mitomycin C (MMC) lipid-based prodrug; and examine the efficacy and toxicity of Promitil with concurrent radiation in colorectal cancer models. Methods and Materials: Promitil was obtained from Lipomedix Pharmaceuticals (Jerusalem, Israel). We tested the effects of radiation on release of active MMC from Promitil in vitro. We next examined the radiosensitization effect of Promitil in vitro. We further evaluated the toxicity of a single injection of free MMC or Promitil when combined with radiation by assessing the effects on blood counts and in-fieldmore » skin and hair toxicity. Finally, we compared the efficacy of MMC and Promitil in chemoradiotherapy using mouse xenograft models. Results: Mitomycin C was activated and released from Promitil in a controlled-release profile, and the rate of release was significantly increased in medium from previously irradiated cells. Both Promitil and MMC potently radiosensitized HT-29 cells in vitro. Toxicity of MMC (8.4 mg/kg) was substantially greater than with equivalent doses of Promitil (30 mg/kg). Mice treated with human-equivalent doses of MMC (3.3 mg/kg) experienced comparable levels of toxicity as Promitil-treated mice at 30 mg/kg. Promitil improved the antitumor efficacy of 5-fluorouracil–based chemoradiotherapy in mouse xenograft models of colorectal cancer, while equitoxic doses of MMC did not. Conclusions: We demonstrated that Promitil is an attractive agent for chemoradiotherapy because it demonstrates a radiation-triggered release of active drug. We further demonstrated that Promitil is a well-tolerated and potent radiosensitizer at doses not achievable with free MMC. These results support clinical investigations using Promitil in chemoradiotherapy.« less

Self-efficacy perceptions of interprofessional education and practice in undergraduate healthcare students.

PubMed

Williams, Brett; Beovich, Bronwyn; Ross, Linda; Wright, Caroline; Ilic, Dragan

2017-05-01

Self-efficacy is an individual's perception of their ability to be successful in a given endeavour and it has been shown to have an important role in successful university education and clinical performance of healthcare workers. This article examines the self-efficacy beliefs of undergraduate healthcare students (n = 388) for the skills required for interprofessional education and interprofessional collaboration. The students were enrolled at an Australian university from the disciplines of public health, social work, and paramedic practice. The Self-Efficacy for Interprofessional Experiential Learning (SEIEL) scale, which is a valid and reliable scale, was used to determine the self-reported perceptions of self-efficacy in this cohort. The 16-item scale was developed for use with medicine and other healthcare professional undergraduate students. Student t-tests were used to compare scores between males and females, with one-way ANOVAs used to explore SEIEL scores across disciplines and year level. A significant difference was found between genders for the scores on SEIEL subscale 2 "Interprofessional evaluation and feedback" (p = 0.01) with the male mean being 2.65 units higher (Cohen's d = 0.29). There was also a significant gender difference for the overall SEIEL scale (p = 0.029) with the male mean being 4.1 units higher (Cohen's d = 0.238). No significant gender differences were demonstrated for the subscale "Interprofessional interaction." Neither subscale demonstrated significant differences between healthcare disciplines or course year. Further investigation is required to explore the reasons for the outcomes of this study. With the increasing importance of interprofessional education and practice within healthcare, it would also appear reasonable to consider further research into the development and support of student self-efficacy for the skills required for interprofessional education and interprofessional collaboration within healthcare curricula.

The use of alectinib in the first-line treatment of anaplastic lymphoma kinase-positive non-small-cell lung cancer.

PubMed

Gadgeel, Shirish M

2018-03-14

Anaplastic lymphoma kinase (ALK) gene rearrangements as driver genetic alterations occur in approximately 2-4% of non-small-cell lung cancer (NSCLC) patients. Alectinib, a next generation ALK inhibitor, recently demonstrated, in two separate Phase III trials, superior efficacy to crizotinib, the first ALK inhibitor to demonstrate clinical efficacy in ALK-positive NSCLC patients. Alectinib also demonstrated superior efficacy in the CNS. The data from these two Phase III studies suggest that the efficacy of starting with alectinib is superior to the overall clinical efficacy of starting with crizotinib followed by switching to alectinib at the time of disease progression. These results have changed the standard of care to alectinib as front-line therapy for advanced ALK-positive NSCLC patients. Areas covered: this paper reviews the available data on alectinib as front-line therapy in patients with ALK-positive NSCLC patients including its activity against brain metastases. In addition, the paper will review the data with other ALK inhibitors as front-line therapy.

Receptor residence time trumps drug-likeness and oral bioavailability in determining efficacy of complement C5a antagonists

PubMed Central

Seow, Vernon; Lim, Junxian; Cotterell, Adam J.; Yau, Mei-Kwan; Xu, Weijun; Lohman, Rink-Jan; Kok, W. Mei; Stoermer, Martin J.; Sweet, Matthew J.; Reid, Robert C.; Suen, Jacky Y.; Fairlie, David P.

2016-01-01

Drug discovery and translation are normally based on optimizing efficacy by increasing receptor affinity, functional potency, drug-likeness (rule-of-five compliance) and oral bioavailability. Here we demonstrate that residence time of a compound on its receptor has an overriding influence on efficacy, exemplified for antagonists of inflammatory protein complement C5a that activates immune cells and promotes disease. Three equipotent antagonists (3D53, W54011, JJ47) of inflammatory responses to C5a (3nM) were compared for drug-likeness, receptor affinity and antagonist potency in human macrophages, and anti-inflammatory efficacy in rats. Only the least drug-like antagonist (3D53) maintained potency in cells against higher C5a concentrations and had a much longer duration of action (t1/2 ~ 20 h) than W54011 or JJ47 (t1/2 ~ 1–3 h) in inhibiting macrophage responses. The unusually long residence time of 3D53 on its receptor was mechanistically probed by molecular dynamics simulations, which revealed long-lasting interactions that trap the antagonist within the receptor. Despite negligible oral bioavailability, 3D53 was much more orally efficacious than W54011 or JJ47 in preventing repeated agonist insults to induce rat paw oedema over 24 h. Thus, residence time on a receptor can trump drug-likeness in determining efficacy, even oral efficacy, of pharmacological agents. PMID:27094554

Receptor residence time trumps drug-likeness and oral bioavailability in determining efficacy of complement C5a antagonists

NASA Astrophysics Data System (ADS)

Seow, Vernon; Lim, Junxian; Cotterell, Adam J.; Yau, Mei-Kwan; Xu, Weijun; Lohman, Rink-Jan; Kok, W. Mei; Stoermer, Martin J.; Sweet, Matthew J.; Reid, Robert C.; Suen, Jacky Y.; Fairlie, David P.

2016-04-01

Drug discovery and translation are normally based on optimizing efficacy by increasing receptor affinity, functional potency, drug-likeness (rule-of-five compliance) and oral bioavailability. Here we demonstrate that residence time of a compound on its receptor has an overriding influence on efficacy, exemplified for antagonists of inflammatory protein complement C5a that activates immune cells and promotes disease. Three equipotent antagonists (3D53, W54011, JJ47) of inflammatory responses to C5a (3nM) were compared for drug-likeness, receptor affinity and antagonist potency in human macrophages, and anti-inflammatory efficacy in rats. Only the least drug-like antagonist (3D53) maintained potency in cells against higher C5a concentrations and had a much longer duration of action (t1/2 ~ 20 h) than W54011 or JJ47 (t1/2 ~ 1-3 h) in inhibiting macrophage responses. The unusually long residence time of 3D53 on its receptor was mechanistically probed by molecular dynamics simulations, which revealed long-lasting interactions that trap the antagonist within the receptor. Despite negligible oral bioavailability, 3D53 was much more orally efficacious than W54011 or JJ47 in preventing repeated agonist insults to induce rat paw oedema over 24 h. Thus, residence time on a receptor can trump drug-likeness in determining efficacy, even oral efficacy, of pharmacological agents.

Pharmacological therapy of osteoarthritis.

PubMed

Hochberg, M C; Dougados, M

2001-10-01

In 2000, both the American College of Rheumatology (ACR) and the European League of Associations of Rheumatology (EULAR) published recommendations for the use of pharmacological therapy in the treatment of patients with lower limb osteoarthritis. These recommendations are based on the level of evidence observed in systematic reviews and/or meta-analyses of published randomized controlled trials as well as expert opinion. Acetaminophen (paracetamol) is considered as first-line oral therapy for symptomatic lower limb osteoarthritis with mild to moderate pain because it is more efficacious than placebo and is generally considered to be safe and well tolerated. Data obtained in recent trials and the results of a meta-analysis, however, show that acetaminophen is not as efficacious as non-steroidal anti-inflammatory drugs (NSAIDs) for pain at rest and pain on motion. Furthermore, data from a recent epidemiological study suggest that use of high-dose acetaminophen (>2 g/day) may convey the same magnitude of increased risk for serious upper gastrointestinal adverse events as NSAIDs.NSAIDs have demonstrated efficacy superior to placebo in patients with osteoarthritis. The newer cyclo-oxygenase (COX)-2-specific inhibitors (coxibs) have comparable efficacy to traditional dual inhibitor NSAIDs and have demonstrated a better gastrointestinal safety profile. Thus, for patients who have severe pain and/or signs of inflammation or who have failed to respond to acetaminophen, the use of a coxib should be considered, especially if the patient is at increased risk for serious upper gastrointestinal adverse events from a traditional NSAID.Compounds different from pure analgesics and NSAIDs are also used for the management of patients with osteoarthritis. Recent clinical trials have demonstrated statistically significant efficacy of such compounds (e.g. chondroitin sulphate, diacerhein, glucosamine sulphate) with the following characteristics: (1) the effect size seems to be of slightly lower magnitude than that seen for NSAIDs; (2) the onset of action is delayed for approximately 4 to 6 weeks; and (3) the symptomatic effect is maintained after stopping the treatment for periods of 4 to 8 weeks.The methodology for evaluating the possible structure-modifying effect of drugs has dramatically improved during the past decade. Two agents have demonstrated a beneficial structural effect: glucosamine sulphate in osteoarthritis of the knee, and diacerhein in osteoarthritis of the hip. The clinical relevance of such an effect needs to be further evaluated in long-term outcome studies. Copyright 2001 Harcourt Publishers Ltd.

A randomized, double-blind, placebo-controlled study of acetaminophen 1000 mg versus acetaminophen 650 mg for the treatment of postsurgical dental pain.

PubMed

Qi, Daniel S; May, Lisa G; Zimmerman, Brenda; Peng, Penny; Atillasoy, Evren; Brown, Jean D; Cooper, Stephen A

2012-12-01

Although acetaminophen is one of the oldest and most widely used of all analgesic drugs, the incremental benefit of the 1000-mg dose compared with the 650-mg dose has been questioned. The aim of this study was to assess the relative efficacy of acetaminophen 1000 mg versus acetaminophen 650 mg over a 6-hour period in patients experiencing at least moderate postsurgical dental pain. This single-center, randomized, double-blind, placebo-controlled, single-dose study enrolled patients aged 16 to 50 years who experienced at least moderate pain after surgical removal of impacted third molars. Each patient received either acetaminophen 1000 mg (n = 239), acetaminophen 650 mg (n = 241), or placebo (n = 60) when they had at least moderate pain and a score ≥50 on the 100-mm Visual Analog Scale (VAS) postsurgically. Pain intensity and pain relief were measured over 6 hours (VAS 0-100 mm). All 540 patients (52% female; age range, 16-30 years; 95% white) were included in the efficacy analysis. For the primary efficacy endpoint (weighted sum of the pain intensity difference from baseline [PID] and pain relief [PAR] scores over 6 hours [SPRID6]), acetaminophen 1000 mg demonstrated a 24% improvement compared with acetaminophen 650 mg (529.4 vs 427.3; P = 0.001). In addition, acetaminophen 650 mg was significantly superior compared with placebo (P < 0.001). The weighted sum of PID over 6 hours (SPID6), the weighted total pain relief over 6 hours (TOTPAR6), and the percentage of patients with >50% of the maximum possible TOTPAR6 score were significantly greater for patients treated with acetaminophen 1000 mg compared with those receiving acetaminophen 650 mg (P ≤ 0.006) or placebo (P < 0.001) and for patients treated with acetaminophen 650 mg compared with placebo (P < 0.001). Time to rescue, rescue rates through 4 and 6 hours, and patient global assessment demonstrated similar findings. Patients treated with acetaminophen 1000 mg or 650 mg had a significantly different distribution in times to confirmed perceptible and meaningful pain relief compared with those receiving placebo (P < 0.001). Adverse events were reported by 18.5% of patients, with no clinically important difference between active treatment groups and placebo. Acetaminophen 1000 mg provided clinically meaningful and statistically significantly greater efficacy in treating postsurgical dental pain compared with acetaminophen 650 mg and placebo. The outcomes of this study are limited to the single-dose design of this study. ClinicalTrials.gov identifier: NCT01115673. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

Efficacy of bladder neck incision on urodynamic abnormalities in patients with posterior urethral valves.

PubMed

Sarin, Yogesh K; Sinha, Shalini

2013-04-01

This study aims to study the efficacy of simultaneous endoscopic bladder neck incision (BNI) and primary endoscopic valve incision (PEVI) in patients with posterior urethral valves (PUV). Nine PUV patients underwent PEVI and BNI over a year. They were compared to nine comparable historical controls that had undergone only PEVI. Trends in renal function tests, urodynamics and changes in the upper urinary tracts were evaluated after 3 months during which no pharmacotherapy was given. The incidence of bladder dysfunction in the two groups was similar-55.5 % in case group and 66.6 % in control group. Hypocompliant, high-pressure bladder was the predominant cystometric finding in both groups. Three patients in the case group and two patients in the control group had high end infusion pressure (EIP) with poor compliance. Detrusor overactivity (DOA) was seen in 23.1 % patients in the case group as compared to 55.5 % patients in the control group (P = 0.3348). Five patients in both groups were later started on anticholinergics due to raised EIP, small capacity bladder and/or DOA. Although BNI should theoretically improve the outcome of PUV patients, the current pilot study failed to demonstrate any significant difference. A larger sample size and longer follow-up are required to prove or disprove its efficacy.

Clinical studies of sweat rate reduction by an over-the-counter soft-solid antiperspirant and comparison with a prescription antiperspirant product in male panelists.

PubMed

Swaile, D F; Elstun, L T; Benzing, K W

2012-03-01

Individuals with axillary hyperhidrosis have much higher than average sweat rates and are often prescribed anhydrous aluminum chloride (AlCl(3)) solutions. Topical application of these solutions can be irritating to the skin, resulting in poor compliance and lower than desired efficacy. Demonstrate the efficacy of an over the counter "clinical strength" soft-solid antiperspirant using a night time application regimen and compare to a prescription aluminum chloride (6.5%) antiperspirant using male panelists. Gravimetric hot room efficacy testing (100 F and 35% Humidity) was performed comparing an over the counter soft-solid antiperspirant to placebo in a single test. Two separate gravimetric tests were placed comparing a prescription aluminum chloride (6.5%) antiperspirant to the same soft solid product using an intent to treat model. Skin irritation was assessed daily by a trained grader. Placebo testing resulted in 85% of panelists having a reduction in sweating rate greater than 50%. Comparison testing showed the over the counter soft solid reduced sweat rate by an average of 34% better than the prescription product while resulting significantly less skin irritation. Over the counter "clinical strength" soft-solid antiperspirants can be considered as an alternative treatment to aluminum chloride antiperspirants for the treatment of heavy sweating. © 2012 The Author. BJD © 2012 British Association of Dermatologists.

Hummingbird wing efficacy depends on aspect ratio and compares with helicopter rotors

PubMed Central

Kruyt, Jan W.; Quicazán-Rubio, Elsa M.; van Heijst, GertJan F.; Altshuler, Douglas L.; Lentink, David

2014-01-01

Hummingbirds are the only birds that can sustain hovering. This unique flight behaviour comes, however, at high energetic cost. Based on helicopter and aeroplane design theory, we expect that hummingbird wing aspect ratio (AR), which ranges from about 3.0 to 4.5, determines aerodynamic efficacy. Previous quasi-steady experiments with a wing spinner set-up provide no support for this prediction. To test this more carefully, we compare the quasi-steady hover performance of 26 wings, from 12 hummingbird taxa. We spun the wings at angular velocities and angles of attack that are representative for every species and measured lift and torque more precisely. The power (aerodynamic torque × angular velocity) required to lift weight depends on aerodynamic efficacy, which is measured by the power factor. Our comparative analysis shows that AR has a modest influence on lift and drag forces, as reported earlier, but interspecific differences in power factor are large. During the downstroke, the power required to hover decreases for larger AR wings at the angles of attack at which hummingbirds flap their wings (p < 0.05). Quantitative flow visualization demonstrates that variation in hover power among hummingbird wings is driven by similar stable leading edge vortices that delay stall during the down- and upstroke. A side-by-side aerodynamic performance comparison of hummingbird wings and an advanced micro helicopter rotor shows that they are remarkably similar. PMID:25079868

Stimuli-free programmable drug release for combination chemo-therapy

NASA Astrophysics Data System (ADS)

Fan, Li; Jin, Boquan; Zhang, Silu; Song, Chaojun; Li, Quan

2016-06-01

Combinational chemotherapy capable of targeted delivery and programmable multi-drug release leads to enhanced drug efficacy, and is highly desired for cancer treatment. However, effective approaches for achieving both features in a single treatment are limited. In the present work, we demonstrated programmed delivery of both chemotherapeutic and immunotherapeutic agents with tumor cell targeting capability by using SiO2 based self-decomposable nanoparticulate systems. The programmable drug delivery is realized by manipulating drug loading configurations instead of relying on external stimuli. Both in vitro and in vivo results showed specific drug binding to FAT1-expressing colon cancer cells. The loaded dual drugs were demonstrated to be delivered in a sequential manner with specific time intervals between their peak releases, which maximize the synergistic effect of the chemotherapeutics. These features led to significantly enhanced drug efficacy and reduced system toxicity. The tumor weight decreased by 1/350, together with a moderate increase in rats' body weight, which were observed when adopting the dual drug loaded nanoparticles, as compared to those of the control groups. The present system provides a simple and feasible method for the design of targeting and combination chemotherapy with programmed drug release.Combinational chemotherapy capable of targeted delivery and programmable multi-drug release leads to enhanced drug efficacy, and is highly desired for cancer treatment. However, effective approaches for achieving both features in a single treatment are limited. In the present work, we demonstrated programmed delivery of both chemotherapeutic and immunotherapeutic agents with tumor cell targeting capability by using SiO2 based self-decomposable nanoparticulate systems. The programmable drug delivery is realized by manipulating drug loading configurations instead of relying on external stimuli. Both in vitro and in vivo results showed specific drug binding to FAT1-expressing colon cancer cells. The loaded dual drugs were demonstrated to be delivered in a sequential manner with specific time intervals between their peak releases, which maximize the synergistic effect of the chemotherapeutics. These features led to significantly enhanced drug efficacy and reduced system toxicity. The tumor weight decreased by 1/350, together with a moderate increase in rats' body weight, which were observed when adopting the dual drug loaded nanoparticles, as compared to those of the control groups. The present system provides a simple and feasible method for the design of targeting and combination chemotherapy with programmed drug release. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06305a

The MUC1 Ectodomain: A Novel and Efficient Target for Gold Nanoparticle Clustering and Vapor Nanobubble Generation

PubMed Central

Danysh, Brian P.; Constantinou, Pamela E.; Lukianova-Hleb, Ekaterina Y.; Lapotko, Dmitri O.; Carson, Daniel D.

2012-01-01

MUC1 is a large, heavily glycosylated transmembrane glycoprotein that is proposed to create a protective microenvironment in many adenocarcinomas. Here we compare MUC1 and the well studied cell surface receptor target, EGFR, as gold nanoparticle (AuNP) targets and their subsequent vapor nanobubble generation efficacy in the human epithelial cell line, HES. Although EGFR and MUC1 were both highly expressed in these cells, TEM and confocal images revealed MUC1 as a superior target for nanoparticle intracellular accumulation and clustering. The MUC1-targeted AuNP intracellular clusters also generated significantly larger vapor nanobubbles. Our results demonstrate the promising opportunities MUC1 offers to improve the efficacy of targeted nanoparticle based approaches. PMID:22916077

A meta-analysis of anxiety symptom prevention with cognitive-behavioral interventions.

PubMed

Zalta, Alyson K

2011-06-01

This meta-analysis assessed efficacy of cognitive-behavioral interventions in preventing anxiety symptoms. A systematic review identified 15 independent pretest-posttest randomized or quasi-randomized efficacy trials for analysis. At posttest, intervention groups demonstrated significantly greater symptom reduction compared to control groups resulting in weighted mean effect sizes (Hedges' g) of 0.25 for general anxiety, 0.24 for disorder-specific symptoms, and 0.22 for depression after the removal of outliers. These effects appeared to diminish over 6- and 12-month follow-up. Exploratory moderator analyses indicated that individually administered media interventions were more effective than human-administered group interventions at preventing general anxiety and depression symptoms. Implications of current findings are discussed with attention to existing gaps in the literature.

Azelaic acid gel 15% in the management of papulopustular rosacea: a status report on available efficacy data and clinical application.

PubMed

Del Rosso, James Q; Bhatia, Neal

2011-08-01

Azelaic acid (AzA) gel 15% is approved by the US Food and Drug Administration (FDA) for the treatment of papulopustular rosacea (PPR). Its efficacy and safety as monotherapy have been demonstrated. Release of active drug from the gel formulation is superior to the cream. The combination of AzA gel 15% with oral doxycycline appears to expedite and augment response, especially in cases of PPR of greater severity, and AzA gel 15% maintains control of PPR over 6 months as compared to vehicle. Adjunctive skin care is recommended to augment the therapeutic outcome of PPR and reduce the potential for irritation that can occur with topical therapy.

Attenuation of neurobehavioral and neurochemical abnormalities in animal model of cognitive deficits of Alzheimer's disease by fermented soybean nanonutraceutical.

PubMed

Bhatt, Prakash Chandra; Pathak, Shruti; Kumar, Vikas; Panda, Bibhu Prasad

2018-02-01

The present study was performed to evaluate the efficacy of nanonutraceuticals (NN) for attenuation of neurobehavioral and neurochemical abnormalities in Alzheimer's disease. Solid-state fermentation of soybean with Bacillus subtilis was performed to produce different metabolites (nattokinase, daidzin, genistin and glycitin and menaquinone-7). Intoxication of rats with colchicine caused impairment in learning and memory which was demonstrated in neurobehavioral paradigms (Morris water maze and passive avoidance) linked with decreased activity of acetylcholinesterase (AChE). NN treatment led to a significant increase in TLT in the retention trials as compared to acquisition trial TLT suggesting an improved learning and memory in rats. Further, treatment of NN caused an increase in the activity of AChE (42%), accompanied with a reduced activity of glutathione (42%), superoxide dismutase (43%) and catalase (41%). It also decreased the level of lipid peroxidation (28%) and protein carbonyl contents (30%) in hippocampus as compared to those treated with colchicine alone, suggesting a possible neuroprotective efficacy of NN. Interestingly, in silico studies also demonstrated an effective amyloid-β and BACE-1 inhibition activity. These findings clearly indicated that NN reversed colchicine-induced behavioral and neurochemical alterations through potent antioxidant activity and could possibly impart beneficial effects in cognitive defects associated with Alzheimer's disease.

The relationship between nature of science understandings and science self-efficacy beliefs of sixth grade students

NASA Astrophysics Data System (ADS)

Parker, Elisabeth Allyn

Bandura (1986) posited that self-efficacy beliefs help determine what individuals do with the knowledge and skills they have and are critical determinants of how well skill and knowledge are acquired. Research has correlated self-efficacy beliefs with academic success and subject interest (Pajares, Britner, & Valiante, 2000). Similar studies report a decreasing interest by students in school science beginning in middle school claiming that they don't enjoy science because the classes are boring and irrelevant to their lives (Basu & Barton, 2007). The hypothesis put forth by researchers is that students need to observe models of how science is done, the nature of science (NOS), so that they connect with the human enterprise of science and thereby raise their self-efficacy (Britner, 2008). This study examined NOS understandings and science self-efficacy of students enrolled in a sixth grade earth science class taught with explicit NOS instruction. The research questions that guided this study were (a) how do students' self-efficacy beliefs change as compared with changes in their nature of science understandings?; and (b) how do changes in students' science self-efficacy beliefs vary with gender and ethnicity segregation? A mixed method design was employed following an embedded experimental model (Creswell & Plano Clark, 2007). As the treatment, five NOS aspects were first taught by the teachers using nonintegrated activities followed by integrated instructional approach (Khishfe, 2008). Students' views of NOS using the Views on Nature of Science (VNOS) (Lederman, Abd-El-Khalick, & Schwartz, 2002) along with their self-efficacy beliefs using three Likert-type science self-efficacy scales (Britner, 2002) were gathered. Changes in NOS understandings were determined by categorizing student responses and then comparing pre- and post-instructional understandings. To determine changes in participants' self-efficacy beliefs as measured by the three subscales, a multivariate analysis of covariance (MANCOVA) was conducted. Findings indicated that explicit NOS instruction was effective for all students except minority (Black, Hispanic, Asian, or multiracial) male students in improving NOS understandings. Furthermore, all students that received NOS instruction demonstrated decreased anxiety towards science. Future research should focus on long-term investigations of changes in anxiety and value of research constructs with regards to NOS instruction.

The outcomes of anxiety, confidence, and self-efficacy with Internet health information retrieval in older adults: a pilot study.

PubMed

Chu, Adeline; Mastel-Smith, Beth

2010-01-01

Technology has a great impact on nursing practice. With the increasing numbers of older Americans using computers and the Internet in recent years, nurses have the capability to deliver effective and efficient health education to their patients and the community. Based on the theoretical framework of Bandura's self-efficacy theory, the pilot project reported findings from a 5-week computer course on Internet health searches in older adults, 65 years or older, at a senior activity learning center. Twelve participants were recruited and randomized to either the intervention or the control group. Measures of computer anxiety, computer confidence, and computer self-efficacy scores were analyzed at baseline, at the end of the program, and 6 weeks after the completion of the program. Analysis was conducted with repeated-measures analysis of variance. Findings showed participants who attended a structured computer course on Internet health information retrieval reported lowered anxiety and increased confidence and self-efficacy at the end of the 5-week program and 6 weeks after the completion of the program as compared with participants who were not in the program. The study demonstrated that a computer course can help reduce anxiety and increase confidence and self-efficacy in online health searches in older adults.

Clinical efficacy and safety of bevacizumab monotherapy in patients with metastatic melanoma: predictive importance of induced early hypertension.

PubMed

Schuster, Cornelia; Eikesdal, Hans P; Puntervoll, Hanne; Geisler, Jürgen; Geisler, Stephanie; Heinrich, Daniel; Molven, Anders; Lønning, Per E; Akslen, Lars A; Straume, Oddbjørn

2012-01-01

VEGF driven angiogenesis plays a key role in cancer progression. We determined the clinical efficacy of bevacizumab monotherapy in patients with metastatic melanoma. Thirty-five patients with metastatic melanoma in progression were enrolled in this phase II, single arm clinical trial. Each patient received bevacizumab monotherapy 10 mg/kg q14 d until intolerable toxicity or disease progression occurred. Clinical efficacy was evaluated as objective response, disease control (DC), and survival. We observed one complete (3%) and 5 partial (14%) responses. In addition, 5 patients experienced stable disease >6 months (14%) while 24 patients had progressive disease (PD, 69%), corresponding to a total DC at 6 months in 11 out of 35 patients (31%). Median progression free survival (PFS) was 2.14 months and median overall survival (OS) was 9 months (1.12-49). Seven of the 11 patients experiencing DC developed early hypertension (<2 months) compared to 3/24 of patients with PD (P = 0.001), and hypertension was associated with PFS (P = 0.005) and OS (P = 0.013). Bevacizumab monotherapy demonstrated promising clinical efficacy in patients with metastatic melanoma with disease control in 31% of the patients. Induced early hypertension was a marker for clinical efficacy of bevacizumab. ClinicalTrials.gov NCT00139360.

Clinical efficacy and safety of olmesartan/hydrochlorothiazide combination therapy in patients with essential hypertension

PubMed Central

Ruilope, Luis M

2008-01-01

Hypertension is a major risk factor for cardiovascular disease that contributes to the premature death of millions of people each year, and identification and treatment of hypertension continues to be a challenge. Guidelines recommend that many patients will require two or more antihypertensive agents from different classes. Combining an angiotensin II receptor blocker (ARB) with hydrochlorothiazide (HCTZ) has been shown in clinical studies to increase the antihypertensive efficacy of both agents compared with either agent alone. This review covers several clinical trials and aims to examine several aspects of the efficacy of the combination of olmesartan and HCTZ, including dose-responsiveness, long-term efficacy, goal rate achievement, and efficacy in patients with moderate to severe hypertension. The results presented here demonstrate that olmesartan is effective when added to HCTZ monotherapy or when HCTZ is added to olmesartan monotherapy, both over the short and long term. Moderate to severe hypertension responds well to olmesartan/HCTZ combination therapy, and the great majority of patients are able to achieve recommended blood pressure targets. Thus olmesartan/HCTZ is a well-tolerated option for patients who fail to respond to monotherapy and as initial therapy in those who require large reductions in diastolic blood pressure or systolic blood pressure to achieve goal blood pressure. PMID:19337537

The Efficacy of Internet-based Cognitive Behavioral Therapy on the Anxiety Disorders among Adolescent Girls

PubMed Central

Karbasi, Afsaneh; Haratian, Azadeh

2018-01-01

Background: The prevalence of anxiety disorders among children and adolescents are found to be approximately between 8–12 and 5–10, respectively, and the long-lasting effects of such disorders can expose the sufferers to impairment and dysfunction in several areas of life the examples of which are poor educational performance, low self-esteem, and depression. The present study aims to evaluate the efficacy of internet-based, cognitive-behavioral therapy (ICBT) in treating the anxiety disorders among adolescent females. Materials and Methods: The sample included thirty girls aged between 10 and 18 years suffering from a variety of anxiety disorders, under pharmaceutical therapy and referred to clinics of child and adolescent psychiatry specialists in Isfahan. The sample was selected through diagnostic interviews by psychiatrists based on the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision; afterward, they were randomly assigned to either the experimental or the control groups. To evaluate the efficacy of an ICBT in reducing anxiety disorder symptoms, Screen for Child Anxiety Related Emotional Disorders questionnaire was administered among the patients both before and 4 weeks after the treatment. Results: The covariance analysis results aimed to compare the anxiety disorder score variations between the two groups which demonstrate the fact that anxiety disorder scores in these two groups differ from one another (P < 0.001). Conclusions: This study is comprised of two Conclusions.the significant reduction in the mean of anxiety disorders scores in the experimental group compared to those in control group can be indicative of the efficacy of ICBT. In addition the significant reduction in the average of anxiety disorders symptoms’ scores according to the type of anxiety disorders in the experimental group, compared to those in control group, can be indicative of the efficacy of ICBT. PMID:29456984

Efficacy and tolerability assessment of a topical formulation containing copper sulfate and hypericum perforatum on patients with herpes skin lesions: a comparative, randomized controlled trial.

PubMed

Clewell, Amy; Barnes, Matt; Endres, John R; Ahmed, Mansoor; Ghambeer, Daljit K S

2012-02-01

Topical Acyclovir has moderate efficacy on recurrent HSV symptoms, requiring repeat applications for several days. Topical Dynamiclear, which requires only a single dose application, may provide a more effective and convenient treatment option for symptomatic management of HSV. The study assessed the comparative efficacy and tolerability of a single use, topical formulation containing copper sulfate pentahydrate and Hypericum perforatum that is marketed as Dynamiclear™ to a topical 5% Acyclovir cream standard preparation and use. A prospective, randomized, multi-centered, comparative, open-label clinical study was conducted. A total of 149 participants between 18 and 55 years of age with active HSV-1 and HSV-2 lesions were recruited for the 14-day clinical trial. Participants were randomized into two groups: A (n=61), those receiving the Dynamiclear formulation, and B (n=59), those receiving 5% Acyclovir. Efficacy parameters were assessed via physical examination at baseline (day 1), day 2, 3, 8, and 14. Laboratory safety tests were conducted at baseline and on day 14. Use of the Dynamiclear formulation was found to have no significant adverse effects and was well tolerated by participants. All hematological and biochemical markers were within normal range for the Dynamiclear group. Statistically, odds for being affected by burning and stinging sensation were 1.9 times greater in the Acyclovir group in comparison to the Dynamiclear group. Similarly, the odds of being affected by symptoms of acute pain, erythema and vesiculation were 1.8, 2.4, and 4.4 times higher in the Acyclovir group in comparison to the Dynamiclear group. The Dynamiclear formulation was well tolerated, and efficacy was demonstrated in a number of measured parameters, which are helpful in the symptomatic management of HSV-1 and HSV-2 lesions in adult patients. Remarkably, the effects seen from this product came from a single application.

Superior therapeutic efficacy of nab-paclitaxel over cremophor-based paclitaxel in locally advanced and metastatic models of human pancreatic cancer.

PubMed

Rajeshkumar, N V; Yabuuchi, Shinichi; Pai, Shweta G; Tong, Zeen; Hou, Shihe; Bateman, Scott; Pierce, Daniel W; Heise, Carla; Von Hoff, Daniel D; Maitra, Anirban; Hidalgo, Manuel

2016-08-09

Albumin-bound paclitaxel (nab-paclitaxel, nab-PTX) plus gemcitabine (GEM) combination has demonstrated efficient antitumour activity and statistically significant overall survival of patients with metastatic pancreatic ductal adenocarcinoma (PDAC) compared with GEM monotherapy. This regimen is currently approved as a standard of care treatment option for patients with metastatic PDAC. It is unclear whether cremophor-based PTX combined with GEM provide a similar level of therapeutic efficacy in PDAC. We comprehensively explored the antitumour efficacy, effect on metastatic dissemination, tumour stroma and survival advantage following GEM, PTX and nab-PTX as monotherapy or in combination with GEM in a locally advanced, and a highly metastatic orthotopic model of human PDAC. Nab-PTX treatment resulted in significantly higher paclitaxel tumour plasma ratio (1.98-fold), robust stromal depletion, antitumour efficacy (3.79-fold) and survival benefit compared with PTX treatment. PTX plus GEM treatment showed no survival gain over GEM monotherapy. However, nab-PTX in combination with GEM decreased primary tumour burden, metastatic dissemination and significantly increased median survival of animals compared with either agents alone. These therapeutic effects were accompanied by depletion of dense fibrotic tumour stroma and decreased proliferation of carcinoma cells. Notably, nab-PTX monotherapy was equivalent to nab-PTX plus GEM in providing survival advantage to mice in a highly aggressive metastatic PDAC model, indicating that nab-PTX could potentially stop the progression of late-stage pancreatic cancer. Our data confirmed that therapeutic efficacy of PTX and nab-PTX vary widely, and the contention that these agents elicit similar antitumour response was not supported. The addition of PTX to GEM showed no survival advantage, concluding that a clinical combination of PTX and GEM may unlikely to provide significant survival advantage over GEM monotherapy and may not be a viable alternative to the current standard-of-care nab-PTX plus GEM regimen for the treatment of PDAC patients.

Treatment of tardive dyskinesia with tetrabenazine or valbenazine: a systematic review.

PubMed

Caroff, Stanley N; Aggarwal, Saurabh; Yonan, Charles

2018-02-01

Up to 30% of patients taking antipsychotics may develop tardive dyskinesia (TD). Recent evidence-based recommendations demonstrate an unmet need for effective TD management. This systematic review was designed to update the evidence for TD treatment, comparing two vesicular monoamine transporter 2 (VMAT2) inhibitors, tetrabenazine and valbenazine. Of 487 PubMed/Embase search results, 11 studies met the review criteria. Valbenazine efficacy was demonstrated in rigorously designed clinical trials that meet the guidelines for AAN Class I evidence. Due to differences in study designs and a lack of standardized and controlled trials with tetrabenazine, a formal meta-analysis comparing the agents was not possible. However, valbenazine appears to have fewer side effects and a more favorable once-daily dosing regimen for the treatment of TD.

Efficacy of a novel topical fipronil, (S)-methoprene, eprinomectin and praziquantel combination against naturally acquired intestinal nematode and cestode infections in cats.

PubMed

Knaus, Martin; Abu-Madi, Marawan A; Ibarra-Velarde, Froylán; Kok, Dawie J; Kusi, Ilir; Postoli, Rezart; Chester, S Theodore; Rosentel, Joseph; Alva, Roberto; Irwin, Jennifer; Visser, Martin; Winter, Renate; Rehbein, Steffen

2014-04-28

The efficacy of a novel topical combination formulation of fipronil, (S)-methoprene, eprinomectin and praziquantel against naturally acquired intestinal nematode and cestode infections in cats was evaluated in seven negative control, blinded studies. Cats were selected based on a pre-treatment faecal examination indicating a patent infection with at least hookworms (two studies), Toxocara ascarids (one study), taeniid cestodes (two studies) or Dipylidium cestodes (two studies). In each study, cats were assigned randomly to blocks of two animals each, based on decreasing pre-treatment body weight and were randomly allocated to one of two groups of six to 12 cats: untreated (control) or treated with topical fipronil (8.3%, w/v), (S)-methoprene (10%, w/v), eprinomectin (0.4%, w/v) and praziquantel (8.3%, w/v) (BROADLINE(®), Merial) at 0.12 mL/kg body weight (providing a minimum of 10mg fipronil+12 mg S-methoprene+0.5mg eprinomectin+10mg praziquantel per kg body weight). The topical treatment was administered directly on the skin in the midline of the neck in a single spot once on Day 0. For parasite recovery and count, cats were euthanized humanely and necropsied seven or ten days after treatment. A single treatment with the novel topical combination product provided 91% efficacy against Ancylostoma braziliense, ≥ 99% efficacy against Ancylostoma tubaeforme, and >97% efficacy against Toxocara cati. Similarly, excellent efficacy was established against Taenia taeniaeformis, Dipylidium caninum and Diplopylidium spp. as demonstrated by >97% and up to 100% reductions of cestode counts in the treated cats when compared to the untreated controls (P<0.01). All cats accepted the treatment well based on health observations post-treatment and daily health observations. No adverse experiences or other health problems were observed throughout the studies. The results of this series of controlled studies demonstrated high efficacy and excellent acceptability of the novel topical combination formulation of fipronil, (S)-methoprene, eprinomectin and praziquantel against a broad range of feline intestinal nematode and cestode infections. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Preclinical assessment of a new recombinant ADAMTS-13 drug product (BAX930) for the treatment of thrombotic thrombocytopenic purpura.

PubMed

Kopić, A; Benamara, K; Piskernik, C; Plaimauer, B; Horling, F; Höbarth, G; Ruthsatz, T; Dietrich, B; Muchitsch, E-M; Scheiflinger, F; Turecek, M; Höllriegl, W

2016-07-01

Essentials ADAMTS-13-deficiency is a cause of thrombotic thrombocytopenic purpura (TTP). Preclinical safety of recombinant human ADAMTS-13 (BAX930) was shown in animal models. Preclinical efficacy of BAX930 was shown in a mouse model of TTP. BAX930 showed advantageous efficacy over fresh frozen plasma, the current standard of care. Click to hear Dr Cataland and Prof. Lämmle present a seminar on Thrombotic Thrombocytopenic Purpura (TTP): new Insights in Pathogenesis and Treatment Modalities. Background Thrombotic thrombocytopenic purpura (TTP) is a rare blood disorder characterized by microthrombosis in small blood vessels of the body, resulting in a low platelet count. Baxalta has developed a new recombinant ADAMTS-13 (rADAMTS-13) product (BAX930) for on-demand and prophylactic treatment of patients with hereditary TTP (hTTP). Objectives To evaluate the pharmacokinetics, efficacy and safety of BAX930 in different species, by use of an extensive preclinical program. Methods The prophylactic and therapeutic efficacies of BAX930 were tested in a previously established TTP mouse model. Pharmacokinetics were evaluated after single intravenous bolus injection in mice and rats, and after repeated dosing in cynomolgus monkeys. Toxicity was assessed in rats and monkeys, safety pharmacology in monkeys, and local tolerance in rabbits. Results BAX930 was shown to be efficacious, as demonstrated by a stabilized platelet count in ADAMTS-13 knockout mice that were thrombocytopenic when treated. Prophylactic efficacy was dose-dependent and comparable with that achieved by treatment with fresh frozen plasma, the mainstay of hTTP treatment. Therapeutic efficacy was treatment interval-dependent. Safety pharmacology evaluation did not show any deleterious effects of BAX930 on cardiovascular and respiratory functions in monkeys. The compound's pharmacokinetics were similar and dose-proportional in mice, rats, and monkeys. BAX930 was well tolerated in rats, monkeys, and rabbits, even at the highest doses tested. Conclusions These results demonstrate that BAX930 has a favorable preclinical profile, and support the clinical development of rADAMTS-13 for the treatment of hTTP. © 2016 International Society on Thrombosis and Haemostasis.

Increasing Daily Water Intake and Fluid Adherence in Children Receiving Treatment for Retentive Encopresis

PubMed Central

Hoodin, Flora; Rice, Jennifer; Felt, Barbara T.; Rausch, Joseph R.; Patton, Susana R.

2010-01-01

Objective To examine the efficacy of an enhanced intervention (EI) compared to standard care (SC) in increasing daily water intake and fluid goal adherence in children seeking treatment for retentive encopresis. Methods Changes in beverage intake patterns and fluid adherence were examined by comparing 7-week diet diary data collected during participation in the EI to achieved data for families who had previously completed the SC. Results Compared to children in SC (n = 19), children in the EI (n = 18) demonstrated a significantly greater increase in daily water intake from baseline to the conclusion of treatment ( p ≤ .001), and were four and six times more likely to meet fluid targets in Phases 1 (Weeks 3–4) and 2 (Weeks 5–6) of fluid intervention, respectively (both p ≤ .001). Conclusions Enhanced education and behavioral strategies were efficacious in increasing children’s intake of water and improving fluid adherence. Future research should replicate the findings in a prospective randomized clinical trial to discern their effectiveness. PMID:20439348

Efficacy and durability of nevirapine in antiretroviral drug näive patients.

PubMed

Lange, Joep M A

2003-09-01

Nevirapine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that was first reported in the scientific literature in 1990. Varying doses of nevirapine (NVP) and a number of regimens containing this NNRTI have been studied in antiretroviral (ARV) näive patients. Four key studies have compared the efficacy and safety of triple drug regimens containing NVP in ARV näive, HIV-1 infected patients. The INCAS study was the first demonstration of how to use NVP in an effective and durable manner: as a component of a triple drug regimen. The COMBINE Study was a comparison of protease inhibitor (PI)-based and NVP-based triple regimens. The Atlantic Study is comparing the safety and efficacy of three triple drug regimens in ARV näive patients. In this study, treatment consists of a divergent drug regimen (PI and nucleoside reverse transcriptase inhibitors, NRTIs) targeting both HIV-1 protease and reverse transcriptase or a convergent regimen targeting reverse transcriptase alone (three NRTIs or two NRTIs plus a NNRTI). A clinical endpoint study (BI 1090) compared the efficacy and durability of multi-drug regimens in ARV näive patients with high baseline plasma HIV-1 RNA levels (pVLs) and low peripheral blood CD4+ lymphocyte counts. Data from these studies confirm that triple regimens containing NVP suppressed viral replication for up to one year, even when the ARV näive patients had low CD4+ cell counts at baseline. Nevirapine-containing regimens suppressed pVLs to < 50 copies/ mL in approximately 50% of patients in the studies discussed (Intent to Treat analyses). Data from 96 weeks of follow up in the Atlantic Study demonstrates that the regimens containing didanosine and stavudine plus indinavir or NVP were significantly more successful in suppressing pVLs to < 50 copies/mL during this period than a regimen composed of these NRTIs and lamivudine (p < or = 0.001). As with other ARV drugs, NVP should always be used as part of a fully suppressive ARV regimen. When used in this way, it is an effective ARV drug, which contributes to durable virological and immunological responses in approximately half of all treated patients. Nevirapine-containing regimens are effective in patients with advanced HIV-1 infection, i.e., low CD4+ cell counts. Data will soon be available from the 2NN Study that compares the efficacy and safety of four different regimens using NVP once daily, NVP twice daily, efavirenz once daily or a combination of NVP and efavirenz. All four arms of the study include a backbone of stavudine and lamivudine.

Societal and Economic Effect of Meniscus Scaffold Procedures for Irreparable Meniscus Injuries.

PubMed

Rongen, Jan J; Govers, Tim M; Buma, Pieter; Grutters, Janneke P C; Hannink, Gerjon

2016-07-01

Meniscus scaffolds are currently evaluated clinically for their efficacy in preventing the development of osteoarthritis as well as for their efficacy in treating patients with chronic symptoms. Procedural costs, therapeutic consequences, clinical efficacy, and future events should all be considered to maximize the monetary value of this intervention. To examine the socioeconomic effect of treating patients with irreparable medial meniscus injuries with a meniscus scaffold. Economic and decision analysis; Level of evidence, 2. Two Markov simulation models for patients with an irreparable medial meniscus injury were developed. Model 1 was used to investigate the lifetime cost-effectiveness of a meniscus scaffold compared with standard partial meniscectomy by the possibility of preventing the development of osteoarthritis. Model 2 was used to investigate the short-term (5-year) cost-effectiveness of a meniscus scaffold compared with standard partial meniscectomy by alleviating clinical symptoms, specifically in chronic patients with previous meniscus surgery. For both models, probabilistic Monte Carlo simulations were applied. Treatment effectiveness was expressed as quality-adjusted life-years (QALYs), while costs (estimated in euros) were assessed from a societal perspective. We assumed €20,000 as a reference value for the willingness to pay per QALY. Next, comprehensive sensitivity analyses were performed to identify the most influential variables on the cost-effectiveness of meniscus scaffolds. Model 1 demonstrated an incremental cost-effectiveness ratio of a meniscus scaffold treatment of €54,463 per QALY (€5991/0.112). A threshold analysis demonstrated that a meniscus scaffold should offer a relative risk reduction of at least 0.34 to become cost-effective, assuming a willingness to pay of €20,000. Decreasing the costs of the meniscus scaffold procedure by 33% (€10,160 instead of €15,233; an absolute change of €5073) resulted in an incremental cost-effectiveness ratio of €7876 per QALY. Model 2 demonstrated an incremental cost-effectiveness ratio of a meniscus scaffold treatment of €297,727 per QALY (€9825/0.033). On the basis of the current efficacy data, a meniscus scaffold provides a relative risk reduction of "limited benefit" postoperatively of 0.37 compared with standard treatment. A threshold analysis revealed that assuming a willingness to pay of €20,000, a meniscus scaffold would not be cost-effective within a period of 5 years. Most influential variables on the cost-effectiveness of meniscus scaffolds were the cost of the scaffold procedure, cost associated with osteoarthritis, and quality of life before and after the scaffold procedure. Results of the current health technology assessment emphasize that the monetary value of meniscus scaffold procedures is very much dependent on a number of influential variables. Therefore, before implementing the technology in the health care system, it is important to critically assess these variables in a relevant context. The models can be improved as additional clinical data regarding the efficacy of the meniscus scaffold become available. © 2016 The Author(s).

Comparative oncology evaluation of intravenous recombinant oncolytic Vesicular Stomatitis Virus therapy in spontaneous canine cancer

PubMed Central

Naik, Shruthi; Galyon, Gina D.; Jenks, Nathan J.; Steele, Michael B.; Miller, Amber C.; Allstadt, Sara D.; Suksanpaisan, Lukkana; Peng, Kah Whye; Federspiel, Mark J.; Russell, Stephen J.; LeBlanc, Amy K.

2017-01-01

Clinical translation of intravenous therapies to treat disseminated or metastatic cancer is imperative. Comparative oncology, the evaluation of novel cancer therapies in animals with spontaneous cancer, can be utilized to inform and accelerate clinical translation. Preclinical murine studies demonstrate that single shot systemic therapy with a VSV-IFNβ-NIS, a novel recombinant oncolytic Vesicular stomatitis virus (VSV), can induce curative remission in tumor bearing mice. Clinical translation of VSV-IFNβ-NIS therapy is dependent on comprehensive assessment of clinical toxicities, virus shedding, pharmacokinetics, and efficacy in clinically relevant models. Dogs spontaneously develop cancer with comparable etiology, clinical progression and response to therapy as human malignancies. A comparative oncology study was carried out to investigate feasibility and tolerability of intravenous oncolytic VSV-IFNβ-NIS therapy in pet dogs with spontaneous cancer. Nine dogs with various malignancies were treated with a single intravenous dose of VSV-IFNβ-NIS. Two dogs with high-grade peripheral T-cell lymphoma had rapid but transient remission of disseminated disease and transient hepatotoxicity that resolved spontaneously. There was no shedding of infectious virus. Correlative pharmacokinetic studies revealed elevated levels of VSV RNA in blood in dogs with measurable disease remission. This is the first evaluation of intravenous oncolytic virus therapy for spontaneous canine cancer, demonstrating that VSV-IFNβ-NIS is well-tolerated and safe in dogs with advanced or metastatic disease. This approach has informed clinical translation, including dose and target indication selection, leading to a clinical investigation of intravenous VSV-IFNβ-NIS therapy, and provided preliminary evidence of clinical efficacy, and potential biomarkers that correlate with therapeutic response. PMID:29158470

Self-Efficacy for Resolving Environmental Uncertainties: Implications for Entrepreneurial Educational and Support Programs

ERIC Educational Resources Information Center

Pushkarskaya, Helen; Usher, Ellen L.

2010-01-01

Using a unique sample of rural Kentucky residents, we demonstrated that, in the domain of operational and competitive environmental uncertainties, self-efficacy beliefs are significantly higher among nascent entrepreneurs than among non-entrepreneurs. We employed the hierarchical logistic regression analysis to demonstrate that this result is…

Iron deficiency up-regulates iron absorption from ferrous sulphate but not ferric pyrophosphate and consequently food fortification with ferrous sulphate has relatively greater efficacy in iron-deficient individuals.

PubMed

Zimmermann, Michael B; Biebinger, Ralf; Egli, Ines; Zeder, Christophe; Hurrell, Richard F

2011-04-01

Fe absorption from water-soluble forms of Fe is inversely proportional to Fe status in humans. Whether this is true for poorly soluble Fe compounds is uncertain. Our objectives were therefore (1) to compare the up-regulation of Fe absorption at low Fe status from ferrous sulphate (FS) and ferric pyrophosphate (FPP) and (2) to compare the efficacy of FS with FPP in a fortification trial to increase body Fe stores in Fe-deficient children v. Fe-sufficient children. Using stable isotopes in test meals in young women (n 49) selected for low and high Fe status, we compared the absorption of FPP with FS. We analysed data from previous efficacy trials in children (n 258) to determine whether Fe status at baseline predicted response to FS v. FPP as salt fortificants. Plasma ferritin was a strong negative predictor of Fe bioavailability from FS (P < 0·0001) but not from FPP. In the efficacy trials, body Fe at baseline was a negative predictor of the change in body Fe for both FPP and FS, but the effect was significantly greater with FS (P < 0·01). Because Fe deficiency up-regulates Fe absorption from FS but not from FPP, food fortification with FS may have relatively greater impact in Fe-deficient children. Thus, more soluble Fe compounds not only demonstrate better overall absorption and can be used at lower fortification levels, but they also have the added advantage that, because their absorption is up-regulated in Fe deficiency, they innately 'target' Fe-deficient individuals in a population.

Tumor Necrosis Factor Inhibitor Primary Failure Predicts Decreased Ustekinumab Efficacy in Psoriasis Patients.

PubMed

Sorensen, Eric P; Fanucci, Kristina A; Saraiya, Ami; Volf, Eva; Au, Shiu-chung; Argobi, Yahya; Mansfield, Ryan; Gottlieb, Alice B

2015-08-01

Additional studies are needed to examine the efficacy of ustekinumab in psoriasis patients who have previously been exposed to tumor necrosis factor inhibitors (TNFi). To examine the predictive effect of TNFi primary failure and the number of TNFi exposures on the efficacy of ustekinumab in psoriasis treatment. This retrospective study examined 44 psoriasis patients treated at the Tufts Medical Center Department of Dermatology between January 2008 and July 2014. Patients were selected if they were treated with ustekinumab and had ≥ 1 previous TNFi exposure. The following subgroups were compared: patients with vs without a previous TNFi primary failure, and patients with one vs multiple previous TNFi exposures. The efficacy measure used was the previously validated Simple Measure for Assessing Psoriasis Activity (S-MAPA), which is calculated by the product of the body surface area and physician global assessment. The primary outcome was the percentage improvement S-MAPA from course baseline at week 12 of ustekinumab treatment. Secondary outcomes were the psoriasis clearance, primary failure, and secondary failure rates with ustekinumab treatment. Patients with a previous TNFi primary failure had a significantly lower percentage improvement in S-MAPA score at week 12 of ustekinumab treatment compared with patients without TNFi primary failure (36.2% vs 61.1%, P=.027). Multivariate analysis demonstrated that this relationship was independent of patient demographics and medical comorbidities. Patients with multiple TNFi exposures had a non-statistically significant lower percentage S-MAPA improvement at week 12 (40.5% vs 52.9%, P=.294) of ustekinumab treatment compared with patients with a single TNFi exposure. Among psoriasis patients previously exposed to TNFi, a history of a previous TNFi primary failure predicts a decreased response to ustekinumab independent of patient demographics and medical comorbidities.

Ziprasidone Augmentation of Escitalopram for Major Depressive Disorder: Efficacy Results From a Randomized, Double-Blind, Placebo-Controlled Study.

PubMed

Papakostas, George I; Fava, Maurizio; Baer, Lee; Swee, Michaela B; Jaeger, Adrienne; Bobo, William V; Shelton, Richard C

2015-12-01

The authors sought to test the efficacy of adjunctive ziprasidone in adults with nonpsychotic unipolar major depression experiencing persistent symptoms after 8 weeks of open-label treatment with escitalopram. This was an 8-week, randomized, double-blind, parallel-group, placebo-controlled trial conducted at three academic medical centers. Participants were 139 outpatients with persistent symptoms of major depression after an 8-week open-label trial of escitalopram (phase 1), randomly assigned in a 1:1 ratio to receive adjunctive ziprasidone (escitalopram plus ziprasidone, N=71) or adjunctive placebo (escitalopram plus placebo, N=68), with 8 weekly follow-up assessments. The primary outcome measure was clinical response, defined as a reduction of at least 50% in score on the 17-item Hamilton Depression Rating Scale (HAM-D). The Hamilton Anxiety Rating scale (HAM-A) and Visual Analog Scale for Pain were defined a priori as key secondary outcome measures. Rates of clinical response (35.2% compared with 20.5%) and mean improvement in HAM-D total scores (-6.4 [SD=6.4] compared with -3.3 [SD=6.2]) were significantly greater for the escitalopram plus ziprasidone group. Several secondary measures of antidepressant efficacy also favored adjunctive ziprasidone. The escitalopram plus ziprasidone group also showed significantly greater improvement on HAM-A score but not on Visual Analog Scale for Pain score. Ten (14%) patients in the escitalopram plus ziprasidone group discontinued treatment because of intolerance, compared with none in the escitalopram plus placebo group. Ziprasidone as an adjunct to escitalopram demonstrated antidepressant efficacy in adult patients with major depressive disorder experiencing persistent symptoms after 8 weeks of open-label treatment with escitalopram.

Pharmacokinetics and efficacy of intraocular flurbiprofen.

PubMed

Blazaki, S; Tsika, C; Tzatzarakis, M; Naoumidi, E; Tsatsakis, A; Tsatsanis, C; Tsilimbaris, Miltiadis K

2017-12-01

Intravitreal delivery of non-steroidal anti-inflammatory drugs could be an effective way to treat macular edema caused by posterior segment inflammation. In this study, we evaluated the intravitreal bioavailability and anti-inflammatory efficacy of flurbiprofen in rabbit eyes. For pharmacokinetics, 0.1 ml of 7.66 mg/ml flurbiprofen solution was injected intravitreally and vitreous drug levels were analyzed at specific time points using LC-MS technique. For efficacy, 100 ng lipopolysaccharide of E.coli was injected intravitreally in rabbits to induce inflammation. The animals were separated in three groups and received intraocular flurbiprofen, dexamethasone and PBS to serve as control. Complete ocular examination and total cell count in aqueous fluid were determined to evaluate the extent of inflammation. Eyes were then enucleated for histopathology analysis. The efficacy in the uveitis model was determined by clinical signs of inflammation, total leukocyte count and histology findings. No adverse events were observed during pharmacokinetic assessment. No signs of inflammation, hemorrhage or retina detachment were detected. The recovery of flurbiprofen from vitreous samples was 92.6%. The half-life of flurbiprofen was estimated to be 1.92 h with an elimination constant rate (K) of 0.36. Treatment with intraocular injections of flurbiprofen and dexamethasone significantly reduced total leukocyte count in a manner comparable to dexamethasone [reduction of 96.84% (p < 0.05) and 97.44% (p < 0.05), respectively]. Histologic studies demonstrated significantly less signs of ocular inflammation after flurbiprofen injection compared to control eyes. Flurbiprofen is effective in suppressing inflammation in this experimental uveitis model. In our experimental setting, intravitreal flurbiprofen seem to have a therapeutic result comparable to dexamethasone. However, the half-life of the drug remains short, necessitating further research to prolong its presence in the vitreous cavity.

Effect of a triclosan/PVM/MA copolymer/fluoride dentifrice on volatile sulfur compounds in vitro.

PubMed

Pilch, S; Williams, M I; Cummins, D

2005-01-01

The objective of the investigation was to document the in vitro efficacy of a triclosan/PVM/MA copolymer/fluoride (TCF) dentifrice against the formation of volatile sulfur compounds (VSC) as well as the growth of H2S-producing bacteria. Clinical studies using organoleptic judges, gas chromatography, or a portable sulfide monitor have generally been employed in the assessment of treatments for the control of oral malodor. However, these studies are not appropriate for screening purposes because of the expense and time required. An in vitro method was developed for the purpose of screening new compounds, agents or formulations for their ability to control VSC formation and for determining bio-equivalence of efficacy when implementing changes in existing formulations. The method combines basic microbiological methods, dynamic flow cell techniques and head space analysis. The in vitro VSC method was validated by comparing the efficacy of two dentifrices containing TCF with a control fluoride dentifrice as the TCF products have been clinically proven to control oral malodor. In the validation studies, the TCF-containing dentifrices were significantly better (P < 0.05) than the control dentifrice in inhibiting VSC formation and reducing H(2)S-producing bacteria. For example, when compared with baseline, the TCF dentifrices reduced VSC formation between 42 and 49% compared with the control dentifrice which reduced VSC formation 3%. There was no significant difference (P > 0.05) between the two TCF dentifrice formulations. Using an in vitro breath VSC model, it has been demonstrated that two variants of a dentifrice containing triclosan, PVM/MA copolymer and fluoride have efficacy that is significantly better than a control fluoridated dentifrice and that there is no significant difference between the triclosan/PVM/MA copolymer/fluoride dentifrice variants.

Comparing effectiveness of generic and disease-specific self-management interventions for people with diabetes in a practice context.

PubMed

Ghahari, Setareh; Packer, Tanya; Boldy, Duncan; Melling, Lauren; Parsons, Richard

2015-10-01

The effectiveness of self-management interventions has been demonstrated. However, the benefits of generic vs. disease-specific programs are unclear, and their efficacy within a practice setting has yet to be fully explored. To compare the outcomes of the diabetes-specific self-management program (Diabetes) and the generic chronic disease Self-management Program (Chronic Condition) and to explore whether program characteristics, evaluated using the Quality Self-Management Assessment Framework (Q-SAF), provide insight into the results of the outcome evaluation. A pragmatic pretest, post-test design with 12-week follow up was used to compare the 2 self-management interventions. Outcomes were quality of life, self-efficacy, loneliness, self-management skills, depression, and health behaviours. People with diabetes self-selected attendance at the Diabetes or Chronic Condition program offered as part of routine practice. Participants with diabetes in the 2 programs (Diabetes=200; Chronic Condition=90) differed significantly in almost all demographic and clinical characteristics. Both programs yielded positive outcomes. Controlling for baseline and demographic characteristics, random effects modelling showed an interaction between time and program for 1 outcome: self-efficacy (p=0.029). Participants in the Chronic Condition group experienced greater improvements over time than did those in the Diabetes group. The Q-SAF analysis showed differences in program content, delivery and workforce capacity. People with diabetes benefited from both programs, but participation in the generic program resulted in greater improvements in self-efficacy for participants who had self-selected that program. Both programs in routine care led to health-related improvements. The Q-SAF can be used to assess the quality of programs. Copyright © 2015 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

Enterohepatic recirculation of bioactive ginger phytochemicals is associated with enhanced tumor growth-inhibitory activity of ginger extract

PubMed Central

Gundala, Sushma R.; Mukkavilli, Rao; Yang, Chunhua; Aneja, Ritu

2014-01-01

Phytochemical complexity of plant foods confers health-promoting benefits including chemopreventive and anticancer effects. Isolating single constituents from complex foods may render them inactive, emphasizing the importance of preserving the natural composition of whole extracts. Recently, we demonstrated in vitro synergy among the most abundant bioactive constituents of ginger extract (GE), viz., 6-gingerol (6G), 8-gingerol (8G), 10-gingerol (10G) and 6-shogaol (6S). However, no study has yet examined the in vivo collaboration among ginger phytochemicals or evaluated the importance, if any, of the natural ‘milieu’ preserved in whole extract. Here, we comparatively evaluated in vivo efficacy of GE with an artificial quasi-mixture (Mix) formulated by combining four most active ginger constituents at concentrations equivalent to those present in whole extract. Orally fed GE showed 2.4-fold higher tumor growth-inhibitory efficacy than Mix in human prostate tumor xenografts. Pharmacokinetic evaluations and bioavailability measurements addressed the efficacy differences between GE and Mix. Plasma concentration-time profiles revealed multiple peaking phenomenon for ginger constituents when they were fed as GE as opposed to Mix, indicating enterohepatic recirculation. Bioavailability of 6G, 8G, 10G and 6S was 1.6-, 1.1-, 2.5- and 3.4-fold higher, respectively, when dosed with GE compared with Mix. In addition, gingerol glucuronides were detected in feces upon intravenous administration confirming hepatobiliary elimination. These data ascribe the superior in vivo efficacy of GE to higher area under the concentration time curves, greater residence time and enhanced bioavailability, of ginger phytochemicals, when fed as a natural extract compared with artificial Mix, emphasizing the usefulness of consuming whole foods over single agents. PMID:24431413

Analytical similarity assessment of rituximab biosimilar CT-P10 to reference medicinal product

PubMed Central

Lee, Kyoung Hoon; Kim, Yeon Jung; Kang, Hyun Ah; Kim, Sung Hwan; Lee, So Jung; Lim, Ki Jung; Jung, Soon Kwan; Chang, Shin Jae

2018-01-01

ABSTRACT CT-P10 (Truxima™) was recently approved as the world's first rituximab biosimilar product in the European Union (EU) and South Korea. To demonstrate biosimilarity of CT-P10 with the reference medicinal product (RMP), extensive 3-way similarity assessment has been conducted between CT-P10, EU-Rituximab and US-Rituximab, focusing on the physicochemical and biological quality attributes. A multitude of state-of-the-art analyses revealed that CT-P10 has identical primary and higher order structures compared to the original product. Purity/impurity profiles of CT-P10 measured by the levels of aggregates, fragments, non-glycosylated form and process-related impurities were also found to be comparable with those of RMPs. In terms of the post-translational modification, CT-P10 contains slightly less N-terminal pyro-glutamate variant, which has been known not to affect product efficacy or safety. Oligosaccharide profiling has revealed that, although CT-P10 contains the same conserved glycan species and relative proportion with the RMPs, the content of total afucosylated glycan in CT-P10 was slightly higher than in EU- or US-Rituximab. Nevertheless, the effect of the observed level of afucosylation in CT-P10 drug product on Fc receptor binding affinity or antibody-dependent cell-mediated cytotoxicity was found to be negligible based on the spiking study with highly afucosylated sample. Arrays of biological assays representative of known and putative mechanisms of action for rituximab have shown that biological activities of CT-P10 are within the quality range of RMPs. Recent results of clinical studies have further confirmed that the CT-P10 exhibits equivalent clinical efficacy and safety profiles compared to EU- and US-Rituximab. The current 3-way similarity assessment together with clinical study results confidently demonstrate that CT-P10 is highly similar with EU- and US-Rituximab in terms of physicochemical properties, biological activities, efficacy, and safety for its final approval as a biosimilar product. PMID:29469653

Long-term effectiveness of ranibizumab for age-related macular degeneration and diabetic macular edema

PubMed Central

Fong, Angie HC; Lai, Timothy YY

2013-01-01

Neovascular age-related macular degeneration (AMD) and diabetic macular edema (DME) are major causes of visual impairment in the elderly population worldwide. With the aging population, the prevalence of neovascular AMD and DME has increased substantially over the recent years. Vascular endothelial growth factor (VEGF) has been implicated as playing an important role in the pathogenesis of both neovascular AMD and DME. Since its introduction in 2006, ranibizumab, a recombinant, humanized, monoclonal antibody fragment against all isoforms of VEGF-A, has revolutionized the treatment of neovascular AMD and DME. The efficacy and safety of ranibizumab in neovascular AMD has been demonstrated in the ANCHOR and MARINA trials. Further studies including the PIER, PrONTO, and SUSTAIN trials have also evaluated the optimal dosing regimen of ranibizumab in neovascular AMD. The CATT and IVAN trials compared the safety and efficacy of ranibizumab with off-label use of bevacizumab. Studies such as SUSTAIN and HORIZON have shown that ranibizumab has a good safety profile and is well tolerated for over 4 years with very few serious ocular and systemic adverse events. For DME, Phase II RESOLVE study and Phase III RISE and RIDE studies have demonstrated superiority of ranibizumab treatment in improving vision over placebo controls. Phase II READ and Phase III RESOLVE and REVEAL studies have shown that ranibizumab is more effective both as monotherapy and in combination with laser compared with laser monotherapy. The 3-year results from the DRCRnet protocol I study found that ranibizumab with deferred laser resulted in better long-term visual outcome compared with ranibizumab with prompt laser. This review summarizes various important clinical trials on the long-term efficacy and safety of ranibizumab in the treatment of neovascular AMD and DME. The pharmacological properties of ranibizumab, its cost effectiveness, and impact on quality of life will also be discussed. PMID:23766636

Analytical similarity assessment of rituximab biosimilar CT-P10 to reference medicinal product.

PubMed

Lee, Kyoung Hoon; Lee, Jihun; Bae, Jin Soo; Kim, Yeon Jung; Kang, Hyun Ah; Kim, Sung Hwan; Lee, So Jung; Lim, Ki Jung; Lee, Jung Woo; Jung, Soon Kwan; Chang, Shin Jae

2018-04-01

CT-P10 (Truxima™) was recently approved as the world's first rituximab biosimilar product in the European Union (EU) and South Korea. To demonstrate biosimilarity of CT-P10 with the reference medicinal product (RMP), extensive 3-way similarity assessment has been conducted between CT-P10, EU-Rituximab and US-Rituximab, focusing on the physicochemical and biological quality attributes. A multitude of state-of-the-art analyses revealed that CT-P10 has identical primary and higher order structures compared to the original product. Purity/impurity profiles of CT-P10 measured by the levels of aggregates, fragments, non-glycosylated form and process-related impurities were also found to be comparable with those of RMPs. In terms of the post-translational modification, CT-P10 contains slightly less N-terminal pyro-glutamate variant, which has been known not to affect product efficacy or safety. Oligosaccharide profiling has revealed that, although CT-P10 contains the same conserved glycan species and relative proportion with the RMPs, the content of total afucosylated glycan in CT-P10 was slightly higher than in EU- or US-Rituximab. Nevertheless, the effect of the observed level of afucosylation in CT-P10 drug product on Fc receptor binding affinity or antibody-dependent cell-mediated cytotoxicity was found to be negligible based on the spiking study with highly afucosylated sample. Arrays of biological assays representative of known and putative mechanisms of action for rituximab have shown that biological activities of CT-P10 are within the quality range of RMPs. Recent results of clinical studies have further confirmed that the CT-P10 exhibits equivalent clinical efficacy and safety profiles compared to EU- and US-Rituximab. The current 3-way similarity assessment together with clinical study results confidently demonstrate that CT-P10 is highly similar with EU- and US-Rituximab in terms of physicochemical properties, biological activities, efficacy, and safety for its final approval as a biosimilar product.

Efficacy and safety of the biosimilar ABP 501 compared with adalimumab in patients with moderate to severe rheumatoid arthritis: a randomised, double-blind, phase III equivalence study

PubMed Central

Cohen, Stanley; Genovese, Mark C; Choy, Ernest; Perez-Ruiz, Fernando; Matsumoto, Alan; Pavelka, Karel; Pablos, Jose L; Rizzo, Warren; Hrycaj, Pawel; Zhang, Nan; Shergy, William; Kaur, Primal

2017-01-01

Objectives ABP 501 is a Food and Drug Administration-approved biosimilar to adalimumab; structural, functional and pharmacokinetic evaluations have shown that the two are highly similar. We report results from a phase III study comparing efficacy, safety and immunogenicity between ABP 501 and adalimumab. Methods In this randomised, double-blind, active comparator-controlled, 26-week equivalence study, patients with moderate to severe active rheumatoid arthritis (RA) despite methotrexate were randomised (1:1) to ABP 501 or adalimumab (40 mg) every 2 weeks. Primary endpoint was risk ratio (RR) of ACR20 between groups at week 24. Primary hypothesis that the treatments were equivalent would be confirmed if the 90% CI for RR of ACR20 at week 24 fell between 0.738 and 1.355, demonstrating that ABP 501 is similar to adalimumab. Secondary endpoints included Disease Activity Score 28-joint count-C reactive protein (DAS28-CRP). Safety was assessed via adverse events (AEs) and laboratory evaluations. Antidrug antibodies were assessed to determine immunogenicity. Results A total of 526 patients were randomised (n=264, ABP 501; n=262 adalimumab) and 494 completed the study. ACR20 response at week 24 was 74.6% (ABP 501) and 72.4% (adalimumab). At week 24, the RR of ACR20 (90% CI) between groups was 1.039 (0.954, 1.133), confirming the primary hypothesis. Changes from baseline in DAS28-CRP, ACR50 and ACR70 were similar. There were no clinically meaningful differences in AEs and laboratory abnormalities. A total of 38.3% (ABP 501) and 38.2% (adalimumab) of patients tested positive for binding antidrug antibodies. Conclusions Results from this study demonstrate that ABP 501 is similar to adalimumab in clinical efficacy, safety and immunogenicity in patients with moderate to severe RA. Trial registration number NCT01970475; Results. PMID:28584187

Tofacitinib in patients with ankylosing spondylitis: a phase II, 16-week, randomised, placebo-controlled, dose-ranging study.

PubMed

van der Heijde, Désirée; Deodhar, Atul; Wei, James C; Drescher, Edit; Fleishaker, Dona; Hendrikx, Thijs; Li, David; Menon, Sujatha; Kanik, Keith S

2017-08-01

To compare efficacy and safety of various doses of tofacitinib, an oral Janus kinase inhibitor, with placebo in patients with active ankylosing spondylitis (AS, radiographic axial spondyloarthritis). In this 16-week (12-week treatment, 4-week washout), phase II, multicentre, dose-ranging trial, adult patients with active AS were randomised (N=51, 52, 52, 52, respectively) to placebo or tofacitinib 2, 5 or 10 mg twice daily. The primary efficacy endpoint was Assessment of SpondyloArthritis International Society 20% improvement (ASAS20) response rate at week 12. Secondary endpoints included objective measures of disease activity, patient-reported outcomes and MRI of sacroiliac joints and spine. Safety was monitored. Emax model analysis of the primary endpoint predicted a tofacitinib 10 mg twice daily ASAS20 response rate of 67.4%, 27.3% higher than placebo. Supportive normal approximation analysis demonstrated tofacitinib 5 mg twice daily ASAS20 response rate significantly higher than placebo (80.8% vs 41.2%; p<0.001); tofacitinib 2 and 10 mg twice daily demonstrated greater response rate than placebo (51.9% and 55.8%, respectively; not significant). Secondary endpoints generally demonstrated greater improvements with tofacitinib 5 and 10 mg twice daily than placebo. Objective (including MRI) endpoints demonstrated clear dose response. Adverse events were similar across treatment groups with no unexpected safety findings. Dose-dependent laboratory outcome changes returned close to baseline by week 16. Tofacitinib 5 and 10 mg twice daily demonstrated greater clinical efficacy versus placebo in reducing signs, symptoms and objective endpoints of active AS in adult patients with a similar 12-week safety profile as reported in other indications. NCT01786668. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Selective serotonin reuptake inhibitors (SSRIs) for post-partum depression (PPD): a systematic review of randomized clinical trials.

PubMed

De Crescenzo, Franco; Perelli, Federica; Armando, Marco; Vicari, Stefano

2014-01-01

The treatment of postpartum depression with selective serotonin reuptake inhibitors (SSRIs) has been claimed to be both efficacious and well tolerated, but no recent systematic reviews have been conducted. A qualitative systematic review of randomized clinical trials on women with postpartum depression comparing SSRIs to placebo and/or other treatments was performed. A comprehensive literature search of online databases, the bibliographies of published articles and grey literature were conducted. Data on efficacy, acceptability and tolerability were extracted and the quality of the trials was assessed. Six randomised clinical trials, comprising 595 patients, met quality criteria for inclusion in the analysis. Cognitive-behavioural intervention, psychosocial community-based intervention, psychodynamic therapy, cognitive behavioural therapy, a second-generation tricyclic antidepressant and placebo were used as comparisons. All studies demonstrated higher response and remission rates among those treated with SSRIs and greater mean changes on depression scales, although findings were not always statistically significant. Dropout rates were high in three of the trials but similar among treatment and comparison groups. In general, SSRIs were well tolerated and trial quality was good. There are few trials, patients included in the trials were not representative of all patients with postpartum depression, dropout rates in three trials were high, and long-term efficacy and tolerability were assessed in only two trials. SSRIs appear to be efficacious and well tolerated in the treatment of postpartum depression, but the available evidence fails to demonstrate a clear superiority over other treatments. © 2013 Elsevier B.V. All rights reserved.

In Vivo Anticancer Efficacy and Toxicity Studies of a Novel Polymer Conjugate N-Acetyl Glucosamine (NAG)-PEG-Doxorubicin for Targeted Cancer Therapy.

PubMed

Pawar, Smita; Mahajan, Ketan; Vavia, Pradeep

2017-11-01

A novel polymer-drug conjugate, polyethylene glycol-N-(acetyl)-glucosamine-doxorubicin (PEG-NAG-DOX) was evaluated in this study for its in vivo potential for treatment of tumours demonstrating improved efficacy and reduced toxicity. The proposed polymer-drug conjugate comprised of polyethylene glycol-maleimide (mPEG-MAL, 30000 Da) as a carrier, doxorubicin (DOX) as an anticancer drug and N-acetyl glucosamine (NAG) as a targeting moiety as well as penetration enhancer. Doxorubicin has a potent and promising anticancer activity; however, severe cardiotoxicity limits its application in cancer treatment. By modifying DOX in PEG-NAG-DOX prodrug conjugate, we aimed to eliminate this limitation. In vivo anticancer efficacy of the conjugate was evaluated using BDF mice-induced skin melanoma model by i.v. administration of DOX conjugates. Anticancer efficacy studies were done by comparing tumour volume, body weight, organ index and percent survival rate of the animals. Tumour suppression achieved by PEG-NAG-DOX at the cumulative dose of 7.5 mg/kg was two-fold better than that achieved by DOX solution. Also, the survival rate for PEG-NAG-DOX conjugate was >70% as compared to <50% survival rate for DOX solution. In addition, toxicity studies and histopathological studies revealed that while maintaining its cytotoxicity towards tumour cells, PEG-NAG-DOX conjugate showed no toxicities to major organs. Therefore, PEG-NAG-DOX conjugate can be suggested as a desirable candidate for targeted cancer therapy.

Upfront plerixafor plus G-CSF versus cyclophosphamide plus G-CSF for stem cell mobilization in multiple myeloma: efficacy and cost analysis study.

PubMed

Afifi, S; Adel, N G; Devlin, S; Duck, E; Vanak, J; Landau, H; Chung, D J; Lendvai, N; Lesokhin, A; Korde, N; Reich, L; Landgren, O; Giralt, S; Hassoun, H

2016-04-01

Cyclophosphamide plus G-CSF (C+G-CSF) is one of the most widely used stem cell (SC) mobilization regimens for patients with multiple myeloma (MM). Plerixafor plus G-CSF (P+G-CSF) has demonstrated superior SC mobilization efficacy when compared with G-CSF alone and has been shown to rescue patients who fail mobilization with G-CSF or C+G-CSF. Despite the proven efficacy of P+G-CSF in upfront SC mobilization, its use has been limited, mostly due to concerns of high price of the drug. However, a comprehensive comparison of the efficacy and cost effectiveness of SC mobilization using C+G-CSF versus P+G-CSF is not available. In this study, we compared 111 patients receiving C+G-CSF to 112 patients receiving P+G-CSF. The use of P+G-CSF was associated with a higher success rate of SC collection defined as ⩾5 × 10(6) CD34+ cells/kg (94 versus 83%, P=0.013) and less toxicities. Thirteen patients in the C+G-CSF arm were hospitalized owing to complications while none in the P+G-CSF group. C+G-CSF was associated with higher financial burden as assessed using institutional-specific costs and charges (P<0.001) as well as using Medicare reimbursement rates (P=0.27). Higher rate of hospitalization, increased need for salvage mobilization, and increased G-CSF use account for these differences.

Efficacy and Safety of Antiintegrin Antibody for Inflammatory Bowel Disease

PubMed Central

Lin, Lianjie; Liu, Xiang; Wang, Dongxu; Zheng, Changqing

2015-01-01

Abstract We sought to evaluate the safety and efficacy of available biologics that inhibit T-cell migration by blocking α4β7 integrins in inflammatory bowel diseases. The aim of this study is to evaluate whether Crohn disease (CD) patients receiving either vedolizumab or natalizumab have any different effect in CD Activity Index (CDAI). Using Medline, Excerpta Medica dataBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar until October 31, 2013, we identified 10 studies examining the safety and efficacy of specific integrin inhibitors—vedolizumab, which targets an epitope comprising the α4β7 heterodimer; natalizumab, which recognizes the α4 integrin subunit; etrolizumab, which is specific for the β7 subunit—in the treatment of CD and ulcerative colitis (UC). CD patients receiving either vedolizumab or natalizumab demonstrated a modest increase in remission rate, when compared with that of the placebo group. Further, although both treatments reduced the CDAI slightly, the observed clinical response was less robust than that of the remission rate. UC patients treated with vedolizumab and natalizumab were found to show more prominent increases in both remission and clinical response, compared with placebo, than patients with CD. Etrolizumab, however, was not found to significantly affect either response or remission rates in UC patients. Biologics targeting integrins show promise as therapeutics in the treatment of inflammatory bowel disease in patients who are either nonresponsive or intolerant to traditional approaches, though further research is necessary to optimize treatment efficacies. PMID:25761174

Tenofovir alafenamide, emtricitabine, elvitegravir, and cobicistat combination therapy for the treatment of HIV.

PubMed

Imaz, Arkaitz; Podzamczer, Daniel

2017-03-01

Tenofovir alafenamide (TAF) is a novel prodrug of the nucleotide analogue reverse-transcriptase inhibitor, tenofovir. TAF has been co-formulated with emtricitabine (FTC), elvitegravir (EVG) and the EVG metabolic enhancer, cobicistat (COBI) as a single-tablet regimen being the first TAF-containing antiretroviral combination available. Areas covered: This article summarizes the available information on the pharmacology of the novel compound TAF and overviews TAF/FTC/EVG/COBI use for HIV-1 infected patients, with specific focus on clinical efficacy and safety data. Information sources include peer-reviewed scientific literature, conference proceedings and publically available regulatory reports. Compared to tenofovir disoproxil fumarate, TAF results in higher concentrations of the active metabolite tenofovir diphosphate within lymphoid cells, whereas plasma tenofovir exposure is about 90% lower. The efficacy and safety of TAF/FTC/EVG/COBI in treatment-naïve HIV-infected patients has been assessed in phase-III randomized trials, showing non-inferior virological suppression in comparison with TDF/FTC/EVG/COBI, and significantly lower renal and bone toxicity. In addition, TAF/FTC/EVG/COBI has demonstrated efficacy and safety as a switching strategy in suppressed HIV-1 infected individuals, including those with mild or moderate renal impairment. Expert commentary: Approval of the single-tablet TAF/FTC/EVG/COBI regimen is an important advance in HIV therapy, as it is associated with very high efficacy and a better kidney and bone safety profile compared to TDF-containing regimens due to the incorporation of TAF.

Tenofovir Alafenamide.

PubMed

Gibson, Amanda K; Shah, Bhavik M; Nambiar, Puja H; Schafer, Jason J

2016-11-01

To review the pharmacology, efficacy, safety, and place in therapy for tenofovir alafenamide (TAF). A search using PubMed was conducted (2004 to May 2016) using the following keywords: tenofovir alafenamide, TAF, and GS-7340. Articles were evaluated for content, and bibliographies were reviewed. Data available exclusively as abstracts from major infectious diseases and HIV conferences were also evaluated for inclusion. Studies included were in vitro investigations; phase I, II, and III clinical trials; and pharmacokinetic and pharmacodynamic evaluations. Similar to tenofovir disoproxil fumarate (TDF), TAF is a prodrug of tenofovir but results in significantly higher intracellular tenofovir concentrations and lower serum levels. As a result, TAF is expected to have efficacy similar to that of TDF while reducing tenofovir-associated nephrotoxicity and bone mineral density losses. Clinical trials evaluating the safety and efficacy of TAF-containing antiretroviral regimens have confirmed these expectations, consistently demonstrating similar virological suppression compared with TDF-containing regimens as well as significant improvements in markers of kidney function and bone health. Three combination products containing TAF were approved by the United States Food and Drug Administration for the management of HIV-1 infection. The first of these was a single tablet regimen containing elvitegravir, cobicistat, emtricitabine, and TAF which is now a recommended regimen in clinical practice guidelines for initial treatment in antiretroviral-naïve patients. TAF is a novel nucleotide reverse transcriptase inhibitor for the treatment of HIV-1 infection that has efficacy similar to that of TDF and improved safety compared with TDF.

Identification of Compounds with Efficacy against Malaria Parasites from Common North American Plants.

PubMed

Cai, Shengxin; Risinger, April L; Nair, Shalini; Peng, Jiangnan; Anderson, Timothy J C; Du, Lin; Powell, Douglas R; Mooberry, Susan L; Cichewicz, Robert H

2016-03-25

Some of the most valuable antimalarial compounds, including quinine and artemisinin, originated from plants. While these drugs have served important roles over many years for the treatment of malaria, drug resistance has become a widespread problem. Therefore, a critical need exists to identify new compounds that have efficacy against drug-resistant malaria strains. In the current study, extracts prepared from plants readily obtained from local sources were screened for activity against Plasmodium falciparum. Bioassay-guided fractionation was used to identify 18 compounds from five plant species. These compounds included eight lupane triterpenes (1-8), four kaempferol 3-O-rhamnosides (10-13), four kaempferol 3-O-glucosides (14-17), and the known compounds amentoflavone and knipholone. These compounds were tested for their efficacy against multi-drug-resistant malaria parasites and counterscreened against HeLa cells to measure their antimalarial selectivity. Most notably, one of the new lupane triterpenes (3) isolated from the supercritical extract of Buxus sempervirens, the common boxwood, showed activity against both drug-sensitive and -resistant malaria strains at a concentration that was 75-fold more selective for the drug-resistant malaria parasites as compared to HeLa cells. This study demonstrates that new antimalarial compounds with efficacy against drug-resistant strains can be identified from native and introduced plant species in the United States, which traditionally have received scant investigation compared to more heavily explored tropical and semitropical botanical resources from around the world.

Preclinical Study of Single-Dose Moxidectin, a New Oral Treatment for Scabies: Efficacy, Safety, and Pharmacokinetics Compared to Two-Dose Ivermectin in a Porcine Model.

PubMed

Bernigaud, Charlotte; Fang, Fang; Fischer, Katja; Lespine, Anne; Aho, Ludwig Serge; Dreau, Dominique; Kelly, Andrew; Sutra, Jean-François; Moreau, Francis; Lilin, Thomas; Botterel, Françoise; Guillot, Jacques; Chosidow, Olivier

2016-10-01

Scabies is one of the commonest dermatological conditions globally; however it is a largely underexplored and truly neglected infectious disease. Foremost, improvement in the management of this public health burden is imperative. Current treatments with topical agents and/or oral ivermectin (IVM) are insufficient and drug resistance is emerging. Moxidectin (MOX), with more advantageous pharmacological profiles may be a promising alternative. Using a porcine scabies model, 12 pigs were randomly assigned to receive orally either MOX (0.3 mg/kg once), IVM (0.2 mg/kg twice) or no treatment. We evaluated treatment efficacies by assessing mite count, clinical lesions, pruritus and ELISA-determined anti-S. scabiei IgG antibodies reductions. Plasma and skin pharmacokinetic profiles were determined. At day 14 post-treatment, all four MOX-treated but only two IVM-treated pigs were mite-free. MOX efficacy was 100% and remained unchanged until study-end (D47), compared to 62% (range 26-100%) for IVM, with one IVM-treated pig remaining infected until D47. Clinical scabies lesions, pruritus and anti-S. scabiei IgG antibodies had completely disappeared in all MOX-treated but only 75% of IVM-treated pigs. MOX persisted ~9 times longer than IVM in plasma and skin, thereby covering the mite's entire life cycle and enabling long-lasting efficacy. Our data demonstrate that oral single-dose MOX was more effective than two consecutive IVM-doses, supporting MOX as potential therapeutic approach for scabies.

Efficacy of the Roux-en-Y gastric bypass compared to medically managed controls in meeting the American Diabetes Association composite end point goals for management of type 2 diabetes mellitus.

PubMed

Leslie, Daniel B; Dorman, Robert B; Serrot, Federico J; Swan, Therese W; Kellogg, Todd A; Torres-Villalobos, Gonzalo; Buchwald, Henry; Slusarek, Bridget M; Sampson, Barbara K; Bantle, John P; Ikramuddin, Sayeed

2012-03-01

The treatment goals recommended by the American Diabetes Association (ADA) for patients with type 2 diabetes mellitus include hemoglobin A1c (HbA1C) <7.0%, low-density lipoprotein (LDL) <100 mg/dL, and systolic blood pressure (SBP) <130 mmHg. Only 10% of conventionally treated patients reach these goals as a composite endpoint. The efficacy of the Roux-en-Y gastric bypass (RYGB) in meeting this composite endpoint has not been reported. We compared our database of patients with type 2 diabetes undergoing RYGB to a database of patients with medically managed type 2 diabetes and at least 2 years of follow-up data. Ultimately, 152 RYGB patients were compared to 115 routine medical management (RMM) patients for whom data on the composite endpoint were available over 2 years. The results show significant decrease in body mass index (kilograms per square meter) in the RYGB group compared to the RMM group (P < 0.001). HbA1C, LDL cholesterol, and SBP all significantly improved in the RYGB group (all P ≤ 0.01) and did not demonstrate any significant change in the RMM group. Over 2 years, when evaluating all three endpoints, the RYGB group (10.5% to 38.2%, P < 0.001) demonstrated increased achievement of the ADA goals compared to the RMM group (13.9% to 17.4%, P = 0.47). There was a significant decrease in medication use in the RYGB cohort; however, discontinuation of medications was sometimes inappropriate. RYGB achieves the ADA composite endpoint more frequently than conventional therapy and with less medication.

Android Robot-Mediated Mock Job Interview Sessions for Young Adults with Autism Spectrum Disorder: A Pilot Study

PubMed Central

Kumazaki, Hirokazu; Warren, Zachary; Corbett, Blythe A.; Yoshikawa, Yuichiro; Matsumoto, Yoshio; Higashida, Haruhiro; Yuhi, Teruko; Ikeda, Takashi; Ishiguro, Hiroshi; Kikuchi, Mitsuru

2017-01-01

The feasibility and preliminary efficacy of an android robot-mediated mock job interview training in terms of both bolstering self-confidence and reducing biological levels of stress in comparison to a psycho-educational approach human interview was assessed in a randomized study. Young adults (ages 18–25 years) with autism spectrum disorder (ASD) were randomized to participate either in a mock job interview training with our android robot system (n = 7) or a self-paced review of materials about job-interviewing skills (n = 8). Baseline and outcome measurements of self-reported performance/efficacy and salivary cortisol were obtained after a mock job interview with a human interviewer. After training sessions, individuals with ASD participating in the android robot-mediated sessions reported marginally improved self-confidence and demonstrated significantly lower levels of salivary cortisol as compared to the control condition. These results provide preliminary support for the feasibility and efficacy of android robot-mediated learning. PMID:28955254

Android Robot-Mediated Mock Job Interview Sessions for Young Adults with Autism Spectrum Disorder: A Pilot Study.

PubMed

Kumazaki, Hirokazu; Warren, Zachary; Corbett, Blythe A; Yoshikawa, Yuichiro; Matsumoto, Yoshio; Higashida, Haruhiro; Yuhi, Teruko; Ikeda, Takashi; Ishiguro, Hiroshi; Kikuchi, Mitsuru

2017-01-01

The feasibility and preliminary efficacy of an android robot-mediated mock job interview training in terms of both bolstering self-confidence and reducing biological levels of stress in comparison to a psycho-educational approach human interview was assessed in a randomized study. Young adults (ages 18-25 years) with autism spectrum disorder (ASD) were randomized to participate either in a mock job interview training with our android robot system ( n  = 7) or a self-paced review of materials about job-interviewing skills ( n  = 8). Baseline and outcome measurements of self-reported performance/efficacy and salivary cortisol were obtained after a mock job interview with a human interviewer. After training sessions, individuals with ASD participating in the android robot-mediated sessions reported marginally improved self-confidence and demonstrated significantly lower levels of salivary cortisol as compared to the control condition. These results provide preliminary support for the feasibility and efficacy of android robot-mediated learning.

A novel multi-target regression framework for time-series prediction of drug efficacy.

PubMed

Li, Haiqing; Zhang, Wei; Chen, Ying; Guo, Yumeng; Li, Guo-Zheng; Zhu, Xiaoxin

2017-01-18

Excavating from small samples is a challenging pharmacokinetic problem, where statistical methods can be applied. Pharmacokinetic data is special due to the small samples of high dimensionality, which makes it difficult to adopt conventional methods to predict the efficacy of traditional Chinese medicine (TCM) prescription. The main purpose of our study is to obtain some knowledge of the correlation in TCM prescription. Here, a novel method named Multi-target Regression Framework to deal with the problem of efficacy prediction is proposed. We employ the correlation between the values of different time sequences and add predictive targets of previous time as features to predict the value of current time. Several experiments are conducted to test the validity of our method and the results of leave-one-out cross-validation clearly manifest the competitiveness of our framework. Compared with linear regression, artificial neural networks, and partial least squares, support vector regression combined with our framework demonstrates the best performance, and appears to be more suitable for this task.

The evaluation of prophylactic efficacy of newly developed reversible inhibitors of acetylcholinesterase in soman-poisoned mice - a comparison with commonly used pyridostigmine.

PubMed

Kassa, Jiri; Korabecny, Jan; Sepsova, Vendula; Tumova, Martina

2014-12-01

The ability of four newly developed reversible inhibitors of acetylcholinesterase (PC-37, PC-48, JaKo 39, JaKo 40) and currently available carbamate pyridostigmine to increase the resistance of mice against soman and the efficacy of antidotal treatment of soman-poisoned mice was evaluated and compared. No reversible inhibitor of acetylcholinesterase studied was able to decrease the LD50 value of soman in mice. Thus, the pharmacological pre-treatment with pyridostigmine or newly synthesized inhibitors of acetylcholinesterase was not able to significantly protect mice against soman-induced lethal acute toxicity. In addition, neither pyridostigmine nor new reversible inhibitors of acetylcholinesterase was able to increase the efficacy of antidotal treatment (the oxime HI-6 in combination with atropine) of soman-poisoned mice. These findings demonstrate that pharmacological pre-treatment of soman-poisoned mice with tested reversible inhibitors of acetylcholinesterase is not promising. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

A novel multi-target regression framework for time-series prediction of drug efficacy

PubMed Central

Li, Haiqing; Zhang, Wei; Chen, Ying; Guo, Yumeng; Li, Guo-Zheng; Zhu, Xiaoxin

2017-01-01

Excavating from small samples is a challenging pharmacokinetic problem, where statistical methods can be applied. Pharmacokinetic data is special due to the small samples of high dimensionality, which makes it difficult to adopt conventional methods to predict the efficacy of traditional Chinese medicine (TCM) prescription. The main purpose of our study is to obtain some knowledge of the correlation in TCM prescription. Here, a novel method named Multi-target Regression Framework to deal with the problem of efficacy prediction is proposed. We employ the correlation between the values of different time sequences and add predictive targets of previous time as features to predict the value of current time. Several experiments are conducted to test the validity of our method and the results of leave-one-out cross-validation clearly manifest the competitiveness of our framework. Compared with linear regression, artificial neural networks, and partial least squares, support vector regression combined with our framework demonstrates the best performance, and appears to be more suitable for this task. PMID:28098186

An Education Intervention to Enhance Staff Self-Efficacy to Provide Dementia Care in an Acute Care Hospital in Canada

PubMed Central

Gillies, Leslie; Coker, Esther; Pizzacalla, Anne; Montemuro, Maureen; Suva, Grace; McLelland, Victoria

2016-01-01

Education is needed for enhanced capacity of acute hospitals to provide dementia care. A nonrandomized controlled, repeated-measures design was used to evaluate a dementia education program delivered to an intervention group (IG, n = 468), compared to a wait-listed group (n = 277), representing separate sites of a multisite hospital. Participants completed self-efficacy for dementia and satisfaction measures and provided written descriptions of dementia care collected at baseline, postintervention (IG only), and at 8-week follow-up. Oral narratives were gathered from IG participants 8 weeks postintervention. The IG demonstrated significant improvement in self-efficacy scores from baseline to immediately postintervention (P < .001), sustained at 8 weeks. There were no changes from baseline to 8 weeks postintervention evident in the wait-listed group (P = .21). Intervention group participants described positive impacts including implementation of person-centered care approaches. Implementation of dementia care education programs throughout hospital settings is promising for the enhancement of dementia care. PMID:27659392

A preliminary investigation on the efficacy of N-acetyl cysteine for mania or hypomania.

PubMed

Magalhães, Pedro Vieira da Silva; Dean, Olivia M; Bush, Ashley I; Copolov, David L; Malhi, Gin S; Kohlmann, Kristy; Jeavons, Susan; Schapkaitz, Ian; Anderson-Hunt, Murray; Berk, Michael

2013-06-01

Oxidative imbalance has emerged as a treatment target in bipolar disorder. As very limited data are available on the clinical use of antioxidants for mania, we report here results from a post hoc and exploratory subgroup analysis of a randomized, placebo-controlled trial of N-acetyl cysteine (NAC). This was a placebo-controlled, randomized, clinical trial assessing the effect of NAC over 24 weeks in mania or hypomania. Symptomatic and functional outcomes were collected over the study period. Fifteen participants were available for this report; two participants in each group failed to complete all assessments. Within-group analyses pointed to an improvement in the NAC group on manic symptoms and worsening in the placebo group on depressive symptoms at endpoint. Although the sample size was small, these results indicated within-group efficacy for this glutathione precursor as compared to placebo. Future trials specifically designed to demonstrate the efficacy of NAC in mania are needed.

Biologic and oral disease-modifying antirheumatic drug monotherapy in rheumatoid arthritis

PubMed Central

Emery, Paul; Sebba, Anthony; Huizinga, Tom W J

2013-01-01

Clinical evidence demonstrates coadministration of tumour necrosis factor inhibitor (TNFi) agents and methotrexate (MTX) is more efficacious than administration of TNFi agents alone in patients with rheumatoid arthritis, leading to the perception that coadministration of MTX with all biologic agents or oral disease-modifying antirheumatic drugs is necessary for maximum efficacy. Real-life registry data reveal approximately one-third of patients taking biologic agents use them as monotherapy. Additionally, an analysis of healthcare claims data showed that when MTX was prescribed in conjunction with a biologic agent, as many as 58% of patients did not collect the MTX prescription. Given this discrepancy between perception and real life, we conducted a review of the peer-reviewed literature and rheumatology medical congress abstracts to determine whether data support biologic monotherapy as a treatment option for patients with rheumatoid arthritis. Our analysis suggests only for tocilizumab is there evidence that the efficacy of biologic monotherapy is comparable with combination therapy with MTX. PMID:23918035

Histone deacetylase inhibition enhances the lymphomacidal activity of the anti-CD22 monoclonal antibody HB22.7.

PubMed

Kong, YanGuo; Barisone, Gustavo A; Abuhay, Mastewal; O'Donnell, Robert T; Buksh, Zaneb; Yousefian, Faraz; Tuscano, Joseph M

2014-11-01

HB22.7, an anti-CD22 monoclonal antibody has shown consistent preclinical activity against non-Hodgkin lymphoma (NHL). Histone deacetylase inhibitors (HDACi) have demonstrated efficacy in lymphoma and can modulate cell surface receptor expression. To augment the lymphomacidal activity of HB22.7 we examined the combination of AR42 (an HDACi) and HB22.7 in vitro and in vivo. The combination resulted in 10-fold increased potency in 6 NHL cell lines when compared to either drug alone. Both drugs reduced tumor progression in xenografts, but the combination was significantly more efficacious and resulted in regression of established tumors, without toxicity. AR42 inhibited HB22.7-mediated CD22 internalization, suggesting that increased efficacy could be due to higher availability of CD22. Overall, the synergistic effects of HB22.7 and AR42 on in vitro cytotoxicity and in vivo anti-tumor activity make this combination an attractive option for further pre-clinical and clinical evaluation. Published by Elsevier Ltd.

New treatment options for chronic constipation: Mechanisms, efficacy and safety

PubMed Central

Camilleri, Michael

2011-01-01

The present review has several objectives, the first of which is to review the pharmacology and selectivity of serotonergic agents to contrast the older serotonergic agents (which were withdrawn because of cardiac or vascular adverse effects) with the newer generation serotonin receptor subtype 4 agonists. Second, the chloride ion secretagogues that act through the guanylate cyclase C receptor are appraised and their pharmacology is compared with the approved medication, lubiprostone. Third, the efficacy and safety of the application of bile acid modulation to treat constipation are addressed. The long-term studies of surgically induced excess bile acid delivery to the colon are reviewed to ascertain the safety of this therapeutic approach. Finally, the new drugs for opiate-induced constipation are introduced. Assuming these drugs are approved, practitioners will have a choice; however, patient responsiveness will be based on trial and error. Nevertheless, the spectrum of mechanisms and demonstrated efficacy and safety augur well for satisfactory treatment outcomes. PMID:22114755

Composition of gut microbiota and its influence on the immunogenicity of oral rotavirus vaccines.

PubMed

Magwira, Cliff A; Taylor, Maureen B

2018-05-08

The introduction of oral rotavirus vaccines (ORVVs) has led to a reduction in number of hospitalisations and deaths due to rotavirus (RV) infection. However, the efficacy of the vaccines has been varied with low-income countries showing significantly lower efficacy as compared to high-income countries. The reasons for the disparity are not fully understood but are thought to be multi-factorial. In this review article, we discuss the concept that the disparity in the efficacy of oral rotavirus vaccines between the higher and lower socio-economical countries could be due the nature of the bacteria that colonises and establishes in the gut early in life. We further discuss recent studies that has demonstrated significant correlations between the composition of the gut bacteria and the immunogenicity of oral vaccines, and their implications in the development of novel oral RV vaccines or redesigning the current ones for maximum impact. Copyright © 2018. Published by Elsevier Ltd.

iStart smart: a primary-care based and community partnered childhood obesity management program for Chinese-American children: feasibility study.

PubMed

Chen, Jyu-Lin; Kwan, Monica; Mac, Allison; Chin, Nai-Ching; Liu, Katrina

2013-12-01

Children who are ethnic minorities, low income and live in urban neighborhoods are at higher risk for obesity. This study examined the feasibility and efficacy of a primary care-based and community partnered obesity intervention in Chinese American children. An experimental design with a historical comparison group was used to explore the feasibility of an obesity intervention for overweight Chinese American children, ages 7-12. Data were collected on weight, height, blood pressure, waist circumference, physical activity, food intake, knowledge, and self-efficacy about diet and physical activity at baseline, 2 months, and 6 months post-baseline. Significant improvements in BMI, blood pressure, and nutrition knowledge and self-efficacy were found in the intervention group. Intervention group reduced their BMI compared to the comparison group (F = 8.65, p = .004). An obesity intervention in primary care setting is feasible and demonstrates a short-term effect on weight loss in Chinese American children.

Efficacy of Silver Dihydrogen Citrate and Steam Vapor against a Human Norovirus Surrogate, Feline Calicivirus, in Suspension, on Glass, and on Carpet.

PubMed

Buckley, David; Dharmasena, Muthu; Fraser, Angela; Pettigrew, Charles; Anderson, Jeffery; Jiang, Xiuping

2018-06-15

Carpets and other soft surfaces have been associated with prolonged and reoccurring human norovirus (HuNoV) outbreaks. Environmental hygiene programs are important to prevent and control HuNoV outbreaks. Despite our knowledge of HuNoV transmission via soft surfaces, no commercially available disinfectants have been evaluated on carpets. Our aim was to adapt a current standardized method for virucidal testing by assessing two disinfection technologies, silver dihydrogen citrate (SDC) and steam vapor, against one HuNoV surrogate, feline calicivirus (FCV), on wool and nylon carpets. First, we evaluated the effect of both technologies on the appearance of carpet. Next, we evaluated the efficacy of SDC in suspension and the efficacy of SDC and steam vapor against FCV on a glass surface, each with and without serum. Lastly, we tested both technologies on two types of carpet, wool and nylon. Both carpets exhibited no obvious color changes; however, SDC treatments left a residue while steam vapor left minor abrasions to fibers. SDC in suspension and on glass reduced FCV by 4.65 log 10 and >4.66 log 10 PFU, respectively, but demonstrated reduced efficacy in the presence of serum. However, SDC was only efficacious against FCV on nylon (3.62-log 10 PFU reduction) and not wool (1.82-log 10 PFU reduction). Steam vapor reduced FCV by >4.93 log 10 PFU on glass in 10 s and >3.68 log 10 PFU on wool and nylon carpet carriers in 90 s. There was a limited reduction of FCV RNA under both treatments compared to that of infectivity assays, but RNA reductions were higher in samples that contained serum. IMPORTANCE Human noroviruses (HuNoV) account for ca. 20% of all diarrheal cases worldwide. Disease symptoms may include diarrhea and vomit, with both known to contribute to transmission. The prevention and control of HuNoV are difficult because they are environmentally resilient and resistant to many disinfectants. Several field studies have linked both hard and soft surfaces to HuNoV outbreaks. However, many disinfectants efficacious against HuNoV surrogates are recommended for hard surfaces, but no commercially available products have demonstrated efficacy against these surrogates on soft surfaces. Our research objectives were to evaluate liquid and steam-based technologies in suspension and on hard surface carriers in addition to adapting and testing a protocol for assessing the virucidal effects of disinfection technologies on carpet carriers. These results will inform both the government and industry regarding a standard method for evaluating the virucidal effects of disinfectants on carpet while demonstrating their efficacy relative to suspension and hard-surface tests. Copyright © 2018 American Society for Microbiology.

Myeloid cells are capable of synthesizing aldosterone to exacerbate damage in muscular dystrophy.

PubMed

Chadwick, Jessica A; Swager, Sarah A; Lowe, Jeovanna; Welc, Steven S; Tidball, James G; Gomez-Sanchez, Celso E; Gomez-Sanchez, Elise P; Rafael-Fortney, Jill A

2016-12-01

FDA-approved mineralocorticoid receptor (MR) antagonists are used to treat heart failure. We have recently demonstrated efficacy of MR antagonists for skeletal muscles in addition to heart in Duchenne muscular dystrophy mouse models and that mineralocorticoid receptors are present and functional in skeletal muscles. The goal of this study was to elucidate the underlying mechanisms of MR antagonist efficacy on dystrophic skeletal muscles. We demonstrate for the first time that infiltrating myeloid cells clustered in damaged areas of dystrophic skeletal muscles have the capacity to produce the natural ligand of MR, aldosterone, which in excess is known to exacerbate tissue damage. Aldosterone synthase protein levels are increased in leukocytes isolated from dystrophic muscles compared with controls and local aldosterone levels in dystrophic skeletal muscles are increased, despite normal circulating levels. All genes encoding enzymes in the pathway for aldosterone synthesis are expressed in muscle-derived leukocytes. 11β-HSD2, the enzyme that inactivates glucocorticoids to increase MR selectivity for aldosterone, is also increased in dystrophic muscle tissues. These results, together with the demonstrated preclinical efficacy of antagonists, suggest MR activation is in excess of physiological need and likely contributes to the pathology of muscular dystrophy. This study provides new mechanistic insight into the known contribution of myeloid cells to muscular dystrophy pathology. This first report of myeloid cells having the capacity to produce aldosterone may have implications for a wide variety of acute injuries and chronic diseases with inflammation where MR antagonists may be therapeutic. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Formulation of nanotized curcumin and demonstration of its antimalarial efficacy

PubMed Central

Ghosh, Aparajita; Banerjee, Tanushree; Bhandary, Suman; Surolia, Avadhesha

2014-01-01

Aim The present study was conducted to overcome the disadvantages associated with the poor water solubility and low bioavailability of curcumin by synthesizing nanotized curcumin and demonstrating its efficacy in treating malaria. Materials and methods Nanotized curcumin was prepared by a modified emulsion-diffusion-evaporation method and was characterized by means of transmission electron microscopy, atomic force microscopy, dynamic light scattering, Zetasizer, Fourier transform infrared spectroscopy, and differential thermal analysis. The novelty of the prepared nanoformulation lies in the fact that it was devoid of any polymeric matrices used in conventional carriers. The antimalarial efficacy of the prepared nanotized curcumin was then checked both in vitro and in vivo. Results The nanopreparation was found to be non-toxic and had a particle size distribution of 20–50 nm along with improved aqueous dispersibility and an entrapment efficiency of 45%. Nanotized curcumin (half maximal inhibitory concentration [IC50]: 0.5 μM) was also found to be ten-fold more effective for growth inhibition of Plasmodium falciparum in vitro as compared to its native counterpart (IC50: 5 μM). Oral bioavailability of nanotized curcumin was found to be superior to that of its native counterpart. Moreover, when Plasmodium berghei-infected mice were orally treated with nanotized curcumin, it prolonged their survival by more than 2 months with complete clearance of parasites in comparison to the untreated animals, which survived for 8 days only. Conclusion Nanotized curcumin holds a considerable promise in therapeutics as demonstrated here for treating malaria as a test system. PMID:25484584

Laboratory evaluation of anti-biofilm agents for use in dental unit waterlines.

PubMed

Meiller, T F; Kelley, J I; Baqui, A A; DePaola, L G

2001-01-01

Dental unit waterline biofilm has been recognized as a potential point of contamination and a risk to patients with any level of immunocompromise. Biofilm in dental unit waterlines, once established, has proven formidable to efforts in disinfection/disruption. This project compared standardized evaluation techniques by assessing the efficacy of a variety of agents that have been reported or suggested as useful in surface disinfection and/or antiseptic protocols. The zones of inhibition, minimum inhibitory/bactericidal concentrations and use-dilution with stainless steel carrier replicates tests assessed the disinfection of planktonic organisms using standardized microbial testing procedures. The disruption and/or disinfection of planktonic and biofilm organisms within naturally occurring dental unit waterlines were evaluated by culture and scanning electron microscopy. The six commercially available antimicrobial agents used to assess the techniques were bleach (sodium hypochlorite), Cavicide, glutaraldehyde, Listerine Antiseptic, Peridex and Sterilex Ultra. Comparisons between the results for each technique evaluated were determined for each product. All six agents demonstrated antimicrobial efficacy at the working concentrations designated by the manufacturers. Biofilm matrix elimination evaluated by scanning electron microscopy found virtually 0% elimination by glutaraldehyde to an estimated 90% elimination by Sterilex Ultra and bleach after one treatment. Treatment with Cavicide, Listerine Antiseptic and Peridex resulted in negligible elimination of the biofilm matrix. For comparability, the use of standardized testing techniques to evaluate a disinfection agent's efficacy against dental unit waterline contamination is essential. This project demonstrates a model system for evaluating disinfection agents potentially useful in the management of dental unit waterline biofilm, and should assist in educating the dental clinician in the appraisal of existing and future product claims.

Measuring affiliation in group therapy for substance use disorders in the Women's Recovery Group study: Does it matter whether the group is all-women or mixed-gender?

PubMed

Sugarman, Dawn E; Wigderson, Sara B; Iles, Brittany R; Kaufman, Julia S; Fitzmaurice, Garrett M; Hilario, E Yvette; Robbins, Michael S; Greenfield, Shelly F

2016-10-01

A Stage II, two-site randomized clinical trial compared the manualized, single-gender Women's Recovery Group (WRG) to mixed-gender group therapy (Group Drug Counseling; GDC) and demonstrated efficacy. Enhanced affiliation and support in the WRG is a hypothesized mechanism of efficacy. This study sought to extend results of the previous small Stage I trial that showed the rate of supportive affiliative statements occurred more frequently in WRG than GDC. Participants (N = 158; 100 women, 58 men) were 18 years or older, substance dependent, and had used substances within the past 60 days. Women were randomized to WRG (n = 52) or GDC (n = 48). Group therapy videos were coded by two independent raters; Rater 1 coded 20% of videos (n = 74); Rater 2 coded 25% of videos coded by Rater 1 (n = 19). The number of affiliative statements made in WRG was 66% higher than in GDC. Three of eight affiliative statement categories occurred more frequently in WRG than GDC: supportive, shared experience, and strategy statements. This larger Stage II trial provided a greater number of group therapy tapes available for analysis. Results extended our previous findings, demonstrating both greater frequency of all affiliative statements, as well as specific categories of statements, made in single-gender WRG than mixed-gender GDC. Greater frequency of affiliative statements among group members may be one mechanism of enhanced support and efficacy in women-only WRG compared with standard mixed-gender group therapy for substance use disorders. (Am J Addict 2016;25:573-580). © 2016 American Academy of Addiction Psychiatry.

A randomized, double-blind, 24-week study of escitalopram (10 mg/day) versus citalopram (20 mg/day) in primary care patients with major depressive disorder.

PubMed

Colonna, Lucien; Andersen, Henning Friis; Reines, Elin Heldbo

2005-10-01

A randomized, double-blind, 24-week-fixed-dose study comparing the efficacy and safety of escitalopram to that of citalopram was safety was conducted in primary care patients with moderate to severe major depressive disorder (MDD). This was a randomized, double-blind, 24-week fixeddose study. Patients were randomly assigned to treatment with escitalopram 10 mg/day (n = 175) or citalopram 20 mg/day (n = 182). Clinical response was evaluated using the Montgomery-Asberg Depression Rating Scale (MADRS) and Clinical Global Impression-Severity (CGI-S) scale. The prospectively defined primary parameter of antidepressant efficacy was the change from baseline in the mean MADRS total score during the 24 weeks of double-blind treatment, using a repeated measures analysis of variance to compare the treatment groups over all assessment points simultaneously. Based on the primary parameter, escitalopram was at least as efficacious as citalopram. Based on the prospectively defined secondary parameter, mean change from baseline in the CGI-S score, escitalopram was statistically significantly superior to citalopram at Week 24. The importance of long-term treatment could be demonstrated, in that more than half (55% and 51%) of the patients who had not responded by Week 8 achieved remission by Week 24. Both escitalopram and citalopram were safe and well tolerated in acute and long-term treatment, and the overall adverse event profiles for the two drugs were similar. For the intent-to-treat population, there were statistically significantly fewer withdrawals in the escitalopram group than in the citalopram group, particularly after Week 8. Patients with MDD responded well to long-term treatment with either escitalopram or citalopram. This study demonstrated the importance of extending treatment of depression beyond 8 weeks.

Comparison of magnetic nanoparticle and microwave hyperthermia cancer treatment methodology and treatment effect in a rodent breast cancer model.

PubMed

Petryk, Alicia A; Giustini, Andrew J; Gottesman, Rachel E; Trembly, B Stuart; Hoopes, P Jack

2013-12-01

The purpose of this study was to compare the efficacy of iron oxide/magnetic nanoparticle hyperthermia (mNPH) and 915 MHz microwave hyperthermia at the same thermal dose in a mouse mammary adenocarcinoma model. A thermal dose equivalent to 60 min at 43 °C (CEM60) was delivered to a syngeneic mouse mammary adenocarcinoma flank tumour (MTGB) via mNPH or locally delivered 915 MHz microwaves. mNPH was generated with ferromagnetic, hydroxyethyl starch-coated magnetic nanoparticles. Following mNP delivery, the mouse/tumour was exposed to an alternating magnetic field (AMF). The microwave hyperthermia treatment was delivered by a 915 MHz microwave surface applicator. Time required for the tumour to reach three times the treatment volume was used as the primary study endpoint. Acute pathological effects of the treatments were determined using conventional histopathological techniques. Locally delivered mNPH resulted in a modest improvement in treatment efficacy as compared to microwave hyperthermia (p = 0.09) when prescribed to the same thermal dose. Tumours treated with mNPH also demonstrated reduced peritumoral normal tissue damage. Our results demonstrate similar tumour treatment efficacy when tumour heating is delivered by locally delivered mNPs and 915 MHz microwaves at the same measured thermal dose. However, mNPH treatments did not result in the same type or level of peritumoral damage seen with the microwave hyperthermia treatments. These data suggest that mNP hyperthermia is capable of improving the therapeutic ratio for locally delivered tumour hyperthermia. These results further indicate that this improvement is due to improved heat localisation in the tumour.

Long-term (6 and 12 months) follow-up of two prospective, randomized, controlled phase III trials of photodynamic therapy with BF-200 ALA and methyl aminolaevulinate for the treatment of actinic keratosis

PubMed Central

Dirschka, T; Radny, P; Dominicus, R; Mensing, H; Brüning, H; Jenne, L; Karl, L; Sebastian, M; Oster-Schmidt, C; Klövekorn, W; Reinhold, U; Tanner, M; Gröne, D; Deichmann, M; Simon, M; Hübinger, F; Hofbauer, G; Krähn-Senftleben, G; Borrosch, F; Reich, K; Berking, C; Wolf, P; Lehmann, P; Moers-Carpi, M; Hönigsmann, H; Wernicke-Panten, K; Hahn, S; Pabst, G; Voss, D; Foguet, M; Schmitz, B; Lübbert, H; Szeimies, R-M

2013-01-01

Background Two phase III trials of photodynamic therapy (PDT) with BF-200 ALA, a recently approved nanoemulsion formulation of 5-aminolaevulinic acid (ALA) demonstrated high clearance rates in mild-to-moderate actinic keratosis (AK). The comparison to a registered methyl aminolaevulinate (MAL) cream demonstrated significantly superior total patient clearance rates. Objectives To evaluate long-term efficacy and safety of PDT for AK 6 and 12 months after the last PDT with BF-200 ALA, MAL or placebo. Methods The follow-up phase (FUP) was performed with patients of two phase III studies. Both studies compared BF-200 ALA with placebo, one of the studies additionally with MAL. Overall recurrence rates and various subgroups (light source, lesion severity, lesion location, complete responders after first PDT) were assessed 6 and 12 months after the last PDT. Results Recurrence rates were similar for BF-200 ALA and MAL, with a tendency to lower recurrence rates for BF-200 ALA. The proportion of patients who were fully cleared during PDT and remained completely clear for at least 12 months after PDT were 47% for BF-200 ALA (both studies) and 36% for MAL treatment. The subgroup that was illuminated with narrow wavelength LED lamps reached 69% and 53% for BF-200 ALA (both studies, respectively) and 41% for MAL. No safety concerns were reported. Conclusions The FUP data confirmed the high efficacy and safety of PDT with BF-200 ALA. The slightly lower recurrence rates after BF-200 ALA treatment compared with MAL treatment enhanced the better treatment outcome due to the significantly superior efficacy. PMID:23252768

Long-term (6 and 12 months) follow-up of two prospective, randomized, controlled phase III trials of photodynamic therapy with BF-200 ALA and methyl aminolaevulinate for the treatment of actinic keratosis.

PubMed

Dirschka, T; Radny, P; Dominicus, R; Mensing, H; Brüning, H; Jenne, L; Karl, L; Sebastian, M; Oster-Schmidt, C; Klövekorn, W; Reinhold, U; Tanner, M; Gröne, D; Deichmann, M; Simon, M; Hübinger, F; Hofbauer, G; Krähn-Senftleben, G; Borrosch, F; Reich, K; Berking, C; Wolf, P; Lehmann, P; Moers-Carpi, M; Hönigsmann, H; Wernicke-Panten, K; Hahn, S; Pabst, G; Voss, D; Foguet, M; Schmitz, B; Lübbert, H; Szeimies, R-M

2013-04-01

Two phase III trials of photodynamic therapy (PDT) with BF-200 ALA, a recently approved nanoemulsion formulation of 5-aminolaevulinic acid (ALA) demonstrated high clearance rates in mild-to-moderate actinic keratosis (AK). The comparison to a registered methyl aminolaevulinate (MAL) cream demonstrated significantly superior total patient clearance rates. To evaluate long-term efficacy and safety of PDT for AK 6 and 12 months after the last PDT with BF-200 ALA, MAL or placebo. The follow-up phase (FUP) was performed with patients of two phase III studies. Both studies compared BF-200 ALA with placebo, one of the studies additionally with MAL. Overall recurrence rates and various subgroups (light source, lesion severity, lesion location, complete responders after first PDT) were assessed 6 and 12 months after the last PDT. Recurrence rates were similar for BF-200 ALA and MAL, with a tendency to lower recurrence rates for BF-200 ALA. The proportion of patients who were fully cleared during PDT and remained completely clear for at least 12 months after PDT were 47% for BF-200 ALA (both studies) and 36% for MAL treatment. The subgroup that was illuminated with narrow wavelength LED lamps reached 69% and 53% for BF-200 ALA (both studies, respectively) and 41% for MAL. No safety concerns were reported. The FUP data confirmed the high efficacy and safety of PDT with BF-200 ALA. The slightly lower recurrence rates after BF-200 ALA treatment compared with MAL treatment enhanced the better treatment outcome due to the significantly superior efficacy. © 2012 Biofrontera Bioscience GmbH BJD © 2012 British Association of Dermatologists.

Long-term Efficacy and Biocompatibility of Encapsulated Islet Transplantation With Chitosan-Coated Alginate Capsules in Mice and Canine Models of Diabetes.

PubMed

Yang, Hae Kyung; Ham, Dong-Sik; Park, Heon-Seok; Rhee, Marie; You, Young Hye; Kim, Min Jung; Shin, Juyoung; Kim, On-You; Khang, Gilson; Hong, Tae Ho; Kim, Ji-Won; Lee, Seung-Hwan; Cho, Jae-Hyoung; Yoon, Kun-Ho

2016-02-01

Clinical application of encapsulated islet transplantation is hindered by low biocompatibility of capsules leading to pericapsular fibrosis and decreased islet viability. To improve biocompatibility, we designed a novel chitosan-coated alginate capsules and compared them to uncoated alginate capsules. Alginate capsules were formed by crosslinking with BaCl2, then they were suspended in chitosan solution for 10 minutes at pH 4.5. Xenogeneic islet transplantation, using encapsulated porcine islets in 1,3-galactosyltransferase knockout mice, and allogeneic islet transplantation, using encapsulated canine islets in beagles, were performed without immunosuppressants. The chitosan-alginate capsules showed similar pore size, islet viability, and insulin secretory function compared to alginate capsules, in vitro. Xenogeneic transplantation of chitosan-alginate capsules demonstrated a trend toward superior graft survival (P = 0.07) with significantly less pericapsular fibrosis (cell adhesion score: 3.77 ± 0.41 vs 8.08 ± 0.05; P < 0.001) compared to that of alginate capsules up to 1 year after transplantation. Allogeneic transplantation of chitosan-alginate capsules normalized the blood glucose level up to 1 year with little evidence of pericapsular fibrotic overgrowth on graft explantation. The efficacy and biocompatibility of chitosan-alginate capsules were demonstrated in xenogeneic and allogeneic islet transplantations using small and large animal models of diabetes. This capsule might be a potential candidate applicable in the treatment of type 1 diabetes mellitus patients, and further studies in nonhuman primates are required.

Community-based peer-led diabetes self-management: a randomized trial.

PubMed

Lorig, Kate; Ritter, Philip L; Villa, Frank J; Armas, Jean

2009-01-01

The purpose of this study is to determine the effectiveness of a community-based diabetes self-management program comparing treatment participants to a randomized usual-care control group at 6 months. A total of 345 adults with type 2 diabetes but no criteria for high A1C were randomized to a usual-care control group or 6-week community-based, peer-led diabetes self-management program (DSMP). Randomized participants were compared at 6 months. The DSMP intervention participants were followed for an additional 6 months (12 months total). A1C and body mass index were measured at baseline, 6 months, and 12 months. All other data were collected by self-administered questionnaires. At 6 months, DSMP participants did not demonstrate improvements in A1C as compared with controls. Baseline A1C was much lower than in similar trials. Participants did have significant improvements in depression, symptoms of hypoglycemia, communication with physicians, healthy eating, and reading food labels (P < .01). They also had significant improvements in patient activation and self-efficacy. At 12 months, DSMP intervention participants continued to demonstrate improvements in depression, communication with physicians, healthy eating, patient activation, and self-efficacy (P < .01). There were no significant changes in utilization measures. These findings suggest that people with diabetes without elevated A1C can benefit from a community-based, peer-led diabetes program. Given the large number of people with diabetes and lack of low-cost diabetes education, the DSMP deserves consideration for implementation.

Pharmacokinetics, safety and efficacy of a recombinant factor IX product, trenonacog alfa in previously treated haemophilia B patients.

PubMed

Collins, P W; Quon, D V K; Makris, M; Chowdary, P; Kempton, C L; Apte, S J; Ramanan, M V; Hay, C R M; Drobic, B; Hua, Y; Babinchak, T J; Gomperts, E D

2018-01-01

Trenonacog alfa (IB1001) is a recombinant factor IX (rFIX) manufactured in Chinese hamster ovary (CHO) cells. IB1001 was evaluated in a multicentre clinical trial with haemophilia B patients. The aim was to establish IB1001 pharmacokinetic non-inferiority to comparator rFIX, safety and efficacy in previously treated patients (PTPs) with haemophilia B. Subjects were severe or moderately severe haemophilia B adult and adolescent PTPs with no history of FIX inhibitors. IB1001 PK non-inferiority to comparator rFIX was demonstrated through ratio of AUC 0-∞ in 32 subjects. IB1001 was well tolerated in all 76 treated subjects; the most common adverse drug reaction was headache (2.6% of subjects) and there were no reports of FIX inhibitors. Transient non-inhibitory binding FIX antibodies and anti-CHO cell protein antibodies developed in 21% and 29% of subjects respectively; no safety concerns were associated with development of these antibodies. Prophylaxis (mean duration ± SD: 17.9 ± 9.6 months, mean dose: 55.5 ± 12.9 IU/kg, median 1.0 infusion per week) was effective in preventing bleeds (median annual bleed rate: 1.52, interquartile range: 0.0-3.46). One or two IB1001 infusions resolved 84% of the bleeds, while for 84% of treatments haemostatic efficacy of IB1001 was rated excellent or good. IB1001 haemostatic efficacy for all 19 major surgeries was rated adequate or better than adequate. IB1001 is safe and efficacious for treatment of bleeds, routine prophylaxis and perioperative management in haemophilia B patients. © 2017 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

SkQ1 Ophthalmic Solution for Dry Eye Treatment: Results of a Phase 2 Safety and Efficacy Clinical Study in the Environment and During Challenge in the Controlled Adverse Environment Model.

PubMed

Petrov, Anton; Perekhvatova, Natalia; Skulachev, Maxim; Stein, Linda; Ousler, George

2016-01-01

This Phase 2 clinical trial assessed the efficacy and safety of the novel antioxidative, renewable compound SkQ1 for topical treatment of dry eye signs and symptoms. In a single-center, randomized, double-masked, placebo-controlled, 29-day study, 91 subjects with mild to moderate dry eye instilled the study drug twice daily and recorded dry eye symptoms daily. Subjects were randomized 1:1:1 into one of three ophthalmic solution treatment groups: SkQ1 1.55 µg/mL, SkQ1 0.155 µg/mL, or 0.0 µg/mL (placebo). Subjects were exposed to a controlled adverse environment chamber at 3 of the 4 study visits (Day -7, Day 1, and Day 29). Investigator assessments occurred at all study visits. SkQ1 was safe and efficacious in treating dry eye signs and symptoms. Statistically significant improvements with SkQ1 compared to placebo occurred for the dry eye signs of corneal fluorescein staining and lissamine green staining in the central region and lid margin redness, and for the dry eye symptoms of ocular discomfort, dryness, and grittiness. In addition, SkQ1 demonstrated greater efficacy compared to placebo, although the differences were not statistically significant, for corneal fluorescein staining in other regions and/or time points (total staining score, central region, corneal sum score, and temporal region), lissamine green staining for the central and nasal regions, and blink rate scores. This Phase 2 study indicated that SkQ1 is safe and efficacious for the treatment of dry eye signs and symptoms and supported previous study results. Clinicaltrials.gov identifier: NCT02121301. Miotech S.A.

A Meta-Analysis of D-Cycloserine in Exposure-Based Treatment: Moderators of Treatment Efficacy, Response, and Diagnostic Remission

PubMed Central

McGuire, Joseph F.; Wu, Monica S.; Piacentini, John; McCracken, James T.; Storch, Eric A.

2018-01-01

Objective This meta-analysis examined treatment efficacy, treatment response, and diagnostic remission effect sizes (ES) and moderators of d-cycloserine (DCS) augmented exposure treatment in randomized controlled trials (RCTs) of individuals with anxiety disorders, obsessive-compulsive disorder (OCD), and posttraumatic stress disorder (PTSD). Data Sources and Study Selection Using search terms d-cycloserine AND randomized controlled trial, PubMED (1965-May 2015), PsycInfo, and Scopus were searched for randomized placebo-controlled trials of DCS-augmented exposure therapy for anxiety disorders, OCD, and PTSD. Data Extraction Clinical variables and ES were extracted from 20 RCTs (957 participants). A random effects model calculated the ES for treatment efficacy, treatment response, and diagnostic remission using standardized rating scales. Subgroup analyses and meta-regression examined potential moderators. Results A small non-significant benefit of DCS augmentation compared to placebo augmentation was identified across treatment efficacy (g=0.15), response (RR=1.08), and remission (RR=1.109), with a moderately significant effect for anxiety disorders specifically (g=0.33, p=.03). At initial follow-up assessments, a small non-significant ES of DCS augmentation compared to placebo was found for treatment efficacy (g=0.21), response (RR=1.06), and remission (RR=1.12). Specific treatment moderators (e.g., comorbidity, medication status, gender, publication year) were found across conditions for both acute treatment and initial follow-up assessments. Conclusions DCS does not universally enhance treatment outcomes, but demonstrates promise for anxiety disorders. Distinct treatment moderators may account for discrepant findings across RCTs and disorders. Future trials may be strengthened by accounting for identified moderators in their design, with ongoing research needed on the mechanisms of DCS to tailor treatment protocols and maximize its benefit. PMID:27314661

A Systematic Review of the Safety and Efficacy of Mesenchymal Stem Cells for Disc Degeneration: Insights and Future Directions for Regenerative Therapeutics

PubMed Central

Yim, Rita Lok-Hay; Lee, Juliana Tsz-Yan; Bow, Cora H.; Meij, Björn; Leung, Victor; Cheung, Kenneth M.C.; Vavken, Patrick

2014-01-01

Intervertebral disc degeneration is associated with low-back pain. Mesenchymal stem cells (MSCs) have been used to “regenerate” the disc. The aim of this study was to perform a systematic review of comparative controlled studies that have assessed the safety and efficacy of using MSCs for disc regeneration. Literature databases were extensively searched. Trial design, subject-type, MSC sources, injection method, disc assessment, outcome intervals, and complication events were assessed. Validity of each study was performed. Twenty-four animal studies were included with 20.8% of the studies reporting randomization of groups. Trials in humans fulfilling inclusion criteria were not noted. The studies represented 862 discs that were injected with MSCs and 1,603 discs as controls. All three types of MSCs (ie, bone marrow, synovial, and adipose tissues) showed successful inhibition of disc degeneration. Bone-marrow-derived MSCs demonstrated superior quality of repair compared with other non-MSC treatments. A 2.7% overall complication rate was noted, whereby complications were noted only in rabbits. Overall, evidence suggested that MSCs increased disc space height in the majority of animal models. This is the first systematic review to assess the safety and efficacy of MSCs for the treatment of disc degeneration. Short-term MSC transplantation is safe and effective; however, additional, larger, and higher-quality studies are needed to assess the long-term safety and efficacy. Inconsistencies in methodological design and outcome parameters prevent any robust conclusions. Human-based clinical trials are needed. Recommendations are further made to improve efficacy, reduce potential complications, and standardize techniques for future studies. PMID:25050446

Impact of a cell phone intervention on mediating mechanisms of smoking cessation in individuals living with HIV/AIDS.

PubMed

Vidrine, Damon J; Arduino, Roberto C; Gritz, Ellen R

2006-12-01

Mounting evidence suggests that smokers living with HIV/AIDS have a significantly increased risk of numerous adverse health outcomes (both AIDS- and non-AIDS-related) compared with HIV-positive nonsmokers. Therefore, efforts to design and implement effective cessation programs for this ever-growing special population are warranted. The present study assessed the effects of a cell phone intervention (CPI) on hypothesized mediators (i.e., changes in depression, anxiety, social support, and self-efficacy) demonstrated to influence cessation outcomes in other populations. Ninety-five participants from an inner-city AIDS clinic were randomized to receive either the CPI or recommended standard of care (RSOC) smoking cessation treatment. Participants randomized to the RSOC group (n=47) received brief advice to quit, a 10-week supply of nicotine patches, and self-help materials. Participants randomized to the CPI group (n=48) received RSOC components plus a series of eight proactive counseling sessions delivered via cell phones. A series of regression analyses (linear and logistic) was used to assess the relationships between treatment group, the hypothesized mediators, and biochemically confirmed smoking cessation outcomes. Results indicated that the CPI group experienced greater reductions in anxiety and depression, and increases in self-efficacy compared with the RSOC group. Further, changes in depression, anxiety, and self-efficacy weakened the association between treatment group and cessation outcome. The mediator hypothesis, however, for social support was rejected, as the difference score was not significantly associated with treatment group. These results suggest that the efficacy of the CPI is at least partially mediated by its ability to decrease symptoms of distress while increasing self-efficacy.

A randomized waitlist-controlled trial of cognitive behavior therapy to improve emotion regulation in children with autism.

PubMed

Weiss, Jonathan A; Thomson, Kendra; Burnham Riosa, Priscilla; Albaum, Carly; Chan, Victoria; Maughan, Andrea; Tablon, Paula; Black, Karen

2018-04-23

Mental health problems are common among individuals with autism spectrum disorder (ASD), and difficulties with emotion regulation processes may underlie these issues. Cognitive behavior therapy (CBT) is considered an efficacious treatment for anxiety in children with ASD. Additional research is needed to examine the efficacy of a transdiagnostic treatment approach, whereby the same treatment can be applied to multiple emotional problems, beyond solely anxiety. The purpose of the present study was to examine the efficacy of a manualized and individually delivered 10-session, transdiagnostic CBT intervention, aimed at improving emotion regulation and mental health difficulties in children with ASD. Sixty-eight children (M age = 9.75, SD = 1.27) and their parents participated in the study, randomly allocated to either a treatment immediate (n = 35) or waitlist control condition (n = 33) (ISRCTN #67079741). Parent-, child-, and clinician-reported measures of emotion regulation and mental health were administered at baseline, postintervention/postwaitlist, and at 10-week follow-up. Children in the treatment immediate condition demonstrated significant improvements on measures of emotion regulation (i.e., emotionality, emotion regulation abilities with social skills) and aspects of psychopathology (i.e., a composite measure of internalizing and externalizing symptoms, adaptive behaviors) compared to those in the waitlist control condition. Treatment gains were maintained at follow-up. This study is the first transdiagnostic CBT efficacy trial for children with ASD. Additional investigations are needed to further establish its relative efficacy compared to more traditional models of CBT for children with ASD and other neurodevelopmental conditions. © 2018 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.

Comparison of a novel microcrystalline tyrosine adjuvant with aluminium hydroxide for enhancing vaccination against seasonal influenza.

PubMed

Heath, M D; Swan, N J; Marriott, A C; Silman, N J; Hallis, B; Prevosto, C; Gooch, K E; Skinner, M A

2017-03-27

Vaccination against seasonal influenza strains is recommended for "high risk" patient groups such as infants, elderly and those with respiratory or circulatory diseases. However, efficacy of the trivalent influenza vaccine (TIV) is poor in many cases and in the event of an influenza pandemic, mono-valent vaccines have been rapidly developed and deployed. One of the main issues with use of vaccine in pandemic situations is the lack of a suitable quantity of vaccine early enough during the pandemic to exert a major influence on the transmission of virus and disease outcome. One approach is to use a dose-sparing regimen which inevitably involves enhancing the efficacy using adjuvants. In this study we compare the use of a novel microcrystalline tyrosine (MCT) adjuvant, which is currently used in a niche area of allergy immunotherapy, for its ability to enhance the efficacy of a seasonal TIV preparation. The efficacy of the MCT adjuvant formulation was compared to alum adjuvanted TIV and to TIV administered without adjuvant using a ferret challenge model to determine vaccine efficacy. The MCT was found to possess high protein-binding capacity. In the two groups where TIV was formulated with adjuvant, the immune response was found to be higher (as determined by HAI titre) than vaccine administered without adjuvant and especially so after challenge with a live influenza virus. Vaccinated animals exhibited lower viral loads (as determined using RT-PCR) than control animals where no vaccine was administered. The attributes of each adjuvant in stimulating single-dose protection against a poorly immunogenic vaccine was demonstrated. The properties of MCT that lead to the reported effectiveness warrants further exploration in this and other vaccine targets - particularly where appropriate immunogenic, biodegradable and stable alternative adjuvants are sought.

The Efficacy of the Wee1 Inhibitor MK-1775 Combined with Temozolomide Is Limited by Heterogeneous Distribution across the Blood-Brain Barrier in Glioblastoma.

PubMed

Pokorny, Jenny L; Calligaris, David; Gupta, Shiv K; Iyekegbe, Dennis O; Mueller, Dustin; Bakken, Katrina K; Carlson, Brett L; Schroeder, Mark A; Evans, Debra L; Lou, Zhenkun; Decker, Paul A; Eckel-Passow, Jeanette E; Pucci, Vincenzo; Ma, Bennett; Shumway, Stuart D; Elmquist, William F; Agar, Nathalie Y R; Sarkaria, Jann N

2015-04-15

Wee1 regulates key DNA damage checkpoints, and in this study, the efficacy of the Wee1 inhibitor MK-1775 was evaluated in glioblastoma multiforme (GBM) xenograft models alone and in combination with radiation and/or temozolomide. In vitro MK-1775 efficacy alone and in combination with temozolomide, and the impact on DNA damage, was analyzed by Western blotting and γH2AX foci formation. In vivo efficacy was evaluated in orthotopic and heterotopic xenografts. Drug distribution was assessed by conventional mass spectrometry (MS) and matrix-assisted laser desorption/ionization (MALDI)-MS imaging. GBM22 (IC50 = 68 nmol/L) was significantly more sensitive to MK-1775 compared with five other GBM xenograft lines, including GBM6 (IC50 >300 nmol/L), and this was associated with a significant difference in pan-nuclear γH2AX staining between treated GBM22 (81% cells positive) and GBM6 (20% cells positive) cells. However, there was no sensitizing effect of MK-1775 when combined with temozolomide in vitro. In an orthotopic GBM22 model, MK-1775 was ineffective when combined with temozolomide, whereas in a flank model of GBM22, MK-1775 exhibited both single-agent and combinatorial activity with temozolomide. Consistent with limited drug delivery into orthotopic tumors, the normal brain to whole blood ratio following a single MK-1775 dose was 5%, and MALDI-MS imaging demonstrated heterogeneous and markedly lower MK-1775 distribution in orthotopic as compared with heterotopic GBM22 tumors. Limited distribution to brain tumors may limit the efficacy of MK-1775 in GBM. ©2015 American Association for Cancer Research.

The efficacy of the Wee1 inhibitor MK-1775 combined with temozolomide is limited by heterogeneous distribution across the blood-brain barrier in glioblastoma

PubMed Central

Pokorny, Jenny L.; Calligaris, David; Gupta, Shiv K.; Iyekegbe, Dennis O.; Mueller, Dustin; Bakken, Katrina K.; Carlson, Brett L.; Schroeder, Mark A.; Evans, Debra L.; Lou, Zhenkun; Decker, Paul A.; Eckel-Passow, Jeanette E.; Pucci, Vincenzo; Ma, Bennett; Shumway, Stuart D.; Elmquist, William; Agar, Nathalie Y.; Sarkaria, Jann N.

2015-01-01

Purpose Wee1 regulates key DNA damage checkpoints, and in this study, the efficacy of the Wee1 inhibitor MK-1775 was evaluated in GBM xenograft models alone and in combination with radiation and/or temozolomide (TMZ). Experimental design In vitro MK-1775 efficacy alone and in combination with TMZ, and the impact on DNA damage was analyzed by western blotting and γH2AX foci formation. In vivo efficacy was evaluated in orthotopic and heterotopic xenografts. Drug distribution was assessed by conventional mass spectrometry (MS) and matrix-assisted laser desorption/ionization (MALDI) -MS imaging. Results GBM22 (IC50 = 68 nM) was significantly more sensitive to MK-1775 compared to 5 other GBM xenograft lines including GBM6 (IC50 >300 nM), and this was associated with a significant difference in pan-nuclear γH2AX staining between treated GBM22 (81% cells positive) and GBM6 (20% cells positive) cells. However, there was no sensitizing effect of MK-1775 when combined with TMZ in vitro. In an orthotopic GBM22 model, MK-1775 was ineffective when combined with TMZ, while in a flank model of GBM22, MK-1775 exhibited both single agent and combinatorial activity with TMZ. Consistent with limited drug delivery into orthotopic tumors, the normal brain to whole blood ratio following a single MK-1775 dose was 5%, and MALDI-MS imaging demonstrated heterogeneous and markedly lower MK-1775 distribution in orthotopic as compared to heterotopic GBM22 tumors. Conclusions Limited distribution to brain tumors may limit the efficacy of MK-1775 in GBM. PMID:25609063

Superior Efficacy and Improved Renal and Bone Safety After Switching from a Tenofovir Disoproxil Fumarate- to a Tenofovir Alafenamide-Based Regimen Through 96 Weeks of Treatment.

PubMed

DeJesus, Edwin; Haas, Bernard; Segal-Maurer, Sorana; Ramgopal, Moti N; Mills, Anthony; Margot, Nicolas; Liu, Ya-Pei; Makadzange, Tariro; McCallister, Scott

2018-04-01

We previously demonstrated superior efficacy and safety advantages in HIV-infected, virologically suppressed adults switched to a regimen containing tenofovir alafenamide (TAF) as compared with those remaining on a tenofovir disoproxil fumarate (TDF) regimen through week 48. We now report long-term data through week 96. In this randomized, active-controlled, multicenter, open-label, noninferiority trial (ClinicalTrials.gov No. NCT01815736), we randomized virologically suppressed (HIV-1 RNA <50 copies/ml) adults (2:1) to receive a once-daily, single-tablet regimen containing elvitegravir (EVG), cobicistat (COBI), emtricitabine (FTC), and TAF group or to continue one of four TDF-containing regimens (TDF group) for 96 weeks. We evaluated efficacy (HIV-1 RNA <50 copies/ml using the FDA snapshot algorithm) and prespecified bone and renal endpoints at week 96. We randomized and treated 1,436 participants in this study (TAF n = 959, TDF n = 477). At week 96, TAF was superior to TDF in virologic efficacy, with 93% on TAF and 89% on TDF having HIV-1 RNA <50 copies/ml (difference 3.7%, 95% confidence interval: 0.4%-7.0%). Improvements in hip and spine bone mineral density for those assigned to TAF versus TDF continued through week 96 (p < .001). Significant improvements in urine protein or albumin to creatinine ratios were also seen among those in the TAF group versus TDF through week 96 (p < .001). There were no cases of investigator-reported proximal renal tubulopathy in the TAF group as compared with one case in the TDF group. Switching to EVG/COBI/FTC/TAF (E/C/F/TAF) was associated with statistically significant efficacy and safety advantages over remaining on a standard-of-care TDF-based regimen.

Can we well assess the relative efficacy and tolerability of a new drug versus others at the time of marketing authorization using mixed treatment comparisons? A detailed illustration with escitalopram

PubMed Central

Llorca, Pierre-Michel; Lançon, Christophe; Brignone, Mélanie; Painchault, Caroline; Rive, Benoit; Toumi, Mondher; François, Clément

2015-01-01

Objective To assess the variation of relative efficacy and tolerability of an antidepressant versus others based on both pre-marketing (registration studies) and post-marketing studies versus pre-marketing studies only in patients with major depressive disorder. Methods The relative efficacy and tolerability of antidepressants was assessed by mixed treatment comparisons (MTCs) using data acquired over two time periods: before registration of the reference drug escitalopram (1989–2002) and up to 5 years later (1989–2007). Ranking probability outputs were presented for efficacy, using change from baseline to 8 weeks on Montgomery–Åsberg Depression Rating Scale total score, and tolerability, using withdrawals due to adverse events. Results The relative efficacy and tolerability of some selected antidepressants, including escitalopram, varied considerably over the two time periods. The improved relative efficacy and tolerability of escitalopram over time, compared with citalopram, was demonstrated by greater separation of ranking probability curves for efficacy and tolerability. In 2002, escitalopram ranked low with 13.9% and 5.1% probability of being in the top four antidepressants’ relative efficacy and tolerability, respectively. In 2007, ranking probabilities for relative efficacy and tolerability of escitalopram increased to 52.5% and 82.1%, respectively. Conclusions Time of marketing authorization may not be the most appropriate time to evaluate the relative efficacy and tolerability of a new antidepressant based on MTC approach due to the asymmetry of information between new and older compounds. However, the first evaluation of relative effect of a new drug for health technology assessment recommendations is commonly done at this time. Re-evaluation of a drug several years after its launch is likely to provide a more accurate indication of its relative efficacy and tolerability. PMID:27123184

Designing clinical trials to assess antiepileptic drugs as monotherapy : difficulties and solutions.

PubMed

Perucca, Emilio

2008-01-01

Designing monotherapy trials in epilepsy is fraught with many hurdles, including diagnostic and classification difficulties, sparse information regarding the natural history of the disorder, and ethical objections to the use of placebo or a suboptimal comparator in a condition where the consequences of therapeutic failure can be serious. These issues are further complicated by regulatory differences between the US and the EU.In the US, the FDA considers that evidence of efficacy requires demonstration of superiority to a comparator. Because available antiepileptic drugs possess relatively high efficacy, in most settings it is unrealistic to expect that a new treatment will be superior to a standard treatment used at optimized dosages. To circumvent this problem, trial designs have been developed whereby patients in the control group are assigned to receive a suboptimal comparator and are required to exit from the trial if seizure deterioration occurs. This allows demonstration of a between-group difference in efficacy endpoints, such as time to exit or time to first seizure. Although these trials have come under increasing criticism because of ethical concerns, extensive information is now available on the outcome of patients with chronic epilepsy randomized to suboptimal treatment in similarly designed conversion to monotherapy trials. This has allowed the construction of a dataset of historical controls against which response to a fully active treatment can be compared. A number of studies using this novel approach are now in progress.In the EU, in addition to requiring data on conversion to monotherapy in refractory patients, the European Medicines Agency stipulates that a monotherapy indication in newly diagnosed epilepsy can only be granted if a candidate drug has shown at least a similar benefit/risk balance compared with an acknowledged standard at its optimal use during an assessment period of no less than 1 year. This has led to the implementation of noninferiority trials, one of which has been completed and which led to approval of the monotherapy indication for levetiracetam in the EU. Noninferiority trials provide valuable data in a setting that most closely resembles routine clinical practice, but their interpretation can be complicated by uncertainties on assay sensitivity.Major evidence gaps in the treatment of epilepsy still remain and it is hoped that these will be addressed in the near future. High quality monotherapy trials are particularly needed to assess the comparative efficacy of older and newer drugs in less common epilepsy syndromes, including most generalized epilepsies, and to investigate the different treatment options in populations homogeneous not only in terms of syndromic classification, but also in terms of underlying aetiology and associated phenotypes.

Effect of odanacatib on bone turnover markers, bone density and geometry of the spine and hip of ovariectomized monkeys: a head-to-head comparison with alendronate.

PubMed

Williams, Donald S; McCracken, Paul J; Purcell, Mona; Pickarski, Maureen; Mathers, Parker D; Savitz, Alan T; Szumiloski, John; Jayakar, Richa Y; Somayajula, Sangeetha; Krause, Stephen; Brown, Keenan; Winkelmann, Christopher T; Scott, Boyd B; Cook, Lynn; Motzel, Sherri L; Hargreaves, Richard; Evelhoch, Jeffrey L; Cabal, Antonio; Dardzinski, Bernard J; Hangartner, Thomas N; Duong, Le T

2013-10-01

Odanacatib (ODN) is a selective and reversible Cathepsin K (CatK) inhibitor currently being developed as a once weekly treatment for osteoporosis. Here, effects of ODN compared to alendronate (ALN) on bone turnover, DXA-based areal bone mineral density (aBMD), QCT-based volumetric BMD (vBMD) and geometric parameters were studied in ovariectomized (OVX) rhesus monkeys. Treatment was initiated 10 days after ovariectomy and continued for 20 months. The study consisted of four groups: L-ODN (2 mg/kg, daily p.o.), H-ODN (8/4 mg/kg daily p.o.), ALN (15 μg/kg, twice weekly, s.c.), and VEH (vehicle, daily, p.o.). L-ODN and ALN doses were selected to approximate the clinical exposures of the ODN 50-mg and ALN 70-mg once-weekly, respectively. L-ODN and ALN effectively reduced bone resorption markers uNTx and sCTx compared to VEH. There was no additional efficacy with these markers achieved with H-ODN. Conversely, ODN displayed inversely dose-dependent reduction of bone formation markers, sP1NP and sBSAP, and L-ODN reduced formation to a lesser degree than ALN. At month 18 post-OVX, L-ODN showed robust increases in lumbar spine aBMD (11.4%, p<0.001), spine trabecular vBMD (13.7%, p<0.001), femoral neck (FN) integral (int) vBMD (9.0%, p<0.001) and sub-trochanteric proximal femur (SubTrPF) int vBMD, (6.4%, p<0.001) compared to baseline. L-ODN significantly increased FN cortical thickness (Ct.Th) and cortical bone mineral content (Ct.BMC) by 22.5% (p<0.001) and 21.8% (p<0.001), respectively, and SubTrPF Ct.Th and Ct.BMC by 10.9% (p<0.001) and 11.3% (p<0.001) respectively. Compared to ALN, L-ODN significantly increased FN Ct. BMC by 8.7% (p<0.05), and SubTrPF Ct.Th by 7.6% (p<0.05) and Ct.BMC by 6.2% (p<0.05). H-ODN showed no additional efficacy compared to L-ODN in OVX-monkeys in prevention mode. Taken together, the results from this study have demonstrated that administration of ODN at levels which approximate clinical exposure in OVX-monkeys had comparable efficacy to ALN in DXA-based aBMD and QCT-based vBMD. However, FN cortical mineral content clearly demonstrated superior efficacy of ODN versus ALN in this model of estrogen-deficient non-human primates. © 2013 Elsevier Inc. All rights reserved.

Rivastigmine From Capsules to Patch: Therapeutic Advances in the Management of Alzheimer’s Disease and Parkinson’s Disease Dementia

PubMed Central

Micca, Joseph L.; Grossberg, George T.; Velting, Drew M.

2014-01-01

Objective: To discuss the pharmacology, mechanism of action, and chemical properties of the cholinesterase inhibitor (ChEI) rivastigmine; to provide a rationale for transdermal delivery and supportive clinical data, along with practical guidance on rivastigmine patch use in Alzheimer’s disease and Parkinson’s disease dementia. Data Sources: Pivotal studies of rivastigmine capsules and patch were identified using PubMed and the rivastigmine US prescribing information. PubMed searches were performed in 2013 using rivastigmine as a keyword. Study Selection: English-language articles related to rivastigmine considered of relevance to primary care physicians were included. Data Synthesis: Pharmacologic differences exist between rivastigmine and ChEIs. Clinical studies demonstrate symptomatic efficacy of oral rivastigmine across all stages of Alzheimer’s disease and mild-to-moderate Parkinson’s disease dementia. However, gastrointestinal adverse events limit access to optimal therapeutic doses. Strategies that lower maximum plasma concentrations (Cmax) and prolong time to Cmax, ie, transdermal delivery, may improve tolerability. Clinical registration studies have demonstrated improved tolerability of rivastigmine 9.5-mg/24-h patch versus 6-mg twice-daily capsules in mild-to-moderate Alzheimer’s disease, and a positive benefit-risk profile of 13.3-mg/24-h versus 9.5-mg/24-h patch in patients needing enhanced efficacy. Clinical data comparing 13.3-mg/24-h versus 4.6-mg/24-h patch in severe Alzheimer’s disease demonstrated efficacy on cognition and activities of daily living. These data led to approval of rivastigmine patch in severe Alzheimer’s disease. Transdermal delivery also has practical advantages, including simple, once-daily administration and a visual indicator of compliance. Potential application site reactions can be minimized and need not be a barrier to treatment. Conclusions: In addition to practical advantages, rivastigmine patch may improve clinical outcomes throughout the course of Alzheimer’s disease by providing access to high-dose efficacy without compromising tolerability. PMID:25667813

Updated efficacy analysis including secondary population results for OAK: a randomized phase III study of atezolizumab vs docetaxel in patients with previously treated advanced non-small cell lung cancer.

PubMed

Fehrenbacher, L; von Pawel, J; Park, K; Rittmeyer, A; Gandara, D R; Ponce Aix, S; Han, J-Y; Gadgeel, S M; Hida, T; Cortinovis, D L; Cobo, M; Kowalski, D M; De Marinis, F; Gandhi, M; Danner, B; Matheny, C; Kowanetz, M; He, P; Felizzi, F; Patel, H; Sandler, A; Ballinger, M; Barlesi, F

2018-05-16

The efficacy and safety of atezolizumab vs docetaxel as second- or third-line treatment in patients with advanced non-small cell lung cancer in the primary (n=850; ITT850) and secondary (n=1225; ITT1225) efficacy populations of the randomized phase III OAK study at an updated data cutoff were assessed. Patients received atezolizumab 1200mg or docetaxel 75mg/m 2 intravenously every 3 weeks until loss of clinical benefit or disease progression, respectively. The primary endpoint was overall survival (OS) in the intention-to-treat (ITT) population and programmed death-ligand 1 (PD-L1)-expressing subgroup. A sensitivity analysis was conducted to evaluate the impact of subsequent immunotherapy use in the docetaxel arm on observed survival benefit with atezolizumab. Atezolizumab demonstrated OS benefit vs docetaxel in the updated ITT850 (hazard ratio [HR] 0.75; 95% CI 0.64-0.89; P = .0006) and the ITT1225 (HR 0.80; 0.70-0.92; P = .0012) after minimum follow-up of 26 and 21 months, respectively. Improved survival with atezolizumab was observed across PD-L1 and histology subgroups. The relative OS benefit with atezolizumab was slightly greater in the immunotherapy sensitivity analysis in the ITT850 (HR 0.69) and ITT1225 (HR 0.74) compared to conventional OS estimation. Fewer patients receiving atezolizumab experienced grade 3/4 treatment-related adverse events (14.9%) than those receiving docetaxel (42.4%); no grade 5 events related to atezolizumab were observed. The updated ITT850 and initial ITT1225 analyses were consistent with the primary efficacy analysis demonstrating survival benefit with atezolizumab vs docetaxel. Atezolizumab continued to demonstrate a favorable safety profile after longer treatment exposure and follow-up. Copyright © 2018. Published by Elsevier Inc.

Therapy of Pancreatic Neuroendocrine Tumors: Fine Needle Intervention including Ethanol and Radiofrequency Ablation

PubMed Central

Lakhtakia, Sundeep

2017-01-01

Pancreatic neuroendocrine tumors (PNETs) are increasingly being detected, though usually as incidental findings. Majority of the PNETs are non-functional and surgical resection is the standard of care for most of them. However, in patients with small PNETs localized within the pancreas, who are unfit or unwilling for surgery, alternate methods of treatment are needed. Direct methods of ablation of PNETs, using either ethanol injection or radiofrequency ablation (RFA), are emerging as effective methods. The limited literature available as case reports or case series on endoscopic ultrasound (EUS)-guided local ablation using either ethanol or RFA has demonstrated safety and efficacy along with short- to medium-term sustained relief. Long-term benefits with these local ablative therapies are awaited. Comparative studies are needed to show which of these two competing technologies is superior. Finally, comparative trials of EUS-guided ablation with surgical resection in terms of efficacy and safety will ensure their place in the management algorithm. PMID:29207860

Efficacy of bacteriophage therapy in a model of Burkholderia cenocepacia pulmonary infection

PubMed Central

Carmody, Lisa A.; Gill, Jason J.; Summer, Elizabeth J.; Sajjan, Uma S.; Gonzalez, Carlos F.; Young, Ryland F.; LiPuma, John J.

2009-01-01

The therapeutic potential of bacteriophage (phage) in a mouse model of acute B. cenocepacia pulmonary infection was assessed. Phage were administered by either intranasal (i.n.) inhalation or intraperitoneal (i.p.) injection. Bacterial density, macrophage inflammatory protein-2 (MIP-2), and tumor necrosis factor-α (TNFα) levels were significantly reduced in lungs of mice treated with i.p. phage. No significant differences in lung bacterial density or MIP-2 levels were found between untreated mice and mice treated with i.n. phage, i.p. UV-inactivated phage, or i.p. λ phage controls. Mock-infected mice treated with phage showed no significant increase in lung MIP-2 or TNFα levels compared to mock-infected / mock-treated mice. We have demonstrated the efficacy of phage therapy in an acute B. cenocepacia lung infection model. Systemic administration of phage was more effective than inhalational administration, suggesting that circulating phage have better access to bacteria in lung compared to topical phage. PMID:20001604

Intranasal Dexmedetomidine for Procedural Sedation in Children, a Suitable Alternative to Chloral Hydrate.

PubMed

Cozzi, Giorgio; Norbedo, Stefania; Barbi, Egidio

2017-04-01

Sedation is often required for children undergoing diagnostic procedures. Chloral hydrate has been one of the sedative drugs most used in children over the last 3 decades, with supporting evidence for its efficacy and safety. Recently, chloral hydrate was banned in Italy and France, in consideration of evidence of its carcinogenicity and genotoxicity. Dexmedetomidine is a sedative with unique properties that has been increasingly used for procedural sedation in children. Several studies demonstrated its efficacy and safety for sedation in non-painful diagnostic procedures. Dexmedetomidine's impact on respiratory drive and airway patency and tone is much less when compared to the majority of other sedative agents. Administration via the intranasal route allows satisfactory procedural success rates. Studies that specifically compared intranasal dexmedetomidine and chloral hydrate for children undergoing non-painful procedures showed that dexmedetomidine was as effective as and safer than chloral hydrate. For these reasons, we suggest that intranasal dexmedetomidine could be a suitable alternative to chloral hydrate.

Comparative efficacy of tadalafil once daily in men with erectile dysfunction who demonstrated previous partial responses to as-needed sildenafil, tadalafil, or vardenafil.

PubMed

Kim, Edward; Seftel, Allen; Goldfischer, Evan; Baygani, Simin; Burns, Patrick

2015-02-01

Phosphodiesterase type-5 inhibitors (PDE5Is) are first-line therapies for erectile dysfunction (ED). Sildenafil (SIL) and vardenafil (VAR) are approved for as-needed (PRN) dosing; tadalafil (TAD) is approved for both PRN and once-a-day (OaD) dosing for ED. Recent evidence suggests that TAD-OaD may be effective as therapy in men with an incomplete response to PRN-PDE5I therapy. This study evaluated whether TAD-OaD provides similar efficacy in men with ED who had previously demonstrated a partial response to PRN-PDE5I therapy. In this randomized, double-blind, placebo-controlled trial, men with a ≥3 month ED history received SIL 100 mg, TAD 20 mg, or VAR 20 mg during a 4 week open-label lead-in period. Those with International Index of Erectile Function - Erectile Function (IIEF-EF) domain scores <26 following lead-in treatment completed a 4 week washout period, then randomized to TAD 2.5 mg up-titrated to 5 mg, TAD 5 mg, or placebo (PBO) OaD for 12 weeks. MAIN OUTCOME MEASURES obtained from patients treated with TAD-OaD were compared to PBO-treated patients. Additionally, results of treatment with TAD-OaD were compared to results obtained from 4 week PRN-PDE5I therapy to determine whether OaD and PRN regimens provided comparable efficacy. NCT01130532. International Index of Erectile Function (IIEF) domain scores; Sexual Encounter Profile (SEP) questions 2-5. Endpoint data was obtained from 590 men (391 TAD; 199 PBO). RESULTS for all IIEF and SEP measures were significantly better for TAD-OaD (p < 0.001 for all) compared to PBO and were comparable to those observed during PRN-PDE5I treatment. TAD 2.5 mg and TAD 5 mg OaD therapy were safe and generally well tolerated. Tadalafil once daily is a viable alternative to as-needed PDE5I therapy in men with ED. Key limitations include the lack of a PRN PDE5I study group during the double-blind period, and that many more patients took tadalafil than sildenafil or vardenafil during the PRN period.

Self-efficacy with application to nursing education: a concept analysis.

PubMed

Robb, Meigan

2012-01-01

Concept analysis and self-efficacy. This article analyzes the concept self-efficacy and its relationship to nursing education using Walker and Avant's methodology. Published literature. Nursing literature suggests increasing students' perceived self-efficacy will help to narrow the theory-practice gap. Self-efficacy is a cognitive variable that affects performance behaviors and affective processes. Perceived self-efficacy can be influenced by a direct experience, vicarious experience, or verbal persuasion. Individuals with high levels of self-efficacy demonstrate the defining attributes of confidence, perceived capability, and perseverance. © 2012 Wiley Periodicals, Inc.

Measuring Practicing and Prospective Elementary Teachers' Efficacy for Classroom Management: A Preliminary Development and Validation Study

ERIC Educational Resources Information Center

Putman, S. Michael

2013-01-01

Research has shown efficacy exerts a powerful influence on behavior. Classroom management represents one vehicle for demonstrations of these behaviors, yet few instruments focus solely on the measurement of this domain-specific form of efficacy. This research explored the relationship between teacher self-efficacy and classroom management through…

A comparison of the efficacy of newly developed reversible inhibitors of acetylcholinesterase with commonly used pyridostigmine as pharmacological pre-treatment of soman-poisoned mice.

PubMed

Kassa, Jiri; Musilek, Kamil; Koomlova, Marketa; Bajgar, Jiri

2012-04-01

The ability of three newly developed reversible inhibitors of acetylcholinesterase (AChE) (K298, K344 and K474) and currently available carbamate pyridostigmine to increase the resistance of mice against soman and the efficacy of antidotal treatment of soman-poisoned mice was compared. Neither pyridostigmine nor new reversible inhibitors of AChE were able to increase the LD(50) value of soman. Thus, the pharmacological pre-treatment with pyridostigmine or newly synthesized inhibitors of AChE was not able to protect mice against soman-induced lethal acute toxicity. The pharmacological pre-treatment with pyridostigmine alone or with K474 was able to slightly increase the efficacy of antidotal treatment (the oxime HI-6 in combination with atropine) of soman-poisoned mice, but the increase in the efficacy of antidotal treatment was not significant. The other newly developed reversible inhibitors of AChF (K298, K344) were completely ineffective. These findings demonstrate that pharmacological pre-treatment of soman-poisoned mice with tested reversible inhibitors of AChF is not promising. © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.

Protective efficacy of recombinant BCG Tokyo (Ag85A) in rhesus monkeys (Macaca mulatta) infected intratracheally with H37Rv Mycobacterium tuberculosis.

PubMed

Sugawara, I; Sun, L; Mizuno, S; Taniyama, T

2009-01-01

We have reported previously that recombinant BCG Tokyo (Ag85A) (rBCG-Ag85A[Tokyo]) shows promise as a tuberculosis vaccine, demonstrating protective efficacy in cynomolgus monkeys. As a next step, rhesus monkeys were utilized because they are also susceptible to Mycobacterium tuberculosis and show a continuous course of infection resembling human tuberculosis. The recombinant BCG vaccine (5x10(5) CFU per monkey) was administered once intradermally into the back skin to three groups of rhesus monkeys, and its protective efficacy was compared for 4months with that of its parental BCG Tokyo strain. Eight week vaccination of the monkeys with rBCG-Ag85A[Tokyo] resulted in a reduction of tubercle bacilli CFU (p<0.01) and lung pathology in animals infected intratracheally with 3000 CFU H37Rv M. tuberculosis. Vaccination prevented an increase in the old tuberculin test after challenge with M. tuberculosis and reaction of M. tuberculosis-derived antigen. Thus, it was shown that even in rhesus monkeys rBCG-Ag85A[Tokyo] induced higher protective efficacy than BCG Tokyo.

Highly Efficient Small Form Factor LED Retrofit Lamp

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steven Allen; Fred Palmer; Ming Li

2011-09-11

This report summarizes work to develop a high efficiency LED-based MR16 lamp downlight at OSRAM SYLVANIA under US Department of Energy contract DE-EE0000611. A new multichip LED package, electronic driver, and reflector optic were developed for these lamps. At steady-state, the lamp luminous flux was 409 lumens (lm), luminous efficacy of 87 lumens per watt (LPW), CRI (Ra) of 87, and R9 of 85 at a correlated color temperature (CCT) of 3285K. The LED alone achieved 120 lumens per watt efficacy and 600 lumen flux output at 25 C. The driver had 90% electrical conversion efficiency while maintaining excellent powermore » quality with power factor >0.90 at a power of only 5 watts. Compared to similar existing MR16 lamps using LED sources, these lamps had much higher efficacy and color quality. The objective of this work was to demonstrate a LED-based MR16 retrofit lamp for replacement of 35W halogen MR16 lamps having (1) luminous flux of 500 lumens, (2) luminous efficacy of 100 lumens per watt, (3) beam angle less than 40{sup o} and center beam candlepower of at least 1000 candelas, and (4) excellent color quality.« less

Early Experience with a Brief, Multimodal, Multidisciplinary Treatment Program for Fibromyalgia

PubMed Central

Vincent, Ann; Whipple, Mary O.; Oh, Terry H.; Guderian, Janet A.; Barton, Debra L.; Luedtke, Connie A.

2014-01-01

Fibromyalgia is a complex, heterogeneous disorder for which a multidisciplinary individualized approach is currently advocated. We executed a 1 week multidisciplinary fibromyalgia clinical program with 7 patients, based on our previous experience with our existing 1.5 day multidisciplinary fibromyalgia program that has demonstrated both short- and long-term benefits. The current expanded program was not designed as a clinical study, but rather as a clinical feasibility assessment and was multidisciplinary in nature, with cognitive behavioral therapy, activity pacing and graded exercise therapy as major components. We assessed changes in individual patients at 1 week and 3 months following the program utilizing validated self-report measures of pain, fatigue, and self-efficacy. All patients indicated at least small improvements in pain and physical symptoms both at 1 week and 3 months and all but one patient showed improvement in self-efficacy at 1 week and 3 months. Similar trends were observed for fatigue. Based on our early clinical experience, we conclude that the 1 week multidisciplinary fibromyalgia program is logistically feasible and has potential for clinical efficacy. Further research is needed and is planned to test the clinical efficacy of this program and compare it with other interventions. PMID:24315246

The clinical trials supporting benzyl alcohol lotion 5% (Ulesfia): a safe and effective topical treatment for head lice (pediculosis humanus capitis).

PubMed

Meinking, Terri L; Villar, Maria E; Vicaria, Maureen; Eyerdam, Debbie H; Paquet, Diane; Mertz-Rivera, Kamara; Rivera, Hector F; Hiriart, Javier; Reyna, Susan

2010-01-01

Benzyl alcohol lotion 5% (BAL 5%) is a non-neurotoxic topical head lice treatment that is safe and effective in children as young as 6 months of age. The safety and efficacy of this pediculicide has been studied in 695 (confirm number) subjects in all phases of clinical development. Scanning electron micrographs (SEM) demonstrated that the active agent appears to stun the breathing spiracles open, enabling the vehicle to penetrate the respiratory mechanism (spiracles), therefore asphyxiating the lice. Initial phase II trials compared this novel product to RID using identical volumes of treatment (4 oz/application) and yielding, almost, identical efficacy. This outcome pointed to the significant importance of completely saturating the hair with the product in order to achieve maximum treatment success. A second phase II trial, which allowed the use of sufficient product to saturate the hair, resulted in 100% efficacy after both 10 and 30 minute treatments. A third phase II trial verified an effective dose. Phase III trials compared BAL 5% to vehicle placebo for two 10-minute applications. It proved to be safe and effective (p < 0.001) for treatment of head lice and is the first FDA-approved non-neurotoxic lice treatment, now available in the United States as Ulesfia lotion.

The use of electrocautery as the primary ablation modality for malignant and benign airway obstruction.

PubMed

Wahidi, Momen M; Unroe, Mark A; Adlakha, Natasha; Beyea, Mathew; Shofer, Scott L

2011-09-01

Laser has been the main ablative modality in the airways, but a growing experience with endobronchial electrocautery suggests a comparable efficacy and safety profile. To evaluate the efficacy and safety of electrocautery as the primary heat therapy for malignant and benign airway obstruction. A retrospective review of all patients undergoing endobronchial electrocautery, alone or in combination with other airway tools, at Duke University Medical Center between April 2004 and November 2009. Data on efficacy (luminal patency, symptomatic, radiographic, or physiologic improvement) and safety (complication rate) were collected. Ninety-four patients underwent 117 procedures with endobronchial electrocautery for endobronchial malignant and nonmalignant disease. Endoscopic improvement was seen in 94% of cases. Seventy-one percent of patients reported symptomatic improvement. Radiographic studies demonstrated luminal improvement in 78% of patients on chest computed tomography, improved aeration on chest computed tomography and chest x-ray in 63% and 43% of patients, respectively. The rate of major complications was 0.8%, whereas minor complications occurred in 6.8% of cases. There was no perioperative mortality. Endobronchial electrocautery is effective and safe when used as an ablative modality in malignant and benign airway obstruction and has a comparable profile to laser with the advantage of lower cost.

The NICE recommendation for drug-coated balloons and its global impact.

PubMed

Eccleshall, Simon; Waliszewski, M

2015-06-01

The clinical efficacy and safety of drug-coated balloon (DCB) angioplasty in patients with coronary in-stent restenosis (ISR) has been demonstrated. The objective of this article is to provide comparative cost efficacy data for DCB angioplasty in various countries based on the original methodology of the Medical Technologies Evaluation Programme (MTEP) at the National Institute for Health and Clinical Excellence (NICE) in 2010. Published and unpublished Health Technology Assessment (HTA) reports were evaluated for comparison in selected countries. Furthermore, a systematic review of economic evaluations of DCB angioplasty versus standard treatments (uncoated balloon angioplasty or drug-eluting stent implantations) was conducted. National cost efficacy data were evaluated using Markov state transition models which were adapted to fit each country's device and procedure related costs. The clinical input for adverse events was defined with two relevant trials for in-stent restenosis of bare metal stents (BMS-ISR) and of drug-eluting stents (DES-ISR). In the UK, Germany, Switzerland, South Africa, Japan and Brazil, DCB angioplasty is cost-effective when compared with drug-eluting stents to treat either BMS-ISR or DES-ISR. DCB angioplasty ought to be the preferred treatment option for patients with BMS-ISR and DES-ISR from the payers' point of view. © The Author(s), 2015.

A comparison of maximal bioenergetic enzyme activities obtained with commonly used homogenization techniques.

PubMed

Grace, M; Fletcher, L; Powers, S K; Hughes, M; Coombes, J

1996-12-01

Homogenization of tissue for analysis of bioenergetic enzyme activities is a common practice in studies examining metabolic properties of skeletal muscle adaptation to disease, aging, inactivity or exercise. While numerous homogenization techniques are in use today, limited information exists concerning the efficacy of specific homogenization protocols. Therefore, the purpose of this study was to compare the efficacy of four commonly used approaches to homogenizing skeletal muscle for analysis of bioenergetic enzyme activity. The maximal enzyme activity (Vmax) of citrate synthase (CS) and lactate dehydrogenase (LDH) were measured from homogenous muscle samples (N = 48 per homogenization technique) and used as indicators to determine which protocol had the highest efficacy. The homogenization techniques were: (1) glass-on-glass pestle; (2) a combination of a mechanical blender and a teflon pestle (Potter-Elvehjem); (3) a combination of the mechanical blender and a biological detergent; and (4) the combined use of a mechanical blender and a sonicator. The glass-on-glass pestle homogenization protocol produced significantly higher (P < 0.05) enzyme activities compared to all other protocols for both enzymes. Of the four protocols examined, the data demonstrate that the glass-on-glass pestle homogenization protocol is the technique of choice for studying bioenergetic enzyme activity in skeletal muscle.

Safety analysis of sofosbuvir and ledipasvir for treating hepatitis C.

PubMed

Fazel, Yousef; Lam, Brian; Golabi, Pegah; Younossi, Zobair

2015-08-01

The approval of sofosbuvir (SOF), a nucleotide analogue NS5B polymerase inhibitor, and ledipasvir (LDV), a NS5A inhibitor, marked a new chapter in IFN and ribavirin-free treatment of hepatitis C virus (HCV). This drug reduces adverse events associated with IFN therapy. The purpose of this paper is to evaluate the safety and efficacy of LDV/SOF. Clinical trials illustrating safety and efficacy of LDV/SOF are reviewed and compared to other IFN and ribavirin-free treatment options available. In trials enrolling more than 3000 patients, LDV/SOF is well tolerated with a good safety and side-effect profile in diverse cohorts, including previous direct-acting antiviral (DAA) treatment failures, liver transplant recipients, decompensated cirrhosis and HIV/HCV co-infection. As with all DAAs, the potential for drug-drug interactions must be carefully evaluated, as demonstrated by recent post-marketing reports of symptomatic bradycardia when LDV/SOF is co-administered with amiodarone. Currently, dose recommendations cannot be given for patients with advanced renal disease. Trials in this population are ongoing, more study is warranted. When surveying the DAA regimens available, efficacy, safety and tolerability of LDV/SOF is comparable or better, and LDV/SOF provides an option with convenient single-tablet, once daily, ribavirin-free dosing with relatively few significant drug-drug interactions.

The safety and efficacy of 3% Cannabis seeds extract cream for reduction of human cheek skin sebum and erythema content.

PubMed

Ali, Atif; Akhtar, Naveed

2015-07-01

Escalated sebum fabrication is seen with an unattractive look and adds to the growth of acne. We aimed to investigate the efficacy and safety of 3% Cannabis seeds extract cream on human cheek skin sebum and erythema content. For this purpose, base plus 3% Cannabis seeds extract and base (control) were prepared for single blinded and comparative study. Healthy males were instructed to apply the base plus 3% Cannabis seeds extract and base twice a day to their cheeks for 12 weeks. Adverse events were observed to determine skin irritation. Measurements for sebum and erythema content were recorded at baseline, 2nd, 4th, 6th, 8th, 10th and 12th week in a control room with Sebumeter and Mexameter. Base plus 3% Cannabis seeds extract was found to be safe in volunteers. Measurements demonstrated that skin sebum and erythema content of base plus 3% Cannabis seeds extract treated side showed significant decrease (p<0.05) compared with base treated side. Base plus 3% Cannabis seeds extract showed safety. It was well tolerated for the reduction of skin sebum and erythema content. Its improved efficacy could be suggested for treatment of acne vulgaris, seborrhea, papules and pustules to get attractive facial appearance.

A randomised, double-blind, parallel-group study to demonstrate equivalence in efficacy and safety of CT-P13 compared with innovator infliximab when coadministered with methotrexate in patients with active rheumatoid arthritis: the PLANETRA study

PubMed Central

Yoo, Dae Hyun; Hrycaj, Pawel; Miranda, Pedro; Ramiterre, Edgar; Piotrowski, Mariusz; Shevchuk, Sergii; Kovalenko, Volodymyr; Prodanovic, Nenad; Abello-Banfi, Mauricio; Gutierrez-Ureña, Sergio; Morales-Olazabal, Luis; Tee, Michael; Jimenez, Renato; Zamani, Omid; Lee, Sang Joon; Kim, HoUng; Park, Won; Müller-Ladner, Ulf

2013-01-01

Objectives To compare the efficacy and safety of innovator infliximab (INX) and CT-P13, an INX biosimilar, in active rheumatoid arthritis patients with inadequate response to methotrexate (MTX) treatment. Methods Phase III randomised, double-blind, multicentre, multinational, parallel-group study. Patients with active disease despite MTX (12.5–25 mg/week) were randomised to receive 3 mg/kg of CT-P13 (n=302) or INX (n=304) with MTX and folic acid. The primary endpoint was the American College of Rheumatology 20% (ACR20) response at week 30. Therapeutic equivalence of clinical response according to ACR20 criteria was concluded if the 95% CI for the treatment difference was within ±15%. Secondary endpoints included ACR response criteria, European League Against Rheumatism (EULAR) response criteria, change in Disease Activity Score 28 (DAS28), Medical Outcomes Study Short-Form Health Survey (SF-36), Simplified Disease Activity Index, Clinical Disease Activity Index, as well as pharmacokinetic (PK) and pharmacodynamic (PD) parameters, safety and immunogenicity. Results At week 30, ACR20 responses were 60.9% for CT-P13 and 58.6% for INX (95% CI −6% to 10%) in the intention-to-treat population. The proportions in CT-P13 and INX groups achieving good or moderate EULAR responses (C reactive protein (CRP)) at week 30 were 85.8% and 87.1%, respectively. Low disease activity or remission according to DAS28–CRP, ACR–EULAR remission rates, ACR50/ACR70 responses and all other PK and PD endpoints were highly similar at week 30. Incidence of drug-related adverse events (35.2% vs 35.9%) and detection of antidrug antibodies (48.4% vs 48.2%) were highly similar for CT-P13 and INX, respectively. Conclusions CT-P13 demonstrated equivalent efficacy to INX at week 30, with a comparable PK profile and immunogenicity. CT-P13 was well tolerated, with a safety profile comparable with that of INX. ClinicalTrials.gov Identifier NCT01217086 PMID:23687260

Economic evaluations of trastuzumab in HER2-positive metastatic breast cancer: a systematic review and critique.

PubMed

Parkinson, Bonny; Pearson, Sallie-Anne; Viney, Rosalie

2014-01-01

Published economic evaluations of trastuzumab for the treatment of HER2-positive metastatic breast cancer have arrived at different conclusions regarding the cost-effectiveness of trastuzumab, despite comparative efficacy being demonstrated by a small set of randomised controlled trials (RCTs). This article aims to provide insight into the quality of the evaluations and explore the possible drivers of the conflicting conclusions. A systematic literature review was conducted to identify all published economic evaluations that compared the incremental costs and outcomes of trastuzumab versus a comparator. Fifteen economic evaluations were identified. In the evaluations that estimated efficacy using an RCT, the key drivers of the conclusions regarding cost-effectiveness were: the approach used to estimate overall survival in the control group given crossover to trastuzumab following progression in the trials; the inclusion of treatment beyond progression; inclusion of wastage due to unused vial portions, adverse events, and the cost of HER2 testing. Four evaluations used non-randomised approaches to estimate efficacy, thus introducing the potential for confounding. As a result these evaluations reported relatively optimistic estimates of comparative effectiveness. Finally the evaluations used different thresholds to determine whether treatment with trastuzumab was cost-effective. There were numerous drivers of the different conclusions regarding the cost-effectiveness of trastuzumab, many of which are due to judgements made by the authors when translating data from RCTs. Many of the potential drivers were not identified by the published systematic reviews of economic evaluations and perhaps more remain unidentified because of inconsistent and limited reporting.

Safety and efficacy of bridging with low molecular weight heparins: a systematic review and partial meta-analysis.

PubMed

Eijgenraam, Pieter; ten Cate, Hugo; Ten Cate-Hoek, Arina

2013-01-01

Surgical interventions in patients on long term vitamin K antagonist (VKA) treatment create a dilemma; periprocedural interruption of anticoagulation raises the risk of thrombosis, while continuation raises the risk of bleeding. The anticoagulation- free interval is minimized by "bridging" with parenteral anticoagulants. The efficacy and safety of bridging with low molecular weight heparins (LMWH) has however not been unequivocally established. We performed an EMBASE and MEDLINE search for studies that compared bridging anticoagulation with continuation or cessation of VKA without bridging; with thromboembolism (TE) and bleeding as outcomes. We identified 878 articles and finally selected 17. Results of individual studies were pooled. None of the included studies reported significant differences in incidence of TEs between the bridging group and the comparator group; 4 out of 13 studies reported zero TEs. Heparin was identified as a risk factor for bleeding in multivariable adjusted analyses in 3 studies on pacemaker/implantable cardioverter defibrillator (PM/ICD) surgery. In 5 studies (different types of surgery) with unadjusted analyses, bridging was compared to warfarin cessation: 3 studies reported null results for bleeding; 2 studies identified bridging as a risk factor. We pooled a subset of 6 studies regarding postoperative bleeding after PM/ICD surgery and found a relative risk (RR) of 3.03 (95% confidence interval (CI), 1.86-4.95) for bridging compared to continuation of VKA. While the antithrombotic efficacy of bridging with LMWH has not been demonstrated, increased bleeding risk is observed in different types of surgery. PM/ICD surgery can be safely performed on continued VKA.

Relationship of amotivation to neurocognition, self-efficacy and functioning in first-episode psychosis: a structural equation modeling approach.

PubMed

Chang, W C; Kwong, V W Y; Hui, C L M; Chan, S K W; Lee, E H M; Chen, E Y H

2017-03-01

Better understanding of the complex interplay among key determinants of functional outcome is crucial to promoting recovery in psychotic disorders. However, this is understudied in the early course of illness. We aimed to examine the relationships among negative symptoms, neurocognition, general self-efficacy and global functioning in first-episode psychosis (FEP) patients using structural equation modeling (SEM). Three hundred and twenty-one Chinese patients aged 26-55 years presenting with FEP to an early intervention program in Hong Kong were recruited. Assessments encompassing symptom profiles, functioning, perceived general self-efficacy and a battery of neurocognitive tests were conducted. Negative symptom measurement was subdivided into amotivation and diminished expression (DE) domain scores based on the ratings in the Scale for the Assessment of Negative Symptoms. An initial SEM model showed no significant association between functioning and DE which was removed from further analysis. A final trimmed model yielded very good model fit (χ2 = 15.48, p = 0.63; comparative fit index = 1.00; root mean square error of approximation <0.001) and demonstrated that amotivation, neurocognition and general self-efficacy had a direct effect on global functioning. Amotivation was also found to mediate a significant indirect effect of neurocognition and general self-efficacy on functioning. Neurocognition was not significantly related to general self-efficacy. Our results indicate a critical intermediary role of amotivation in linking neurocognitive impairment to functioning in FEP. General self-efficacy may represent a promising treatment target for improvement of motivational deficits and functional outcome in the early illness stage.

The Vaginal Microbiome and its Potential to Impact Efficacy of HIV Pre-exposure Prophylaxis for Women.

PubMed

Velloza, Jennifer; Heffron, Renee

2017-10-01

This review describes existing evidence addressing the potential modulation of pre-exposure prophylaxis (PrEP) products, specifically 1% tenofovir (TFV) gel and oral tenofovir-based PrEP, by vaginal dysbiosis and discusses future considerations for delivering novel, long-acting PrEP products to women at high risk for vaginal dysbiosis and HIV. We describe results from analyses investigating the modification of PrEP efficacy by vaginal dysbiosis and studies of biological mechanisms that could render PrEP ineffective in the presence of specific microbiota. A secondary analysis from the CAPRISA-004 cohort demonstrated that there is no effect of the 1% TFV gel in the presence of non-Lactobacillus dominant microbiota. Another recent analysis comparing oral tenofovir-based PrEP efficacy among women with and without bacterial vaginosis in the Partners PrEP Study found that oral PrEP efficacy is not modified by bacterial vaginosis. Gardnerella vaginalis, commonly present in women with vaginal dysbiosis, can rapidly metabolize TFV particularly when it is locally applied and thereby prevent TFV integration into cells. Given that vaginal dysbiosis appears to modulate efficacy for 1% TFV gel but not for oral tenofovir-based PrEP, vaginal dysbiosis is potentially less consequential to HIV protection from TFV in the context of systemic drug delivery and high product adherence. Vaginal dysbiosis may undermine the efficacy of 1% TFV gel to protect women from HIV but not the efficacy of oral PrEP. Ongoing development of novel ring, injectable, and film-based PrEP products should investigate whether vaginal dysbiosis can reduce efficacy of these products, even in the presence of high adherence.

Safety and efficacy of rivaroxaban compared with warfarin in patients undergoing peripheral arterial procedures.

PubMed

Talukdar, Anjan; Wang, S Keisin; Czosnowski, Lauren; Mokraoui, Nassim; Gupta, Alok; Fajardo, Andres; Dalsing, Michael; Motaganahalli, Raghu

2017-10-01

Rivaroxaban is a United States Food and Drug Administration-approved oral anticoagulant for venous thromboembolic disease; however, there is no information regarding the safety and its efficacy to support its use in patients after open or endovascular arterial interventions. We report the safety and efficacy of rivaroxaban vs warfarin in patients undergoing peripheral arterial interventions. This single-institution retrospective study analyzed all sequential patients from December 2012 to August 2014 (21 months) who were prescribed rivaroxaban or warfarin after a peripheral arterial procedure. Our study population was then compared using American College of Chest Physicians guidelines with patients then stratified as low, medium, or high risk for bleeding complications. Statistical analyses were performed using the Student t-test and χ 2 test to compare demographics, readmissions because of bleeding, and the need for secondary interventions. Logistic regression models were used for analysis of variables associated with bleeding complications and secondary interventions. The Fisher exact test was used for power analysis. There were 44 patients in the rivaroxaban group and 50 patients in the warfarin group. Differences between demographics and risk factors for bleeding between groups or reintervention rate were not statistically significant (P = .297). However, subgroup evaluation of the safety profile suggests that patients who were aged ≤65 years and on warfarin had an overall higher incidence of major bleeding (P = .020). Patients who were aged >65 years, undergoing open operation, had a significant risk for reintervention (P = .047) when they received rivaroxaban. Real-world experience using rivaroxaban and warfarin in patients after peripheral arterial procedures suggests a comparable safety and efficacy profile. Subgroup analysis of those requiring an open operation demonstrated a decreased bleeding risk when rivaroxaban was used (in those aged <65 years) but an increased risk for secondary interventions. Further studies with a larger cohort are required to validate our results. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Insulin glulisine: an evaluation of its pharmacodynamic properties and clinical application.

PubMed

Helms, Kristen L; Kelley, Kristi W

2009-04-01

To evaluate the pharmacodynamic properties, efficacy, safety, and clinical application of insulin glulisine, a rapid-acting insulin analog, in the treatment of diabetes mellitus in ambulatory and hospitalized patients. Searches were performed with the headings glulisine, insulin analog, [LysB3, GluB29] insulin, insulin glulisine, rDNA insulin, rapid-acting insulin, SoloStar, safety, efficacy, pharmacodynamics, and cost analysis within MEDLINE and PubMed, American Diabetes Association (ADA), the Food and Drug Administration (FDA), and Sanofi-aventis Pharmaceuticals (1990-August 2008). Phase 1, Phase 2, Phase 3, and postmarketing trials examining the efficacy and safety of glulisine in type 1 or type 2 diabetes were reviewed. Studies published as abstracts and the manufacturer's product information supplemented data absent from clinical trials. Insulin glulisine is a rapid-acting insulin with relative equivalence in efficacy and safety to other short- and rapid-acting insulins. Glulisine's onset of action of 20 minutes and 4-hour duration of action allow for bolus administration 15-20 minutes prior to or up to 20 minutes after meals. Clinical trials have demonstrated the safety and efficacy in adults with type 1 or type 2 diabetes. Several studies indicated a statistically significant decrease of hemoglobin A1C (A1C) with glulisine compared with regular insulin (0.10 decrease); however, no difference in A1C control was found compared with insulin aspart or lispro. Significant adverse effects appear to be limited to localized and systemic allergic reactions and hypoglycemia. Insulin glulisine is a safe and effective rapid-acting insulin analog for the treatment of adults with diabetes. Clinical benefit over other short- and rapid-acting insulin products is not established. Addition of insulin glulisine to a formulary should be based on institution-specific availability and cost differences between glulisine, lispro, and aspart in the absence of superiority of clinical efficacy or safety and data beyond 26 weeks.

Advances in stem cell therapy for the lower urinary tract.

PubMed

Lin, Ching-Shwun

2010-02-26

Lower urinary tract diseases are emotionally and financially burdensome to the individual and society. Current treatments are ineffective or symptomatic. Conversely, stem cells (SCs) are regenerative and may offer long-term solutions. Among the different types of SCs, bone marrow SCs (BMSCs) and skeletal muscle-derived SCs (SkMSCs) have received the most attention in pre-clinical and clinical trial studies concerning the lower urinary tract. In particular, clinical trials with SkMSCs for stress urinary incontinence have demonstrated impressive efficacy. However, both SkMSCs and BMSCs are difficult to obtain in quantity and therefore neither is optimal for the eventual implementation of SC therapy. On the other hand, adipose tissue-derived SCs (ADSCs) can be easily and abundantly obtained from "discarded" adipose tissue. Moreover, in several head-on comparison studies, ADSCs have demonstrated equal or superior therapeutic potential compared to BMSCs. Therefore, across several different medical disciplines, including urology, ADSC research is gaining wide attention. For the regeneration of bladder tissues, possible differentiation of ADSCs into bladder smooth muscle and epithelial cells has been demonstrated. For the treatment of bladder diseases, specifically hyperlipidemia and associated overactive bladder, ADSCs have also demonstrated efficacy. For the treatment of urethral sphincter dysfunction associated with birth trauma and hormonal deficiency, ADSC therapy was also beneficial. Finally, ADSCs were able to restore erectile function in various types of erectile dysfunction (ED), including those associated with diabetes, hyperlipidemia, and nerve injuries. Thus, ADSCs have demonstrated remarkable therapeutic potentials for the lower urinary tract.

Comparative evaluation of the antimicrobial efficacy of aloe vera tooth gel and two popular commercial toothpastes: an in vitro study.

PubMed

George, Dilip; Bhat, Sham S; Antony, Beena

2009-01-01

Aloe vera (Aloe barbadensis Miller) has been suggested for a wide variety of ailments but its use in dentistry is limited. This article reviews the uses of the plant and describes an in vitro investigation that compared the antimicrobial effectiveness of aloe vera tooth gel with two popular, commercially available dentifrices. The preliminary results showed that aloe vera tooth gel and the toothpastes were equally effective against Candida albicans, Streptococcus mutans, Lactobacillus acidophilus, Enterococcus faecalis, Prevotella intermedia, and Peptostreptococcus anaerobius. Aloe vera tooth gel demonstrated enhanced antibacterial effect against S. mitis.

Direct imaging of small scatterers using reduced time dependent data

NASA Astrophysics Data System (ADS)

Cakoni, Fioralba; Rezac, Jacob D.

2017-06-01

We introduce qualitative methods for locating small objects using time dependent acoustic near field waves. These methods have reduced data collection requirements compared to typical qualitative imaging techniques. In particular, we only collect scattered field data in a small region surrounding the location from which an incident field was transmitted. The new methods are partially theoretically justified and numerical simulations demonstrate their efficacy. We show that these reduced data techniques give comparable results to methods which require full multistatic data and that these time dependent methods require less scattered field data than their time harmonic analogs.

Superior effect of combination vs. single steroid therapy in keloid disease: a comparative in vitro analysis of glucocorticoids.

PubMed

Syed, Farhatullah; Singh, Subir; Bayat, Ardeshir

2013-01-01

Keloid disease (KD) is a fibroproliferative disorder of unknown etiology. Current use of corticosteroid injection is partially beneficial with 80% recurrence rate. Additionally, the efficacy of different steroids, alone or in combination as opposed to monotherapy, in treating KD remains unclear. Here, we compared the single and combined efficacy of glucocorticoids-dexamethasone (Dex), triamcinolone (TAC), and methylprednisolone (Medrol)-on primary keloid fibroblasts (KFs) (n = 27) and normal skin (n = 19) fibroblasts at cellular, protein, and messenger RNA levels in vitro. Our results demonstrated that cytotoxicity to steroids was dose dependent. Cell spreading, attachment, and proliferation were significantly (p < 0.05) reduced by Medrol and TAC. Migration and invasion properties of KF were inhibited significantly (p < 0.05) by Medrol and TAC compared with Dex. At both protein and messenger RNA levels, keloid-associated fibrotic markers were significantly (p < 0.05) decreased by Medrol and TAC compared with Dex. However, vascular endothelial growth factor expression was significantly (p = 0.01) decreased by Dex compared with TAC and Medrol. Medrol and TAC caused significant (p < 0.04) apoptosis, whereas Dex inhibited the UV-induced apoptosis and up-regulated survivin. Blocking of glucocorticoid receptor by RU486 inhibited cytoprotective property of Dex and apoptotic properties of TAC and Medrol. Double treatment with Dex + TAC and Dex + Medrol significantly (p < 0.05) induced apoptosis. In conclusion, this is the first study to report the efficacy of three well-known steroids on KF and suggest that combination may be superior than using a single steroid in treating KD. © 2012 by the Wound Healing Society.

Plaque triclosan concentration and antimicrobial efficacy of a new calcium carbonate toothpaste with 0.3% triclosan compared to a marketed 0.3% triclosan toothpaste.

PubMed

Srinivasan, Shashank; Chandrasekhar, Sembian; Shashikumar, K V; Payne, David; Maclure, Robert; Kapadiya, Bhavin; Schäfer, Fred; Adams, Suzi

2013-01-01

To compare the delivery and retention of triclosan in dental plaque, and to compare the antibacterial efficacy of a newly developed toothpaste to a marketed calcium carbonate toothpaste. Two clinical delivery/retention studies were carried out to determine the concentration of triclosan in plaque 10 minutes, and two and four hours after brushing with a new triclosan-containing toothpaste with magnesium aluminium silicate or a marketed triclosan-containing toothpaste. Both studies had a double-blind, randomized, complete cross-over design. Supragingival plaque samples (minimum 2 microg) were taken from smooth surfaces of all teeth (1-7) in all four quadrants for the 10-minute plaque measurements and in two randomly allocated quadrants at the two- and four-hour time points. Triclosan concentration was measured by HPLC. Antibacterial efficacy was evaluated in vitro using a biofilm formation approach. Three replicate experiments were carried out to check for repeatability and consistency of the assay. Toothpaste slurries were prepared by stirring one part by weight of each toothpaste with two parts by weight of deionized water. An overnight culture suspension of Streptococcus mutans (ATCC 25175) was prepared and then adjusted to give a bacterial count of approximately 10(7) CFU/ml. Sterile HAP discs were used as substrate and treated with the toothpaste slurry before inoculation with the standardized culture suspension of S. mutans. Following incubation in brain heart infusion (BHI) broth containing 2% sucrose for four hours, standard Total Viable Count (TVC) procedures were carried out and colonies counted (log10 values). Brushing with the new calcium carbonate/triclosan toothpaste resulted in a higher triclosan concentration in plaque after 10 minutes, and two and four hours compared to a marketed triclosan toothpaste. The increase ranged from 14% to 35% and was statistically significant (p < 0.05). The antibacterial efficacy of the new calcium carbonate/triclosan toothpaste, measured four hours after application, was greater than that of a marketed toothpaste with 0.3% triclosan. The difference was statistically significant (p < 0.05). The new calcium carbonate toothpaste with 0.3% triclosan and magnesium aluminium silicate demonstrated significantly greater efficacy four hours post-brushing both in terms of in vivo delivery and in vitro antibacterial action compared to a marketed calcium carbonate toothpaste with 0.3% triclosan.

Distributed Environment Control Using Wireless Sensor/Actuator Networks for Lighting Applications

PubMed Central

Nakamura, Masayuki; Sakurai, Atsushi; Nakamura, Jiro

2009-01-01

We propose a decentralized algorithm to calculate the control signals for lights in wireless sensor/actuator networks. This algorithm uses an appropriate step size in the iterative process used for quickly computing the control signals. We demonstrate the accuracy and efficiency of this approach compared with the penalty method by using Mote-based mesh sensor networks. The estimation error of the new approach is one-eighth as large as that of the penalty method with one-fifth of its computation time. In addition, we describe our sensor/actuator node for distributed lighting control based on the decentralized algorithm and demonstrate its practical efficacy. PMID:22291525

Local and systemic antimicrobial therapy in periodontics.

PubMed

Herrera, David; Matesanz, Paula; Bascones-Martínez, Antonio; Sanz, Mariano

2012-09-01

This review aimed to update the current evidence on the efficacy of the adjunctive use of local and systemic antimicrobials in the treatment of periodontitis and to assess whether it might improve the clinical limitations and shortcomings of standard nonsurgical treatment in the management of periodontitis. Relevant randomized clinical trials (RCT) with more than 3 months of follow-up, published from 2010 to 2012 for systemic antimicrobials and from 2008 to 2012 for local antimicrobials, were searched in Medline and critically analyzed. Scientific evidence evaluated in different systematic reviews and reviews presented at European and World Workshops were also included. Only adjunctive therapies were considered in the present review: articles comparing debridement alone or plus placebo, versus debridement plus systemic or local antimicrobials were included. Adjunctive systemic antimicrobials have been evaluated both in aggressive and chronic periodontitis: in aggressive periodontitis, amoxicillin and metronidazole have been extensively studied, reporting clinical and microbiological benefits; in chronic periodontitis, different products are under scrutiny, such as azithromycin. The clinical efficacy of local antimicrobials, although extensively demonstrated, is still surrounded by a constant debate on the cost-effectiveness evaluation and on its adequate indications. Despite the clinical efficacy of the adjunctive use of local and systemic antimicrobials, demonstrated in RCTs and in systematic reviews, there is a lack of evidence to support well-defined clinical protocols, including products and dosages. Copyright © 2012 Elsevier Inc. All rights reserved.

Infliximab Biosimilar (CT-P13; Infliximab-dyyb): A Review in Autoimmune Inflammatory Diseases.

PubMed

Blair, Hannah A; Deeks, Emma D

2016-10-01

Infliximab biosimilar (CT-P13/infliximab-dyyb; Remsima ® , Inflectra ® ) is approved in several countries for use in all indications for which reference infliximab (Remicade ® ) is approved, including rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis, psoriasis, Crohn's disease, and ulcerative colitis. Clinical data contributing to the EU approval of infliximab biosimilar were obtained from two pivotal double-blind clinical trials in patients with AS (PLANETAS) or RA (PLANETRA). Infliximab biosimilar demonstrated equivalence to reference infliximab in terms of its pharmacokinetic profile in patients with AS, patients with RA, and in healthy volunteers, and in terms of its efficacy in patients with RA. Clinical response rates in patients with RA or AS were maintained over the longer term (up to 102 weeks). In addition, the efficacy of infliximab biosimilar in patients with RA or Crohn's disease and ulcerative colitis [i.e. inflammatory bowel disease (IBD)] has been demonstrated in the real-world setting. Infliximab biosimilar was generally well tolerated, with a tolerability profile similar to that of reference infliximab. Switching from reference infliximab to infliximab biosimilar had no detrimental effect on efficacy, safety, or immunogenicity compared with continuous infliximab biosimilar therapy, according to the extensions of PLANETAS and PLANETRA, and real-world data in IBD. Current evidence therefore suggests that infliximab biosimilar is a useful alternative to reference infliximab in patients with autoimmune inflammatory diseases.

The relative efficacy of connectivity guided and symptom based EEG biofeedback for autistic disorders.

PubMed

Coben, Robert; Myers, Thomas E

2010-03-01

Autism is a neurodevelopmental disorder characterized by deficits in communication, social interaction, and a limited range of interests with repetitive stereotypical behavior. Various abnormalities have been documented in the brains of individuals with autism, both anatomically and functionally. The connectivity theory of autism is a recently developed theory of the neurobiological cause of autisic symptoms. Different patterns of hyper- and hypo-connectivity have been identified with the use of quantitative electroencephalogray (QEEG), which may be amenable to neurofeedback. In this study, we compared the results of two published controlled studies examining the efficacy of neurofeedback in the treatment of autism. Specifically, we examined whether a symptom based approach or an assessment/connectivity guided based approach was more effective. Although both methods demonstrated significant improvement in symptoms of autism, connectivity guided neurofeedback demonstrated greater reduction on various subscales of the Autism Treatment Evaluation Checklist (ATEC). Furthermore, when individuals were matched for severity of symptoms, the amount of change per session was significantly higher in the Coben and Padolsky (J Neurother 11:5-23, 2007) study for all five measures of the ATEC. Our findings suggest that an approach guided by QEEG based connectivity assessment may be more efficacious in the treatment of autism. This permits the targeting and amelioration of abnormal connectivity patterns in the brains of people who are autistic.

Innovation in sexually transmitted disease and HIV prevention: internet and mobile phone delivery vehicles for global diffusion.

PubMed

Swendeman, Dallas; Rotheram-Borus, Mary Jane

2010-03-01

Efficacious behavioral interventions and practices have not been universally accepted, adopted, or diffused by policy makers, administrators, providers, advocates, or consumers. Biomedical innovations for sexually transmitted disease (STD) and HIV prevention have been embraced but their effectiveness is hindered by behavioral factors. Behavioral interventions are required to support providers and consumers for adoption and diffusion of biomedical innovations, protocol adherence, and sustained prevention for other STDs. Information and communication technology such as the Internet and mobile phones can deliver behavioral components for STD/HIV prevention and care to more people at less cost. Recent innovations in STD/HIV prevention with information and communication technology-mediated behavioral supports include STD/HIV testing and partner interventions, behavioral interventions, self-management, and provider care. Computer-based and Internet-based behavioral STD/HIV interventions have demonstrated efficacy comparable to face-to-face interventions. Mobile phone STD/HIV interventions using text-messaging are being broadly utilized but more work is needed to demonstrate efficacy. Electronic health records and care management systems can improve care, but interventions are needed to support adoption. Information and communication technology is rapidly diffusing globally. Over the next 5-10 years smart-phones will be broadly disseminated, connecting billions of people to the Internet and enabling lower cost, highly engaging, and ubiquitous STD/HIV prevention and treatment support interventions.

Therapeutic Outcome of Intralesional Immunotherapy in Cutaneous Warts Using the Mumps, Measles, and Rubella Vaccine

PubMed Central

Awal, Guneet

2018-01-01

Background: Various treatment modalities have been described in the literature for treating warts, but none thus far have demonstrated optimal results. Recently, the mumps, measles, and rubella (MMR) antigen has gained popularity because of its proven efficacy in the treatment of warts. Aim: The goal was to evaluate the efficacy and safety of intralesional MMR antigen in the treatment of cutaneous warts. Methods: Patients were divided into an MMR (study) group and a normal saline (control) group. Injections were administered into the single largest wart on each patient every two weeks. Follow-up was done at six weeks and 16 weeks after the last injection for any side effects and/or recurrence. Results: Out of 150 patients, 72 received the MMR injection and 50 received normal saline injections. Twenty-eight patients did not complete the study. A statistically significant (p<0.00001) difference in results was found between the two groups: 68 percent of patients in the MMR group showed complete response compared to 10 percent in the control group. Pain during injection was the most common side effect and was seen in both groups. Conclusion: MMR injection has shown significant results with almost negligible adverse effects. The MMR antigen vaccine has therapeutic potential as a treatment for warts with its demonstrated efficacy, safety profile, and cost-effectiveness. PMID:29785233

Effects of Role-Playing Scenarios on the Self-efficacy of Students in Resisting Against Substance Addiction: A Pilot Study.

PubMed

Karatay, Gülnaz; Gürarslan Baş, Nazan

2017-01-01

During the first phases of adolescent development, young people have little self-efficacy and resistance against substance use. The aim of this study was to demonstrate the effectiveness of role-playing scenarios on the self-efficacy of students in resisting substance use. A pre test and post test study design was used with a single group. The study was carried out with 245 secondary school students. The scenario-based training, developed by the researchers, was presented by the school counselors once a week for 4 weeks. For this purpose, a booklet of scenarios was prepared for the teachers. The role-playing scenarios were intended to improve adolescents' abilities to say "no" to substance offers, to prevent them from becoming addicted to certain substances, and to call for help if needed. The data of the study were collected using the Personal Information Form and the Self-Efficacy for Adolescences Protecting Substance Abuse Scale . The obtained data were assessed using percentages, chi-square, t test, and F test in the SPSS software. Results showed that, after the training, the mean score in the Self-Efficacy for Adolescences Protecting Substance Abuse Scale increased significantly (103.20 ± 20.00) compared with before the training (92.11 ± 17.08) ( P < .05). Short-term outcomes of the class-based scenario training were observed to be effective in the development of students' self-efficacy to resist the temptations of substance use.

Efficacy and safety of bilastine 20 mg compared with cetirizine 10 mg and placebo in the treatment of perennial allergic rhinitis.

PubMed

Sastre, Joaquín; Mullol, Joaquim; Valero, Antonio; Valiente, Román

2012-01-01

Bilastine is a non-sedating second-generation H(1) antihistamine with proven efficacy and safety in the treatment of patients with seasonal allergic rhinitis and urticaria. The objective of this study was to demonstrate the efficacy and safety of bilastine in patients with perennial allergic rhinitis (PAR). In a multicenter, randomized, placebo-controlled, double-blind, parallel-group study, patients with symptomatic PAR (n = 650) from Argentina, Europe, and South Africa received bilastine 20 mg, cetirizine 10 mg, or placebo once daily for 4 weeks. The primary efficacy outcome was the mean area under the curve (AUC) of reflective total 6-symptom scores (rT6SS) from baseline visit to day 28 (D28). Secondary outcome measures included mean AUC of instantaneous total 6-symptom scores (iT6SS), and mean AUCs of reflective and instantaneous total 4-nasal symptom scores (T4NSS) and total 2-ocular symptom scores (T2OSS) from baseline to D28. An open-label extension phase evaluated the safety of bilastine 20 mg administered to patients (n = 513) for one year. In the overall population no significant differences in efficacy outcomes were found between active treatments and placebo. On account of the high placebo response in South Africa, a post-hoc analysis was conducted. This analysis demonstrated that statistically significant differences existed between active treatments and placebo in the mean AUC of rT6SS (p < 0.05) and T4NSS (p < 0.02), respectively, from baseline to D28 visit for the intent-to-treat population in patients from Europe and Argentina, whereas the difference was not statistically significant in South Africa. Whether this is related to differences in the demographic or clinical characteristics of South African patients (they had PAR for longer and reported more severe symptoms) and/or the disease management process compared with their European and Argentinean counterparts warrants further investigation. A post-hoc analysis indicated that bilastine and cetirizine were similarly effective and more effective than placebo during a 4-week treatment period in patients with PAR. In addition, bilastine was shown to be safe and well-tolerated over a 1-year treatment period. NCT01127620.

Examining the Efficacy of a Family Peer Advocate Model for Black and Hispanic Caregivers of Children with Autism Spectrum Disorder.

PubMed

Jamison, J M; Fourie, E; Siper, P M; Trelles, M P; George-Jones, Julia; Buxbaum Grice, A; Krata, J; Holl, E; Shaoul, J; Hernandez, B; Mitchell, L; McKay, M M; Buxbaum, J D; Kolevzon, Alexander

2017-05-01

Autism spectrum disorder (ASD) affects individuals across all racial and ethnic groups, yet rates of diagnosis are disproportionately higher for Black and Hispanic children. Caregivers of children with ASD experience significant stressors, which have been associated with parental strain, inadequate utilization of mental health services and lower quality of life. The family peer advocate (FPA) model has been utilized across service delivery systems to provide family-to-family support, facilitate engagement, and increase access to care. This study used a randomized controlled design to examine the efficacy of FPAs in a racially and ethnically diverse sample. Results demonstrate significantly increased knowledge of ASD and reduced levels of stress for caregivers who received the FPA intervention as compared to treatment as usual.

QIAD assay for quantitating a compound’s efficacy in elimination of toxic Aβ oligomers

PubMed Central

Brener, Oleksandr; Dunkelmann, Tina; Gremer, Lothar; van Groen, Thomas; Mirecka, Ewa A.; Kadish, Inga; Willuweit, Antje; Kutzsche, Janine; Jürgens, Dagmar; Rudolph, Stephan; Tusche, Markus; Bongen, Patrick; Pietruszka, Jörg; Oesterhelt, Filipp; Langen, Karl-Josef; Demuth, Hans-Ulrich; Janssen, Arnold; Hoyer, Wolfgang; Funke, Susanne A.; Nagel-Steger, Luitgard; Willbold, Dieter

2015-01-01

Strong evidence exists for a central role of amyloid β-protein (Aβ) oligomers in the pathogenesis of Alzheimer’s disease. We have developed a fast, reliable and robust in vitro assay, termed QIAD, to quantify the effect of any compound on the Aβ aggregate size distribution. Applying QIAD, we studied the effect of homotaurine, scyllo-inositol, EGCG, the benzofuran derivative KMS88009, ZAβ3W, the D-enantiomeric peptide D3 and its tandem version D3D3 on Aβ aggregation. The predictive power of the assay for in vivo efficacy is demonstrated by comparing the oligomer elimination efficiency of D3 and D3D3 with their treatment effects in animal models of Alzheimer´s disease. PMID:26394756

Peer Support and Adolescents' Physical Activity: The Mediating Roles of Self-Efficacy and Enjoyment.

PubMed

Chen, Han; Sun, Haichun; Dai, Jun

2017-06-01

The present study aimed to contrast the mediating magnitude of self-efficacy and enjoyment connecting peer support and adolescents' physical activity (PA). Participants were 9th-12th grade students ( N  = 409; 56.5% boys) who were randomly chosen from six public schools located in Fuzhou city in southeast China. The bootstrapping method in structural equation modeling was conducted to examine the direct and indirect effects of peer support on adolescents' PA. Peer support did not directly impact PA. Rather, peer support indirectly influenced PA through either self-efficacy or enjoyment, with self-efficacy demonstrating a stronger mediating effect. Additionally, we found a significant serial mediating effect with enjoyment, and self-efficacy sequentially mediated the relationship between peer support and PA. The findings highlight the role of self-efficacy and enjoyment as mediators connecting peer support and PA. Self-efficacy seems to be more important, as it demonstrated a significantly greater mediating effect. © The Author 2017. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Fosfomycin: A First-Line Oral Therapy for Acute Uncomplicated Cystitis

PubMed Central

Zhanel, George G.; Walkty, Andrew J.; Karlowsky, James A.

2016-01-01

Fosfomycin is a new agent to Canada approved for the treatment of acute uncomplicated cystitis (AUC) in adult women infected with susceptible isolates of E. coli and Enterococcus faecalis. We reviewed the literature regarding the use of oral fosfomycin for the treatment of AUC. All English-language references from 1975 to October 2015 were reviewed. In Canada, fosfomycin tromethamine is manufactured as Monurol® and is available as a 3-gram single dose sachet. Fosfomycin has a unique chemical structure, inhibiting peptidoglycan synthesis at an earlier site compared to β-lactams with no cross-resistance with other agents. Fosfomycin displays broad-spectrum activity against ESBL-producing, AmpC-producing, carbapenem-non-susceptible, and multidrug-resistant (MDR) E. coli. Resistance to fosfomycin in E. coli is rare (<1%). Fosfomycin is excreted unchanged in the urine by glomerular filtration with peak urinary concentration ~4000 µg/mL and remains at concentrations >100 µg/mL for 48 hours after a single 3-gram oral dose. No dosage adjustments are required in elderly patients, in pregnant patients, or in either renal or hepatic impairment. Fosfomycin demonstrates a favorable safety profile, and clinical trials have demonstrated efficacy in AUC that is comparable to ciprofloxacin, nitrofurantoin, and trimethoprim-sulfamethoxazole. Fosfomycin's in vitro activity against common uropathogens, including MDR isolates, its favorable safety profile including pregnancy patients, drug interactions, and clinical trials data demonstrating efficacy in AUC, has resulted in Canadian, US, and European guidelines/authorities recommending fosfomycin as a first line agent for the treatment of AUC. PMID:27366158

The Role of Collective Efficacy in Closing Student Achievement Gaps: A Mixed Methods Study of School Leadership for Excellence and Equity

ERIC Educational Resources Information Center

Goddard, Roger D.; Skrla, Linda; Salloum, Serena J.

2017-01-01

Previous research demonstrates that collective efficacy positively predicts students' academic achievement (e.g., Bandura, 1993; Goddard et al., 2000). However, unaddressed by the current literature is whether collective efficacy also works to reduce inequity by closing achievement gaps. To learn about the operation of collective efficacy, we…

The application of hyaluronic acid-derivatized carbon nanotubes in hematoporphyrin monomethyl ether-based photodynamic therapy for in vivo and in vitro cancer treatment

PubMed Central

Shi, Jinjin; Ma, Rourou; Wang, Lei; Zhang, Jing; Liu, Ruiyuan; Li, Lulu; Liu, Yan; Hou, Lin; Yu, Xiaoyuan; Gao, Jun; Zhang, Zhenzhong

2013-01-01

Carbon nanotubes (CNTs) have shown great potential in both photothermal therapy and drug delivery. In this study, a CNT derivative, hyaluronic acid-derivatized CNTs (HA-CNTs) with high aqueous solubility, neutral pH, and tumor-targeting activity, were synthesized and characterized, and then a new photodynamic therapy agent, hematoporphyrin monomethyl ether (HMME), was adsorbed onto the functionalized CNTs to develop HMME-HA-CNTs. Tumor growth inhibition was investigated both in vivo and in vitro by a combination of photothermal therapy and photodynamic therapy using HMME-HA-CNTs. The ability of HMME-HA-CNT nanoparticles to combine local specific photodynamic therapy with external near-infrared photothermal therapy significantly improved the therapeutic efficacy of cancer treatment. Compared with photodynamic therapy or photothermal therapy alone, the combined treatment demonstrated a synergistic effect, resulting in higher therapeutic efficacy without obvious toxic effects to normal organs. Overall, it was demonstrated that HMME-HA-CNTs could be successfully applied to photodynamic therapy and photothermal therapy simultaneously in future tumor therapy. PMID:23843694

Folate and Heptamethine Cyanine Modified Chitosan-Based Nanotheranostics for Tumor Targeted Near-Infrared Fluorescence Imaging and Photodynamic Therapy.

PubMed

Zhang, Yingying; Lv, Tingting; Zhang, Huijuan; Xie, Xiaodong; Li, Ziying; Chen, Haijun; Gao, Yu

2017-07-10

Folate (FA) and heptamethine cyanine (Cy7)-modified chitosan (CF7) was synthesized by click chemistry and its self-assembled nanoparticles (CF7Ns) were developed for tumor-specific imaging and photodynamic therapy. The characterization spectrum confirmed CF7 had a good FA and Cy7 conjugation efficacy. The diameter of CF7Ns measured by DLS was about 291.6 nm, and the morphology observed with AFM showed filamentous clusters of particles. The results of targeting ability of CF7Ns demonstrated enhanced targeting behaviors of CF7Ns compared with non-FA-modified nanoparticles C7Ns in FA receptor-positive HeLa cells. The cytotoxicity and cell apoptosis assay showed that CF7Ns under near-infrared light irradiation led to more apoptotic cell death in HeLa cells to improve the therapeutic efficacy. The mechanisms of the photodynamic effects of CF7Ns were demonstrated through measurement of intracellular reactive oxygen species and the apoptosis-related cytokines. These results suggested that CF7Ns are promising tumor targeting carriers for simultaneous fluorescence imaging and photodynamic therapy.

Treatment Outcomes and Efficacy in the Schools.

ERIC Educational Resources Information Center

Logemann, Jeri A.

1998-01-01

Introduces six articles which address treatment outcomes and efficacy in audiology and speech-language pathology in the schools. Stresses the importance of practitioners participating in studies of treatment outcomes and efficacy to demonstrate that their evaluations and treatments make a significant difference to individuals served. (DB)

Efficacy of an experimental toothpaste containing 5% calcium sodium phosphosilicate in the relief of dentin hypersensitivity: An 8-week randomized study (Study 1).

PubMed

Sufi, Farzana; Hall, Claire; Mason, Stephen; Shaw, David; Kennedy, Liam; Gallob, John T

2016-04-01

To evaluate the efficacy of an experimental toothpaste containing 5% (w/w) calcium sodium phosphosilicate (CSPS) in relieving dentin hypersensitivity (DH) compared with control toothpastes containing no known anti-sensitivity ingredients. This was the first of two exploratory, randomized, four-treatment, examiner-blind, parallel-design, single-site, 8-week studies in healthy subjects with self-reported and clinically diagnosed DH. The experimental toothpaste contained 5% CSPS with a modified surfactant system, developed to enhance its organoleptic properties. Efficacy was evaluated against an abrasivity-matched placebo formulation (0% CSPS) with additional abrasive silica replacing the CSPS, and two commercially available fluoride toothpastes as controls. After an initial lead-in period, subjects were randomized to one of the four study treatments and instructed to brush twice daily for the next 8 weeks. DH was assessed at baseline and following 4 and 8 weeks of treatment by response to tactile and evaporative (air) stimuli, and using a Dentine Hypersensitivity Experience Questionnaire (DHEQ; a validated quality-of-life measure for DH). A total of 134 subjects were randomized and completed the study. All treatments demonstrated statistically significant reductions in sensitivity from baseline at Week 4 and Week 8 for each clinical measure of sensitivity (all P ≤ 0.001). The 0% CSPS toothpaste demonstrated small but statistically significant reductions in Schiff sensitivity score compared with the other study toothpastes at Week 8 (all P< 0.05), whereas the experimental 5% CSPS toothpaste significantly improved the tactile threshold at Week 4 compared with the 0% CSPS toothpaste (P = 0.0467). The DHEQ responses did not reveal any consistent statistically significant within-treatment changes from baseline or between-treatment differences. Correlation analysis showed weak-to-moderate associations between the DHEQ outcomes and clinical endpoints. Study treatments were well tolerated. The treatment differences observed in this exploratory study were small and inconsistent between measures. The reasons for the inconsistencies are not clear but may be related to the properties of the abrasivity-matched 0% CSPS formulation, with the increased level of dental silica conferring an advantage in terms of reducing DH. The ability of dental silicas to occlude exposed dentin tubules and thereby reduce DH has been demonstrated in previous studies, and may warrant further clinical investigation.

Relationships between parenting self-efficacy and distress in parents who have school-aged children and have been treated with hematopoietic stem cell transplant or have no cancer history.

PubMed

Cessna, Julie M; Pidala, Joseph; Jacobsen, Paul B

2016-03-01

Studies demonstrate that parents with cancer experience distress and that parenting self-efficacy (PSE) is related to distress among parents without cancer. However, no study to date has examined the relationships between PSE and psychological distress among parents with cancer. This study sought to address this issue by comparing parents with cancer who had undergone hematopoietic stem cell transplantation (HSCT) to parents without cancer on measures of PSE and psychological distress. A sample of 57 patients diagnosed with cancer who had undergone HSCT and a control group of 57 parents with no history of cancer were recruited for participation in the study. Medical record reviews assessed clinical variables, and participants filled out self-report measures of demographics, PSE, general self-efficacy, and psychological distress. As hypothesized, parents with cancer reported less PSE and more psychological distress than controls (all p-values ≤ 0.05). Furthermore, findings indicated that both PSE and general self-efficacy mediated the relationship between cancer status and psychological distress. Findings expand understanding of the potential sources of distress among parents with cancer who have been treated with HSCT and who have school-aged children. They also suggest that interventions aimed at reducing distress in these individuals should seek to target both parenting and general self-efficacy. Copyright © 2015 John Wiley & Sons, Ltd.

Epidural steroid injections: update on efficacy, safety, and newer medications for injection.

PubMed

Kozlov, N; Benzon, H T; Malik, K

2015-08-01

The best evidence for epidural injection appears to be in the setting of radicular pain with epidural steroid and non-steroid injections more efficacious than non-epidural injections. Studies showed the efficacy of non-particulate steroid to approach the efficacy of particulate steroid and very limited comparisons demonstrated no significant difference between epidural steroid and epidural non-steroid (local anesthetic) injection. Preliminary studies evaluating epidural injection of disease modifying anti-rheumatic drugs such etanercept and tocilizumab showed conflicting results and had significant limitations. Randomized studies support better efficacy of transforaminal injection due to greater incidence of ventral epidural spread of injectate when compared to interlaminar injection. Thus, the transforaminal approach is recommended when unilateral radicular pain is limited to one nerve root. However, the transforaminal approach is associated with greater incidence of central nervous system injury, including paraplegia, attributed to embolization of the particulate steroid. Recent studies showed that non-particulate steroids potentially last as long as particulate steroids. Therefore non-particulate steroid should be used in initial transforaminal epidural injection. Future studies should look into the role of adjunct diagnostic aids, including digital subtraction angiography, in detecting intravascular injection and the ideal site of needle placement, whether it is the safe triangle or the triangle of Kambin. Finally, the role of epidural disease -modifying antirheumatic drugs in the management of back pain needs to be better elucidated.

Adenoviral Delivery of Tumor Necrosis Factor-α and Interleukin-2 Enables Successful Adoptive Cell Therapy of Immunosuppressive Melanoma.

PubMed

Siurala, Mikko; Havunen, Riikka; Saha, Dipongkor; Lumen, Dave; Airaksinen, Anu J; Tähtinen, Siri; Cervera-Carrascon, Víctor; Bramante, Simona; Parviainen, Suvi; Vähä-Koskela, Markus; Kanerva, Anna; Hemminki, Akseli

2016-08-01

Adoptive T-cell transfer is a promising treatment approach for metastatic cancer, but efficacy in solid tumors has only been achieved with toxic pre- and postconditioning regimens. Thus, adoptive T-cell therapies would benefit from complementary modalities that enable their full potential without excessive toxicity. We aimed to improve the efficacy and safety of adoptive T-cell transfer by using adenoviral vectors for direct delivery of immunomodulatory murine cytokines into B16.OVA melanoma tumors with concomitant T-cell receptor transgenic OT-I T-cell transfer. Armed adenoviruses expressed high local and low systemic levels of cytokine when injected into B16.OVA tumors, suggesting safety of virus-mediated cytokine delivery. Antitumor efficacy was significantly enhanced with adenoviruses coding for murine interleukin-2 (mIL-2) and tumor necrosis factor-α (mTNFα) when compared with T-cell transfer alone or viruses alone. Further improvement in efficacy was achieved with a triple combination of mIL-2, mTNFα, and OT-I T-cells. Mechanistic studies suggest that mIL-2 has an important role in activating T-cells at the tumor, while mTNFα induces chemokine expression. Furthermore, adenovirus treatments enhanced tumor-infiltration of OT-I T-cells as demonstrated by SPECT/CT imaging of (111)In-labeled cells. Our results suggest the utility of cytokine-coding adenoviruses for improving the efficacy of adoptive T-cell therapies.

Secukinumab is Efficacious and Safe in Hispanic Patients with Moderate-to-Severe Plaque Psoriasis: Pooled Analysis of Four Phase 3 Trials.

PubMed

Adsit, Sandra; Zaldivar, Enrique Rivas; Sofen, Howard; Dei-Cas, Ignacio; Maldonado-García, César; Peñaranda, Elkin O; Puig, Luís; Meng, Xiangyi; Fox, Todd; Guana, Adriana

2017-06-01

There is little evidence available on the efficacy and safety of biologic therapies for the treatment of psoriasis in Hispanic patients. Secukinumab is demonstrated to be highly effective for clearing psoriasis. The aim of this study was to compare the efficacy and safety of secukinumab in Hispanic and non-Hispanic patients. Data were pooled from four phase 3 studies of secukinumab in patients with moderate-to-severe plaque psoriasis. Patients who self-identified as Hispanic were included in the Hispanic subgroup. Efficacy responses (Psoriasis Area and Severity Index [PASI] 75/90/100 and Investigator's Global Assessment 2011 modified version 0/1) for secukinumab 300 mg were greater than for etanercept at week 12 in the Hispanic and non-Hispanic patient subgroups. At week 12 with secukinumab 300 mg, PASI 90/100 responses were achieved by 70.6%/35.9% of Hispanic patients and 58.0%/28.1% of non-Hispanic patients. At week 12 with secukinumab 150 mg, PASI 90/100 responses were achieved by 59.5%/25.1% of Hispanic patients and 41.2%/13.4% of non-Hispanic patients. In both subgroups, peak efficacy responses with secukinumab were observed at week 16 and were maintained to week 52. Secukinumab is highly effective for clearing psoriasis in both Hispanic and non-Hispanic patients. Novartis Pharmaceutical Corporation.

Clinical Efficacy and Safety of Bevacizumab Monotherapy in Patients with Metastatic Melanoma: Predictive Importance of Induced Early Hypertension

PubMed Central

Schuster, Cornelia; Eikesdal, Hans P.; Puntervoll, Hanne; Geisler, Jürgen; Geisler, Stephanie; Heinrich, Daniel; Molven, Anders; Lønning, Per E.; Akslen, Lars A.; Straume, Oddbjørn

2012-01-01

Background VEGF driven angiogenesis plays a key role in cancer progression. We determined the clinical efficacy of bevacizumab monotherapy in patients with metastatic melanoma. Methods and Findings Thirty-five patients with metastatic melanoma in progression were enrolled in this phase II, single arm clinical trial. Each patient received bevacizumab monotherapy 10 mg/kg q14 d until intolerable toxicity or disease progression occurred. Clinical efficacy was evaluated as objective response, disease control (DC), and survival. We observed one complete (3%) and 5 partial (14%) responses. In addition, 5 patients experienced stable disease >6 months (14%) while 24 patients had progressive disease (PD, 69%), corresponding to a total DC at 6 months in 11 out of 35 patients (31%). Median progression free survival (PFS) was 2.14 months and median overall survival (OS) was 9 months (1.12–49). Seven of the 11 patients experiencing DC developed early hypertension (<2 months) compared to 3/24 of patients with PD (P = 0.001), and hypertension was associated with PFS (P = 0.005) and OS (P = 0.013). Conclusion Bevacizumab monotherapy demonstrated promising clinical efficacy in patients with metastatic melanoma with disease control in 31% of the patients. Induced early hypertension was a marker for clinical efficacy of bevacizumab. Trial Registration ClinicalTrials.gov NCT00139360. PMID:22719881

Conversion from twice-daily tacrolimus to once-daily extended release tacrolimus (LCPT): the phase III randomized MELT trial.

PubMed

Bunnapradist, S; Ciechanowski, K; West-Thielke, P; Mulgaonkar, S; Rostaing, L; Vasudev, B; Budde, K

2013-03-01

Phase III noninferiority trial examining efficacy and safety of converting stable renal transplant recipients from twice-daily tacrolimus to a novel extended-release once-daily tacrolimus formulation (LCPT) with a controlled agglomeration technology. Controls maintained tacrolimus twice daily. The primary efficacy endpoint was proportion of patients with efficacy failures (death, graft failure, locally read biopsy-proven acute rejection [BPAR], or loss to follow-up) within 12 months. Starting LCPT dose was 30% lower (15% for blacks) than preconversion tacrolimus dose; target trough levels were 4-15 ng/mL. A total of 326 patients were randomized; the mITT population (n = 162 each group) was similar demographically in the two groups. Mean daily dose of LCPT was significantly (p < 0.0001) lower than preconversion tacrolimus dose at each visit; mean trough levels between groups were similar. There were four efficacy failures in each group; safety outcomes were similar between groups. Frequency of premature study drug discontinuation was LCPT: 12% versus tacrolimus twice daily: 5% (p = 0.028). LCPT demonstrated noninferiority to tacrolimus twice daily in efficacy failure rates. LCPT may offer a safe and effective alternative for converting patients to a once-daily formulation. Compared to currently available tacrolimus formulation, LCPT requires lower doses to achieve target trough levels. © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.

An optical microfluidic platform for spatiotemporal biofilm treatment monitoring

NASA Astrophysics Data System (ADS)

Kim, Young Wook; Mosteller, Matthew P.; Subramanian, Sowmya; Meyer, Mariana T.; Bentley, William E.; Ghodssi, Reza

2016-01-01

Bacterial biofilms constitute in excess of 65% of clinical microbial infections, with the antibiotic treatment of biofilm infections posing a unique challenge due to their high antibiotic tolerance. Recent studies performed in our group have demonstrated that a bioelectric effect featuring low-intensity electric signals combined with antibiotics can significantly improve the efficacy of biofilm treatment. In this work, we demonstrate the bioelectric effect using sub-micron thick planar electrodes in a microfluidic device. This is critical in efforts to develop microsystems for clinical biofilm infection management, including both in vivo and in vitro applications. Adaptation of the method to the microscale, for example, can enable the development of localized biofilm infection treatment using microfabricated medical devices, while augmenting existing capabilities to perform biofilm management beyond the clinical realm. Furthermore, due to scale-down of the system, the voltage requirement for inducing the electric field is reduced further below the media electrolysis threshold. Enhanced biofilm treatment using the bioelectric effect in the developed microfluidic device elicited a 56% greater reduction in viable cell density and 26% further decrease in biomass growth compared to traditional antibiotic therapy. This biofilm treatment efficacy, demonstrated in a micro-scale device and utilizing biocompatible voltage ranges, encourages the use of this method for future clinical biofilm treatment applications.

Lactoferrin-modified PEGylated liposomes loaded with doxorubicin for targeting delivery to hepatocellular carcinoma

PubMed Central

Wei, Minyan; Guo, Xiucai; Tu, Liuxiao; Zou, Qi; Li, Qi; Tang, Chenyi; Chen, Bao; Xu, Yuehong; Wu, Chuanbin

2015-01-01

Lactoferrin (Lf) is a potential-targeting ligand for hepatocellular carcinoma (HCC) cells because of its specific binding with asialoglycoprotein receptor (ASGPR). In this present work, a doxorubicin (DOX)-loaded, Lf-modified, polyethylene glycol (PEG)ylated liposome (Lf-PLS) system was developed, and its targeting effect and antitumor efficacy to HCC was also explored. The DOX-loaded Lf-PLS system had spherical or oval vesicles, with mean particle size approximately 100 nm, and had an encapsulation efficiency of 97%. The confocal microscopy and flow cytometry indicated that the cellular uptake of Lf-PLS was significantly higher than that of PEGylated liposome (PLS) in ASGPR-positive cells (P<0.05) but not in ASGPR-negative cells (P>0.05). Cytotoxicity assay by MTT demonstrated that DOX-loaded Lf-PLS showed significantly stronger antiproliferative effects on ASGPR-positive HCC cells than did PLS without the Lf modification (P<0.05). The in vivo antitumor studies on male BALB/c nude mice bearing HepG2 xenografts demonstrated that DOX-loaded Lf-PLS had significantly stronger antitumor efficacy compared with PLS (P<0.05) and free DOX (P<0.05). All these results demonstrated that a DOX-loaded Lf-PLS might have great potential application for HCC-targeting therapy. PMID:26316745

Comparison of sirolimus plus tacrolimus versus sirolimus plus cyclosporine in high-risk renal allograft recipients: results from an open-label, randomized trial.

PubMed

Gaber, A Osama; Kahan, Barry D; Van Buren, Charles; Schulman, Seth L; Scarola, Joseph; Neylan, John F

2008-11-15

The efficacy and safety of sirolimus (SRL) plus tacrolimus (TAC) versus SRL plus cyclosporine (CsA) were compared in high-risk renal allograft recipients. Evaluable patients (448) were randomly assigned (1:1) before transplant to receive SRL+TAC or SRL+CsA with corticosteroids. Eligible patients were black and/or repeat transplant recipients, and/or those with high titer of panel-reactive antibodies. Demographics were similar between groups. Both treatments demonstrated equivalent efficacy of the composite endpoint at 12 months with efficacy failure rates of 21.9% vs. 23.2% (SRL+TAC vs. SRL+CsA, respectively, 95% CI -10.0 to 7.1, P=0.737). Biopsy-confirmed acute rejection rate (13.8% vs. 17.4%) and graft survival rate (89.7% vs. 90.2%) were similar (SRL+TAC vs. SRL+CsA, respectively). In evaluable patients (received at least 1 dose of study drug), renal function (calculated Nankivell glomerular filtration rate) was not superior in SRL+TAC versus SRL+CsA (54.5 vs. 52.6 mL/min, P=0.466); however, in on-therapy patients, glomerular filtration rate was significantly higher in SRL+TAC at most time points. At 12 months, there were no significant differences in rates of death, discontinuation because of adverse events, hypercholesterolemia, hyperlipemia, or proteinuria. Diarrhea and herpes simplex infections occurred significantly more often in SRL+TAC patients. Hypertension, cardiomegaly, increased creatinine, overdose (primarily calcineurin inhibitor toxicity), acne, urinary tract disorders, lymphocele, and ovarian cysts occurred significantly more often in SRL+CsA patients. This study demonstrated that SRL-based therapy was efficacious in high-risk renal allograft recipients in the first year after transplant, providing equivalent efficacy with CsA or TAC, similar graft survival, low biopsy-confirmed acute rejection rates, excellent renal function, and an acceptable safety profile.

Evaluation of an interactive web-based nursing course with streaming videos for medication administration skills.

PubMed

Sowan, Azizeh K; Idhail, Jamila Abu

2014-08-01

Nursing students should exhibit competence in nursing skills in order to provide safe and quality patient care. This study describes the design and students' response to an interactive web-based course using streaming video technology tailored to students' needs and the course objectives of the fundamentals of nursing skills clinical course. A mixed-methodology design was used to describe the experience of 102 first-year undergraduate nursing students at a school of nursing in Jordan who were enrolled in the course. A virtual course with streaming videos was designed to demonstrate medication administration fundamental skills. The videos recorded the ideal lab demonstration of the skills, and real-world practice performed by registered nurses for patients in a hospital setting. After course completion, students completed a 30-item satisfaction questionnaire, 8 self-efficacy scales, and a 4-item scale solicited their preferences of using the virtual course as a substitute or a replacement of the lab demonstration. Students' grades in the skill examination of the procedures were measured. Relationships between the main variables and predictors of satisfaction and self-efficacy were examined. Students were satisfied with the virtual course (3.9 ± 0.56, out of a 5-point scale) with a high-perceived overall self-efficacy (4.38 ± 0.42, out of a 5-point scale). Data showed a significant correlation between student satisfaction, self-efficacy and achievement in the virtual course (r = 0.45-0.49, p < 0.01). The majority of students accessed the course from home and some faced technical difficulties. Significant predictors of satisfaction were ease of access the course and gender (B = 0.35, 0.25, CI = 0.12-0.57, 0.02-0.48 respectively). The mean achievement score of students in the virtual class (7.5 ± 0.34) was significantly higher than that of a previous comparable cohort who was taught in the traditional method (6.0 ± 0.23) (p < 0.05). Nearly 40% of the students believed that the virtual course is a sufficient replacement of the lab demonstration. The use of multimedia within an interactive online learning environment is a valuable teaching strategy that yields a high level of nursing student satisfaction, self-efficacy, and achievement. The creation and delivery of a virtual learning environment with streaming videos for clinical courses is a complex process that should be carefully designed to positively influence the learning experience. However, the learning benefits gained from such pedagogical approach are worth faculty, institution and students' efforts. Published by Elsevier Ireland Ltd.

Product Differences in Intra-articular Hyaluronic Acids for Osteoarthritis of the Knee.

PubMed

Altman, Roy D; Bedi, Asheesh; Karlsson, Jon; Sancheti, Parag; Schemitsch, Emil

2016-08-01

Knee osteoarthritis (OA) is a common and often disabling joint disorder among adults that may result in impaired activity and daily function. A variety of treatment options are currently available and prescribed for knee OA depending on the severity of the disorder and physician preference. Intra-articular hyaluronic acid (IA-HA) injection is a treatment for knee OA that reportedly provides numerous biochemical and biological benefits, including shock absorption, chondroprotection, and anti-inflammatory effects within the knee. Clarity is needed as to whether the available IA-HA products should be considered for therapy as a group or whether there are significant differences in the products that need to be considered in treatment of OA of the knee. To determine whether there are differences in efficacy and safety with respect to intrinsic properties of available IA-HA injections for knee OA. Meta-analysis. A comprehensive literature search of the Medline, EMBASE, and PubMed databases was conducted for all existing randomized trials of IA-HA. The primary outcome measure analyzed was the mean pain score at the reported follow-up nearest to 26 weeks after injection. Pooled efficacy and safety results were recorded for subgroupings of HA product characteristics. A total of 68 studies were included for analysis. Products with an average molecular weight ≥3000 kDa provided favorable efficacy results when compared with products of an average molecular weight <3000 kDa. Products with a molecular weight ≥3000 kDa demonstrated significantly fewer discontinuations due to treatment-related adverse events than did ≤1500 kDa counterparts, while trial discontinuation rates were similar between biological fermentation-derived HA products and avian-derived HA. The results did not demonstrate a significant difference in the occurrence of effusion across molecular weight subgroups. Additionally, biological fermentation-derived HA had a significantly smaller incidence of effusion than did avian-derived HA. Biological fermentation-derived HA demonstrated fewer acute flare-ups at the injection site than did avian-derived HA products, while high-molecular-weight products demonstrated the highest rate of injection site flare-up. Despite similarities, IA-HA products should not be treated as a group, as there are differences in IA-HA products that influence both efficacy and safety. In the available literature, IA-HA products with a molecular weight ≥3000 kDa and those derived from biological fermentation relate to superior efficacy and safety-factors that may influence selection an IA-HA product for OA of the knee. © 2015 The Author(s).

Pharmacotherapies for Obesity: Past, Current, and Future Therapies

PubMed Central

Ioannides-Demos, Lisa L.; Piccenna, Loretta; McNeil, John J.

2011-01-01

Past therapies for the treatment of obesity have typically involved pharmacological agents usually in combination with a calorie-controlled diet. This paper reviews the efficacy and safety of pharmacotherapies for obesity focusing on drugs approved for long-term therapy (orlistat), drugs approved for short-term use (amfepramone [diethylpropion], phentermine), recently withdrawn therapies (rimonabant, sibutamine) and drugs evaluated in Phase III studies (taranabant, pramlintide, lorcaserin and tesofensine and combination therapies of topiramate plus phentermine, bupropion plus naltrexone, and bupropion plus zonisamide). No current pharmacotherapy possesses the efficacy needed to produce substantial weight loss in morbidly obese patients. Meta-analyses support a significant though modest loss in bodyweight with a mean weight difference of 4.7 kg (95% CI 4.1 to 5.3 kg) for rimonabant, 4.2 kg (95% CI 3.6 to 4.8 kg) for sibutramine and 2.9 kg (95% CI 2.5 to 3.2 kg) for orlistat compared to placebo at ≥12 months. Of the Phase III pharmacotherapies, lorcaserin, taranabant, topiramate and bupropion with naltrexone have demonstrated significant weight loss compared to placebo at ≥12 months. Some pharmacotherapies have also demonstrated clinical benefits. Further studies are required in some populations such as younger and older people whilst the long term safety continues to be a major consideration and has led to the withdrawal of several drugs. PMID:21197148

Cognitive behavioral therapy for anxiety and related disorders: A meta-analysis of randomized placebo-controlled trials.

PubMed

Carpenter, Joseph K; Andrews, Leigh A; Witcraft, Sara M; Powers, Mark B; Smits, Jasper A J; Hofmann, Stefan G

2018-06-01

The purpose of this study was to examine the efficacy of cognitive behavioral therapy (CBT) for anxiety-related disorders based on randomized placebo-controlled trials. We included 41 studies that randomly assigned patients (N = 2,843) with acute stress disorder, generalized anxiety disorder (GAD), obsessive compulsive disorder (OCD), panic disorder (PD), posttraumatic stress disorder (PTSD), or social anxiety disorder (SAD) to CBT or a psychological or pill placebo condition. Findings demonstrated moderate placebo-controlled effects of CBT on target disorder symptoms (Hedges' g = 0.56), and small to moderate effects on other anxiety symptoms (Hedges' g = 0.38), depression (Hedges' g = 0.31), and quality of life (Hedges' g = 0.30). Response rates in CBT compared to placebo were associated with an odds ratio of 2.97. Effects on the target disorder were significantly stronger for completer samples than intent-to-treat samples, and for individuals compared to group CBT in SAD and PTSD studies. Large effect sizes were found for OCD, GAD, and acute stress disorder, and small to moderate effect sizes were found for PTSD, SAD, and PD. In PTSD studies, dropout rates were greater in CBT (29.0%) compared to placebo (17.2%), but no difference in dropout was found across other disorders. Interventions primarily using exposure strategies had larger effect sizes than those using cognitive or cognitive and behavioral techniques, though this difference did not reach significance. Findings demonstrate that CBT is a moderately efficacious treatment for anxiety disorders when compared to placebo. More effective treatments are especially needed for PTSD, SAD, and PD. © 2018 Wiley Periodicals, Inc.

Variations in glycoprotein B contribute to immunogenic difference between PRV variant JS-2012 and Bartha-K61.

PubMed

Yu, Zhi-Qing; Tong, Wu; Zheng, Hao; Li, Li-Wei; Li, Guo-Xin; Gao, Fei; Wang, Tao; Liang, Chao; Ye, Chao; Wu, Ji-Qiang; Huang, Qinfeng; Tong, Guang-Zhi

2017-09-01

A newly emerged pseudorabies virus (PRV) variant has been identified in many Bartha-K61-vaccinated pig farms. This variant has caused great economic losses to the swine industry in China since 2011. Sequence analysis demonstrated that the gB gene of the emerging PRV variant JS-2012 had multiple variations compared with the vaccine strain Bartha-K61. In the study, a specific CRISPR/Cas9 system combined with homologous recombination was used to construct two recombinant viruses, BJB (Bartha-K61+JS-2012gB) and JBJ (JS-2012-ΔgE/gI+Bartha-K61gB), by interchanging the full-length gB genes between Bartha-K61 and JS-2012-ΔgE/gI. The two recombinant viruses showed similar characteristics in growth kinetics in vitro and similar pathogenicity in mice, as compared to their parental strains. Immunization of mice with inactivated BJB or JBJ followed by challenge of JS-2012 showed that BJB could increase protective efficacy to 80%, compared to only 40% protection by the parental Bartha-K61 strain. JBJ had a decreased protective efficacy of 65%, as compared to 90% protection by its parental JS-2012-ΔgE/gI strain. Exchange of the gB gene markedly altered the immunogenicity of the recombinant PRV. These data suggest that variations in gB might play an important role in the virulence of the reemergent PRV variant in China. Our results demonstrate the importance of gB in protective immunity and suggest that the recombinant virus BJB could be a promising vaccine candidate for eradication of the PRV variant. Copyright © 2017 Elsevier B.V. All rights reserved.

The novel antiepileptic drug imepitoin compares favourably to other GABA-mimetic drugs in a seizure threshold model in mice and dogs.

PubMed

Löscher, Wolfgang; Hoffmann, Katrin; Twele, Friederike; Potschka, Heidrun; Töllner, Kathrin

2013-11-01

Recently, the imidazolinone derivative imepitoin has been approved for treatment of canine epilepsy. Imepitoin acts as a low-affinity partial agonist at the benzodiazepine (BZD) site of the GABAA receptor and is the first compound with such mechanism that has been developed as an antiepileptic drug (AED). This mechanism offers several advantages compared to full agonists, including less severe adverse effects and a lack of tolerance and dependence liability, which has been demonstrated in rodents, dogs, and nonhuman primates. In clinical trials in epileptic dogs, imepitoin was shown to be an effective and safe AED. Recently, seizures in dogs have been proposed as a translational platform for human therapeutic trials on new epilepsy treatments. In the present study, we compared the anticonvulsant efficacy of imepitoin, phenobarbital and the high-affinity partial BZD agonist abecarnil in the timed i.v. pentylenetetrazole (PTZ) seizure threshold test in dogs and, for comparison, in mice. Furthermore, adverse effects of treatments were compared in both species. All drugs dose-dependently increased the PTZ threshold in both species, but anticonvulsant efficacy was higher in dogs than mice. At the doses selected for this study, imepitoin was slightly less potent than phenobarbital in increasing seizure threshold, but markedly more tolerable in both species. Effective doses of imepitoin in the PTZ seizure model were in the same range as those suppressing spontaneous recurrent seizures in epileptic dogs. The study demonstrates that low-affinity partial agonists at the benzodiazepine site of the GABAA receptor, such as imepitoin, offer advantages as a new category of AEDs. Copyright © 2013 Elsevier Ltd. All rights reserved.

Engaging Students: An Examination of the Effects of Teaching Strategies on Self-Efficacy and Course Climate in a Nonmajors Physics Course

ERIC Educational Resources Information Center

Fencl, Heidi; Scheel, Karen

2005-01-01

Given the success of self-efficacy theory for predicting student success in scientific study, and the demonstrated effect that teaching approaches have on student self-efficacy in majors courses, the purpose of this study is to ask if similar relationships between pedagogy and self-efficacy exist in introductory science courses for non-physical…

Efficacy of 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a in photodynamic therapy of human esophageal squamous cancer cells.

PubMed

Wu, Dengpan; Liu, Zhen; Fu, Yanni; Zhang, Yuan; Tang, Nan; Wang, Qin; Tao, Liang

2013-10-01

The present study investigated the effects of 2-(1-hexyloxyethyl)-2-devinylpyro pheophorbide-a (HPPH)-mediated photodynamic therapy (PDT) on in vitro cell survival and in vivo tumor growth derived from human esophageal squamous cancer cells (Eca109). A cell counting kit 8 (CCK8) assay was used to assess the phototoxicity of HPPH-mediated PDT in cultured Eca109 cells. The inhibition of tumor growth was determined by the changes in the relative tumor volume (RTV) and tumor weight. The results revealed that HPPH, in the range of 0.005-1 μg/ml, exhibited no cytotoxicity in the Eca109 cells without light exposure and that the in vitro efficiency of HPPH-mediated PDT was higher compared with that of Photofrin ® -mediated PDT. The in vivo results indicated that graded doses of HPPH-mediated PDT significantly inhibited the xenograft tumor growth derived from the Eca109 cells in a dose-dependent manner. The inhibition efficacy of 0.6 and 1.0 mg/kg HPPH-mediated PDT was similar to that of 10 mg/kg Photofrin-mediated PDT. Furthermore, HPPH possessed a lower toxicity than Photofrin at the dose that achieved the same efficacy in mice bearing Eca109 subcutaneous tumors. The histopathological findings indicated that the tumor tissues in the photosensitizer (PS)-treated mice demonstrated varying degrees of necrosis. HPPH and Photofrin exhibited vascular cytotoxicity on the treated tumors. In conclusion, the present study demonstrated that the phototoxicity of HPPH-mediated PDT is higher than that of Photofrin-mediated PDT of the same dose. HPPH possessed lower toxicity than Photofrin at the dose that achieved the same efficacy. Therefore, HPPH may be a promising agent for treating human esophageal squamous cell cancer (ESCC).

Efficacy of 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a in photodynamic therapy of human esophageal squamous cancer cells

PubMed Central

WU, DENGPAN; LIU, ZHEN; FU, YANNI; ZHANG, YUAN; TANG, NAN; WANG, QIN; TAO, LIANG

2013-01-01

The present study investigated the effects of 2-(1-hexyloxyethyl)-2-devinylpyro pheophorbide-a (HPPH)-mediated photodynamic therapy (PDT) on in vitro cell survival and in vivo tumor growth derived from human esophageal squamous cancer cells (Eca109). A cell counting kit 8 (CCK8) assay was used to assess the phototoxicity of HPPH-mediated PDT in cultured Eca109 cells. The inhibition of tumor growth was determined by the changes in the relative tumor volume (RTV) and tumor weight. The results revealed that HPPH, in the range of 0.005–1 μg/ml, exhibited no cytotoxicity in the Eca109 cells without light exposure and that the in vitro efficiency of HPPH-mediated PDT was higher compared with that of Photofrin®-mediated PDT. The in vivo results indicated that graded doses of HPPH-mediated PDT significantly inhibited the xenograft tumor growth derived from the Eca109 cells in a dose-dependent manner. The inhibition efficacy of 0.6 and 1.0 mg/kg HPPH-mediated PDT was similar to that of 10 mg/kg Photofrin-mediated PDT. Furthermore, HPPH possessed a lower toxicity than Photofrin at the dose that achieved the same efficacy in mice bearing Eca109 subcutaneous tumors. The histopathological findings indicated that the tumor tissues in the photosensitizer (PS)-treated mice demonstrated varying degrees of necrosis. HPPH and Photofrin exhibited vascular cytotoxicity on the treated tumors. In conclusion, the present study demonstrated that the phototoxicity of HPPH-mediated PDT is higher than that of Photofrin-mediated PDT of the same dose. HPPH possessed lower toxicity than Photofrin at the dose that achieved the same efficacy. Therefore, HPPH may be a promising agent for treating human esophageal squamous cell cancer (ESCC). PMID:24137473

Non-daily pre-exposure prophylaxis for HIV prevention

PubMed Central

Anderson, Peter L.; García-Lerma, J. Gerardo; Heneine, Walid

2015-01-01

Purpose of review To discuss non-daily pre-exposure prophylaxis (PrEP) modalities that may provide advantages compared with daily PrEP in cost and cumulative toxicity, but may have lower adherence forgiveness. Recent Findings Animal models have informed our understanding of early viral transmission events, which help guide event-driven PrEP dosing strategies. These models indicate early establishment of viral replication in rectal or cervicovaginal tissues, so event-driven PrEP should rapidly deliver high mucosal drug concentrations within hours of the potential exposure event. Macaque models have demonstrated the high biological efficacy for event-driven dosing of oral tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) against both vaginal and rectal virus transmission. In humans, the IPERGAY study demonstrated 86% efficacy for event-driven oral TDF/FTC dosing among men who have sex with men (MSM), while no similar efficacy data are available on women or heterosexual men. The HPTN 067 study showed that certain MSM populations adhere well to non-daily PrEP while other populations of women adhere more poorly to non-daily versus daily regimens. Pharmacokinetic studies following oral TDF/FTC dosing in humans, indicate that TFV-diphosphate (the active form of TFV) accumulates to higher concentrations in rectal versus cervicovaginal tissue but non-adherence in trials complicates the interpretation of differential mucosal drug concentrations. Summary Event-driven dosing for TFV-based PrEP has promise for HIV prevention in MSM. Future research of event-driven PrEP in women and heterosexual men should be guided by a better understanding of the importance of mucosal drug concentrations for PrEP efficacy and its sensitivity to adherence. PMID:26633641

Efficacy and safety of topical NSAIDs in the management of osteoarthritis: Evidence from real-life setting trials and surveys.

PubMed

Rannou, François; Pelletier, Jean-Pierre; Martel-Pelletier, Johanne

2016-02-01

Topical non-steroidal anti-inflammatory drugs (NSAIDs) are recommended in international and national guidelines as an early treatment option for the symptomatic management of knee and hand osteoarthritis (OA), and may be used ahead of oral NSAIDs due to their superior safety profile. The European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) treatment algorithm recommends topical NSAIDs for knee OA in addition to the pharmacological background of symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) and rescue analgesia with paracetamol and non-pharmacological treatment, if the patient is still symptomatic. Topical NSAIDs have a moderate effect on pain relief, with efficacy similar to that of oral NSAIDs, with the advantage of a better risk:benefit ratio. In real-life studies, topical and oral NSAIDs demonstrate an equivalent effect on knee pain over 1 year of treatment, with fewer adverse events due to lower systemic absorption of topical NSAIDs compared with oral NSAIDs. As a result, topical NSAIDs may be the preferred treatment option, especially in OA patients aged ≥75 years, and those with co-morbidities or at an increased risk of cardiovascular, gastrointestinal, or renal side effects. Furthermore, using topical NSAIDs in inflammatory rheumatic diseases leads to a 40% reduction in the need for concomitant oral NSAIDs. When selecting a topical NSAID, absorption and bioavailability are important because of heterogeneity among topical drug formulations. Molecules like etofenamate have a bioavailability of >20% and evidence for accumulation in synovial tissues, with efficacy demonstrated as improvement in pain and function in real-life studies of OA patients. Diclofenac also shows good efficacy alongside evidence that diclofenac accumulates in the synovium. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Intrathecal administration of AYX2 DNA decoy produces a long-term pain treatment in rat models of chronic pain by inhibiting the KLF6, KLF9, and KLF15 transcription factors

PubMed Central

Klukinov, Michael; Harris, Scott; Manning, Donald C; Xie, Simon; Pascual, Conrado; Taylor, Bradley K; Donahue, Renee R; Yeomans, David C

2017-01-01

Background Nociception is maintained by genome-wide regulation of transcription in the dorsal root ganglia—spinal cord network. Hence, transcription factors constitute a promising class of targets for breakthrough pharmacological interventions to treat chronic pain. DNA decoys are oligonucleotides and specific inhibitors of transcription factor activities. A methodological series of in vivo–in vitro screening cycles was performed with decoy/transcription factor couples to identify targets capable of producing a robust and long-lasting inhibition of established chronic pain. Decoys were injected intrathecally and their efficacy was tested in the spared nerve injury and chronic constriction injury models of chronic pain in rats using repetitive von Frey testing. Results Results demonstrated that a one-time administration of decoys binding to the Kruppel-like transcription factors (KLFs) 6, 9, and 15 produces a significant and weeks–month long reduction in mechanical hypersensitivity compared to controls. In the spared nerve injury model, decoy efficacy was correlated to its capacity to bind KLF15 and KLF9 at a specific ratio, while in the chronic constriction injury model, efficacy was correlated to the combined binding capacity to KLF6 and KLF9. AYX2, an 18-bp DNA decoy binding KLF6, KLF9, and KLF15, was optimized for clinical development, and it demonstrated significant efficacy in these models. Conclusions These data highlight KLF6, KLF9, and KLF15 as transcription factors required for the maintenance of chronic pain and illustrate the potential therapeutic benefits of AYX2 for the treatment of chronic pain. PMID:28814144

Assessment of Efficacy and Quality of Two Albendazole Brands Commonly Used against Soil-Transmitted Helminth Infections in School Children in Jimma Town, Ethiopia

PubMed Central

Suleman, Sultan; Mohammed, Tesfaye; Deti, Habetewold; D'Hondt, Matthias; Wynendaele, Evelien; Mekonnen, Zeleke; Vercruysse, Jozef; Duchateau, Luc; De Spiegeleer, Bart; Levecke, Bruno

2015-01-01

Background There is a worldwide upscale in mass drug administration (MDA) programs to control the morbidity caused by soil-transmitted helminths (STHs): Ascaris lumbricoides, Trichuris trichiura and hookworm. Although anthelminthic drugs which are used for MDA are supplied by two pharmaceutical companies through donation, there is a wide range of brands available on local markets for which the efficacy against STHs and quality remain poorly explored. In the present study, we evaluated the drug efficacy and quality of two albendazole brands (Bendex and Ovis) available on the local market in Ethiopia. Methodology/Principal Findings A randomized clinical trial was conducted according to the World Health Organization (WHO) guidelines to assess drug efficacy, by means of egg reduction rate (ERR), of Bendex and Ovis against STH infections in school children in Jimma, Ethiopia. In addition, the chemical and physicochemical quality of the drugs was assessed according to the United States and European Pharmacopoeia, encompassing mass uniformity of the tablets, amount of active compound and dissolution profile. Both drugs were highly efficacious against A. lumbricoides (>97%), but showed poor efficacy against T. trichiura (~20%). For hookworms, Ovis was significantly (p < 0.05) more efficacious compared to Bendex (98.1% vs. 88.7%). Assessment of the physicochemical quality of the drugs revealed a significant difference in dissolution profile, with Bendex having a slower dissolution than Ovis. Conclusion/Significance The study revealed that differences in efficacy between the two brands of albendazole (ABZ) tablets against hookworm are linked to the differences in the in-vitro drug release profile. Differences in uptake and metabolism of this benzimidazole drug among different helminth species may explain that this efficacy difference was only observed in hookworms and not in the two other species. The results of the present study underscore the importance of assessing the chemical and physicochemical quality of drugs before conducting efficacy assessment in any clinical trials to ensure appropriate therapeutic efficacy and to exclude poor drug quality as a factor of reduced drug efficacy other than anthelminthic resistance. Overall, this paper demonstrates that “all medicines are not created equal”. PMID:26406600

Assessment of Efficacy and Quality of Two Albendazole Brands Commonly Used against Soil-Transmitted Helminth Infections in School Children in Jimma Town, Ethiopia.

PubMed

Belew, Sileshi; Getachew, Mestawet; Suleman, Sultan; Mohammed, Tesfaye; Deti, Habetewold; D'Hondt, Matthias; Wynendaele, Evelien; Mekonnen, Zeleke; Vercruysse, Jozef; Duchateau, Luc; De Spiegeleer, Bart; Levecke, Bruno

2015-09-01

There is a worldwide upscale in mass drug administration (MDA) programs to control the morbidity caused by soil-transmitted helminths (STHs): Ascaris lumbricoides, Trichuris trichiura and hookworm. Although anthelminthic drugs which are used for MDA are supplied by two pharmaceutical companies through donation, there is a wide range of brands available on local markets for which the efficacy against STHs and quality remain poorly explored. In the present study, we evaluated the drug efficacy and quality of two albendazole brands (Bendex and Ovis) available on the local market in Ethiopia. A randomized clinical trial was conducted according to the World Health Organization (WHO) guidelines to assess drug efficacy, by means of egg reduction rate (ERR), of Bendex and Ovis against STH infections in school children in Jimma, Ethiopia. In addition, the chemical and physicochemical quality of the drugs was assessed according to the United States and European Pharmacopoeia, encompassing mass uniformity of the tablets, amount of active compound and dissolution profile. Both drugs were highly efficacious against A. lumbricoides (>97%), but showed poor efficacy against T. trichiura (~20%). For hookworms, Ovis was significantly (p < 0.05) more efficacious compared to Bendex (98.1% vs. 88.7%). Assessment of the physicochemical quality of the drugs revealed a significant difference in dissolution profile, with Bendex having a slower dissolution than Ovis. The study revealed that differences in efficacy between the two brands of albendazole (ABZ) tablets against hookworm are linked to the differences in the in-vitro drug release profile. Differences in uptake and metabolism of this benzimidazole drug among different helminth species may explain that this efficacy difference was only observed in hookworms and not in the two other species. The results of the present study underscore the importance of assessing the chemical and physicochemical quality of drugs before conducting efficacy assessment in any clinical trials to ensure appropriate therapeutic efficacy and to exclude poor drug quality as a factor of reduced drug efficacy other than anthelminthic resistance. Overall, this paper demonstrates that "all medicines are not created equal".

Efficacy and Safety of Three Cryotherapy Devices for Wart Treatment: A Randomized, Controlled, Investigator-Blinded, Comparative Study.

PubMed

Walczuk, Imko; Eertmans, Frank; Rossel, Bart; Cegielska, Agnieszka; Stockfleth, Eggert; Antunes, Andre; Adriaens, Els

2018-06-01

Cutaneous warts are common skin lesions, caused by human papillomavirus. For years, liquid nitrogen is the cryogen of choice for wart treatment. Alternatively, several cryogenic devices for home treatment are commercially available. The present trial assessed efficacy and safety of a novel nitrous oxide-based cryogenic device for home use (EndWarts Freeze ® in Europe, Compound W ® Nitro-Freeze in the USA). This investigator-blinded, controlled, randomized study compared the nitrous oxide device (test product) with a dimethylether propane-based product (Wartner ® ; comparator 1). Subjects with common or plantar warts (50/50 ratio) were randomized into two groups (n = 58, test product; n = 40, comparator 1). Sequentially, an extra treatment arm (n = 40) was added to compare with a dimethylether-based product with metal nib (Wortie ® ; comparator 2). Main objective implied comparison of the percentage cured subjects after one to maximum three treatments. Efficacy and safety was evaluated by a blinded investigator. After a maximum of three applications, a significantly (p = 0.001) higher cure rate of 70.7% (Intention-to-Treat analysis) was observed with test product versus 46.2% (comparator 1) and 47.5% (comparator 2). Almost three times more subjects were cured after 1 test product application (29.3%), versus comparator 1 (10.4%) and comparator 2 (12.5%). Reported side effects were transient and typical of cryotherapy. All treatments were well-tolerated. The superior cure rates for the test product versus two comparators can be explained by its design. Combination of nitrous oxide (cooling agent), the specific activation method (holding the liquid coolant in the cap), and skin-conforming polyurethane foam, results in higher cooling efficiency (- 80 °C) and more effective wart freezing. This trial demonstrated that the nitrous oxide device is a safe, user-friendly and effective wart treatment for home use, comparing favourably to dimethylether (propane) devices with higher freezing temperature, regardless of the applicator type. Oystershell Laboratories. Clinicaltrials.gov identifier, NCT03129373.

Comparison of efficacy of once daily multimatrix mesalazine 2.4 g/day and 4.8 g/day with other 5-aminosalicylic acid preparation in active ulcerative colitis: a randomized, double-blind study.

PubMed

Ogata, Haruhiko; Yokoyama, Tadashi; Mizushima, Seiichi; Hagino, Atsushi; Hibi, Toshifumi

2018-04-01

This study compared the efficacy of multimatrix mesalazine 2.4 g/day and 4.8 g/day with controlled-release mesalazine 2.25 g/day. In this multicenter, randomized, double-blind study, 251 patients with mildly to moderately active ulcerative colitis received multimatrix mesalazine 2.4 g/day once daily (Multimatrix-2.4), 4.8 g/day once daily (Multimatrix-4.8), or controlled-release (time-dependent) mesalazine 2.25 g/day 3 times daily (Time-2.25) for 8 weeks. The primary efficacy endpoint was the change in the ulcerative colitis-disease activity index (UC-DAI) score. The mean change in the UC-DAI score and standard deviation in the per protocol set was -1.9±2.5 for Multimatrix-2.4 and -2.4±2.8 for Time-2.25. The difference between Multimatrix-2.4 and Time-2.25 was 0.3 (two-sided 95% confidence interval [CI], -0.5 to 1.1), thus non-inferiority was not demonstrated based on the pre-defined non-inferiority margin (1.0). In the full analysis set, the difference between Multimatrix-4.8 and Time-2.25 was -1.2 (two-sided 95% CI, -2.0 to -0.5), and the mean change in UC-DAI score in the FAS was -3.3 (two-sided 95% CI, -3.9 to -2.8) for Multimatrix-4.8 and -1.9 (two-sided 95% CI, -2.5 to -1.3) for Multimatrix-2.4, indicating that Multimatrix-4.8 was more effective than Time-2.25 and Multimatrix-2.4. There was no difference among the treatment groups in terms of safety. This study showed that the efficacy of multimatrix mesalazine 2.4 g/day was comparable to controlled release mesalazine 2.25 g/day, although non-inferiority was not demonstrated. Importantly, this was the first study to indicate that multimatrix mesalazine 4.8 g/day was more effective than 2.4g/day with no associated safety concerns.

Ethnic Disparities in CPAP Adherence in New Zealand: Effects of Socioeconomic Status, Health Literacy and Self-Efficacy

PubMed Central

Bakker, Jessie P.; O'Keeffe, Karyn M.; Neill, Alister M.; Campbell, Angela J.

2011-01-01

Study Objectives: We aimed to investigate the influence of ethnicity on adherence with continuous positive airway pressure (CPAP) in a sample of New Zealand patients. Design: Observational study over one month. Setting: A university-based sleep laboratory. Patients: 126 consecutively consenting CPAP-naïve patients (19.8% Māori, mean±SD apnea-hypopnea index 57.9 ± 38.9 events/h, CPAP 11.1 ± 3.1 cm H2O). Interventions: Patients underwent a 4-week supervised home trial of CPAP following pressure titration. Measurements and Results: Self-identified ethnicity (Māori/non-Māori), Epworth Sleepiness Scale, Self-Efficacy Measure for Sleep Apnea, Rapid Estimate of Adult Literacy in Medicine, New Zealand Deprivation Index (calculated from residential address), New Zealand Individual Deprivation Index (validated 8-item questionnaire), educational history, income, and employment assessed at baseline were compared to objective CPAP adherence after one month. Māori demonstrated significantly lower usage than non-Māori (median 5.11, interquartile range 2.24 h/night compared with median 5.71, interquartile range 2.61 h/night, P = 0.05). There were no significant relationships between adherence and subjective sleepiness, health literacy, or self-efficacy. In a multivariate logistic regression model incorporating 5 variables (ethnicity, eligibility for government-subsidized healthcare, individual deprivation scores, income, and education), non-completion of tertiary education, and high individual socioeconomic deprivation remained significant independent predictors of average CPAP adherence not reaching ≥ 4 h (odds ratio 0.25, 95% CI 0.08-0.83, P = 0.02; odds ratio 0.10, 95% CI 0.02-0.86, P = 0.04, respectively). The overall model explained approximately 23% of the variance in adherence. Conclusions: The disparity in CPAP adherence demonstrated between Māori and non-Māori can be explained in part by lower education levels and socioeconomic status. Citation: Bakker JP; O'Keeffe KM; Neill AM; Campbell AJ. Ethnic disparities in CPAP adherence in New Zealand: effects of socioeconomic status, health literacy and self-efficacy. SLEEP 2011;34(11):1595-1603. PMID:22043130

Extracapsular local infiltration analgesia in hip arthroscopy: a retrospective study

PubMed Central

Kahn, Timothy L; Adeyemi, Temitope F; Maak, Travis G

2018-01-01

ABSTRACT Many hip arthroscopy patients experience significant pain in the immediate postoperative period. Although peripheral nerve blocks have demonstrated efficacy in alleviating some of this pain, they come with significant costs. Local infiltration analgesia (LIA) may be a significantly cheaper and efficacious treatment modality. Although LIA has been well studied in hip and knee arthroplasty, its efficacy in hip arthroscopy is unclear. The purpose of this retrospective study is to determine the efficacy of a single extracapsular injection of bupivacaine–epinephrine during hip arthroscopy in reducing the rate of elective postoperative femoral nerve blocks. A retrospective review of 100 consecutive patients who underwent primary hip arthroscopy at a single medical center was performed. The control group consisted of 50 patients before the implementation of the current LIA protocol, whereas another 50 patients received a 20-ml extracapsular injection of 0.25% bupivacaine–epinephrine under direct arthroscopic visualization after capsular closure. In the post-anesthesia care unit (PACU), patients were offered a femoral nerve block for uncontrolled pain. The rate of femoral nerve block, and total opioid consumption, was compared between groups. The proportion of patients receiving elective femoral nerve blocks was significantly less in the LIA group (34%) as compared with the control group (56%; P = 0.027). There was no significant difference in total PACU opioid consumption between groups (P = 0.740). The decreased utilization of postoperative nerve blocks observed in the LIA group suggests that LIA may improve postoperative pain management and should be considered as a potentially cost-effective tool in pain management in hip arthroscopy patients. Level of Evidence: III PMID:29423252

Evaluation of Brāhmī ghṛtam in children suffering from Attention Deficit Hyperactivity Disorder

PubMed Central

Bhalerao, Supriya; Munshi, Renuka; Nesari, Tanuja; Shah, Heenal

2013-01-01

Introduction: Attention Deficit Hyperactivity Disorder (ADHD) is characterized by a persistent pattern of inattention and/or hyperactivity-impulsivity. In view of the adverse effects associated with psycho-stimulants used for the treatment of this disorder, efficacy of Brāhmī ghṛtam was evaluated in this condition. Materials and Methods: After following due ethical considerations, children of either sex between the age group of 6 and 12 years diagnosed to be suffering from mixed variety of ADHD as per The Diagnostic and Statistical Manual of Mental Disorders (DSM) IV criteria irrespective of other co-morbid psychiatric illnesses were recruited in the study. Initially a pilot study (n = 10) was carried out to confirm the efficacy of the identified dose of Brāhmī ghṛtam. Using this dose, further therapeutic confirmatory study (n = 27) was carried out, wherein Brāhmī ghṛtam was compared with methylphenidate. Effect on ADHD symptoms was assessed using the Dupaul ADHD rating scale and this was the main efficacy parameter. Results: In the pilot exploratory study, Brāhmī ghṛtam showed 66% decrease in total ADHD score. In the therapeutic confirmatory study, only 16% improvement was seen with Brāhmī ghṛtam, which was similar to methylphenidate, standard treatment for ADHD that was used as a comparator in the present study. No side-effects were reported in both studies. Conclusion: Our study thus has adequately demonstrated efficacy and safety of Brāhmī ghṛtam in ADHD. PMID:25284947

Single-course specific immunotherapy with mixed pollen allergoids: results of a multi-centre study.

PubMed

Drachenberg, K J; Pröll, S; Urban, E; Woroniecki, S R

2003-01-01

A short-term immunotherapy vaccine for the treatment of pollen allergy has been developed utilising L-tyrosine adsorbed allergoids. The reduced number of injections could provide advantages over long-term therapy schedules. This would improve compliance and support application of specific immunotherapy (SIT) to a greater extent. We report a multicenter study to evaluate the efficacy and safety of this treatment in a clinical practice setting. Patients (n = 1808) with a diagnosis of sensitivities to various pollens and symptoms of allergic asthma and/or allergic rhinitis and/or allergic conjunctivitis were selected. The vaccine formulation was made up according to individual sensitivities and contained L-tyrosine adsorbed allergoids. The patients were treated with a 3-injection initial course followed by a 3-injection maintenance course. Efficacy was measured by consumption of symptomatic anti-allergic medication compared with that in the previous season and by physician assessment using a 5-point scale. All adverse events were recorded. Efficacy was demonstrated by a considerable decrease in regular and frequent use of medication compared with that in the previous season (p < 0.001). In addition, in 80 % of the patients, the physician's assessment was either "good" or "very good". These outcomes were unaffected by the closeness of the treatment course to the onset of the pollen season. Tolerability was good and most local and systemic reactions were mild. The treatment of pollen-allergic patients with a short-term SIT using a 6-injection pollen allergoid/L-tyrosine vaccine in a clinical practice setting provided a high level of efficacy with a low incidence of mainly mild adverse events.

Efficacy of sequential three-step empirical therapy for chronic cough.

PubMed

Yu, Li; Xu, Xianghuai; Hang, Jingqing; Cheng, Kewen; Jin, Xiaoyan; Chen, Qiang; Lv, Hanjing; Qiu, Zhongmin

2017-06-01

Empirical three-step therapy has been proved in just one hospital. This study aimed to demonstrate applicability of the sequential empirical three-step therapy for chronic cough in different clinical settings. Sequential empirical three-step therapy was given to patients with chronic cough in one tertiary and three secondary care respiratory clinics. Recruiters were initially treated with methoxyphenamine compound as the first-step therapy, followed by corticosteroids as the second-step therapy and the combination of a proton-pump inhibitor and a prokinetic agent as the third-step therapy. The efficacy of the therapy was verified according to the changes in cough symptom score between pre- and post-treatment, and compared among the different clinics. In total 155 patients in one tertiary clinic and 193 patients in secondary care clinics were recruited. The total dropout ratio is significantly higher in the secondary care clinics than that in the tertiary clinic (9.3% versus 3.2%, p = 0.023). The therapeutic success rate for cough was 38.7% at first-step therapy, 32.3% at second-step therapy and 20.0% at third-step therapy in the tertiary clinic, and comparable to corresponding 49.7%, 31.1% and 4.1% in secondary care clinics. Furthermore, the overall cough resolution rate was not significantly different (91.0% versus 85.0%, p = 0.091). However, the efficacy of the third-step therapy is much higher (20.0% versus 4.1%, p = 0.001) in the tertiary clinic than in the secondary care clinics. Sequential empirical three-step therapy is universally efficacious and useful for management of chronic cough in different clinical settings.

The efficacy and safety of irsogladine maleate in nonsteroidal anti-inflammatory drug or aspirin-induced peptic ulcer and gastritis.

PubMed

Shim, Ki-Nam; Kim, Jin Il; Kim, Nayoung; Kim, Sang Gyun; Jo, Yun Ju; Hong, Su Jin; Shin, Jeong Eun; Kim, Gwang Ha; Park, Kyung Sik; Choi, Suck Chei; Kwon, Joong Goo; Kim, Jie-Hyun; Kim, Hyun Jin; Kim, Ji Won

2018-06-01

Irsogladine maleate, an enhancer of gastric mucosal protective factors, has demonstrated its efficacy for various gastric mucosal injuries. The aim of this study was to evaluate the efficacy and safety of irsogladine for prevention of nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin-induced peptic ulcer and gastritis. In this multicenter, randomized, double-blind, exploratory clinical trial, 100 patients over 50 years of age who needed continuous NSAIDs or aspirin for more than 8 weeks were randomly assigned to either test group (irsogladine maleate 2 mg, twice daily, 39 patients for full analysis) or placebo group (37 patients for full analysis). Primary outcomes were incidence of peptic ulcer and ratio of modified Lanza score (MLS) 2 to 4. Secondary outcome was the number of acute erosions confirmed by endoscopy at 8 weeks. Adverse effects were also compared. There were no significant differences in gastric protective effects between test and placebo groups. However, two cases of peptic ulcer in the placebo group but none in the test group were observed. These two cases of peptic ulcer were Helicobacter pylori-negative. In addition, H. pylori-negative group showed significant changes in MLS score (p = 0.0247) and edema score (p = 0.0154) after the treatment compared to those before treatment in the test group. There was no significant difference in adverse events between the two groups. The efficacy of irsogladine maleate was found in H. pylori-negative group, suggesting its potential as a protective agent against NSAIDs or aspirin-induced peptic ulcer and gastritis.

Preclinical Study of Single-Dose Moxidectin, a New Oral Treatment for Scabies: Efficacy, Safety, and Pharmacokinetics Compared to Two-Dose Ivermectin in a Porcine Model

PubMed Central

Bernigaud, Charlotte; Aho, Ludwig Serge; Dreau, Dominique; Kelly, Andrew; Sutra, Jean-François; Moreau, Francis; Lilin, Thomas; Botterel, Françoise; Guillot, Jacques; Chosidow, Olivier

2016-01-01

Background Scabies is one of the commonest dermatological conditions globally; however it is a largely underexplored and truly neglected infectious disease. Foremost, improvement in the management of this public health burden is imperative. Current treatments with topical agents and/or oral ivermectin (IVM) are insufficient and drug resistance is emerging. Moxidectin (MOX), with more advantageous pharmacological profiles may be a promising alternative. Methodology/Principal Findings Using a porcine scabies model, 12 pigs were randomly assigned to receive orally either MOX (0.3 mg/kg once), IVM (0.2 mg/kg twice) or no treatment. We evaluated treatment efficacies by assessing mite count, clinical lesions, pruritus and ELISA-determined anti-S. scabiei IgG antibodies reductions. Plasma and skin pharmacokinetic profiles were determined. At day 14 post-treatment, all four MOX-treated but only two IVM-treated pigs were mite-free. MOX efficacy was 100% and remained unchanged until study-end (D47), compared to 62% (range 26–100%) for IVM, with one IVM-treated pig remaining infected until D47. Clinical scabies lesions, pruritus and anti-S. scabiei IgG antibodies had completely disappeared in all MOX-treated but only 75% of IVM-treated pigs. MOX persisted ~9 times longer than IVM in plasma and skin, thereby covering the mite’s entire life cycle and enabling long-lasting efficacy. Conclusions/Significance Our data demonstrate that oral single-dose MOX was more effective than two consecutive IVM-doses, supporting MOX as potential therapeutic approach for scabies. PMID:27732588

Feasibility, safety, and preliminary efficacy of Low Amplitude Seizure Therapy (LAP-ST): A proof of concept clinical trial in man.

PubMed

Youssef, Nagy A; Sidhom, Emad

2017-11-01

Current pulse amplitude used in clinical ECT may be higher than needed. Reducing pulse amplitude may improve focality of the electric field and thus cognitive adverse effects. Here we examine the feasibility, safety, and whether Low Pulse Amplitude Seizure Therapy (LAP-ST, 0.5-0.6A) minimizes cognitive adverse effects while retaining efficacy. Patients with treatment-resistant primary mood (depressive episodes) or psychotic disorders who were clinically indicated to undergo ECT were offered to be enrolled in an open-label study. The study consisted of a full acute course of LAP-ST under standard anesthesia and muscle relaxation. The primary outcome was feasibility of seizure induction. Clinical outcome measures were: time to reorientation (TRO), Mini Mental State Examination, Montgomery Aberg Depression Scale, and Brief Psychiatric Rating Scale, and Clinical Global Impression Scale. Twenty-two patients consented for enrollment in the study. LAP-ST was feasible, and all patients had seizures in the first session. Participants had a quick orientation with median TRO of 4.5min. Treatment was efficacious for both depressive and psychotic symptoms. Relatively small sample size, non-blinded, and no randomization was performed in this initial proof of concept study. This first human preliminary data of a full course of focal LAP-ST demonstrates that seizure induction is feasible. These results, although preliminary, suggest that the LAP-ST compared to the standard ECT techniques may result in less cognitive side effects, but comparable efficacy. Larger studies are needed to replicate these findings. Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical Modification with High Molecular Weight Polyethylene Glycol Reduces Transduction of Hepatocytes and Increases Efficacy of Intravenously Delivered Oncolytic Adenovirus

PubMed Central

Doronin, Konstantin; Shashkova, Elena V.; May, Shannon M.; Hofherr, Sean E.

2009-01-01

Abstract Oncolytic adenoviruses are anticancer agents that replicate within tumors and spread to uninfected tumor cells, amplifying the anticancer effect of initial transduction. We tested whether coating the viral particle with polyethylene glycol (PEG) could reduce transduction of hepatocytes and hepatotoxicity after systemic (intravenous) administration of oncolytic adenovirus serotype 5 (Ad5). Conjugating Ad5 with high molecular weight 20-kDa PEG but not with 5-kDa PEG reduced hepatocyte transduction and hepatotoxicity after intravenous injection. PEGylation with 20-kDa PEG was as efficient at detargeting adenovirus from Kupffer cells and hepatocytes as virus predosing and warfarin. Bioluminescence imaging of virus distribution in two xenograft tumor models in nude mice demonstrated that PEGylation with 20-kDa PEG reduced liver infection 19- to 90-fold. Tumor transduction levels were similar for vectors PEGylated with 20-kDa PEG and unPEGylated vectors. Anticancer efficacy after a single intravenous injection was retained at the level of unmodified vector in large established prostate carcinoma xenografts, resulting in complete elimination of tumors in all animals and long-term tumor-free survival. Anticancer efficacy after a single intravenous injection was increased in large established hepatocellular carcinoma xenografts, resulting in significant prolongation of survival as compared with unmodified vector. The increase in efficacy was comparable to that obtained with predosing and warfarin pretreatment, significantly extending the median of survival. Shielding adenovirus with 20-kDa PEG may be a useful approach to improve the therapeutic window of oncolytic adenovirus after systemic delivery to primary and metastatic tumor sites. PMID:19469693

Efficacy and safety of bilastine 20 mg compared with cetirizine 10 mg and placebo for the symptomatic treatment of seasonal allergic rhinitis: a randomized, double-blind, parallel-group study.

PubMed

Kuna, P; Bachert, C; Nowacki, Z; van Cauwenberge, P; Agache, I; Fouquert, L; Roger, A; Sologuren, A; Valiente, R

2009-09-01

Bilastine is a new non-sedative H(1) receptor antagonist, indicated for the treatment of allergic rhinitis (AR) (seasonal and perennial). To assess and compare the efficacy and safety of bilastine 20 mg vs. cetirizine 10 mg and placebo in relieving the symptoms of seasonal allergic rhinitis (SAR). Overall, 683 SAR patients, aged 12-70 years, were randomized to a double-blind treatment with bilastine 20 mg, cetirizine 10 mg or placebo, once daily for 14 days, in 61 centres across Europe. Patients recorded reflective (over the past 12 h) and instantaneous nasal (obstruction, rhinorrhoea, itching and sneezing) and non-nasal (ocular tearing, redness and itching) symptom scores (NSS and NNSS, respectively) twice daily, according to a pre-determined severity scale to provide reflective and instantaneous total symptom scores (TSS). The primary efficacy measure was the area under curve (AUC) of reflective TSS over 14 days of treatment (TSS-AUC(0-14 days)). Secondary efficacy measures included mean change from baseline in TSS, NSS and NNSS; discomfort caused by AR; and investigator's clinical global impression of the treatment. Safety was assessed according to adverse events (AEs), laboratory tests and electrocardiograms. The mean TSS-AUC(0-14 days) (score x day) was reduced in bilastine- and cetirizine-treated groups to a similar and significantly greater extent, compared with placebo (76.5, 72.3 and 100.6, respectively; P<0.001). Similarly, bilastine and cetirizine were comparable and significantly superior to placebo for all secondary outcomes. While all treatments were well tolerated and the AE profiles of bilastine and placebo were similar, significantly fewer patients in the bilastine-treated group experienced somnolence (1.8%; P<0.001) and fatigue (0.4%; P=0.02) than patients in the cetirizine-treated group (7.5% and 4.8%, respectively). Bilastine 20 mg once daily was significantly superior to placebo and comparable to cetirizine 10 mg in relieving symptoms of SAR, although it demonstrated a significantly better AE profile than cetirizine.

Efficacy of a piroctone olamine/climbazol shampoo in comparison with a zinc pyrithione shampoo in subjects with moderate to severe dandruff.

PubMed

Schmidt-Rose, T; Braren, S; Fölster, H; Hillemann, T; Oltrogge, B; Philipp, P; Weets, G; Fey, S

2011-06-01

Dandruff is a chronic scalp disorder characterized by scaling and itching. A successful anti-dandruff shampoo not only has to provide superior anti-dandruff relief to ensure patient compliance. It also needs to offer excellent cosmetic and hair conditioning benefits at the same time. In this study, the efficacy of a shampoo containing 0.5% piroctone olamine and 0.45% climbazole (shampoo 1) was compared with a widely available commercial shampoo containing 1% zinc pyrithione (shampoo 2). In vitro studies investigating the anti-mycotic efficacy of a combination of 0.5% piroctone olamine and 0.45% climbazole as well as 1% zinc pyrithione were performed. To study substantivity, pig skin punches were used as a model system and a test of wet combability was performed to characterize combing ease. In vivo home-in-use studies were carried out to determine the efficacy of both shampoos to improve scalp condition and reduce itching in subjects suffering from moderate to severe dandruff. Results demonstrated a comparable anti-fungal effectiveness for 0.5% piroctone olamine plus 0.45% climbazole and 1% zinc pyrithione, respectively. Shampoo 1 showed a significantly higher anti-mycotics substantivity compared to shampoo 2. After treatment with shampoo 1, the wet combing force was significantly reduced compared with shampoo 2, suggesting a better combability following the use of shampoo 1. In an in vivo split head design study, shampoo 1 was shown to be equally effective in reducing the amount of dandruff on the scalp compared with shampoo 2. The approval rate of volunteers regarding the question 'The use of this shampoo decreases the itching of my scalp?' after a 4-week treatment with shampoo 1 equaled 90%. Overall, the shampoo formulation with 0.5% piroctone olamine and 0.45% climbazole effectively reduces the amount of dandruff and, at the same time, provides hair conditioning advantages. © 2011 The Authors. ICS © 2011 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Evaluation of Dalfampridine Extended Release 5 and 10 mg in Multiple Sclerosis

PubMed Central

Yapundich, Robert; Applebee, Angela; Bethoux, Francois; Goldman, Myla D.; Hutton, George J.; Mass, Michele; Pardo, Gabriel; Klingler, Michael; Henney, Herbert R.; Carrazana, Enrique J.

2015-01-01

Background: Dalfampridine extended-release (ER) tablets, 10 mg twice daily, have been shown to improve walking in people with multiple sclerosis. We evaluated the safety and efficacy of dalfampridine-ER 5 mg compared with 10 mg. Methods: Patients were randomized to double-blind treatment with twice-daily dalfampridine-ER tablets, 5 mg (n = 144) or 10 mg (n = 143), or placebo (n = 143) for 4 weeks. Primary efficacy endpoint was change from baseline walking speed by the Timed 25-Foot Walk 3 to 4 hours after the last dose. At 40% of sites, 2-week change from baseline walking distance was measured by the 6-Minute Walk test. Results: At 4 weeks, walking speed changes from baseline were 0.363, 0.423, and 0.478 ft/s (placebo, dalfampridine-ER 5 mg, and dalfampridine-ER 10 mg, respectively [P = NS]). Post hoc analysis of average changes between pretreatment and on-treatment showed that relative to placebo, only dalfampridine-ER 10 mg demonstrated a significant increase in walking speed (mean ± SE): 0.443 ± 0.042 ft/s versus 0.303 ± 0.038 ft/s (P = .014). Improvement in 6-Minute Walk distance was significantly greater with dalfampridine-ER 10 mg (128.6 ft, P = .014) but not with 5 mg (76.8 ft, P = .308) relative to placebo (41.7 ft). Adverse events were consistent with previous studies. No seizures were reported. Conclusions: Dalfampridine-ER 5 and 10 mg twice daily did not demonstrate efficacy on the planned endpoint. Post hoc analyses demonstrated significant increases in walking speed relative to placebo with dalfampridine-ER 10 mg. No new safety signals were observed. PMID:26052259

Measuring School Psychology Trainee Self-Efficacy

ERIC Educational Resources Information Center

Lockwood, Adam B.; Mcclure, John; Sealander, Karen; Baker, Courtney N.

2017-01-01

There is an ever-increasing need for school psychology training programs to demonstrate their ability to produce competent practitioners. One method of addressing this need is through the assessment of self-efficacy. However, little research on self-efficacy in school psychology exists likely due to the lack of a psychometrically sound measure of…

Hardiness, Perceived Employability, and Career Decision Self-Efficacy among Taiwanese College Students

ERIC Educational Resources Information Center

Huang, Jie-Tsuen

2015-01-01

Past empirical evidence has demonstrated that personality traits predict career decision self-efficacy. This study extends previous research by proposing and testing a model that examines the mediating roles of perceived internal and external employability on the relationship between personality hardiness and career decision self-efficacy. Using…

DS-8201a, A Novel HER2-Targeting ADC with a Novel DNA Topoisomerase I Inhibitor, Demonstrates a Promising Antitumor Efficacy with Differentiation from T-DM1.

PubMed

Ogitani, Yusuke; Aida, Tetsuo; Hagihara, Katsunobu; Yamaguchi, Junko; Ishii, Chiaki; Harada, Naoya; Soma, Masako; Okamoto, Hiromi; Oitate, Masataka; Arakawa, Shingo; Hirai, Takehiro; Atsumi, Ryo; Nakada, Takashi; Hayakawa, Ichiro; Abe, Yuki; Agatsuma, Toshinori

2016-10-15

An anti-HER2 antibody-drug conjugate with a novel topoisomerase I inhibitor, DS-8201a, was generated as a new antitumor drug candidate, and its preclinical pharmacologic profile was assessed. In vitro and in vivo pharmacologic activities of DS-8201a were evaluated and compared with T-DM1 in several HER2-positive cell lines and patient-derived xenograft (PDX) models. The mechanism of action for the efficacy was also evaluated. Pharmacokinetics in cynomolgus monkeys and the safety profiles in rats and cynomolgus monkeys were assessed. DS-8201a exhibited a HER2 expression-dependent cell growth-inhibitory activity and induced tumor regression with a single dosing at more than 1 mg/kg in a HER2-positive gastric cancer NCI-N87 model. Binding activity to HER2 and ADCC activity of DS-8201a were comparable with unconjugated anti-HER2 antibody. DS-8201a also showed an inhibitory activity to Akt phosphorylation. DS-8201a induced phosphorylation of Chk1 and Histone H2A.X, the markers of DNA damage. Pharmacokinetics and safety profiles of DS-8201a were favorable and the highest non-severely toxic dose was 30 mg/kg in cynomolgus monkeys, supporting DS-8201a as being well tolerated in humans. DS-8201a was effective in a T-DM1-insensitive PDX model with high HER2 expression. DS-8201a, but not T-DM1, demonstrated antitumor efficacy against several breast cancer PDX models with low HER2 expression. DS-8201a exhibited a potent antitumor activity in a broad selection of HER2-positive models and favorable pharmacokinetics and safety profiles. The results demonstrate that DS-8201a will be a valuable therapy with a great potential to respond to T-DM1-insensitive HER2-positive cancers and low HER2-expressing cancers. Clin Cancer Res; 22(20); 5097-108. ©2016 AACR. ©2016 American Association for Cancer Research.

A Rosa canina - Urtica dioica - Harpagophytum procumbens/zeyheri Combination Significantly Reduces Gonarthritis Symptoms in a Randomized, Placebo-Controlled Double-Blind Study.

PubMed

Moré, Margret; Gruenwald, Joerg; Pohl, Ute; Uebelhack, Ralf

2017-12-01

The special formulation MA212 (Rosaxan) is composed of rosehip ( Rosa canina L.) puree/juice concentrate, nettle ( Urtica dioica L.) leaf extract, and devil's claw ( Harpagophytum procumbens DC. ex Meisn. or Harpagophytum zeyheri Decne.) root extract and also supplies vitamin D. It is a food for special medical purposes ([EU] No 609/2013) for the dietary management of pain in patients with gonarthritis.This 12-week randomized, placebo-controlled double-blind parallel-design study aimed to investigate the efficacy and safety of MA212 versus placebo in patients with gonarthritis.A 3D-HPLC-fingerprint (3-dimensional high pressure liquid chromatography fingerprint) of MA212 demonstrated the presence of its herbal ingredients. Ninety-two randomized patients consumed 40 mL of MA212 (n = 46) or placebo (n = 44) daily. The Western Ontario and McMaster Universities Arthritis Index (WOMAC), quality-of-life scores at 0, 6, and 12 weeks, and analgesic consumption were documented. Statistically, the initial WOMAC subscores/scores did not differ between groups. During the study, their means significantly improved in both groups. The mean pre-post change of the WOMAC pain score (primary endpoint) was 29.87 in the MA212 group and 10.23 in the placebo group. The group difference demonstrated a significant superiority in favor of MA212 (p U  < 0.001; p t  < 0.001). Group comparisons of all WOMAC subscores/scores at 6 and 12 weeks reached same significances. Compared to placebo, both physical and mental quality of life significantly improved with MA212. There was a trend towards reduced analgesics consumption with MA212, compared to placebo. In the final efficacy evaluation, physicians (p Chi  < 0.001) and patients (p Chi  < 0.001) rated MA212 superior to placebo. MA212 was well tolerated.This study demonstrates excellent efficacy for MA212 in gonarthritis patients. Georg Thieme Verlag KG Stuttgart · New York.

Effect of rhBMP-2 on tibial plateau fractures in a canine model.

PubMed

Schaefer, Susan L; Lu, Yan; Seeherman, Howard; Li, X Jian; Lopez, Mandi J; Markel, Mark D

2009-04-01

This study was to determine the efficacy of recombinant human bone morphogenetic protien-2 (rhBMP-2)/calcium phosphate matrix (CPX) paste to accelerate healing in a canine articular fracture model with associated subchondral defect. rhBMP-2/CPX (BMP), CPX alone (CPX) or autogenous bone graft (ABG) was administered to a canine articular tibial plateau osteotomy with a subchondral defect in each of 21 female dogs. The unoperated contralateral limbs served as controls. Ground reaction forces, synovial fluid, radiographic changes, mechanical testing, bone density, and histology of bone and synovium were analyzed at 6 weeks after surgery. Radiographic analysis demonstrated that the BMP and CPX groups showed improved bony healing compared to the ABG group at week 6. Histomorphometric analysis demonstrated that the BMP group had significantly increased trabecular bone volume compared to the CPX and ABG groups. Mechanical testing revealed that the BMP group had significantly greater maximum failure loads than the ABG group. Histological analysis demonstrated that the BMP group had significantly less sub-synovial inflammation than CPX group. This study demonstrated that rhBMP-2/CPX accelerated healing of articular fractures with subchondral defect compared to ABG in most of the parameters evaluated, and had less subsynovial inflammation than the CPX alone in a canine model.

[Clinical and economic evaluation of laparoscopic surgery for inguinal hernia. Return of a difficult clinical choice].

PubMed

Bataille, N

2002-06-01

In the year 2000, the ANAES (National Agency for Accreditation and Evaluation of Health Care) published a technological and economic evaluation of the laparascopic approach to the repair of inguinal hernias based principally on the analysis of randomized studies. This analysis was all the more difficult because of the heterogeneity of the studies for which end results had a very weak level of proof. Laparascopic surgical techniques for inguinal hernia repair require the systematic use of mesh prosthesis and also general anesthesia. Published results are insufficient to compare specific laparascopic techniques with each other. The efficacy of laparoscopic repair compared to open repair with regard to hernia recurrence (the principal criteria of efficacy) has not been demonstrated--mainly because longterm results are not yet available. The overall evaluation of complications is too heterogeneous to show a difference between laparascopic and open surgery. There are, however, certain complications specific to laparascopic repair which, though rare, are potentially very serious. Excellent results reported with laparascopic repair may be due more to the systematic placement of mesh than-to to the approach itself--as has been shown in studies of open repairs "with tension" and "tension free." Superiority of the laparoscopic approach for specific types of hernia (primary unilateral, bilateral, recurrent) has not been demonstrated. Open surgery costs less than laparascopic hernia repair. The evaluation to date for laparascopic inguinal hernia repair is insufficient. Controlled studies with rigorous longterm follow-up and analysis of economic impact must be performed in comparable populations of patients.

Feedback interventions and driving speed: A parametric and comparative analysis

PubMed Central

Houten, Ron Van; Nau, Paul A.

1983-01-01

Five experiments were conducted to assess the effects of several variables on the efficacy of feedback in reducing driving speed. Experiment 1 systematically varied the criterion used to define speeding, and results showed that the use of a lenient criterion (20 km/hr over the speed limit), which allowed for the posting of high percentages of drivers not speeding, was more effective in reducing speeding than the use of a stringent criterion (10 km/hr over the speed limit). In Experiment 2 an analysis revealed that posting feedback reduced speeding on a limited access highway and the effects persisted to some degree up to 6 km. Experiments 3 and 4 compared the effectiveness of an unmanned parked police vehicle (Experiment 3) and a police air patrol speeding program (Experiment 4) with the feedback sign and determined whether the presence of either of these enforcement variables could potentiate the efficacy of the sign. The results of both experiments demonstrated that although the two enforcement programs initially produced larger effects than the feedback sign, the magnitude of their effect attenuated over time. Experiment 5 compared the effectiveness of a traditional enforcement program with a warning program which included handing out a flier providing feedback on the number and types of accidents occuring on the road during the past year. This experiment demonstrated that the warning program produced a marked reduction in speeding and the traditional enforcement program did not. Furthermore, the warning program and a feedback sign together produced an even greater reduction in speeding than either alone. PMID:16795666

Efficacy of visor and helmet for blast protection assessed using a computational head model

NASA Astrophysics Data System (ADS)

Singh, D.; Cronin, D. S.

2017-11-01

Head injury resulting from blast exposure has been identified as a challenge that may be addressed, in part, through improved protective systems. Existing detailed head models validated for blast loading were applied to investigate the influence of helmet visor configuration, liner properties, and shell material stiffness. Response metrics including head acceleration and intracranial pressures (ICPs) generated in brain tissue during primary blast exposure were used to assess and compare helmet configurations. The addition of a visor was found to reduce peak head acceleration and positive ICPs. However, negative ICPs associated with a potential for injury were increased when a visor and a foam liner were present. In general, the foam liner material was found to be more significant in affecting the negative ICP response than positive ICP or acceleration. Shell stiffness was found to have relatively small effects on either metric. A strap suspension system, modeled as an air gap between the head and helmet, was more effective in reducing response metrics compared to a foam liner. In cases with a foam liner, lower-density foam offered a greater reduction of negative ICPs. The models demonstrated the "underwash" effect in cases where no foam liner was present; however, the reflected pressures generated between the helmet and head did not translate to significant ICPs in adjacent tissue, when compared to peak ICPs from initial blast wave interaction. This study demonstrated that the efficacy of head protection can be expressed in terms of load transmission pathways when assessed with a detailed computational model.

Blood Pressure Lowering and Safety Improvements With Liver Angiotensinogen Inhibition in Models of Hypertension and Kidney Injury.

PubMed

Mullick, Adam E; Yeh, Steve T; Graham, Mark J; Engelhardt, Jeffery A; Prakash, Thazha P; Crooke, Rosanne M

2017-09-01

Uncontrolled hypertension is an important contributor to cardiovascular disease. Despite the armamentarium of antihypertensive treatments, there remains a need for novel agents effective in individuals who cannot reach acceptable blood pressure levels. Inhibitors targeting the renin-angiotensin-aldosterone system (RAAS) are widely used but may not optimally inhibit RAAS and demonstrate an acceptable safety profile. Experiments were conducted to characterize a series of AGT (angiotensinogen) antisense oligonucleotides (ASOs) and compare their efficacy and tolerability to traditional RAAS blockade. AGT ASOs which target multiple systemic sites of AGT versus an N-acetylgalactosamine-conjugated AGT ASO that targets the liver were compared with captopril and losartan. Spontaneously hypertensive rats fed an 8% NaCl diet, a model of malignant hypertension resistant to standard RAAS inhibitors, demonstrated robust and durable blood pressure reductions with AGT ASO treatments, which was not observed with standard RAAS blockade. Studies in rat models of acute kidney injury produced by salt deprivation revealed kidney injury with ASO treatment that reduced kidney-expressed AGT, but not in animals treated with the N-acetylgalactosamine AGT ASO despite comparable plasma AGT reductions. Administration of either captopril or losartan also produced acute kidney injury during salt deprivation. Thus, intrarenal RAAS derived from kidney AGT, and inhibited by the standard of care, contributes to the maintenance of renal function during severe RAAS challenge. Such improvements in efficacy and tolerability by a liver-selective AGT inhibitor could be desirable in individuals not at their blood pressure goal with existing RAAS blockade. © 2017 American Heart Association, Inc.

Drug treatment effects on outcomes in heart failure with preserved ejection fraction: a systematic review and meta-analysis

PubMed Central

Zheng, Sean Lee; Chan, Fiona T; Nabeebaccus, Adam A; Shah, Ajay M; McDonagh, Theresa; Okonko, Darlington O; Ayis, Salma

2018-01-01

Background Clinical drug trials in patients with heart failure and preserved ejection fraction have failed to demonstrate improvements in mortality. Methods We systematically searched Medline, Embase and the Cochrane Central Register of Controlled Trials for randomised controlled trials (RCT) assessing pharmacological treatments in patients with heart failure with left ventricular (LV) ejection fraction≥40% from January 1996 to May 2016. The primary efficacy outcome was all-cause mortality. Secondary outcomes were cardiovascular mortality, heart failure hospitalisation, exercise capacity (6-min walk distance, exercise duration, VO2 max), quality of life and biomarkers (B-type natriuretic peptide, N-terminal pro-B-type natriuretic peptide). Random-effects models were used to estimate pooled relative risks (RR) for the binary outcomes, and weighted mean differences for continuous outcomes, with 95% CI. Results We included data from 25 RCTs comprising data for 18101 patients. All-cause mortality was reduced with beta-blocker therapy compared with placebo (RR: 0.78, 95%CI 0.65 to 0.94, p=0.008). There was no effect seen with ACE inhibitors, aldosterone receptor blockers, mineralocorticoid receptor antagonists and other drug classes, compared with placebo. Similar results were observed for cardiovascular mortality. No single drug class reduced heart failure hospitalisation compared with placebo. Conclusion The efficacy of treatments in patients with heart failure and an LV ejection fraction≥40% differ depending on the type of therapy, with beta-blockers demonstrating reductions in all-cause and cardiovascular mortality. Further trials are warranted to confirm treatment effects of beta-blockers in this patient group. PMID:28780577

Rational development of an attenuated recombinant cyprinid herpesvirus 3 vaccine using prokaryotic mutagenesis and in vivo bioluminescent imaging.

PubMed

Boutier, Maxime; Ronsmans, Maygane; Ouyang, Ping; Fournier, Guillaume; Reschner, Anca; Rakus, Krzysztof; Wilkie, Gavin S; Farnir, Frédéric; Bayrou, Calixte; Lieffrig, François; Li, Hong; Desmecht, Daniel; Davison, Andrew J; Vanderplasschen, Alain

2015-02-01

Cyprinid herpesvirus 3 (CyHV 3) is causing severe economic losses worldwide in common and koi carp industries, and a safe and efficacious attenuated vaccine compatible with mass vaccination is needed. We produced single deleted recombinants using prokaryotic mutagenesis. When producing a recombinant lacking open reading frame 134 (ORF134), we unexpectedly obtained a clone with additional deletion of ORF56 and ORF57. This triple deleted recombinant replicated efficiently in vitro and expressed an in vivo safety/efficacy profile compatible with use as an attenuated vaccine. To determine the role of the double ORF56-57 deletion in the phenotype and to improve further the quality of the vaccine candidate, a series of deleted recombinants was produced and tested in vivo. These experiments led to the selection of a double deleted recombinant lacking ORF56 and ORF57 as a vaccine candidate. The safety and efficacy of this strain were studied using an in vivo bioluminescent imaging system (IVIS), qPCR, and histopathological examination, which demonstrated that it enters fish via skin infection similar to the wild type strain. However, compared to the parental wild type strain, the vaccine candidate replicated at lower levels and spread less efficiently to secondary sites of infection. Transmission experiments allowing water contamination with or without additional physical contact between fish demonstrated that the vaccine candidate has a reduced ability to spread from vaccinated fish to naïve sentinel cohabitants. Finally, IVIS analyses demonstrated that the vaccine candidate induces a protective mucosal immune response at the portal of entry. Thus, the present study is the first to report the rational development of a recombinant attenuated vaccine against CyHV 3 for mass vaccination of carp. We also demonstrated the relevance of the CyHV 3 carp model for studying alloherpesvirus transmission and mucosal immunity in teleost skin.

Efficacy of flurbiprofen 8.75 mg delivered as a spray or lozenge in patients with sore throat due to upper respiratory tract infection: a randomized, non-inferiority trial in the Russian Federation

PubMed Central

Radkova, Eugenia; Burova, Natalia; Bychkova, Valeria; DeVito, Robert

2017-01-01

Objective To assess the efficacy of flurbiprofen 8.75 mg delivered as a spray or lozenge in patients with sore throat due to upper respiratory tract infection (URTI). Materials and methods This multicenter, double-blind, double-dummy, non-inferiority study randomized 440 adults with recent-onset, moderate-to-severe sore throat due to URTI to a single dose of either flurbiprofen 8.75 mg spray (n=218) or flurbiprofen 8.75 mg lozenge (n=222). The presence or absence of beta-hemolytic streptococci (A or C) was confirmed by culture tests (throat swab). The primary efficacy end point was the difference from baseline to 2 hours post-dose in sore throat pain intensity scale (STPIS pain intensity difference [PID] 2h), a validated 100 mm visual analog scale (from 0=“no pain” to 100=“severe pain”), with a non-inferiority margin of −6 mm. Secondary end points included STPIS PID at 1 hour (STPIS PID 1h) and over 2 hours (STPIS sum of sore throat pain intensity differences [SPID]0–2h) and ratings of patient satisfaction and investigator assessment of drug efficacy at 2 hours. Safety (adverse events [AEs]) was also assessed. Results Reductions in sore throat pain intensity at 2 hours (STPIS PID 2h) were similar for spray (least square mean −40.51) and lozenge (−40.10) (difference: 0.41, 95% confidence interval [95% CI] −3.20, 4.01), with non-inferiority demonstrated. Subgroup analyses showed similar efficacy (STPIS PID 2h) for patients testing positive or negative for Strep A or C. There was no significant difference between spray and lozenge in STPIS PID 1h or STPIS SPID0–2h, and patient satisfaction and investigators’ assessment of efficacy at 2 hours were similar for both groups. There were no significant differences in AEs between the two groups, with 17 drug-related events across both groups, all being mild and none being serious. Conclusion Both formulations demonstrated comparable efficacy and safety profiles and provide patients with two different treatment formats to choose from for effective symptomatic relief of sore throat, depending on their preference. PMID:28740426

Efficacy of flurbiprofen 8.75 mg delivered as a spray or lozenge in patients with sore throat due to upper respiratory tract infection: a randomized, non-inferiority trial in the Russian Federation.

PubMed

Radkova, Eugenia; Burova, Natalia; Bychkova, Valeria; DeVito, Robert

2017-01-01

To assess the efficacy of flurbiprofen 8.75 mg delivered as a spray or lozenge in patients with sore throat due to upper respiratory tract infection (URTI). This multicenter, double-blind, double-dummy, non-inferiority study randomized 440 adults with recent-onset, moderate-to-severe sore throat due to URTI to a single dose of either flurbiprofen 8.75 mg spray (n=218) or flurbiprofen 8.75 mg lozenge (n=222). The presence or absence of beta-hemolytic streptococci (A or C) was confirmed by culture tests (throat swab). The primary efficacy end point was the difference from baseline to 2 hours post-dose in sore throat pain intensity scale (STPIS pain intensity difference [PID] 2h), a validated 100 mm visual analog scale (from 0="no pain" to 100="severe pain"), with a non-inferiority margin of -6 mm. Secondary end points included STPIS PID at 1 hour (STPIS PID 1h) and over 2 hours (STPIS sum of sore throat pain intensity differences [SPID] 0-2h ) and ratings of patient satisfaction and investigator assessment of drug efficacy at 2 hours. Safety (adverse events [AEs]) was also assessed. Reductions in sore throat pain intensity at 2 hours (STPIS PID 2h) were similar for spray (least square mean -40.51) and lozenge (-40.10) (difference: 0.41, 95% confidence interval [95% CI] -3.20, 4.01), with non-inferiority demonstrated. Subgroup analyses showed similar efficacy (STPIS PID 2h) for patients testing positive or negative for Strep A or C. There was no significant difference between spray and lozenge in STPIS PID 1h or STPIS SPID 0-2h , and patient satisfaction and investigators' assessment of efficacy at 2 hours were similar for both groups. There were no significant differences in AEs between the two groups, with 17 drug-related events across both groups, all being mild and none being serious. Both formulations demonstrated comparable efficacy and safety profiles and provide patients with two different treatment formats to choose from for effective symptomatic relief of sore throat, depending on their preference.

Duloxetine in the treatment of Major Depressive Disorder: a comparison of efficacy in patients with and without melancholic features.

PubMed

Mallinckrodt, Craig H; Watkin, John G; Liu, Chaofeng; Wohlreich, Madelaine M; Raskin, Joel

2005-01-04

The most prominent feature of melancholic depression is a near-total loss of the capacity to derive pleasure from activities or other positive stimuli. Additional symptoms can include psychomotor disturbances, anorexia, excessive guilt, and early awakening from sleep. Melancholic patients may exhibit treatment responses and outcomes that differ from those of non-melancholic patients. Pooled data from double-blind, placebo-controlled studies were utilized to compare the efficacy of duloxetine in depressed patients with and without melancholic features. Efficacy data were pooled from 8 double-blind, placebo-controlled clinical trials of duloxetine. The presence of melancholic features (DSM-IV criteria) was determined using results from the Mini International Neuropsychiatric Interview (MINI). Patients (aged >or= 18 years) meeting DSM-IV criteria for major depressive disorder (MDD) received duloxetine (40-120 mg/d; melancholic, N = 759; non-melancholic, N = 379) or placebo (melancholic, N = 519; non-melancholic, N = 256) for up to 9 weeks. Efficacy measures included the 17-item Hamilton Rating Scale for Depression (HAMD17) total score, HAMD17 subscales (Maier, anxiety, retardation, sleep), the Clinical Global Impression of Severity (CGI-S) and Patient Global Impression of Improvement (PGI-I) scales, and Visual Analog Scales (VAS) for pain. In data from all 8 studies, duloxetine's advantage over placebo did not differ significantly between melancholic and non-melancholic patients (treatment-by-melancholic status interactions were not statistically significant). Duloxetine demonstrated significantly greater improvement in depressive symptom severity, compared with placebo, within both melancholic and non-melancholic cohorts (p

Creation of a computer self-efficacy measure: analysis of internal consistency, psychometric properties, and validity.

PubMed

Howard, Matt C

2014-10-01

Computer self-efficacy is an often studied construct that has been shown to be related to an array of important individual outcomes. Unfortunately, existing measures of computer self-efficacy suffer from several deficiencies, including criterion contamination, outdated wording, and/or inadequate psychometric properties. For this reason, the current article presents the creation of a new computer self-efficacy measure. In Study 1, an over-representative item list is created and subsequently reduced through exploratory factor analysis to create an initial measure, and the discriminant validity of this initial measure is tested. In Study 2, the unidimensional factor structure of the initial measure is supported through confirmatory factor analysis and further reduced into a final, 12-item measure. In Study 3, the convergent and criterion validity of the 12-item measure is tested. Overall, this three study process demonstrates that the new computer self-efficacy measure has superb psychometric properties and internal reliability, and demonstrates excellent evidence for several aspects of validity. It is hoped that the 12-item computer self-efficacy measure will be utilized in future research on computer self-efficacy, which is discussed in the current article.

Protein-Pacing Caloric-Restriction Enhances Body Composition Similarly in Obese Men and Women during Weight Loss and Sustains Efficacy during Long-Term Weight Maintenance.

PubMed

Arciero, Paul J; Edmonds, Rohan; He, Feng; Ward, Emery; Gumpricht, Eric; Mohr, Alex; Ormsbee, Michael J; Astrup, Arne

2016-07-30

Short-Term protein-pacing (P; ~6 meals/day, >30% protein/day) and caloric restriction (CR, ~25% energy deficit) improves total (TBF), abdominal (ABF) and visceral (VAT) fat loss, energy expenditure, and biomarkers compared to heart healthy (HH) recommendations (3 meals/day, 15% protein/day) in obese adults. Less is known whether obese men and women respond similarly to P-CR during weight loss (WL) and whether a modified P-CR (mP-CR) is more efficacious than a HH diet during long-term (52 week) weight maintenance (WM). The purposes of this study were to evaluate the efficacy of: (1) P-CR on TBF, ABF, resting metabolic rate (RMR), and biomarkers between obese men and women during WL (weeks 0-12); and (2) mP-CR compared to a HH diet during WM (weeks 13-64). During WL, men (n = 21) and women (n = 19) were assessed for TBF, ABF, VAT, RMR, and biomarkers at weeks 0 (pre) and 12 (post). Men and women had similar reductions (p < 0.01) in weight (10%), TBF (19%), ABF (25%), VAT (33%), glucose (7%-12%), insulin (40%), leptin (>50%) and increase in % lean body mass (9%). RMR (kcals/kg bodyweight) was unchanged and respiratory quotient decreased 9%. Twenty-four subjects (mP-CR, n = 10; HH, n = 14) completed WM. mP-CR regained significantly less body weight (6%), TBF (12%), and ABF (17%) compared to HH (p < 0.05). Our results demonstrate P-CR enhances weight loss, body composition and biomarkers, and maintains these changes for 52-weeks compared to a traditional HH diet.

Efficacy of tilmicosin phosphate (Pulmotil premix) in feed for the treatment of a clinical outbreak of Actinobacillus pleuropneumoniae infection in growing-finishing pigs.

PubMed

Hoflack, G; Maes, D; Mateusen, B; Verdonck, M; de Kruif, A

2001-11-01

A double-blind randomized clinical trial was carried out to investigate the efficacy of tilmicosin (Pulmotil premix) for the treatment of a clinical outbreak of Actinobacillus pleuropneumoniae infection in growing-finishing pigs. The effects of tilmicosin administration in the feed at 400 mg/kg and an injection therapy of clinically diseased pigs with long-acting oxytetracycline (Terramycine LA) at 20 mg/kg bodyweight were compared. Both groups, totalling 147 pigs, were compared during a medication period of 15 days and a post-medication period of 11 days by means of different clinical and performance parameters. During the medication period, the tilmicosin group showed a significant advantage with respect to the number of new disease cases (P < 0.01), and a non-significant advantage regarding the number of removed pigs (P = 0.16), the number of sick pigs that recovered (P = 0.27) and the time to recovery (P = 0.42). During the post-medication period, the pigs of the tilmicosin group showed numerical non-significant benefits (P > 0.05) with respect to the clinical parameters. During the overall study period (26 days), the average daily gain and the feed conversion ratio were both significantly (P < 0.01) better in pigs from the tilmicosin group compared with pigs from the oxytetracycline group. This study demonstrated that in-feed medication of tilmicosin at a dosage of 400 mg/kg is efficacious for the treatment of a clinical respiratory disease outbreak of A. pleuropneumoniae infection in growing-finishing pigs. Compared with oxytetracycline injection of clinically diseased pigs, the tilmicosin treatment is particularly beneficial in the prevention of new disease cases while increasing or maintaining the performance of the pigs.

Comparing neurostimulation technologies in refractory focal-onset epilepsy.

PubMed

Gooneratne, Inuka Kishara; Green, Alexander L; Dugan, Patricia; Sen, Arjune; Franzini, Angelo; Aziz, Tipu; Cheeran, Binith

2016-11-01

For patients with pharmacoresistant focal epilepsy in whom surgical resection of the epileptogenic focus fails or was not feasible in the first place, there were few therapeutic options. Increasingly, neurostimulation provides an alternative treatment strategy for these patients. Vagal nerve stimulation (VNS) is well established. Deep brain stimulation (DBS) and cortical responsive stimulation (CRS) are newer neurostimulation therapies with recently published long-term efficacy and safety data. In this literature review, we introduce these therapies to a non-specialist audience. Furthermore, we compare and contrast long-term (5-year) outcomes of newer neurostimulation techniques with the more established VNS. A search to identify all studies reporting long-term efficacy (>5 years) of VNS, CRS and DBS in patients with refractory focal/partial epilepsy was conducted using PubMed and Cochrane databases. The outcomes compared were responder rate, percentage seizure frequency reduction, seizure freedom, adverse events, neuropsychological outcome and quality of life. We identified 1 study for DBS, 1 study for CRS and 4 studies for VNS. All neurostimulation technologies showed long-term efficacy, with progressively better seizure control over time. Sustained improvement in quality of life measures was demonstrated in all modalities. Intracranial neurostimulation had a greater side effect profile compared with extracranial stimulation, though all forms of stimulation are safe. Methodological differences between the studies mean that direct comparisons are not straightforward. We have synthesised the findings of this review into a pragmatic decision tree, to guide the further management of the individual patient with pharmacoresistant focal-onset epilepsy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Protein-Pacing Caloric-Restriction Enhances Body Composition Similarly in Obese Men and Women during Weight Loss and Sustains Efficacy during Long-Term Weight Maintenance

PubMed Central

Arciero, Paul J.; Edmonds, Rohan; He, Feng; Ward, Emery; Gumpricht, Eric; Mohr, Alex; Ormsbee, Michael J.; Astrup, Arne

2016-01-01

Short-Term protein-pacing (P; ~6 meals/day, >30% protein/day) and caloric restriction (CR, ~25% energy deficit) improves total (TBF), abdominal (ABF) and visceral (VAT) fat loss, energy expenditure, and biomarkers compared to heart healthy (HH) recommendations (3 meals/day, 15% protein/day) in obese adults. Less is known whether obese men and women respond similarly to P-CR during weight loss (WL) and whether a modified P-CR (mP-CR) is more efficacious than a HH diet during long-term (52 week) weight maintenance (WM). The purposes of this study were to evaluate the efficacy of: (1) P-CR on TBF, ABF, resting metabolic rate (RMR), and biomarkers between obese men and women during WL (weeks 0–12); and (2) mP-CR compared to a HH diet during WM (weeks 13–64). During WL, men (n = 21) and women (n = 19) were assessed for TBF, ABF, VAT, RMR, and biomarkers at weeks 0 (pre) and 12 (post). Men and women had similar reductions (p < 0.01) in weight (10%), TBF (19%), ABF (25%), VAT (33%), glucose (7%–12%), insulin (40%), leptin (>50%) and increase in % lean body mass (9%). RMR (kcals/kg bodyweight) was unchanged and respiratory quotient decreased 9%. Twenty-four subjects (mP-CR, n = 10; HH, n = 14) completed WM. mP-CR regained significantly less body weight (6%), TBF (12%), and ABF (17%) compared to HH (p < 0.05). Our results demonstrate P-CR enhances weight loss, body composition and biomarkers, and maintains these changes for 52-weeks compared to a traditional HH diet. PMID:27483317

Comparing the Psychometric Properties of Two Physical Activity Self-Efficacy Instruments in Urban, Adolescent Girls: Validity, Measurement Invariance, and Reliability

PubMed Central

Voskuil, Vicki R.; Pierce, Steven J.; Robbins, Lorraine B.

2017-01-01

Aims: This study compared the psychometric properties of two self-efficacy instruments related to physical activity. Factorial validity, cross-group and longitudinal invariance, and composite reliability were examined. Methods: Secondary analysis was conducted on data from a group randomized controlled trial investigating the effect of a 17-week intervention on increasing moderate to vigorous physical activity among 5th–8th grade girls (N = 1,012). Participants completed a 6-item Physical Activity Self-Efficacy Scale (PASE) and a 7-item Self-Efficacy for Exercise Behaviors Scale (SEEB) at baseline and post-intervention. Confirmatory factor analyses for intervention and control groups were conducted with Mplus Version 7.4 using robust weighted least squares estimation. Model fit was evaluated with the chi-square index, comparative fit index, and root mean square error of approximation. Composite reliability for latent factors with ordinal indicators was computed from Mplus output using SAS 9.3. Results: Mean age of the girls was 12.2 years (SD = 0.96). One-third of the girls were obese. Girls represented a diverse sample with over 50% indicating black race and an additional 19% identifying as mixed or other race. Both instruments demonstrated configural invariance for simultaneous analysis of cross-group and longitudinal invariance based on alternative fit indices. However, simultaneous metric invariance was not met for the PASE or the SEEB instruments. Partial metric invariance for the simultaneous analysis was achieved for the PASE with one factor loading identified as non-invariant. Partial metric invariance was not met for the SEEB. Longitudinal scalar invariance was achieved for both instruments in the control group but not the intervention group. Composite reliability for the PASE ranged from 0.772 to 0.842. Reliability for the SEEB ranged from 0.719 to 0.800 indicating higher reliability for the PASE. Reliability was more stable over time in the control group for both instruments. Conclusions: Results suggest that the intervention influenced how girls responded to indicator items. Neither of the instruments achieved simultaneous metric invariance making it difficult to assess mean differences in PA self-efficacy between groups. PMID:28824487

Randomized trial of a comparison of the efficacy of TVT-O and single-incision tape TVT SECUR systems in the treatment of stress urinary incontinent women--2-year follow-up.

PubMed

Masata, Jaromir; Svabik, Kamil; Zvara, Karel; Drahoradova, Petra; El Haddad, Rachid; Hubka, Petr; Martan, Alois

2012-10-01

The aim of this study was to compare the efficacy of the use of tension-free vaginal tape obturator (TVT-O) and single-incision TVT SECUR, hammock and U approach (TVT-S, H and U), in the treatment of urodynamic stress urinary incontinence (SUI). This single-center randomized three-arm trial compared the objective and subjective efficacy and early failure rate of the TVT-O and TVT-S H and U approach by objective criteria (cough test) and subjective criteria using the International Consultation on Incontinence Questionnaire--Short Form (ICIQ-UI SF). The objective efficacy rate was defined as the number of patients with a negative cough stress test. Subjective cure was defined by no stress leakage of urine after surgery based on the evaluation of ICIQ-UI SH (when patients ticked "Never"/"Urine does not leak" in answer to question 6: When does urine leak?). Objective and subjective efficacy were evaluated using Last Failure Carried Forward analysis, i.e., final analysis also included patients with early failure. To describe outcome at different time points, the Last Observation Carried Forward method was also implemented. One hundred ninety-seven women with proven SUI were randomized into three groups--TVT-O (n = 68), TVT-S H (n = 64), and TVT-S U (n = 65). Each patient allocated to a treatment group received the planned surgery. There were no differences in each group in preoperative characteristics. Median follow-up after surgery was 2 years (SD, 0.8; range, 0.1 to 3.8 years). Of the subjects, 92.6% in the TVT-O group, 68.8% in the TVT-S H group, and 69.2% in the TVT-S U group had negative stress test (p < 0.001). Of the subjects, 85.3 % in the TVT-O group, 68.8% in the TVT-S H group, and 61.5% in the TVT-S U group were subjectively continent (p = 0.02). Our study demonstrated a significantly lower subjective and objective cure rate in the single-incision TVT group compared to the TVT-O group.

Antibacterial efficacy of the seed extracts of Melia azedarach against some hospital isolated human pathogenic bacterial strains

PubMed Central

Khan, Abdul Viqar; Ahmed, Qamar Uddin; Mir, M Ramzan; Shukla, Indu; Khan, Athar Ali

2011-01-01

Objective To investigate the antibacterial potential of the polar and non-polar extracts of the seeds of Melia azedarach (M. azedarach) L. (Meliaceae) against eighteen hospital isolated human pathogenic bacterial strains. Methods Petrol, benzene, ethyl acetate, methanol, and aqueous extracts at five different concentrations (1, 2, 5, 10 and 15 mg/mL) were evaluated. Disk diffusion method was followed to evaluate the antibacterial efficacy. Results All extracts of the seeds demonstrated significant antibacterial activity against tested pathogens. Among all extracts, ethyl acetate extract revealed the highest inhibition comparatively. The present study also favored the traditional uses reported earlier. Conclusions Results of this study strongly confirm that the seed extracts of M. azedarach could be effective antibiotics, both in controlling gram-positive and gram-negative human pathogenic infections. PMID:23569812

Elagolix, a novel, orally bioavailable GnRH antagonist under investigation for the treatment of endometriosis-related pain.

PubMed

Ezzati, Mohammad; Carr, Bruce R

2015-01-01

Suppression of estrogen production and reduction of menstrual blood flow are the mainstays of medical treatment of endometriosis-related pain and have been traditionally achieved by methods such as combined hormonal contraception, progestins and GnRH analogs, all with comparable efficacies, though different side-effect profiles. Elagolix is the frontrunner among an emerging class of GnRH antagonists, which unlike their peptide predecessors has a nonpeptide structure resulting in its oral bioavailability. Phase I and II clinical trials have demonstrated safety of elagolix and its efficacy in partial and reversible suppression of ovarian estrogen production resulting in improvements in endometriosis-related pain. Phase III clinical trials are currently underway and elagolix may become a valuable addition to the armamentarium of pharmacological agents to treat endometriosis-related pain.

How long will the traffic flow time series keep efficacious to forecast the future?

NASA Astrophysics Data System (ADS)

Yuan, PengCheng; Lin, XuXun

2017-02-01

This paper investigate how long will the historical traffic flow time series keep efficacious to forecast the future. In this frame, we collect the traffic flow time series data with different granularity at first. Then, using the modified rescaled range analysis method, we analyze the long memory property of the traffic flow time series by computing the Hurst exponent. We calculate the long-term memory cycle and test its significance. We also compare it with the maximum Lyapunov exponent method result. Our results show that both of the freeway traffic flow time series and the ground way traffic flow time series demonstrate positively correlated trend (have long-term memory property), both of their memory cycle are about 30 h. We think this study is useful for the short-term or long-term traffic flow prediction and management.

Comparison of N-terminal modifications on neurotensin(8-13) analogues correlates peptide stability but not binding affinity with in vivo efficacy.

PubMed

Orwig, Kevin S; Lassetter, McKensie R; Hadden, M Kyle; Dix, Thomas A

2009-04-09

Neurotensin(8-13) and two related analogues were used as model systems to directly compare various N-terminal peptide modifications representing both commonly used and novel capping groups. Each N-terminal modification prevented aminopeptidase cleavage but surprisingly differed in its ability to inhibit cleavage at other sites, a phenomenon attributed to long-range conformational effects. None of the capping groups were inherently detrimental to human neurotensin receptor 1 (hNTR1) binding affinity or receptor agonism. Although the most stable peptides exhibited the lowest binding affinities and were the least potent receptor agonists, they produced the largest in vivo effects. Of the parameters studied only stability significantly correlated with in vivo efficacy, demonstrating that a reduction in binding affinity at NTR1 can be countered by increased in vivo stability.

Naltrexone/bupropion for the treatment of obesity and obesity with Type 2 diabetes.

PubMed

Apovian, Caroline M

2016-03-01

Contrave(®) is a combination of naltrexone hydrochloride extended release and bupropion hydrochloride extended release for the treatment of obesity, and is used with lifestyle modification. Its safety and efficacy were assessed in four randomized, double-blind, placebo-controlled, 56-week Phase III clinical trials in 4536 adult subjects: COR-1, COR-II, COR-BMOD and COR-DM. All four studies demonstrated statistically significant and clinically meaningful weight loss following up to 52 weeks of treatment with naltrexone/bupropion compared with placebo. The average weight loss from baseline across the four studies was approximately 11-22 lbs (5-9 kg). Results show the efficacy of Contrave for weight loss, as well as significant improvements in cardiometabolic markers. This review focuses on the four studies, their outcomes and the mechanism of action of Contrave.

Final Report DOE SSL Grant (No. DE-EE0006673) Advanced Light Extraction Structure for OLED Lighting

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cooper, Gregory; Monickam, Selina

The innovation proposed in this grant is to demonstrate a novel internal light extraction (ILE) design that can maximize the energy efficiency of Organic Light Emitting Diode (OLED) lighting devices without negatively impacting the device voltage, efficacy or angular color dependences. Even though, OLEDs have unique features compared to its inorganic counterparts, LEDs, in terms of technology development and market readiness levels, it still lags LEDs by several years. The main challenges as identified in the National Research Council’s 2013 Assessment on Solid State Lighting, are the cost of the materials and the low light extraction efficacy [1]. Improving themore » light extraction will improve both the $/Klm and lm/W, two important metrics DOE uses to measure the cost effectiveness of a light source.« less

The break-even point: when medical advances are less important than improving the fidelity with which they are delivered.

PubMed

Woolf, Steven H; Johnson, Robert E

2005-01-01

Society invests billions of dollars in the development of new drugs and technologies but comparatively little in the fidelity of health care, that is, improving systems to ensure the delivery of care to all patients in need. Using mathematical arguments and a nomogram, we demonstrate that technological advances must yield dramatic, often unrealistic increases in efficacy to do more good than could be accomplished by improving fidelity. In 2 examples (the development of anti-platelet agents and statins), we show that enhanced efficacy failed to achieve the health gains that would have occurred by delivering older agents to all eligible patients. Society's huge investment in technological innovations that only modestly improve efficacy, by consuming resources needed for improved delivery of care, may cost more lives than it saves. The misalignment of priorities is driven partly by the commercial interests of industry and by the public's appetite for technological breakthroughs, but health outcomes ultimately suffer. Health, economic, and moral arguments make the case for spending less on technological advances and more on improving systems for delivering care.

Discovery of olodaterol, a novel inhaled beta2-adrenoceptor agonist with a 24 h bronchodilatory efficacy.

PubMed

Bouyssou, Thierry; Hoenke, Christoph; Rudolf, Klaus; Lustenberger, Philipp; Pestel, Sabine; Sieger, Peter; Lotz, Ralf; Heine, Claudia; Büttner, Frank H; Schnapp, Andreas; Konetzki, Ingo

2010-02-15

Compound 4p was identified from a series of 6-hydroxy-4H-benzo[1,4]oxazin-3-ones as potent agonist of the human beta2-adrenoceptor with a high beta1/beta2-selectivity. A complete reversal of acetylcholine-induced bronchoconstriction which lasted over the whole study period of 5h was demonstrated for 4p in a guinea pig in vivo model without any signs of cardiovascular effects up to 10-fold above the first dose reaching 100% bronchoprotection. The enantiomerically pure (R)-form of 4p exerted a bronchodilatory efficacy over 24 h in dogs and guinea pigs in the absence of systemic pharmacodynamic effects. Formoterol which was tested as comparator in the same in vivo models of acetylcholine-induced bronchoconstriction did not retain efficacy after 24 h. In summary, the preclinical profile of compound (R)-4p (olodaterol, also known as BI 1744 CL) suggests a potential for once-daily dosing in man accompanied with an improved safety profile. Copyright 2010 Elsevier Ltd. All rights reserved.

Field evaluation of the efficacy of Mycobacterium bovis BCG vaccine against tuberculosis in goats.

PubMed

Vidal, Enric; Arrieta-Villegas, Claudia; Grasa, Miriam; Mercader, Irene; Domingo, Mariano; Pérez de Val, Bernat

2017-08-17

Control of animal tuberculosis (TB) through vaccination has emerged as a long-term strategy to complement test and slaughter control strategy. A pilot trial under field conditions was conducted in a goat herd with high TB prevalence to assess the efficacy of the Mycobacterium bovis BCG vaccine. Twenty-three goat kids vaccinated with BCG and other 22 unvaccinated control kids were euthanized at 18 months post-vaccination. Gross pathological and histopathological examination of target tissues was performed for detection of tuberculous lesions and assessment of vaccine efficacy. Mycobacterial culture and DNA detection were used to confirm Mycobacterium caprae infection. Vaccination significantly reduced the number of animals with TB lesions compared to unvaccinated controls (35% and 77%, respectively; P < 0.01). This reduction was even higher if only extra-pulmonary infection was considered (17% and 68%, respectively; P < 0.001). This trial demonstrates that BCG vaccination of goats can significantly reduce the TB lesion rates in high disease exposure conditions, indicating that vaccination could contribute to the control of TB in domestic goats.

Crizotinib-loaded polymeric nanoparticles in lung cancer chemotherapy.

PubMed

Jiang, Zhi-Ming; Dai, Shou-Ping; Xu, Yong-Qing; Li, Tao; Xie, Jian; Li, Chong; Zhang, Zhong-Hui

2015-07-01

The study describes the development of polylactide-tocopheryl polyethylene glycol 1000 succinate (PLA-TPGS)-based nanosystem as a carrier of crizotinib (CZT) to achieve superior anticancer efficacy in lung cancer therapy. We have demonstrated that block copolymer and hydrophobic drug is capable of self-assembling into a very stable nanocarrier, with suitable properties that allow their application for cancer drug delivery. Drug release study showed a sustained release pattern as a result of entrapment in the hydrophobic core of micelles. CZT/PT NP showed a noticeable cytotoxic effect in NCIH3122 lung cancer cells in a dose-dependent manner. Furthermore, morphological imaging and Live/Dead assay revealed a superior anticancer efficacy for nanoformulations. The polymeric nanoparticle showed a predominant presence in the cytoplasmic region of cell, indicating a typical endocytosis-mediated cellular uptake. The annexin V/PI staining-based apoptosis assay showed a remarkable ~40 % apoptosis (early and late apoptosis cells) comparing to only ~25 % apoptosis by free CZT. Taken together, Vitamin E TPGS-modified PLA nanoparticles would be a potential drug delivery system to increase the chemotherapeutic efficacy of CZT in lung cancer chemotherapy.

Characterization and efficacy determination of commercially available Central American H5N2 avian influenza vaccines for poultry.

PubMed

Eggert, Dawn; Thomas, Colleen; Spackman, Erica; Pritchard, Nikki; Rojo, Francisco; Bublot, Michel; Swayne, David E

2010-06-23

A poultry vaccination program was implemented in Central America beginning in January 1995 to control both H5N2 low (LPAI) and high pathogenicity avian influenza. This study was conducted to identify seed strain composition and the efficacy of 10 commercially available H5 vaccines against challenge with H5N2 LPAI viruses isolated from Latin America in 2003. The original 1994 vaccine seed virus in commercial inactivated vaccines did not significantly reduce challenge virus shed titers. However, two seed strains of inactivated vaccines, genetically more closely related to the challenge virus, did significantly reduce titers of challenge virus shed from respiratory tract. In addition, a live recombinant fowlpox virus vaccine containing a more distantly related Eurasian lineage H5 gene insert significantly reduced respiratory shedding as compared to sham vaccinates. These results demonstrate the feasibility of identifying vaccine seed strains in commercial finished products for regulatory verification and the need for periodic challenge testing against current field strains in order to select efficacious vaccine seed strains. (c) 2010 Elsevier Ltd. All rights reserved.

Anti-IL-23 Phase II Data for Psoriasis: A Review.

PubMed

Beroukhim, Kourosh; Danesh, Melissa J; Nguyen, Catherine; Austin, Annemieke; Koo, John; Levin, Ethan

2015-10-01

Monoclonal antibodies that target both Interleukin (IL)-12 and IL-23 have shown great efficacy in the treatment of psoriasis. Recent evidence suggests that IL-23 serves a more critical role than IL-12 in the pathogenesis of psoriasis, leading to the development of monoclonal antibodies that specifically target IL-23. We reviewed the results of the phase II clinical trials for the anti-IL-23 agents tildrakizumab and guselkumab, in order to assess the efficacy and safety profile of each agent. By week 16, the proportion of patients achieving Physician Global Assessment (PGA) score of clear (0) or minimal (1) and Psoriasis Area and Severity Index (PASI 75) was above 70% among the most efficacious dosage of each agent (P < 0.001 compared to placebo for all agents). The safety profiles of the agents were similar, with the most frequently reported adverse events of nasopharyngitis, upper respiratory infections, cough, and headache. The anti-IL-23 agents demonstrated a rapid clinical improvement and favorable short-term safety profile. The results of the phase II trials support IL-23 as an essential target in psoriasis treatment.

Virtual Reality Job Interview Training for Individuals with Psychiatric Disabilities

PubMed Central

Smith, Matthew J.; Ginger, Emily J.; Wright, Michael; Wright, Katherine; Humm, Laura Boteler; Olsen, Dale; Bell, Morris D.; Fleming, Michael F.

2014-01-01

Services are available to help support existing employment for individual with psychiatric disabilities; however, there is a gap in services targeting job interview skills that can help obtain employment. We assessed the feasibility and efficacy of Virtual Reality Job Interview Training (VR-JIT) in a randomized controlled trial. Participants were randomized to VR-JIT (n=25) or treatment as usual (TAU) (n=12) groups. VR-JIT consisted of 10 hours of simulated job interviews with a virtual character and didactic online training. Participants attended 95% of lab-based training sessions and found VR-JIT easy-to-use and felt prepared for future interviews. The VR-JIT group improved their job interview role-play performance (p<0.05) and self-confidence (p<0.05) between baseline and follow-up as compared to the TAU group. VR-JIT performance scores increased over time (R-Squared=0.65). VR-JIT demonstrated initial feasibility and efficacy at improving job interview skills and self-confidence. Future research may help clarify whether this intervention is efficacious in community-based settings. PMID:25099298