Techniques for Monitoring Drug Efficacy.

PubMed

Visser, Marike

2018-05-01

The efficacy of drugs can vary greatly between species and individuals. Establishing efficacious drug doses for a species requires integration of population pharmacokinetic and pharmacodynamic data into a dose-response curve. Unfortunately, these data sets are rarely available for exotic species. The use of alternative monitoring techniques is required to determine drug efficacy and safety. This article discusses methods to integrate efficacy monitoring into clinical practice, including the use of diagnostic testing and therapeutic drug monitoring. Copyright © 2018 Elsevier Inc. All rights reserved.

Efficacy and Tolerability of an Acne Treatment Regimen with Antiaging Benefits in Adult Women

PubMed Central

Jiang, Lily I.; Hino, Peter D.; Parker, Lydia; Stephens, Thomas J.; Mccook, John

2018-01-01

Objective: The objective of this study was to assess clinical safety and efficacy of a novel acne treatment regimen in adult women. Methods: Participants in the study included an ethnically diverse group of adult women (n=24) with mild-to-moderate acne who were treated twice daily with a topical regimen (cleanser, acne cream, and rebalancing gel) for eight weeks. Following baseline assessments, subjects returned to clinic at Weeks 2, 4, and 8 for clinical assessments and self-assessment questionnaires. Results: Twenty-one of the 24 enrolled women completed the eight-week clinical trial. Statistically significant clinical improvements were seen in both acne and aging parameters over time. The product regimen was well tolerated without adverse reactions commonly seen with topical acne products. Conclusion: The regimen demonstrated efficacy and tolerability in adult women with acne and signs of skin aging. PMID:29942425

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

Investigating bang for your training buck: a randomized controlled trial comparing three methods of training clinicians in two core strategies of dialectical behavior therapy.

PubMed

Dimeff, Linda A; Harned, Melanie S; Woodcock, Eric A; Skutch, Julie M; Koerner, Kelly; Linehan, Marsha M

2015-05-01

The present study examined the efficacy of online training (OLT), instructor-led training (ILT), and a treatment manual (TM) in training mental health clinicians in two core strategies of Dialectical Behavior Therapy (DBT): chain analysis and validation. A randomized controlled trial compared OLT, ILT, and TM among clinicians naïve to DBT (N=172) who were assessed at baseline, post-training, and 30, 60, and 90 days following training. Primary outcomes included satisfaction, self-efficacy, motivation, knowledge, clinical proficiency, and clinical use. Overall, ILT outperformed OLT and TM in satisfaction, self-efficacy, and motivation, whereas OLT was the most effective method for increasing knowledge. The conditions did not differ in observer-rated clinical proficiency or self-reported clinical use, which both increased to moderate levels after training. In addition, ILT was particularly effective at improving motivation to use chain analysis, whereas OLT was particularly effective at increasing knowledge of validation strategies. These findings suggest that these types of brief, didactic trainings may be effective methods of increasing knowledge of new treatment strategies, but may not be sufficient to enable clinicians to achieve a high level of clinical use or proficiency. Additional research examining the possible advantages of matching training methods to types of treatment strategies may help to determine a tailored, more effective approach to training clinicians in empirically supported treatments. Copyright © 2015. Published by Elsevier Ltd.

Clinical oversight and the avoidance of repeat induced abortion.

PubMed

Jacovetty, Erica L; Clare, Camille A; Squire, Mary-Beatrice; Kubal, Keshar P; Liou, Sherry; Inchiosa, Mario A

2018-06-03

To evaluate the impact of patient counseling, demographics, and contraceptive methods on repeat induced abortion in women attending family planning clinics. A retrospective chart review of repeat induced abortions was performed. The analysis included patients with an initial induced abortion obtained between January 1, 2001, and March 31, 2014, at New York City Health + Hospitals/Metropolitan. The duration of involvement in the family planning program, the use of contraceptive interventions, and 18 patient factors were analyzed for their correlation with the incidence of repeat induced abortions per year of follow-up. A decreased rate of repeat induced abortions was associated with a longer duration of clinical oversight (r 2 =0.449, P<0.001), a higher contraceptive efficacy score (r=0.280, P=0.025), and a larger number of clinic visits for contraception (r=0.333, P=0.007). A continuum of contact with all of the services of a family planning clinic demonstrated a strong efficacy to limit repeat induced abortions. By determining the patient characteristics that most influence repeat induced abortion rates, providers can best choose the most efficacious method of contraception available. © 2018 International Federation of Gynecology and Obstetrics.

Comparative efficacy of golimumab, infliximab, and adalimumab for moderately to severely active ulcerative colitis: a network meta-analysis accounting for differences in trial designs.

PubMed

Thorlund, Kristian; Druyts, Eric; Toor, Kabirraaj; Mills, Edward J

2015-05-01

To conduct a network meta-analysis (NMA) to establish the comparative efficacy of infliximab, adalimumab and golimumab for the treatment of moderately to severely active ulcerative colitis (UC). A systematic literature search identified five randomized controlled trials for inclusion in the NMA. One trial assessed golimumab, two assessed infliximab and two assessed adalimumab. Outcomes included clinical response, clinical remission, mucosal healing, sustained clinical response and sustained clinical remission. Innovative methods were used to allow inclusion of the golimumab trial data given the alternative design of this trial (i.e., two-stage re-randomization). After induction, no statistically significant differences were found between golimumab and adalimumab or between golimumab and infliximab. Infliximab was statistically superior to adalimumab after induction for all outcomes and treatment ranking suggested infliximab as the superior treatment for induction. Golimumab and infliximab were associated with similar efficacy for achieving maintained clinical remission and sustained clinical remission, whereas adalimumab was not significantly better than placebo for sustained clinical remission. Golimumab and infliximab were also associated with similar efficacy for achieving maintained clinical response, sustained clinical response and mucosal healing. Finally, golimumab 50 and 100 mg was statistically superior to adalimumab for clinical response and sustained clinical response, and golimumab 100 mg was also statistically superior to adalimumab for mucosal healing. The results of our NMA suggest that infliximab was statistically superior to adalimumab after induction, and that golimumab was statistically superior to adalimumab for sustained outcomes. Golimumab and infliximab appeared comparable in efficacy.

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.

Evaluation and comparison of predictive individual-level general surrogates.

PubMed

Gabriel, Erin E; Sachs, Michael C; Halloran, M Elizabeth

2018-07-01

An intermediate response measure that accurately predicts efficacy in a new setting at the individual level could be used both for prediction and personalized medical decisions. In this article, we define a predictive individual-level general surrogate (PIGS), which is an individual-level intermediate response that can be used to accurately predict individual efficacy in a new setting. While methods for evaluating trial-level general surrogates, which are predictors of trial-level efficacy, have been developed previously, few, if any, methods have been developed to evaluate individual-level general surrogates, and no methods have formalized the use of cross-validation to quantify the expected prediction error. Our proposed method uses existing methods of individual-level surrogate evaluation within a given clinical trial setting in combination with cross-validation over a set of clinical trials to evaluate surrogate quality and to estimate the absolute prediction error that is expected in a new trial setting when using a PIGS. Simulations show that our method performs well across a variety of scenarios. We use our method to evaluate and to compare candidate individual-level general surrogates over a set of multi-national trials of a pentavalent rotavirus vaccine.

Cutting thread at flexible endoscopy.

PubMed

Gong, F; Swain, P; Kadirkamanathan, S; Hepworth, C; Laufer, J; Shelton, J; Mills, T

1996-12-01

New thread-cutting techniques were developed for use at flexible endoscopy. A guillotine was designed to follow and cut thread at the endoscope tip. A new method was developed for guiding suture cutters. Efficacy of Nd: YAG laser cutting of threads was studied. Experimental and clinical experience with thread-cutting methods is presented. A 2.4 mm diameter flexible thread-cutting guillotine was constructed featuring two lateral holes with sharp edges through which sutures to be cut are passed. Standard suture cutters were guided by backloading thread through the cutters extracorporeally. A snare cutter was constructed to retrieve objects sewn to tissue. Efficacy and speed of Nd: YAG laser in cutting twelve different threads were studied. The guillotine cut thread faster (p < 0.05) than standard suture cutters. Backloading thread shortened time taken to cut thread (p < 0.001) compared with free-hand cutting. Nd: YAG laser was ineffective in cutting uncolored threads and slower than mechanical cutters. Results of thread cutting in clinical studies using sewing machine (n = 77 cutting episodes in 21 patients), in-vivo experiments (n = 156), and postsurgical cases (n = 15 over 15 years) are presented. New thread-cutting methods are described and their efficacy demonstrated in experimental and clinical studies.

Challenges of assessing the clinical efficacy of asexual blood-stage Plasmodium falciparum malaria vaccines.

PubMed

Sheehy, Susanne H; Douglas, Alexander D; Draper, Simon J

2013-09-01

In the absence of any highly effective vaccine candidate against Plasmodium falciparum malaria, it remains imperative for the field to pursue all avenues that may lead to the successful development of such a formulation. The development of a subunit vaccine targeting the asexual blood-stage of Plasmodium falciparum malaria infection has proven particularly challenging with only limited success to date in clinical trials. However, only a fraction of potential blood-stage vaccine antigens have been evaluated as targets, and a number of new promising candidate antigen formulations and delivery platforms are approaching clinical development. It is therefore essential that reliable and sensitive methods of detecting, or ruling out, even modest efficacy of blood-stage vaccines in small clinical trials be established. In this article we evaluate the challenges facing blood-stage vaccine developers, assess the appropriateness and limitations of various in vivo approaches for efficacy assessment and suggest future directions for the field.

Intracellular studies of the nucleoside reverse transcriptase inhibitor active metabolites: a review.

PubMed

Rodriguez Orengo, J F; Santana, J; Febo, I; Diaz, C; Rodriguez, J L; Garcia, R; Font, E; Rosario, O

2000-03-01

Nucleoside reverse transcriptase inhibitors (NRTIs) plasma concentrations do not correlate with clinical efficacy or toxicity. These agents need to be phosphorylated to become active against HIV-infection. Thus, the characterization of the NRTIs intracellular metabolite pharmacological parameters will provide a better understanding that could lead to the development of more rational dose regimens in the HIV-infected population. Furthermore, intracellular measurements of NRTIs may provide a better marker with respect to clinical efficacy and toxicity than plasma concentrations. Thus, in this article we review the latest information regarding the intracellular pharmacological parameters of zidovudine (ZDV) and lamivudine (3TC) active metabolites in HIV-infected patients including the results from our recent clinical studies. We will start the discussion with ZDV and 3TC clinical efficacy, followed by systemic pharmacokinetics studies. We will then discuss the in vitro and in vivo intracellular studies with particular emphasis in the method development to measure these metabolites and we will conclude with the most current data from our clinical trials.

[Advances in studies on toxicity of aconite].

PubMed

Chen, Rong-Chang; Sun, Gui-Bo; Zhang, Qiang; Ye, Zu-Guang; Sun, Xiao-Bo

2013-04-01

Aconite has the efficacy of reviving yang for resuscitation, dispelling cold and relieving pain, which is widely used in clinic, and shows unique efficacy in treating severe diseases. However, aconite has great toxicity, with obvious cardio-toxicity and neurotoxicity. Its toxicological mechanism main shows in the effect on voltage-dependent sodium channels, release of neurotransmitters and changes in receptors, promotion of lipid peroxidation and cell apoptosis in heart, liver and other tissues. Aconite works to reduce toxicity mainly through compatibility and processing. Besides traditional processing methods, many new modern processing techniques could also help achieve the objectives of detoxification and efficacy enhancement. In order to further develop the medicinal value of aconite and reduce its side effect in clinical application, this article gives comprehensive comments on aconite's toxicity characteristics, mechanism and detoxification methods on the basis of relevant reports for aconite's toxicity and the author's experimental studies.

Towards Evidence-Based Practice in Language Intervention for Bilingual Children

ERIC Educational Resources Information Center

Thordardottir, Elin

2010-01-01

Evidence-based practice requires that clinical decisions be based on evidence from rigorously controlled research studies. At this time, very few studies have directly examined the efficacy of clinical intervention methods for bilingual children. Clinical decisions for this population cannot, therefore, be based on the strongest forms of research…

Cognitive-Behavioral Therapy to Promote Smoking Cessation among African American Smokers: A Randomized Clinical Trial

ERIC Educational Resources Information Center

Webb, Monica S.; de Ybarra, Denise Rodriguez; Baker, Elizabeth A.; Reis, Isildinha M.; Carey, Michael P.

2010-01-01

Objective: The health consequences of tobacco smoking disproportionately affect African Americans, but research on whether efficacious interventions can be generalized to this population is limited. This study examined the efficacy of group-based cognitive-behavioral therapy (CBT) for smoking cessation among African Americans. Method: Participants…

Nurses' Lived Experience of Working with Nursing Students in Clinical Wards: a Phenomenological Study

PubMed Central

Parvan, Kobra; Shahbazi, Shahla; Ebrahimi, Hossein; Valizadeh, Susan; Rahmani, Azad; Jabbarzadeh Tabrizi, Faranak; Esmaili, Fariba

2018-01-01

Introduction: Despite being aware of the importance of nurses’ role in providing clinical training to nursing students, studies show that sufficient research has not yet been conducted on the experience of clinical nurses who are engaged in training nursing students outside their normal working hours. The present study aim to describe the experience of these nurses who are training outside their routine working hours. Methods: This study was conducted using descriptive-phenomenology method. Twelve nurses was participated in this research. Data were collected using purposive sampling method and face to face interviews based on nurses’ real life experience of students’ learning in clinical settings through answering open-ended questions. Spiegel burg analysis method was used to analyze the data. Results: The result of data analysis was the derivation of four themes and eight sub-themes. Themes included "nurses as teaching sources", "changes in the balance of doing routine tasks", "professional enthusiasm", and "nurses as students' professional socialization source of inspiration". Sub-themes included "efficient education", "poor education", "support", "interference in the role," "self-efficacy development", "inner satisfaction", "positive imaging" and "being a model". Conclusion: It is necessary that academic centers plan for teaching nurses working on a contractual basis in the field of the evaluation method and various methods of teaching. The findings also suggested the development of individual self-efficacy in clinical nurses who train students. PMID:29637056

Promotion of anagen, increased hair density and reduction of hair fall in a clinical setting following identification of FGF5-inhibiting compounds via a novel 2-stage process

PubMed Central

Burg, Dominic; Yamamoto, Masakuni; Namekata, Masato; Haklani, Joseph; Koike, Koichiro; Halasz, Maria

2017-01-01

Background There are very few effective, scientifically validated treatments with known mechanisms of action for treatment of hair loss in both men and women. Fibroblast growth factor 5 (FGF5) is an important factor in the irreversible transition from anagen to catagen, and inhibition of FGF5 prolongs anagen phase and reduces hair loss. Objective We aimed to screen botanically derived molecules for FGF5 inhibitory activity in vitro and assess efficacy in a clinical setting. Methods We screened for FGF5 inhibitory efficacy via a novel 2-step in vitro pipeline consisting of an engineered FGF5 responsive cell line, followed by an activated dermal papillae (DP) cell method. Efficacy in a clinical setting was assessed in a randomized, single-blind, placebo-controlled trial against early- to mid-stage pattern hair loss in men and women. Results We observed FGF5 inhibitory activity for a number of compounds from the monoterpenoid family, many showing greater inhibitory efficacy than our previously reported crude plant extracts. Evaluation of a lead candidate in a clinical study over 112 days showed a significant improvement in anagen:telogen (AT) ratio (p = 0.002), reduced hair fall (p = 0.007) and improved visual grading (p = 0.004). Scientifically matched photography on a subgroup of randomly chosen participants highlighted significant improvement in hair density, with increases evident in all tested participants compared to baseline. Conclusion Isolates from the monoterpenoid family displayed efficacy in FGF5 inhibition in vitro. A topical formulation containing a leading isolate significantly improved AT ratio, reduced hair fall and increased apparent hair density in the tested population of men and women. PMID:28280377

[Onyx embolization for treatment of dural arteriovenous fistula: comparison of long- distance versus routine injection method].

PubMed

He, Xiao-Yan; Zhang, Guo-Zhong; Li, Ming-Zhou; Wang, Gang; Liu, Dan; Qi, Song-Tao; Li, Wei-Guang; Feng, Wen-Feng

2016-03-01

To compare the efficacy, clinical characteristics, safety, injection time and radiation exposure of Onyx embolization using a long-distance injection method and routine injection method for management of dural arteriovenous fistula (DAVF). The clinical data were retrospectively analyzed in 59 patients with DAVF treated with Onyx embolization using long-distance injection method (28 patients) and routine injection method (31 patients). The efficacy, safety, injection time and radiation exposure during Onyx embolization were compared between the two injections methods. The average radiation dose exposure to the surgeon per procedure was significantly lower in the long-distance injection group than in the routine group. The injection time (P=0.53), injection volume (P=0.78), number of supply arteries (P=0.80), Cognard types (P=0.67), and effect of embolization (P=0.88) were all similar between the two groups. Endovaseular treatment of intracranial DAVF with Onyx embolization using the long-distance injection method is feasible, safe and effective and can reduce the radiation exposure to the surgeon.

[Theory analysis and clinical application of spirit-regulating and pain-relieving acupuncture method].

PubMed

Chen, Liang; Tang, Lewei; Du, Huaibin; Zheng, Hui; Liang, Fanrong

2015-04-01

The theoretical foundation and scientific connotation of spirit-regulating and pain-relieving acupuncture method as well as its clinical application for pain are discussed. During spirit regulation, attention should be paid on regulating heart and brain, while acupoints should be selected mainly from the Heart Meridian, Pericardium Meridian and Governor Vessel. It has significant efficacy for refractory pain in clinical treatment. Spirit-regulating and pain-relieving acupuncture method is development of acupuncture treating spirit, and it is an important method for pain in clinic. Improvement on sensitization of pain center and brain function is considered as one of the mechanisms in spirit-regulating and pain-relieving acupuncture method.

Clinical Teachers' Attitudes toward the Efficacy of Evidence-Based Medicine Workshop and Self-Reported Ability in Evidence-Based Practice in Iran

ERIC Educational Resources Information Center

Kouhpayehzadeh, Jalil; Baradaran, Hamid; Arabshahi, Kamran Soltani; Knill-Jones, Robin

2006-01-01

Introduction: Evidence-based medicine (EBM) has been introduced in medical schools worldwide, but there is little known about effective methods for teaching EBM skills, particularly in developing countries. This study assesses the impact of an EBM workshop on clinical teachers' attitudes and use of EBM skills. Methods: Seventy-two clinical…

Efficacy of communication amongst staff members at plastic and reconstructive surgery section using smartphone and mobile WhatsApp.

PubMed

Wani, Shabeer Ahmad; Rabah, Sari M; Alfadil, Sara; Dewanjee, Nancy; Najmi, Yahya

2013-09-01

The objective of this study is to assess the efficacy of smartphone and its WhatsApp application as a communication method amongst the staff of plastic and reconstructive surgery section at tertiary care health facility. From January 2012 onwards, the authors used smartphones and its WhatsApp application as a communication method amongst their team for various aspects of patient management and as a tool for academic endorsements. During the period of this study, there were 116 episodes regarding patient management, which were handled, in a timely fashion by using this application. In addition opinion of rotating residents in the section was sought regarding the efficacy of this method of communication. Overall majority of residents were satisfied with this mode of communication. This new method of communication is an effective method for clinical and academic endorsements. The method is cheap and quick and easy to operate.

Recent developments in the behavioural and pharmacological enhancement of extinction of drug seeking.

PubMed

Chesworth, Rose; Corbit, Laura H

2017-01-01

One of the principal barriers to overcoming addiction is the propensity to relapse, even after months or years of abstinence. Relapse can be precipitated by cues and contexts associated with drug use; thus, decreasing the conditioned properties of these cues and contexts may assist in preventing relapse. The predictive power of drug cues and contexts can be reduced by repeatedly presenting them in the absence of the drug reinforcer, a process known as extinction. The potential of extinction to limit relapse has generated considerable interest and research over the past few decades. While pre-clinical animal models suggest extinction learning assists relapse prevention, treatment efficacy is often lacking when extinction learning principles are translated into clinical trials. Conklin and Tiffany (Addiction, 2002) suggest the lack of efficacy in clinical practice may be due to limited translation of procedures demonstrated through animal research and propose several methodological improvements to enhance extinction learning for drug addiction. This review will examine recent advances in the behavioural and pharmacological manipulation of extinction learning, based on research from pre-clinical models. In addition, the translation of pre-clinical findings-both those suggested by Conklin and Tiffany () and novel demonstrations from the past 13 years-into clinical trials and the efficacy of these methods in reducing craving and relapse, where available, will be discussed. Finally, we highlight areas where promising pre-clinical models have not yet been integrated into current clinical practice but, if applied, could improve upon existing behavioural and pharmacological methods. © 2015 Society for the Study of Addiction.

High-Level Disinfection of Otorhinolaryngology Clinical Instruments: An Evaluation of the Efficacy and Cost-effectiveness of Instrument Storage.

PubMed

Yalamanchi, Pratyusha; Yu, Jason; Chandler, Laura; Mirza, Natasha

2018-01-01

Objectives Despite increasing interest in individual instrument storage, risk of bacterial cross-contamination of otorhinolaryngology clinic instruments has not been assessed. This study is the first to determine the clinical efficacy and cost-effectiveness of standard high-level disinfection and clinic instrument storage. Methods To assess for cross-contamination, surveillance cultures of otorhinolaryngology clinic instruments subject to standard high-level disinfection and storage were obtained at the start and end of the outpatient clinical workday. Rate of microorganism recovery was compared with cultures of instruments stored in individual peel packs and control cultures of contaminated instruments. Based on historical clinic data, the direct allocation method of cost accounting was used to determine aggregate raw material cost and additional labor hours required to process and restock peel-packed instruments. Results Among 150 cultures of standard high-level disinfected and co-located clinic instruments, 3 positive bacterial cultures occurred; 100% of control cultures were positive for bacterial species ( P < .001). There was no statistical difference between surveillance cultures obtained before and after the clinic day. While there was also no significant difference in rate of contamination between peel-packed and co-located instruments, peel packing all instruments requires 6250 additional labor hours, and conservative analyses place the cost of individual semicritical instrument storage at $97,852.50 per year. Discussion With in vitro inoculation of >200 otorhinolaryngology clinic instruments, this study demonstrates that standard high-level disinfection and storage are equally efficacious to more time-consuming and expensive individual instrument storage protocols, such as peel packing, with regard to bacterial contamination. Implications for Practice Standard high-level disinfection and storage are equally effective to labor-intensive and costly individual instrument storage protocols.

Potential Usefulness of the Kampo Medicine Yokukansan, Containing Uncaria Hook, for Paediatric Emotional and Behavioural Disorders: A Case Series

PubMed Central

2013-01-01

Background. Paediatric emotional and behavioural disorders (EBD) are relatively common diseases. Although nonpharmacologic and pharmacologic treatments are utilized in these cases, it is sometimes difficult to manage the symptoms of EBD. Historically, Uncaria hook has been used for treating nighttime crying and convulsions in children. Recent clinical studies have demonstrated that the Kampo medicine Yokukansan (YKS), which contains Uncaria hook, is efficacious for behaviour disorders in Alzheimer's disease patients. Herein, we investigated the clinical efficacy and safety of YKS in a series of cases with paediatric EBD. Patients and Methods. We retrospectively reviewed all paediatric patients who sought Japanese Kampo therapy at our outpatient clinics between April 1, 2012, and April 30, 2013; we selected patients who were diagnosed with paediatric EBD and were treated with YKS. Results. After screening all candidates, 3 patients were eligible for this analysis. Their average age was 11.6 years (range 10–13 years). All 3 patients responded very well to YKS within 1 month. No drug-related adverse events were observed during the course of YKS treatment. Conclusion. Yokukansan may be efficacious for paediatric EBD. We believe these results warrant further evaluation of the clinical efficacy and safety of Yokukansan for paediatric EBD in a carefully designed, double-blind, randomized clinical study. PMID:24204394

The Evidence for Efficacy of HPV Vaccines: Investigations in Categorical Data Analysis

ERIC Educational Resources Information Center

Gibbs, Alison L.; Goossens, Emery T.

2013-01-01

Recent approval of HPV vaccines and their widespread provision to young women provide an interesting context to gain experience with the application of statistical methods in current research. We demonstrate how we have used data extracted from a meta-analysis examining the efficacy of HPV vaccines in clinical trials with students in applied…

[Clinical and neurophysiological heterogeneity of attention deficit hyperactivity disorder].

PubMed

Chutko, L S; Yakovenko, E A; Surushkina, S Yu; Anisimova, T I; Kropotov, Yu D

To determine clinical/neurophysiological characteristics of different forms of attention deficit hyperactivity disorder (ADHD) and the efficacy of treatment with cerebrolysin. Sixty children, aged 9 to 12 years, with ADHD were examined using clinical and electroencephalographic methods. Idiopathic and residual-organic forms were compared. The study shows significantly higher levels of impulsivity and hyperactivity in children with residual-organic form of the disease. There were significant differences in the amplitude component of engaging in action (P3 Go) and the amplitude of the action suppression component (P3 NOGO) in patients with different forms of ADHD. The high clinical efficacy (improvement in 70.0% of patients with idiopathic form of ADHD and 86.7% of patients with residual-organic form of the disease) was found.

Efficacy of vedolizumab as induction therapy in refractory IBD patients: Amulticenter cohort

PubMed Central

Shelton, Edward; Allegretti, Jessica R.; Stevens, Betsy; Lucci, Matthew; Khalili, Hamed; Nguyen, Deanna D.; Sauk, Jenny; Giallourakis, Cosmas; Garber, John; Hamilton, Matthew J; Tomczak, Michal; Makrauer, Fredrick; Burakoff, Robert B; Levine, Jonathan; de Silva, Punyaganie; Friedman, Sonia; Ananthakrishnan, Ashwin; Korzenik, Joshua R.; Yajnik, Vijay

2015-01-01

Background Vedolizumab (VDZ) demonstrated efficacy in Crohn's disease (CD) and ulcerative colitis (UC) in the GEMINI trials. Our aim was to evaluate the efficacy of VDZ at week 14 in inflammatory bowel disease (IBD) in a multicenter cohort of patients. Methods Patients at Massachusetts General Hospital and Brigham and Women's Hospital were considered for inclusion. VDZ (300mg) was administered at weeks 0, 2, 6 and 14. Efficacy was assessed using the Harvey Bradshaw index (HBI) for CD, the simple clinical colitis activity index (SCCAI) for UC and physician assessment, along with C-reactive protein (CRP) and decrease of corticosteroid therapy. Clinical response was defined as decrease in HBI ≥ 3 and SCCAI ≥ 3 and remission as HBI ≤ 4, SCCAI ≤ 2 and physician assessment of response and remission. Results Our study included 172 patients (107 CD, 59 UC, 6 IBD-U, male 48.3%, mean age 40 years and disease duration 14 years). Fourteen patients had an ostomy and 9 an ileoanal pouch and only 35.5% fulfilled eligibility for the GEMINI trials. Previous treatment failures with ≥ 2 anti-TNFs occurred in 70.9%, one-third were on an immunomodulator and 46% systemic steroids at baseline. In CD, 48.9% and 23.9% and in UC, 53.9% and 29.3% had clinical response and clinical remission at week 14. Adverse events occurred in 10.5%. Conclusions VDZ is safe and well tolerated in refractory IBD patients in a clinical practice with efficacy in UC and CD with responses similar to what was seen in clinical trials. PMID:26288002

State-of-the-Science of Patient Navigation as a Strategy for Enhancing Minority Clinical Trial Accrual

PubMed Central

Ghebre, Rahel G.; Jones, Lovell A.; Wenzel, Jennifer; Martin, Michelle Y.; Durant, Raegan; Ford, Jean G.

2014-01-01

Background Patient navigation programs are emerging, that aim to address disparities in clinical trial participation among medically underserved populations, including racial/ethnic minorities. However, there is a lack of consensus on the role of patient navigators within the clinical trial process, as well as outcome measures to evaluate program effectiveness. Methods A review of the literature was conducted of PubMed, Medline, CINHAL, and other sources to identify qualitative and quantitative studies on patient navigation in clinical trials. The search yielded 212 studies, of which only 12 were eligible for this review. Results The eligible studies reported on development of programs for patient navigation in cancer clinical trials, including training and implementation among African American, American Indian and Native Hawaiians. Low clinical trial refusal, 4% to 6%, was reported among patients enrolled in patient navigation program. However, few studies reported on the efficacy of patient navigation on increasing clinical treatment trial enrollment. Conclusion Outcome measures are proposed to assist in developing and evaluating the efficacy and/or effectiveness of patient navigation programs that aim to increase participation in cancer clinical trials. Future research is needed to evaluate the efficacy of patient navigators in addressing barriers to clinical trial participation and increasing enrollment among medically underserved cancer patients. PMID:24643650

Human tumor xenografts in mouse as a model for evaluating therapeutic efficacy of monoclonal antibodies or antibody-drug conjugate targeting receptor tyrosine kinases.

PubMed

Feng, Liang; Wang, Wei; Yao, Hang-Ping; Zhou, Jianwei; Zhang, Ruiwen; Wang, Ming-Hai

2015-01-01

Targeting receptor tyrosine kinases by therapeutic monoclonal antibodies and antibody-drug conjugates has met with tremendous success in clinical oncology. Currently, numerous therapeutic monoclonal antibodies are under preclinical development. The potential for moving candidate antibodies into clinical trials relies heavily on therapeutic efficacy validated by human tumor xenografts in mice. Here we describe methods used to determine therapeutic efficacy of monoclonal antibodies or antibody-drug conjugates specific to human receptor tyrosine kinase using human tumor xenografts in mice as the model. The end point of the study is to determine whether treatment of tumor-bearing mice with a monoclonal antibody or antibody-drug conjugates results in significant delay of tumor growth.

[The current state and prospect of Chinese medicine gastroenterology].

PubMed

Zhang, Sheng-Sheng; Zhou, Tao

2012-03-01

The progress and existent problems of Chinese medicine (CM) gastroenterology since the National Eleventh Five-Year Plan were discussed in this article in terms of theory innovation, formulation of clinical pathway and diagnosis-treatment consensus, efficacy assessment, formulation of efficacy assessment scale, advantage diseases, and exploration of the syndrome standardization, progress in science research, academic exchange, and the construction of study platform, and so on. Meanwhile, the development of CM gastroenterology was prospected in the following five aspects: to enhance the theory inheritance and innovation, the construction of discipline standardization; to establish scientific clinical efficacy assessment methods and the standard system; to expend treatment technologies and feature therapies; and to clarify the modern scientific connotation of CM theory and treatment.

The Zombie Plot: A Simple Graphic Method for Visualizing the Efficacy of a Diagnostic Test.

PubMed

Richardson, Michael L

2016-08-09

One of the most important jobs of a radiologist is to pick the most appropriate imaging test for a particular clinical situation. Making a proper selection sometimes requires statistical analysis. The objective of this article is to introduce a simple graphic technique, an ROC plot that has been divided into zones of mostly bad imaging efficacy (ZOMBIE, hereafter referred to as the "zombie plot"), that transforms information about imaging efficacy from the numeric domain into the visual domain. The numeric rationale for the use of zombie plots is given, as are several examples of the clinical use of these plots. Two online calculators are described that simplify the process of producing a zombie plot.

Efficacy and safety of ethynodiol diacetate, 1 mg, with ethinyl estradiol, 35 micrograms, with an emphasis on contraceptive efficacy. A phase IV trial.

PubMed

Friedman, A J; Wheeler, J

1991-04-01

A phase IV trial evaluated the efficacy and safety of a monophasic oral contraceptive formulation, ethynodiol diacetate, 1 mg, plus ethinyl estradiol, 35 micrograms (EDA 1 mg with EE 35 micrograms) (Demulen 1/35). Nine hundred eighty-three community-based obstetrician-gynecologists treated a total of 7,759 patients with EDA 1 mg with EE 35 micrograms for one to eight months. Clinical evaluation forms on 6,382 patients were amenable to analysis for safety (including breakthrough bleeding, ovarian cyst formation and complexion changes); 5,412 patients were evaluable for efficacy (prevention of pregnancy), with a total of 21,440 cycles recorded. The study results were interpreted in terms of the impact on clinical management of oral contraceptive users and the methods, strengths and weaknesses of phase IV trials, particularly as they relate to confirmation of the results reported here.

The art and science of choosing efficacy endpoints for rare disease clinical trials.

PubMed

Cox, Gerald F

2018-04-01

An important challenge in rare disease clinical trials is to demonstrate a clinically meaningful and statistically significant response to treatment. Selecting the most appropriate and sensitive efficacy endpoints for a treatment trial is part art and part science. The types of endpoints should align with the stage of development (e.g., proof of concept vs. confirmation of clinical efficacy). The patient characteristics and disease stage should reflect the treatment goal of improving disease manifestations or preventing disease progression. For rare diseases, regulatory approval requires demonstration of clinical benefit, defined as how a patient, feels, functions, or survives, in at least one adequate and well-controlled pivotal study conducted according to Good Clinical Practice. In some cases, full regulatory approval can occur using a validated surrogate biomarker, while accelerated, or provisional, approval can occur using a biomarker that is likely to predict clinical benefit. Rare disease studies are small by necessity and require the use of endpoints with large effect sizes to demonstrate statistical significance. Understanding the quantitative factors that determine effect size and its impact on powering the study with an adequate sample size is key to the successful choice of endpoints. Interpreting the clinical meaningfulness of an observed change in an efficacy endpoint can be justified by statistical methods, regulatory precedence, and clinical context. Heterogeneous diseases that affect multiple organ systems may be better accommodated by endpoints that assess mean change across multiple endpoints within the same patient rather than mean change in an individual endpoint across all patients. © 2018 Wiley Periodicals, Inc.

[Acupuncture for aphasia: a retrospective analysis of clinical literature].

PubMed

Tan, Jie; Zhang, Hong; Han, Guodong; Ai, Kun; Deng, Shifeng

2016-04-01

With the Meta-analysis method, the clinical efficacy of acupuncture and other regular methods for aphasia was evaluated, and the acupoints selection for aphasia was explored. The acupuncture literature of clinical randomized control trials for aphasia published in CNKI, WANFANG, VIP and CBM database was searched; the statistical analysis of clinical efficacy of acupuncture and other regular methods for aphasia was performed by using software Revman 5. 2 provided by Cochrane library. A file of Microsoft Excel was established to perform the analysis of acupoints selection based on frequency analysis method, so as to summarize the characteristics and rules. Totally 385 articles were searched, and 37 articles those met the inclusive criteria was included, involving 1,260 patients in the acupuncture group and 1 238 patients in the control group. The Meta-analysis results showed OR = 3.82, 95% Cl [3.01, 4.85]; rhombus was located on the right side and the funnel plot was nearly symmetry, indicating the treatment effect of the acupuncture group for aphasia was superior to the control group (Z = 11.04, P < 0.000 01). The frequency-analysis results showed that the frequency of acupoints from top to bottom was Lian-quan (CV 23), Tongli (HT 5), Yamen (GV 15), Jinjin (EX-HN 12), Yuye (EX-HN 13), Baihui (GV 20), Yuyan II, Yuyan I and Yuyan III. The frequency of meridians from top to bottom was the governor vessel, extra channels, conception vessel, heart meridian and large intestine meridian. It is concluded that the clinical efficacy of acupuncture combined with speech rehabilitation training and medication treatment for aphasia is superior to that of speech rehabilitation training and medication treatment alone. The clinical treatment for aphasia focuses on its local effect; the main acupoints are in the head and face, and the meridians are governor vessel, extra channels and conception vessel.

The Relationship Between the Supervisory Working Alliance and Student Self-Efficacy in Genetic Counseling Training.

PubMed

Caldwell, Sarah; Wusik, Katie; He, Hua; Yager, Geoffrey; Atzinger, Carrie

2018-06-22

The purpose of this study was to determine if a genetic counseling student's perception of the supervisory working alliance (SWA) is related to their self-efficacy on select clinical practice-based competencies (PBCs), evaluating the second tenet of the Reciprocal Engagement Model of Supervision (REM-S) from a student perspective. Second year genetic counseling students (N = 168) completed a survey containing demographic and clinical rotation experience questions, the Supervisory Working Alliance Inventory-Trainee Form (SWAI-T), and the Genetic Counseling Self-Efficacy Scale (GCSES). Overall, the SWAI-T was significantly associated with all factors of the GCSES. Additionally, the relationship between the SWAI-T and self-efficacy was specific to those who had only one supervisor, thus highlighting the SWA may be most important under these circumstances. This serves as an important step in being able to guide supervisors toward effective methods in supervision, which may include encouraging supervisors to build a strong relationship with their supervisee in order to help strengthen the student's confidence in their clinical skills.

Clinical analysis of bronchoscopic electrocoagulation in pediatric patients

PubMed Central

Ni, Caiyun; Yu, Huafeng; Han, Xiaorong; Meng, Chen; Zhang, Yanqing

2014-01-01

This study is to explore the efficacy and safety of bronchoscopic electrocoagulation treatment for pediatric disease of poor ventilation. Seventy pediatric patients of airway stenosis and obstruction as well as pharyngeal and laryngeal cysts received bronchoscopic electrocoagulation treatment, including 15 cases of epiglottic cyst, 13 cases of cicatricial hyperplasia of fibrous tissue after trachea intubation, 5 cases of foreign body in bronchus and 37 cases of endobronchial tuberculosis. Before and after the last electrocoagulation treatment, treatment efficacy was evaluated by examining the patients’ clinical presentations and lesions in airway under bronchoscope, examining chest CT and pulmonary function, and estimating pulmonary atelectasis and ventilation function. Seventy cases of pediatric patients were treated by bronchoscopic electrocoagulation, with the total treatment number of 106 times. Among them, 66 cases were treated with marked efficacy and 4 cases were with effective treatment. There was no invalid treatment. The treatment efficacy was 100% without complications. Bronchoscopic electrocoagulation treatment is a fast, effective and safe therapeutic method in treating airway stenosis and obstruction, such as foreign body in bronchus, granulation tissue hyperplasia, and epiglottic cysts. It is worthy of being widely applied in clinic. PMID:25664086

The Group Objective Structured Clinical Experience: building communication skills in the clinical reasoning context.

PubMed

Konopasek, Lyuba; Kelly, Kevin V; Bylund, Carma L; Wenderoth, Suzanne; Storey-Johnson, Carol

2014-07-01

Students are rarely taught communication skills in the context of clinical reasoning training. The purpose of this project was to combine the teaching of communication skills using SPs with clinical reasoning exercises in a Group Objective Structured Clinical Experience (GOSCE) to study feasibility of the approach, the effect on learners' self-efficacy and attitude toward learning communication skills, and the effect of providing multiple sources of immediate, collaborative feedback. GOSCE sessions were piloted in Pediatrics and Medicine clerkships with students assessing their own performance and receiving formative feedback on communication skills from peers, standardized patients (SPs), and faculty. The sessions were evaluated using a retrospective pre/post-training questionnaire rating changes in self-efficacy and attitudes, and the value of the feedback. Results indicate a positive impact on attitudes toward learning communication skills and self-efficacy regarding communication in the clinical setting. Also, learners considered feedback by peers, SPs, and faculty valuable in each GOSCE. The GOSCE is an efficient and learner-centered method to attend to multiple goals of teaching communication skills, clinical reasoning, self-assessment, and giving feedback in a formative setting. The GOSCE is a low-resource, feasible strategy for experiential learning in communication skills and clinical reasoning. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Efficacy of Atomoxetine for the Treatment of ADHD Symptoms in Patients with Pervasive Developmental Disorders: A Prospective, Open-Label Study

ERIC Educational Resources Information Center

Fernandez-Jaen, Alberto; Fernandez-Mayoralas, Daniel Martin; Calleja-Perez, Beatriz; Munoz-Jareno, Nuria; Campos Diaz, Maria del Rosario; Lopez-Arribas, Sonia

2013-01-01

Objective: Atomoxetine's tolerance and efficacy were studied in 24 patients with pervasive developmental disorder and symptoms of ADHD. Method: Prospective, open-label, 16-week study was performed, using the variables of the Clinical Global Impression Scale and the Conners' Scale, among others. Results: A significant difference was found between…

Safety and Efficacy of ABT-089 in Pediatric Attention-Deficit/Hyperactivity Disorder: Results from Two Randomized Placebo-Controlled Clinical Trials

ERIC Educational Resources Information Center

Wilens, Timothy E.; Gault, Laura M.; Childress, Ann; Kratochvil, Christopher J.; Bensman, Lindsey; Hall, Coleen M.; Olson, Evelyn; Robieson, Weining Z.; Garimella, Tushar S.; Abi-Saab, Walid M.; Apostol, George; Saltarelli, Mario D.

2011-01-01

Objective: To assess the safety and efficacy of ABT-089, a novel alpha[subscript 4]beta[subscript 2] neuronal nicotinic receptor partial agonist, vs. placebo in children with attention-deficit/hyperactivity disorder (ADHD). Method: Two multicenter, randomized, double-blind, placebo-controlled, parallel-group studies of children 6 through 12 years…

[Thinking about vertigo effectiveness evaluation methods in clinical research of Chinese medicine].

PubMed

Liu, Hong-mei; Li, Tao

2014-10-01

Vertigo is a kind of patients' subjective feelings. The severity of vertigo is closely related to many factors. But we are short of a well accepted quantitative evaluation method capable of accurately and comprehensively evaluating vertigo in clinics. Reducing the onset of vertigo, enhancing the re- covery of equilibrium function, and improving the quality of life of vertigo patients should be taken as the focus of evaluating therapeutic effects. As for establishing a Chinese medical effectiveness evaluation system for vertigo, we believe we should distinguish different "diseases". We could roughly identify it as systemic vertigo and non-systemic vertigo. For systemic vertigo, the efficacy of vertigo could be comprehensively evaluated by UCLA vertigo questionnaire or dizziness handicap inventory combined with equilibrium function testing indices. But for non-systemic vertigo, the efficacy of vertigo could be comprehensively evaluated by taking UCLA vertigo questionnaire or dizziness handicap inventory as main efficacy indices. Secondly, we should analyze different reasons for vertigo, choose symptoms and signs in line with vertigo features as well as with Chinese medical theories, and formulate corresponding syndrome effectiveness standards according to different diseases. We should not simply take syndrome diagnosis standards as efficacy evaluation standards.

Efficacy of communication amongst staff members at plastic and reconstructive surgery section using smartphone and mobile WhatsApp

PubMed Central

Wani, Shabeer Ahmad; Rabah, Sari M.; AlFadil, Sara; Dewanjee, Nancy; Najmi, Yahya

2013-01-01

Objective: The objective of this study is to assess the efficacy of smartphone and its WhatsApp application as a communication method amongst the staff of plastic and reconstructive surgery section at tertiary care health facility. Materials and Methods: From January 2012 onwards, the authors used smartphones and its WhatsApp application as a communication method amongst their team for various aspects of patient management and as a tool for academic endorsements. Results: During the period of this study, there were 116 episodes regarding patient management, which were handled, in a timely fashion by using this application. In addition opinion of rotating residents in the section was sought regarding the efficacy of this method of communication. Overall majority of residents were satisfied with this mode of communication. Conclusions: This new method of communication is an effective method for clinical and academic endorsements. The method is cheap and quick and easy to operate. PMID:24459338

A robust two-stage design identifying the optimal biological dose for phase I/II clinical trials.

PubMed

Zang, Yong; Lee, J Jack

2017-01-15

We propose a robust two-stage design to identify the optimal biological dose for phase I/II clinical trials evaluating both toxicity and efficacy outcomes. In the first stage of dose finding, we use the Bayesian model averaging continual reassessment method to monitor the toxicity outcomes and adopt an isotonic regression method based on the efficacy outcomes to guide dose escalation. When the first stage ends, we use the Dirichlet-multinomial distribution to jointly model the toxicity and efficacy outcomes and pick the candidate doses based on a three-dimensional volume ratio. The selected candidate doses are then seamlessly advanced to the second stage for dose validation. Both toxicity and efficacy outcomes are continuously monitored so that any overly toxic and/or less efficacious dose can be dropped from the study as the trial continues. When the phase I/II trial ends, we select the optimal biological dose as the dose obtaining the minimal value of the volume ratio within the candidate set. An advantage of the proposed design is that it does not impose a monotonically increasing assumption on the shape of the dose-efficacy curve. We conduct extensive simulation studies to examine the operating characteristics of the proposed design. The simulation results show that the proposed design has desirable operating characteristics across different shapes of the underlying true dose-toxicity and dose-efficacy curves. The software to implement the proposed design is available upon request. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Management of intrathecal baclofen therapy for severe acquired brain injury: consensus and recommendations for good clinical practice.

PubMed

De Tanti, Antonio; Scarponi, Federico; Bertoni, Michele; Gasperini, Giulio; Lanzillo, Bernardo; Molteni, Franco; Posteraro, Federico; Vitale, Dino Francesco; Zanpolini, Mauro

2017-08-01

Although widespread in the treatment of generalised spasticity due to severe acquired brain injury, clinical use of intrathecal baclofen administered through an implanted catheter is not yet supported by full scientific evidence. The aim of the study is to provide recommendations for good clinical practice regarding intrathecal baclofen therapy. We used a modified RAND Delphi method to develop consensus-based medical guidelines, involving clinicians who use intrathecal baclofen therapy throughout Italy. The clinicians were asked 38 questions grouped in six areas (patient selection, contraindications for implant, tests prior to implant, method of implant and management of therapy, efficacy evaluation and goal setting, and management of complications). To establish consensus, 75% agreement was required in answers to every question. Consensus was reached on the second round of the Delphi process on 27/38 questions (71%), specifically those regarding identification of objectives, efficacy evaluation, and method of implant and management of therapy, whereas management of complications and contraindications for implant remained critical areas. Despite the limits of our method, a set of recommendations was drawn up for clinical practice in this sector. The study also revealed residual critical areas and indicated future lines of research necessary to reach evidence-based consensus.

Evaluating principal surrogate endpoints with time-to-event data accounting for time-varying treatment efficacy.

PubMed

Gabriel, Erin E; Gilbert, Peter B

2014-04-01

Principal surrogate (PS) endpoints are relatively inexpensive and easy to measure study outcomes that can be used to reliably predict treatment effects on clinical endpoints of interest. Few statistical methods for assessing the validity of potential PSs utilize time-to-event clinical endpoint information and to our knowledge none allow for the characterization of time-varying treatment effects. We introduce the time-dependent and surrogate-dependent treatment efficacy curve, ${\\mathrm {TE}}(t|s)$, and a new augmented trial design for assessing the quality of a biomarker as a PS. We propose a novel Weibull model and an estimated maximum likelihood method for estimation of the ${\\mathrm {TE}}(t|s)$ curve. We describe the operating characteristics of our methods via simulations. We analyze data from the Diabetes Control and Complications Trial, in which we find evidence of a biomarker with value as a PS.

Comparison between videotape and personal teaching as methods of communicating clinical skills to medical students.

PubMed Central

Mir, M A; Marshall, R J; Evans, R W; Hall, R; Duthie, H L

1984-01-01

The efficacy of video recording in transmitting clinical knowledge and skills to medical students was tested by recording on videotape demonstrations of physical examinations given by five clinicians to a randomly selected group of 12 students (personal group) from the first clinical year and then showing these recordings, under identical conditions, to 13 students from the same year (video group). The efficacy of both the personal and video mediums in terms of whether content was retained was tested by a questionnaire completed by all students at the end of the sessions and by a structured clinical assessment in which students were asked to demonstrate some of the same clinical tasks three weeks after the demonstration. In answering the questionnaire the video group obtained a mean (SD) score of 20.8 (7.0) (maximum possible score 40), which was not significantly different from the score achieved by the personal group (17.4 (7.7)). The video group was able to reproduce 44 (10)% of the total clinical steps demonstrated and the personal group 45 (14)%. Videotaped demonstrations can be as effective as personal teaching of clinical methods, and video should be developed as a medium for first line clinical teaching. PMID:6428655

First generation leishmaniasis vaccines: a review of field efficacy trials.

PubMed

Noazin, Sassan; Modabber, Farrokh; Khamesipour, Ali; Smith, Peter G; Moulton, Lawrence H; Nasseri, Kiumarss; Sharifi, Iraj; Khalil, Eltahir A G; Bernal, Ivan Dario Velez; Antunes, Carlos M F; Kieny, Marie Paule; Tanner, Marcel

2008-12-09

First generation candidate vaccines against leishmaniasis, prepared using inactivated whole parasites as their main ingredient, were considered as promising because of their relative ease of production and low cost. These vaccines have been the subject of many investigations over several decades and are the only leishmaniasis vaccine candidates which have undergone phase 3 clinical trial evaluation. Although the studies demonstrated the safety of the vaccines and several studies showed reasonable immunogenicity and some indication of protection, an efficacious prophylactic vaccine is yet to be identified. Despite this overall failure, these trials contributed significantly to increasing knowledge on human leishmaniasis immunology. To provide a collective view, this review discusses the methods and findings of field efficacy trials of first generation leishmaniasis vaccine clinical trials conducted in the Old and New Worlds.

Connecting drug delivery reality to smart materials design.

PubMed

Grainger, David W

2013-09-15

Inflated claims to both design and mechanistic novelty in drug delivery and imaging systems, including most nanotechnologies, are not supported by the generally poor translation of these systems to clinical efficacy. The "form begets function" design paradigm is seductive but perhaps over-simplistic in translation to pharmaceutical efficacy. Most innovations show few clinically important distinctions in their therapeutic benefits in relevant preclinical disease and delivery models, despite frequent claims to the contrary. Long-standing challenges in drug delivery issues must enlist more realistic, back-to-basics approaches to address fundamental materials properties in complex biological systems, preclinical test beds, and analytical methods to more reliably determine fundamental pharmaceutical figures of merit, including drug carrier purity and batch-batch variability, agent biodistribution, therapeutic index (safety), and efficacy. Copyright © 2013 Elsevier B.V. All rights reserved.

Microbicide safety/efficacy studies in animals: macaques and small animal models.

PubMed

Veazey, Ronald S

2008-09-01

A number of microbicide candidates have failed to prevent HIV transmission in human clinical trials, and there is uncertainty as to how many additional trials can be supported by the field. Regardless, there are far too many microbicide candidates in development, and a logical and consistent method for screening and selecting candidates for human clinical trials is desperately needed. The unique host and cell specificity of HIV, however, provides challenges for microbicide safety and efficacy screening, that can only be addressed by rigorous testing in relevant laboratory animal models. A number of laboratory animal model systems ranging from rodents to nonhuman primates, and single versus multiple dose challenges have recently been developed to test microbicide candidates. These models have shed light on both the safety and efficacy of candidate microbicides as well as the early mechanisms involved in transmission. This article summarizes the major advantages and disadvantages of the relevant animal models for microbicide safety and efficacy testing. Currently, nonhuman primates are the only relevant and effective laboratory model for screening microbicide candidates. Given the consistent failures of prior strategies, it is now clear that rigorous safety and efficacy testing in nonhuman primates should be a prerequisite for advancing additional microbicide candidates to human clinical trials.

Microbicide Safety/Efficacy studies in animals -macaques and small animal models

PubMed Central

Veazey, Ronald S.

2009-01-01

Purpose of review A number of microbicide candidates have failed to prevent HIV transmission in human clinical trials, and there is uncertainty as to how many additional trials can be supported by the field. Regardless, there are far too many microbicide candidates in development, and a logical and consistent method for screening and selecting candidates for human clinical trials is desperately needed. However, the unique host and cell specificity of HIV provides challenges for microbicide safety and efficacy screening, that can only be addressed by rigorous testing in relevant laboratory animal models. Recent findings A number of laboratory animal model systems ranging from rodents to nonhuman primates, and single versus multiple dose challenges have recently been developed to test microbicide candidates. These models have shed light on both the safety and efficacy of candidate microbicides as well as the early mechanisms involved in transmission. This article summarizes the major advantages and disadvantages of the relevant animal models for microbicide safety and efficacy testing. Summary Currently, nonhuman primates are the only relevant and effective laboratory model for screening microbicide candidates. Given the consistent failures of prior strategies, it is now clear that rigorous safety and efficacy testing in nonhuman primates should be a pre-requisite for advancing additional microbicide candidates to human clinical trials. PMID:19373023

Iliotibial band friction syndrome

PubMed Central

2010-01-01

Published articles on iliotibial band friction syndrome have been reviewed. These articles cover the epidemiology, etiology, anatomy, pathology, prevention, and treatment of the condition. This article describes (1) the various etiological models that have been proposed to explain iliotibial band friction syndrome; (2) some of the imaging methods, research studies, and clinical experiences that support or call into question these various models; (3) commonly proposed treatment methods for iliotibial band friction syndrome; and (4) the rationale behind these methods and the clinical outcome studies that support their efficacy. PMID:21063495

Effect of simulation-based emergency cardiac arrest education on nursing students' self-efficacy and critical thinking skills: Roleplay versus lecture.

PubMed

Kim, Eunsook

2018-02-01

Simulation education is a learning method for improving self-efficacy and critical thinking skills. However, not much study has been done on how to use it for education on emergency cardiac arrest situations, for which a multidisciplinary team approach is required. This study investigated the effects of simulation education on nursing students' self-efficacy and critical thinking skills in emergency cardiac arrest situations. A quasi-experimental research approach with a crossover design was used to compare two types of simulation instruction methods. This study was conducted with 76 nursing students divided into two groups by order of instruction methods, in November and December 2016. Both groups of participants experienced a simulation lesson based on the same emergency scenario. Group A first completed a roleplay of an emergency cardiac arrest situation in a clinical setting, while Group B first listened to a lecture on the procedure. After ten days, Group A repeated the simulation exercise after listening to the lecture, while Group B completed the simulation exercise after the roleplay. The students' self-efficacy and critical thinking skills were measured using a questionnaire before and after each session. In the first session, self-efficacy and critical thinking skills scores increased greatly from pretest to posttest for Group A in comparison to Group B; no statistically significant difference was found between the two groups. In the second session, Group B showed a significant increase between pretest and posttest, while Group A showed no significant difference. Conducting the simulation exercise after the roleplay was a more effective teaching method than conducting it after the lecture. Moreover, having the nursing students assume various roles in realistic roleplay situations combined with simulation exercises led to a deeper understanding of clinical situations and improved their self-efficacy and critical thinking skills. Copyright © 2017 Elsevier Ltd. All rights reserved.

"Learning to Become a Family Caregiver" Efficacy of an Intervention Program for Caregivers Following Diagnosis of Dementia in a Relative

ERIC Educational Resources Information Center

Ducharme, Francine C.; Levesque, Louise L.; Lachance, Lise M.; Kergoat, Marie-Jeanne; Legault, Alain J.; Beaudet, Line M.; Zarit, Steven H.

2011-01-01

Purpose: The purpose of this experimental study was to test the efficacy of a psychoeducational individual program conceived to facilitate transition to the caregiver role following diagnosis of Alzheimer disease in a relative. Design and Methods: Caregivers were recruited in memory clinics and randomized to an experimental group (n = 62) or a…

The Relationship between Self-Efficacy for Behaviors that Promote Healthy Weight and Clinical Indicators of Adiposity in a Sample of Early Adolescents

ERIC Educational Resources Information Center

Steele, Michael M.; Daratha, Kenn B.; Bindler, Ruth C.; Power, Thomas G.

2011-01-01

Objective: Examine the relationship between self-efficacy and various measures of adiposity in a sample of teens. Methods: A total of 132 teens were selected from schools participating in an existing research study titled Teen Eating and Activity Mentoring in Schools (TEAMS). Teens completed demographic questionnaires and healthy eating-specific…

Systematic Review and Meta-Analysis of the Clinical Efficacy and Adverse Effects of Chinese Herbal Decoction for the Treatment of Gout

PubMed Central

Liu, Xiaoyu; Chen, Pinyi; Liu, Ling; Zhang, Yanqi; Wu, Yazhou; Pettigrew, Julia Christine; Cheng, Dixiang; Yi, Dong

2014-01-01

Background In East Asia, numerous reports describe the utilization of traditional Chinese herbal decoctions to treat gout. However, the reported clinical effects vary. Objectives In this study, we reviewed and analyzed a large number of randomized controlled clinical trials to systematically assess the clinical efficacy and adverse reactions of Chinese herbal decoctions for treating gout. Methods We performed a comprehensive search of databases, such as PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, Chinese biomedical literature database, et al. In addition, we manually searched the relevant meeting information in the library of the Third Military Medical University. Results Finally, 17 randomized controlled trials with a sample size of 1,402 cases met the criteria and were included in the study. The results of the meta-analysis showed that when gout had progressed to the stage of acute arthritis, there was no significant difference in clinical efficacy between Chinese herbal decoctions and traditional Western medicine, as indicated based on the following parameters: serum uric acid (standardized mean difference (SMD):0.35, 95% confidence interval (CI): 0.03 to 0.67), C reactive protein (SMD: 0.25, 95% CI: −0.18 to 0.69), erythrocyte sedimentation rate (SMD: 0.21, 95% CI: −0.02 to 0.45) and overall clinical response (relative risk (RR): 1.05, 95% CI: 1.01 to 1.10). However, the Chinese herbal decoction was significantly better than traditional Western medicine in controlling adverse drug reactions (RR: 0.06, 95% CI: 0.03 to 0.13). Conclusions Through a systematic review of the clinical efficacy and safety of Chinese herbal decoctions and traditional Western medicine for the treatment of gout, we found that Chinese herbal decoction and traditional Western medicine led to similar clinical efficacy, but the Chinese herbal decoctions were superior to Western medicine in terms of controlling adverse drug reactions. PMID:24465466

The scope for qualitative methods in research and clinical trials in dementia.

PubMed

Gibson, Grant; Timlin, Alison; Curran, Stephen; Wattis, John

2004-07-01

In the evaluation of drugs, the randomised double-blind placebo controlled trial is the 'gold standard'. This method, based on a positivist paradigm, answers questions about efficacy and side-effects of treatments that are accepted as valid, reliable and generalisable, provided the study is well designed and properly conducted. In contrast, qualitative research methodologies, originating from the social sciences, embrace a variety of approaches, including phenomenological and other paradigms. Within clinical and health services research, qualitative approaches view the world more subjectively, acknowledging that the researcher is part of what is researched, focusing on meanings and understanding of experience, rather than on what can be reduced to quantitative measures. They can develop new ideas through induction from data, rather than confirming or refuting hypotheses. Qualitative methods have improved our understanding of the experiences of people with dementia and, if used alongside clinical trials, could be used to improve the relevance of outcomes to patients, compliance and user involvement. They could also possibly generate new measures of efficacy and effectiveness in severe dementia.

Extended Safety, Immunogenicity and Efficacy of a Blood-Stage Malaria Vaccine in Malian Children: 24-Month Follow-Up of a Randomized, Double-Blinded Phase 2 Trial

PubMed Central

Laurens, Matthew B.; Thera, Mahamadou A.; Coulibaly, Drissa; Ouattara, Amed; Kone, Abdoulaye K.; Guindo, Ando B.; Traore, Karim; Traore, Idrissa; Kouriba, Bourema; Diallo, Dapa A.; Diarra, Issa; Daou, Modibo; Dolo, Amagana; Tolo, Youssouf; Sissoko, Mahamadou S.; Niangaly, Amadou; Sissoko, Mady; Takala-Harrison, Shannon; Lyke, Kirsten E.; Wu, Yukun; Blackwelder, William C.; Godeaux, Olivier; Vekemans, Johan; Dubois, Marie-Claude; Ballou, W. Ripley; Cohen, Joe; Dube, Tina; Soisson, Lorraine; Diggs, Carter L.; House, Brent; Bennett, Jason W.; Lanar, David E.; Dutta, Sheetij; Heppner, D. Gray; Plowe, Christopher V.; Doumbo, Ogobara K.

2013-01-01

Background The FMP2.1/AS02A candidate malaria vaccine was tested in a Phase 2 study in Mali. Based on results from the first eight months of follow-up, the vaccine appeared well-tolerated and immunogenic. It had no significant efficacy based on the primary endpoint, clinical malaria, but marginal efficacy against clinical malaria in secondary analyses, and high allele-specific efficacy. Extended follow-up was conducted to evaluate extended safety, immunogenicity and efficacy. Methods A randomized, double-blinded trial of safety, immunogenicity and efficacy of the candidate Plasmodium falciparum apical membrane antigen 1 (AMA1) vaccine FMP2.1/AS02A was conducted in Bandiagara, Mali. Children aged 1–6 years were randomized in a 1∶1 ratio to receive FMP2.1/AS02A or control rabies vaccine on days 0, 30 and 60. Using active and passive surveillance, clinical malaria and adverse events as well as antibodies against P. falciparum AMA1 were monitored for 24 months after the first vaccination, spanning two malaria seasons. Findings 400 children were enrolled. Serious adverse events occurred in nine participants in the FMP2.1/AS02A group and three in the control group; none was considered related to study vaccination. After two years, anti-AMA1 immune responses remained significantly higher in the FMP2.1/AS02A group than in the control group. For the entire 24-month follow-up period, vaccine efficacy was 7.6% (p = 0.51) against first clinical malaria episodes and 9.9% (p = 0.19) against all malaria episodes. For the final 16-month follow-up period, vaccine efficacy was 0.9% (p = 0.98) against all malaria episodes. Allele-specific efficacy seen in the first malaria season did not extend into the second season of follow-up. Interpretation Allele-specific vaccine efficacy was not sustained in the second malaria season, despite continued high levels of anti-AMA1 antibodies. This study presents an opportunity to evaluate correlates of partial protection against clinical malaria that waned during the second malaria season. Trial Registration Clinicaltrials.gov NCT00460525 NCT00460525 PMID:24260195

Traditional and new composite endpoints in heart failure clinical trials: facilitating comprehensive efficacy assessments and improving trial efficiency.

PubMed

Anker, Stefan D; Schroeder, Stefan; Atar, Dan; Bax, Jeroen J; Ceconi, Claudio; Cowie, Martin R; Crisp, Adam; Dominjon, Fabienne; Ford, Ian; Ghofrani, Hossein-Ardeschir; Gropper, Savion; Hindricks, Gerhard; Hlatky, Mark A; Holcomb, Richard; Honarpour, Narimon; Jukema, J Wouter; Kim, Albert M; Kunz, Michael; Lefkowitz, Martin; Le Floch, Chantal; Landmesser, Ulf; McDonagh, Theresa A; McMurray, John J; Merkely, Bela; Packer, Milton; Prasad, Krishna; Revkin, James; Rosano, Giuseppe M C; Somaratne, Ransi; Stough, Wendy Gattis; Voors, Adriaan A; Ruschitzka, Frank

2016-05-01

Composite endpoints are commonly used as the primary measure of efficacy in heart failure clinical trials to assess the overall treatment effect and to increase the efficiency of trials. Clinical trials still must enrol large numbers of patients to accrue a sufficient number of outcome events and have adequate power to draw conclusions about the efficacy and safety of new treatments for heart failure. Additionally, the societal and health system perspectives on heart failure have raised interest in ascertaining the effects of therapy on outcomes such as repeat hospitalization and the patient's burden of disease. Thus, novel methods for using composite endpoints in clinical trials (e.g. clinical status composite endpoints, recurrent event analyses) are being applied in current and planned trials. Endpoints that measure functional status or reflect the patient experience are important but used cautiously because heart failure treatments may improve function yet have adverse effects on mortality. This paper discusses the use of traditional and new composite endpoints, identifies qualities of robust composites, and outlines opportunities for future research. © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.

Assessment of Self-Efficacy and its Relationship with Frailty in the Elderly

PubMed Central

Doba, Nobutaka; Tokuda, Yasuharu; Saiki, Keiichirou; Kushiro, Toshio; Hirano, Masumi; Matsubara, Yoshihiro; Hinohara, Shigeaki

2016-01-01

Objective It has been increasingly recognized in various clinical areas that self-efficacy promotes the level of competence in patients. The validity, applicability and potential usefulness of a new, simple model for assessing self-efficacy in the elderly with special reference to frailty were investigated for improving elderly patients' accomplishments. Methods The subjects of the present study comprised 257 elderly people who were members of the New Elder Citizen Movement in Japan and their mean age was 82.3±3.8 years. Interview materials including self-efficacy questionnaires were sent to all participants in advance and all other physical examinations were performed at the Life Planning Center Clinic. Results The internal consistency and close relation among a set of items used as a measure of self-efficacy were evaluated by Cronbach's alpha index, which was 0.79. Although no age-dependent difference was identified in either sex, gender-related differences in some factors were noted. Regarding several parametric parameters, Beck's inventory alone revealed a significant relationship to self-efficacy in both sexes. Additionally, non-parametric items such as stamina, power and memory were strongly correlated with self-efficacy in both sexes. Frailty showed a significant independent relationship with self-efficacy in a multiple linear regression model analysis and using Beck's inventory, stamina, power and memory were identified to be independent factors for self-efficacy. Conclusion The simple assessment of self-efficacy described in this study may be a useful tool for successful aging of elderly people. PMID:27725537

Assessment of Self-Efficacy and its Relationship with Frailty in the Elderly.

PubMed

Doba, Nobutaka; Tokuda, Yasuharu; Saiki, Keiichirou; Kushiro, Toshio; Hirano, Masumi; Matsubara, Yoshihiro; Hinohara, Shigeaki

Objective It has been increasingly recognized in various clinical areas that self-efficacy promotes the level of competence in patients. The validity, applicability and potential usefulness of a new, simple model for assessing self-efficacy in the elderly with special reference to frailty were investigated for improving elderly patients' accomplishments. Methods The subjects of the present study comprised 257 elderly people who were members of the New Elder Citizen Movement in Japan and their mean age was 82.3±3.8 years. Interview materials including self-efficacy questionnaires were sent to all participants in advance and all other physical examinations were performed at the Life Planning Center Clinic. Results The internal consistency and close relation among a set of items used as a measure of self-efficacy were evaluated by Cronbach's alpha index, which was 0.79. Although no age-dependent difference was identified in either sex, gender-related differences in some factors were noted. Regarding several parametric parameters, Beck's inventory alone revealed a significant relationship to self-efficacy in both sexes. Additionally, non-parametric items such as stamina, power and memory were strongly correlated with self-efficacy in both sexes. Frailty showed a significant independent relationship with self-efficacy in a multiple linear regression model analysis and using Beck's inventory, stamina, power and memory were identified to be independent factors for self-efficacy. Conclusion The simple assessment of self-efficacy described in this study may be a useful tool for successful aging of elderly people.

[Evidence-based Chinese medicine：theory and practice].

PubMed

Zhang, Jun-Hua; Li, You-Ping; Zhang, Bo-Li

2018-01-01

The introduction and popularization of evidence-based medicine has opened up a new research field of clinical efficacy evaluation of traditional Chinese medicine(TCM), produced new research ideas and methods, and promoted the progress of clinical research of TCM. After about 20 years assiduous study and earnest practice, the evidence based evaluation method and technique, which conforms to the characteristics of TCM theory and practice, has been developing continuously. Evidence-based Chinese medicine (EBCM) has gradually formed and become an important branch of evidence-based medicine. The basic concept of evidence-based Chinese medicine: EBCM is an applied discipline, following the theory and methodology of evidence-based medicine, to collect, evaluate, produce, transform the evidence of effectiveness, safety and economy of TCM, to reveal the feature and regular pattern of TCM taking effect, and to guide the development of clinical guidelines, clinical pathways and health decisions. The effects and achievements of EBCM development: secondary studies mainly based on systematic review/Meta-analysis were extensively carried out; clinical efficacy studies mainly relying on randomized controlled trials grew rapidly; clinical safety evaluations based on real world study have been conducted; methodological researches mainly focused on study quality control deepened gradually; internationalization researches mainly on report specifications have got some breakthroughs; standardization researches based on treatment specification were strengthened gradually; the research team and talents with the characteristics of inter-disciplinary have been steadily increased. A number of high-quality research findings have been published at international well-known journals; the clinical efficacy and safety evidence of TCM has been increased; the level of clinical rational use of TCM has been improved; a large number of Chinese patent medicines with big market have been cultured. The future missions of EBCM mainly consist of four categories (scientific research, methodology and standard, platform construction and personnel training) with nine tasks. ①Carry out systematic reviews to systematically collect clinical trial reports of TCM and establish database of clinical evidence of TCM; ②Carry out evidence transformation research to lay the foundation for the development of clinical diagnosis and treatment guidelines, clinical pathways of TCM, and for the screening of basic drug list and medical insurance list, and for the policy-making relevant to TCM; ③Conduct researches to evaluate the advantages and effective regular patterns of TCM and form the evidence chain of TCM efficacy; ④Carry out researches for the safety evaluation of TCM, and provide evidence supporting the rational and safe use of TCM in clinical practice; ⑤Conduct researches on methodology of EBCM and provide method for developing high quality evidence; ⑥Carry out researches to develop standards and norms of TCM, and to form methods, standards, specifications and technical systems; ⑦Establish data management platform for evidence-based evaluation of TCM, and promote data sharing; ⑧Build international academic exchange platform to promote international cooperation and mutual recognition of EBCM research; ⑨Carry out education and popularization activities of evidence-based evaluation methods, and train undergraduate students, graduate students, clinical healthcare providers and practitioners of TCM. The development of EBCM, as it was, not only promoted the transformation of clinical research and decision-making mode of TCM, contributed to the modernization and internationalization of TCM, but also enriched the connotation of Evidence-based Medicine. Copyright© by the Chinese Pharmaceutical Association.

Teaching efficacy of nurses in clinical practice education: A cross-sectional study.

PubMed

Kim, Eun-Kyeung; Shin, Sujin

2017-07-01

Clinical nurses play a vital role in clinical practice education; thus, it is necessary to help clinical nurses have teaching efficacy through the development and application of systematic education programs. To identify nurses' teaching efficacy for clinical education and analyze the influencing factors of teaching efficacy. The study used a cross-sectional design. We used a convenience sample of 263 nurses from two hospitals. Teaching efficacy, general characteristics, and perception of clinical practice education were collected via self-reported questionnaires. Teaching efficacy was measured using Hwang's (2006) questionnaire, while perception of clinical practice education was measured using the Clinical Nurse Teacher Survey developed by Nishioka et al. (2014). Participants completed the questionnaire directly. The collected data were then analyzed using descriptive statistics, t-tests, ANOVAs, and multiple regression analysis with PASW Statistics 18.0. The mean total score of teaching efficacy was 72.5 (range 21-105). The leadership for students subscale had the highest score (3.56±0.59). The factors influencing teaching efficacy were length of clinical career (β=0.26, p<0.001) and perceptions of work satisfaction (β=0.20, p=.005), clinical supervisory relationship (β=0.18, p=.010), and nursing at the hospital ward (β=0.13, p=.029). Altogether, these variables explained 28% of the variance in teaching efficacy in nurses. Based on these results, nursing educators might need to develop greater confidence in their knowledge and enhance control of their teaching strategies. Nursing schools and hospitals might need to provide greater support and educational opportunities to nurse clinical practice instructors. Furthermore, constructing a system of cooperation between these colleges and educational hospitals, developing programs to enhance teaching efficacy, and identifying the clinical instructor's role are all necessary to promote clinical practice education. Copyright © 2017. Published by Elsevier Ltd.

Responsiveness of efficacy endpoints in clinical trials with over the counter analgesics for headache.

PubMed

Aicher, Bernhard; Peil, Hubertus; Peil, Barbara; Diener, Hans-Christoph

2012-10-01

To quantify and compare the responsiveness within the meaning of clinical relevance of efficacy endpoints in a clinical trial with over the counter (OTC) analgesics for headache. Efficacy endpoints and observed differences in clinical trials need to be clinically meaningful and mirror the change in the clinical status of a patient. This must be demonstrated for the specific disease indication and the particular patient population based on the application of treatments with proven efficacy. Patient's global efficacy assessment during two study phases (pre-phase and treatment phase) was used to classify patients as satisfied or non-satisfied with the efficacy of their medication. The analysis is based on 1734 patients included in the efficacy analysis of a randomized, placebo-controlled, double-blind, multi-centre parallel group trial with six treatment arms. Based on this classification and the pain intensity recorded by the patients on a 100 mm visual analogue scale, group differences by assessment categories and receiver operating characteristic (ROC) curve methods were used to quantify responsiveness of the efficacy endpoints 'time to 50% pain relief', 'time until reduction of pain intensity to 10 mm', 'weighted sum of pain intensity difference' (%SPIDweighted), 'pain intensity difference (PID) relative to baseline at 2 hours', and 'pain-free at 2 hours'. Clinically relevant differences between patients satisfied and non-satisfied with the treatment were observed for all efficacy endpoints. Patients with the highest rating of efficacy had the fastest and strongest pain relief. In comparison, patients assessing efficacy as 'less good' reached a 50% pain relief on average nearly an hour later than those scoring efficacy as at least 'good'. Simultaneously, their extent of pain relief was only half as great 2 hours after medication intake. Patients scoring efficacy as 'poor' experienced practically no pain relief within the 4 hour observation interval. ROC curve calculations confirmed an adequate responsiveness for all continuous endpoints. The following cut-off points for differentiating between satisfied and non-satisfied patients were deduced from the data in the pre- and treatment phase, respectively: 'time to 50% pain relief' 1:10 and 1:31 h:min, 'time until reduction of pain intensity to 10 mm' 2:40 and 3:00 h:min, '%SPIDweighted' 68 and 64%, 'PID at 2 hours' 35 and 35 mm. The sensitivity and specificity based on these cut-off points ranged from 70 to 79%. The binary endpoint 'pain-free at 2 hours' showed a clearly higher specificity (80 and 87%) than sensitivity (65 and 61%) in the pre- and treatment phase, respectively. When global assessment of efficacy by the patient was used as external criterion, ROC curve calculations confirmed a high responsiveness for all efficacy endpoints included in this study. Clinically relevant differences between patients satisfied and non-satisfied with the treatment were observed. The endpoint '%SPIDweighted' proved slightly but consistently superior to the other endpoints. SPID and %SPIDweighted are not easy to interpret and the time course of pain reduction is of high importance for the patients in the treatment of acute pain, including headache. The endpoint 'pain-free at 2 hours' showed the expected high specificity, but at the cost of a concurrently low sensitivity and clearly makes less use of the available information than the endpoint 'time to 50% pain reduction', which combines the highly relevant aspects of time course and extent of pain reduction. Responsiveness, the ability of an outcome measure to detect clinically important changes in a specific condition of a patient, should be added in future revisions of IHS guidelines for clinical trials in headache disorders.

Preclinical imaging methods for assessing the safety and efficacy of regenerative medicine therapies

NASA Astrophysics Data System (ADS)

Scarfe, Lauren; Brillant, Nathalie; Kumar, J. Dinesh; Ali, Noura; Alrumayh, Ahmed; Amali, Mohammed; Barbellion, Stephane; Jones, Vendula; Niemeijer, Marije; Potdevin, Sophie; Roussignol, Gautier; Vaganov, Anatoly; Barbaric, Ivana; Barrow, Michael; Burton, Neal C.; Connell, John; Dazzi, Francesco; Edsbagge, Josefina; French, Neil S.; Holder, Julie; Hutchinson, Claire; Jones, David R.; Kalber, Tammy; Lovatt, Cerys; Lythgoe, Mark F.; Patel, Sara; Patrick, P. Stephen; Piner, Jacqueline; Reinhardt, Jens; Ricci, Emanuelle; Sidaway, James; Stacey, Glyn N.; Starkey Lewis, Philip J.; Sullivan, Gareth; Taylor, Arthur; Wilm, Bettina; Poptani, Harish; Murray, Patricia; Goldring, Chris E. P.; Park, B. Kevin

2017-10-01

Regenerative medicine therapies hold enormous potential for a variety of currently incurable conditions with high unmet clinical need. Most progress in this field to date has been achieved with cell-based regenerative medicine therapies, with over a thousand clinical trials performed up to 2015. However, lack of adequate safety and efficacy data is currently limiting wider uptake of these therapies. To facilitate clinical translation, non-invasive in vivo imaging technologies that enable careful evaluation and characterisation of the administered cells and their effects on host tissues are critically required to evaluate their safety and efficacy in relevant preclinical models. This article reviews the most common imaging technologies available and how they can be applied to regenerative medicine research. We cover details of how each technology works, which cell labels are most appropriate for different applications, and the value of multi-modal imaging approaches to gain a comprehensive understanding of the responses to cell therapy in vivo.

Using Multiple Assessments to Evaluate Medical Students' Clinical Ability in Psychiatric Clerkships

ERIC Educational Resources Information Center

Wang, Peng-Wei; Cheng, Cheng-Chung; Chou, Frank Huang-Chih; Tsang, Hin-Yeung; Chang, Yu-San; Huang, Mei-Feng; Yen, Cheng-Fang

2011-01-01

Background: No single assessment method can successfully evaluate the clinical ability of medical students in psychiatric clerkships; however, few studies have examined the efficacy of multiple assessments, especially in psychiatry. The aim of this study was to examine the relationship among different types of assessments of medical students'…

Testing the Efficacy of an Education-Based Training Tool to Improve Diagnostic Accuracy of Obsessive-Compulsive Disorder

ERIC Educational Resources Information Center

Glazier, Kimberly

2014-01-01

Objective: The study aimed to increase awareness of OCD symptomatology among doctoral students in clinical, counseling and school psychology through the implementation of a comprehensive OCD education-based training tool. Method: The program directors across all APA-accredited clinical, counseling, and school psychology doctoral graduate programs…

Platelet-Rich Plasma in Bone Regeneration: Engineering the Delivery for Improved Clinical Efficacy

PubMed Central

Rodriguez, Isaac A.; Growney Kalaf, Emily A.; Bowlin, Gary L.; Sell, Scott A.

2014-01-01

Human bone is a tissue with a fairly remarkable inherent capacity for regeneration; however, this regenerative capacity has its limitations, and defects larger than a critical size lack the ability to spontaneously heal. As such, the development and clinical translation of effective bone regeneration modalities are paramount. One regenerative medicine approach that is beginning to gain momentum in the clinical setting is the use of platelet-rich plasma (PRP). PRP therapy is essentially a method for concentrating platelets and their intrinsic growth factors to stimulate and accelerate a healing response. While PRP has shown some efficacy in both in vitro and in vivo scenarios, to date its use and delivery have not been optimized for bone regeneration. Issues remain with the effective delivery of the platelet-derived growth factors to a localized site of injury, the activation and temporal release of the growth factors, and the rate of growth factor clearance. This review will briefly describe the physiological principles behind PRP use and then discuss how engineering its method of delivery may ultimately impact its ability to successfully translate to widespread clinical use. PMID:25050347

Efficacy of clinical and radiological methods to identify second mesiobuccal canals in maxillary first molars.

PubMed

Abuabara, Allan; Baratto-Filho, Flares; Aguiar Anele, Juliana; Leonardi, Denise Piotto; Sousa-Neto, Manoel Damião

2013-01-01

The success of endodontic treatment depends on the identification of all root canals. Technological advances have facilitated this process as well as the assessment of internal anatomical variations. The aim of this study was to compare the efficacy of clinical and radiological methods in locating second mesiobuccal canals (MB2) in maxillary first molars. Fifty patients referred for analysis; access and clinical analysis; cone-beam endodontic treatment of their maxillary first molars were submitted to the following assessments: analysis; access and clinical analysis; cone-beam computed tomography (CBCT); post-CBCT clinical analysis; clinical analysis using an operating microscope; and clinical analysis after Start X ultrasonic inserts in teeth with negative results in all previous analyses. Periapical radiographic analysis revealed the presence of MB2 in four (8%) teeth, clinical analysis in 25 (50%), CBCT analysis in 27 (54%) and clinical analysis following CBCT and using an operating microscope in 27 (54%) and 29 (58%) teeth, respectively. The use of Start X ultrasonic inserts allowed one to detect two additional teeth with MB2 (62%). According to Vertucci's classification 48% of the mesiobuccal canals found were type I, 28% type II, 18% type IV and 6% type V. Statistical analysis showed no significant differences (p > 0.5) in the ability of CBCT to detect MB2 canals when compared with clinical assessment with or without an operating microscope. A significant difference (p < 0.001)was found only between periapical radiography and clinical/CBCT evaluations. Combined use of different methods increased the detection ofthe second canal in MB roots, but without statistical difference among CBCT, operating microscope, Start X and clinical analysis.

A Comparative Study on the Efficacy of Solifenacin Succinate in Patients with Urinary Frequency with or without Urgency

PubMed Central

Han, Ji-Yeon; Lee, Kyu-Sung; Park, Won Hee; Park, Choal Hee; Lee, Jeong Gu; Lee, Jeong Zoo; Kim, Duk Yoon; Na, Yong Gil; Kwon, Dong Deuk; Choo, Myung-Soo

2014-01-01

Objectives Patients with overactive bladder (OAB) often have trouble perceiving urgency because of difficulties in distinguishing between urgency and desire to void. Empirical antimuscarinic treatment of patients with frequency only may be reasonable if conservative management has failed. We compared the efficacy of solifenacin in patients with frequency with or without urgency. Materials and Methods This multicenter, 12-week, open-label, comparative, non-inferiority clinical trial assessed whether the solifenacin efficacy for frequency without urgency is non-inferior to its efficacy for frequency with urgency. All patients had micturition frequency ≥8 voids/day with or without urgency. Primary efficacy variable: daily frequency change at 12 weeks relative to baseline. Secondary efficacy variables: change at 12 weeks relative to baseline in Patients' Perception of Bladder Condition (PPBC), OAB Symptom Score (OABSS), and Benefit, Satisfaction, Willingness to continue (BSW) questionnaire. Results Of the 286 enrolled patients, 240 (83.9%) completed the study (without urgency n = 115; with urgency n = 125). Full dataset analysis revealed that the groups without and with urgency exhibited significant reductions in daily micturition frequency of −2.49±0.35 (mean ± standard error) and −2.63±0.37, respectively. The lower limit of the 95% two-sided CI of the comparison of the two group means was −1.14, which is smaller than the −0.8 margin of clinical equivalence. The two groups did not differ in improvement in PPBC, OABSS, or BSW scores. Both tolerated the treatment well. Conclusions It was not possible to verify that the solifenacin efficacy for frequency alone was non-inferior to its efficacy for OAB. Nevertheless, solifenacin tended to be effective for frequency regardless of urgency. Trial Registration ClinicalTrials.gov NCT00979472 PMID:25401784

[The comparison of efficacy of female sterilization by modified Uchida technique and silver clips in China].

PubMed

Qiu, Hong-yan; Zou, Yan; Li, Li; Liang, Hong; Zhang, Hong-yan; Wu, Shang-chun

2011-02-01

To compare efficacy of female sterilization by modified Uchida technique and silver clips and to evaluate the influence on operation procedure and clinical effect with or without surgery training of service providers. A comparative, multicenter clinical trial was performed in 18 county and township-level service centers. Totally 2198 women underwent sterilization from these 18 study center were divided into 1116 women sterilized by modified Uchida technique and 1082 women by silver clips. Those 18 centers were classified into 9 training groups which provide surgical skills of sterilization and other contents and 9 non training groups. Clinical documents of sterilization were recorded. All women were follow-up at 3, 6 and 12 months after surgery. There were no complications during surgery by both sterilization. The failure rate was 2.03% (22/1082) in silver clip method and the mean operative time were (12.4 ± 6.4) minutes in training group and (14.4 ± 8.1) minutes in non training group. In modified Uchida method, the failure rate was 0.18% (2/1116) and the mean operative time were (16.2 ± 4.9) minutes in training group and (19.0 ± 8.6) minutes in non training group. The mean operative time between two groups reached statistical difference (all P < 0.05). Total ended rate in modified Uchida technique were 2.2/hundred women year in training group and 2.5/hundred women year in non training group, and the rate of silver slips were 3.9/hundred women year and 4.8/hundred women year, which did not show significant difference (all P > 0.05). There was no significant difference in acceptability and side effects of all women between two methods (P > 0.05). The training of service providers could influence acceptability of women (P < 0.05). Clinical efficacy was not influenced by those two methods. The operative time and acceptability were improved by training surgeons in silver clips method.

Efficacy and safety at 24 weeks of daily clinical use of tofacitinib in patients with rheumatoid arthritis

PubMed Central

Tsuji, Sosuke; Takatani, Ayuko; Shimizu, Toshimasa; Fukui, Shoichi; Umeda, Masataka; Nishino, Ayako; Horai, Yoshiro; Koga, Tomohiro; Kawashiri, Shin-ya; Aramaki, Toshiyuki; Ichinose, Kunihiro; Hirai, Yasuko; Tamai, Mami; Nakamura, Hideki; Terada, Kaoru; Origuchi, Tomoki; Eguchi, Katsumi; Ueki, Yukitaka; Kawakami, Atsushi

2017-01-01

Objective We evaluated the efficacy and safety of tofacitinib in patients with rheumatoid arthritis (RA) in a real-world setting. Methods Seventy consecutive patients, for whom tofacitinib was initiated between November 2013 and May 2016, were enrolled. All patients fulfilled the 2010 ACR/EULAR classification criteria for RA. All patients received 5 mg of tofacitinib twice daily and were followed for 24 weeks. Clinical disease activity indicated by disease activity score (DAS)28-ESR, the simplified disease activity index, and the clinical disease activity index as well as adverse events (AEs) were evaluated. Statistical analysis was performed to determine which baseline variables influenced the efficacy of tofacitinib at 24 weeks. Results Fifty-eight patients (82.9%) continued tofacitinib at 24 weeks. Clinical disease activity rapidly and significantly decreased, and this efficacy continued throughout the 24 weeks: i.e., DAS28-ESR decreased from 5.04 ± 1.33 at baseline to 3.83 ± 1.11 at 4 weeks and 3.53 ± 1.17 at 24 weeks (P<0.0001, vs. baseline). 15 AEs including 5 herpes zoster infection occurred during tofacitinib treatment. The efficacy of tofacitinib was not changed in patients without concomitant use of methotrexate (MTX) or patients whose treatment with tocilizumab (TCZ) failed. Multivariable logistic analysis showed that the number of biologic DMARDs (bDMARDs) previously used was independently associated with achievement of DAS-low disease activity. Conclusions Our present study suggests that tofacitinib is effective in real-world settings even without concomitant MTX use or after switching from TCZ. Our results also suggest that its efficacy diminishes if started after use of multiple bDMARDs. PMID:28472115

A consultation on the optimization of controlled human malaria infection by mosquito bite for evaluation of candidate malaria vaccines.

PubMed

Laurens, Matthew B; Duncan, Christopher J; Epstein, Judith E; Hill, Adrian V; Komisar, Jack L; Lyke, Kirsten E; Ockenhouse, Christian F; Richie, Thomas L; Roestenberg, Meta; Sauerwein, Robert W; Spring, Michele D; Talley, Angela K; Moorthy, Vasee S

2012-08-03

Early clinical investigations of candidate malaria vaccines and antimalarial medications increasingly employ an established model of controlled human malaria infection (CHMI). Study results are used to guide further clinical development of vaccines and antimalarial medications as CHMI results to date are generally predictive of efficacy in malaria-endemic areas. The urgency to rapidly develop an efficacious malaria vaccine has increased demand for efficacy studies that include CHMI and the need for comparability of study results among the different centres conducting CHMI. An initial meeting with the goal to optimize and standardise CHMI procedures was held in 2009 with follow-up meetings in March and June 2010 to harmonise methods used at different centres. The end result is a standardised document for the design and conduct of CHMI and a second document for the microscopy methods used to determine the patency endpoint. These documents will facilitate high accuracy and comparability of CHMI studies and will be revised commensurate with advances in the field. Copyright © 2012. Published by Elsevier Ltd.. All rights reserved.

The Efficacy of Acupuncture for the Treatment of Sciatica: A Systematic Review and Meta-Analysis

PubMed Central

Ji, Mei; Wang, Xiaoxia; Chen, Meijuan; Shen, Yan; Zhang, Xu; Yang, Jin

2015-01-01

Background. Sciatica is one of the most frequently reported complaints; it affects quality of life and reduces social and economic efficacy. Clinical studies on the efficacy of acupuncture therapy in sciatica are increasing, while systematic reviews assessing the efficacy of acupuncture therapy are still lacking. Objective. This study aims to assess the effectiveness of acupuncture therapy for sciatica. Methods. Comprehensive searches of 8 databases were conducted up until April 2015. Outcomes included effectiveness (proportion of patients who improved totally or partly in clinical symptoms), pain intensity, and pain threshold. Effect sizes were presented as risk ratio (RR) and mean difference (MD). Pooled effect sizes were calculated by fixed effects or random effects model. Results. A total of 12 studies (involving 1842 participants) were included. Results showed that acupuncture was more effective than conventional Western medicine (CWM) in outcomes effectiveness (RR 1.21, 95% CI: 1.16–1.25), pain intensity (MD −1.25, 95% CI: −1.63 to −0.86), and pain threshold (MD: 1.08, 95% CI: 0.98–1.17). Subgroup and sensitivity analysis found that the results did not change in different treatment method and drug categories substantially. The reported adverse effects were acceptable. Conclusions. Acupuncture may be effective in treating the pain associated with sciatica. PMID:26425130

Retrospective clinical study on the notable efficacy and related factors of infliximab therapy in a rheumatoid arthritis management group in Japan: one-year clinical outcomes (RECONFIRM-2)

PubMed Central

Takeuchi, Tsutomu; Inoue, Eisuke; Saito, Kazuyoshi; Sekiguchi, Naoya; Sato, Eri; Nawata, Masao; Kameda, Hideto; Iwata, Shigeru; Amano, Kouichi; Yamanaka, Hisashi

2008-01-01

Biologics targeting TNF have brought about a paradigm shift in the treatment of rheumatoid arthritis (RA) and infliximab, anti-TNF-α chimeric monoclonal antibody, was marketed in 2003 in Japan. We previously reported on the RECONFIRM study, a retrospective clinical study on the efficacy of infliximab therapy in a RA management group in Japan, where we evaluated the clinical response after 22 weeks of the therapy in 258 patients. The study reported here was aimed at reconfirming the clinical efficacy of the infliximab therapy and demographic factors related to the efficacy over a 54-week study period in 410 RA patients in the same study group. Infliximab was infused according to the domestically approved method, and the clinical response was evaluated following 54 weeks of infliximab therapy using the European League Against Rheumatism (EULAR) response criteria. Disease activity was assessed by DAS28-CRP (Disease Activity Score including a 28-joint count/C-reactive protein). Infliximab was discontinued in 24.4% of the 410 patients at 54 weeks and 9.3% and 8.1% discontinued the therapy due to adverse events and inefficiency, respectively. Average DAS28-CRP decreased from 5.5 at week 0 to 3.1 at week 54 after the therapy. Patients in remission and those showing low-, moderate-, and high-disease activity changed from 0.0, 1.0, 9.0 and 90.0%, respectively, at the start of the study to 27.6, 11.7, 34.4 and 26.3%, respectively, at week 54. Younger age, RF-negativity and low scores of DAS28-CRP showed significant correlations with remission at week 54. EULAR response criteria—good, moderate, and no response to infliximab—were 37.0, 41.7 and 21.2%, respectively. In conclusion, we reconfirmed the clinical efficacy of infliximab and demographic factors related to the efficacy over a 54-week study period in 410 Japanese patients with RA using DAS28-CRP and EULAR response criteria. PMID:18283523

Efficacy testing of cosmetic products. A proposal to the European Community by the Danish Environmental Protection Agency, Ministry of Environment and Energy.

PubMed

Serup, J

2001-08-01

Regulations for cosmetic products primarily address safety of the products that may be used by large populations of healthy consumers. Requirements for documentation of efficacy claims are only fragmentary. This synopsis aims to review and conclude a set of standards that may be acceptable to the European Community, and the cosmetic industry, as a legal standard for efficacy documentation in Europe in the future. Ethical, formal, experimental, statistical and other aspects of efficacy testing are described, including validation, quality control and assurance. The importance of user relevant clinical end points, a controlled randomized trial design and evidence-based cosmetic product documentation, validation of methods, statistical power estimation and proper data handling, reporting and archiving is emphasized. The main principles of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) good clinical practice (GCP) should be followed by the cosmetics industry in a spirit of good documentation standard and scientific soundness, but full GCP is not considered mandatory in the field of cosmetics. Documentation by validated bio-instrumental methods may be acceptable, but efficacy documentation based on information about raw materials, reference to literature and laboratory experiments are only acceptable in exceptional cases. Principles for efficacy substantiation of cosmetic products in Europe, as described in this synopsis, are officially proposed by the Danish Ministry of Environment and Energy to the European Community as a basis for an amendment to the Cosmetics Directive or otherwise implemented as a European Community regulation.

The first clinical experience on efficacy of topical flutamide on melasma compared with topical hydroquinone: a randomized clinical trial

PubMed Central

Adalatkhah, Hassan; Sadeghi-Bazargani, Homayoun

2015-01-01

Background Treatment of melasma is unsatisfactory most of the times. Hormonal role is shown to exist in pathogenesis of the melasma, and sex-hormone related drugs may have an effect on melasma. Aim To investigate efficacy of 1% flutamide cream versus 4% hydroquinone cream on melasma. Methods In a parallel randomized clinical trial, 74 women with melasma were allocated to receive a sunscreen along with 4% hydroquinone cream or 1% flutamide cream. Melasma Area and Severity Index (MASI), mexameter melanin assay, and patient satisfaction were investigated. Results Mean age of the participants was 33.8 years. Mean length of time suffering from Melasma was 96.3 months. The subjects reported in average 1.1 hours per day of exposure to sunlight. Mean standardized total patient satisfaction score was 28.8 (standard deviation [SD] 17.2) in flutamide group patients versus 18 (SD 15.5) in control group (P<0.01). Regardless of treatment group, the skin darkness assessed upon MASI scales was reduced over the treatment course (P<0.001). Using mixed effects, longitudinal modeling showed better treatment efficacy based on MASI scale for flutamide group compared to the hydroquinone group (P<0.05). However, longitudinal analysis of mexameter scores did not reveal any significant difference in melanin measurements between flutamide and hydroquinone. Conclusion Topical flutamide appeared as effective as topical hydroquinone in treating melasma using mexameter assessment but with a better MASI improvement trend and higher patient satisfaction in flutamide treatment versus topical hydroquinone. As the present study is possibly the first clinical experience on efficacy of topical flutamide on melasma, it would be quite unreasonable to recommend clinical use of it before future studies replicate the results on its efficacy and safety. PMID:26345129

Comparing student clinical self-efficacy and team process outcomes for a DEU, blended, and traditional clinical setting: A quasi-experimental research study.

PubMed

Plemmons, Christina; Clark, Michele; Feng, Du

2018-03-01

Clinical education is vital to both the development of clinical self-efficacy and the integration of future nurses into health care teams. The dedicated education unit clinical teaching model is an innovative clinical partnership, which promotes skill development, professional growth, clinical self-efficacy, and integration as a team member. Blended clinical teaching models are combining features of the dedicated education unit and traditional clinical model. The aims of this study are to explore how each of three clinical teaching models (dedicated education unit, blended, traditional) affects clinical self-efficacy and attitude toward team process, and to compare the dedicated education unit model and blended model to traditional clinical. A nonequivalent control-group quasi-experimental design was utilized. The convenience sample of 272 entry-level baccalaureate nursing students included 84 students participating in a dedicated education unit model treatment group, 66 students participating in a blended model treatment group, and 122 students participating in a traditional model control group. Perceived clinical self-efficacy was evaluated by the pretest/posttest scores obtained on the General Self-Efficacy scale. Attitude toward team process was evaluated by the pretest/posttest scores obtained on the TeamSTEPPS® Teamwork Attitude Questionnaire. All three clinical teaching models resulted in significant increases in both clinical self-efficacy (p=0.04) and attitude toward team process (p=0.003). Students participating in the dedicated education unit model (p=0.016) and students participating in the blended model (p<0.001) had significantly larger increases in clinical self-efficacy compared to students participating in the traditional model. These findings support the use of dedicated education unit and blended clinical partnerships as effective alternatives to the traditional model to promote both clinical self-efficacy and team process among entry-level baccalaureate nursing students. Copyright © 2017 Elsevier Ltd. All rights reserved.

Membrane transporters in drug development

PubMed Central

2011-01-01

Membrane transporters can be major determinants of the pharmacokinetic, safety and efficacy profiles of drugs. This presents several key questions for drug development, including which transporters are clinically important in drug absorption and disposition, and which in vitro methods are suitable for studying drug interactions with these transporters. In addition, what criteria should trigger follow-up clinical studies, and which clinical studies should be conducted if needed. In this article, we provide the recommendations of the International Transporter Consortium on these issues, and present decision trees that are intended to help guide clinical studies on the currently recognized most important drug transporter interactions. The recommendations are generally intended to support clinical development and filing of a new drug application. Overall, it is advised that the timing of transporter investigations should be driven by efficacy, safety and clinical trial enrolment questions (for example, exclusion and inclusion criteria), as well as a need for further understanding of the absorption, distribution, metabolism and excretion properties of the drug molecule, and information required for drug labeling. PMID:20190787

Percutaneous Intraductal Radiofrequency Ablation for Extrahepatic Distal Cholangiocarcinoma: A Method for Prolonging Stent Patency and Achieving Better Functional Status and Quality of Life

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

Wu, Tian-tian, E-mail: matthewwu1979@hotmail.com; Li, Wei-min, E-mail: weimin-li-surgery@126.com; Li, Hu-cheng, E-mail: hucheng-li-surgery@126.com

PurposeThe clinical efficacy of intraductal radiofrequency ablation (RFA) with Habib™ EndoHPB catheter, a newly developed intervention for malignant extrahepatic biliary obstruction, remains uncertain. The aim of this study was to investigate the clinical efficacy of intraductal RFA.MethodsData from 71 patients with extrahepatic distal cholangiocarcinoma were retrospectively analyzed. The study patients were divided into RFA and control groups. The RFA group had undergone percutaneous transhepatic intraductal RFA with a Habib™ EndoHPB catheter, followed by placement of covered or uncovered biliary self-expandable metallic stents (SEMs) whereas the control group had undergone percutaneous transhepatic covered or uncovered SEMs placement. Procedure-related complications, stent patency,more » patient survival, and postoperative serum bilirubin concentrations were compared between the two groups. The Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) questionnaire was administered to evaluate functional status, improvement in clinical manifestations, and quality of life.ResultsThe RFA group had a longer median stent patency than the control group (p = 0.001 for uncovered SEMs placement). Higher functional well-being, hepatobiliary-specific cancer subscale, Trial Outcome Index, and total FACT-Hep scores were observed during post-procedure follow-up in the RFA group. However, median survival did not differ significantly between the two groups (p > 0.05).ConclusionsProlongation of stent patency and better functional status and quality of life, which are all important clinical endpoints, were observed in patients treated with intraductal RFA. Prospective randomized controlled clinical trials are necessary to further investigate the clinical efficacy and long-term benefits of intraductal RFA.« less

Enhancing Self-Efficacy in Elementary Science Teaching With Professional Learning Communities

NASA Astrophysics Data System (ADS)

Mintzes, Joel J.; Marcum, Bev; Messerschmidt-Yates, Christl; Mark, Andrew

2013-11-01

Emerging from Bandura's Social Learning Theory, this study of in-service elementary school teachers examined the effects of sustained Professional Learning Communities (PLCs) on self-efficacy in science teaching. Based on mixed research methods, and a non-equivalent control group experimental design, the investigation explored changes in personal self-efficacy and outcome expectancy among teachers engaged in PLCs that featured Demonstration Laboratories, Lesson Study, and annual Summer Institutes. Significant changes favoring the experimental group were found on all quantitative measures of self-efficacy. Structured clinical interviews revealed that observed changes were largely attributable to a wide range of direct (mastery) and vicarious experiences, as well as emotional reinforcement and social persuasion.

[Clinical study on painless labor under drugs combined with acupuncture analgesia].

PubMed

Jin, Y; Wu, L; Xia, Y

1996-01-01

To study the analgesia efficacy of drugs combined with acupuncture analgesia for painless labor, 462 normal pregnancy women were observed. During the latent phase in labor, several analgesia methods: acupuncture analgesia, analgesics, magnetotherapy and auricular acupressure, TENS combined with dihydroetorphine were used respectively. While the intrauterine pressure and the peripheral content of beta-EP were measured during labor, the experiments of SEPS were also performed on healthy adults to demonstrate the analgesia efficacy of those analgesia methods. The combination of drugs with acupuncture is an excellent method for painless labor without any complications and all the mothers and babies are safety. The effectiveness is 97.5%. The results demonstrate that the mechanism of analgesia efficacy should be regulated the incoordinate uterine action and improve the hypertonic status of uterus, but also can decrease the pain threshold and elevate the tolerance of uterine contractions during labor.

[Recent advances in treatment of aseptic femoral shaft nonunion].

PubMed

Zhang, Wei; Chen, Hua; Tang, Peifu

2018-05-01

To review the recent advances in treatment of aseptic femoral shaft nonunion. The clinical studies about the treatments of aseptic femoral shaft nonunion in recent years were widely reviewed and analyzed. There are several surgical methods for aseptic femoral shaft nonunion. Due to uncertain clinical outcome, dynamization of nail should be carefully selected. The exchange nailing is suitable for the hypertrophic nonunion of the isthmal femoral shaft fracture. The exchange lateral plating is suitable for nonunion with obvious malformation. However, wave plate or dual plate should be chosen when the bone nonuinon is combined with the medial defect. The augmentation plating improves the success rate of nailing for femoral shaft nonunion, but it should be carefully selected for patients with obvious deformity or bone defect. Ilizarov technique is suitable for various bone nonunion, especially with complicated or large segmental bone defects. Induced membrane technique is also an important method for the treatment of bone nonunion with large bone defects. The clinical efficacy of the blocking screw remains to be supported by further evidence. Biological stimulants are mainly used for atrophic nonunion, and the clinical efficacy of them alone are still controversial. Due to lack of comparative studies between different surgical methods, the orthopedist should choose the appropriate treatment according to the individual situations of the patient and the types of bone nonunion.

King cobra peptide OH-CATH30 as a potential candidate drug through clinic drug-resistant isolates.

PubMed

Zhao, Feng; Lan, Xin-Qiang; Du, Yan; Chen, Pei-Yi; Zhao, Jiao; Zhao, Fang; Lee, Wen-Hui; Zhang, Yun

2018-03-18

Cationic antimicrobial peptides (AMPs) are considered as important candidate therapeutic agents, which exert potent microbicidal properties against bacteria, fungi and some viruses. Based on our previous findings king cobra cathelicidin (OH-CATH) is a 34-amino acid peptide that exerts strong antibacterial and weak hemolytic activity. The aim of this research is to evaluate the efficacy of both OH-CATH30 and its analog D-OH-CATH30 against clinical isolates comparing with routinely utilized antibiotics in vitro. In this study, 584 clinical isolates were tested (spanning 2013-2016) and the efficacy of the candidate peptides and antibiotics were determined by a broth microdilution method according to the CLSI guidelines. Among the 584 clinical isolates, 85% were susceptible to OH-CATH30 and its analogs. Both L- and D-OH-CATH30 showed higher efficacy against (toward) Gram-positive bacteria and stronger antibacterial activity against nearly all Gram-negative bacteria tested compare with antibiotics. The highest bactericidal activity was detected against Acinetobacter spp., including multi-drug-resistant Acinetobacter baumannii (MRAB) and methicillin-resistant Staphylococcus aureus (MRSA). The overall efficacy of OH-CATH30 and its analogs was higher than that of the 9 routinely used antibiotics. OH-CATH30 is a promising candidate drug for the treatment of a wide variety of bacterial infections which are resistant to many routinely used antimicrobial agents.

Sensitivity and specificity of the Eating Assessment Tool and the Volume-Viscosity Swallow Test for clinical evaluation of oropharyngeal dysphagia

PubMed Central

Rofes, L; Arreola, V; Mukherjee, R; Clavé, P

2014-01-01

Background Oropharyngeal dysphagia (OD) is an underdiagnosed digestive disorder that causes severe nutritional and respiratory complications. Our aim was to determine the accuracy of the Eating Assessment Tool (EAT-10) and the Volume-Viscosity Swallow Test (V-VST) for clinical evaluation of OD. Methods We studied 120 patients with swallowing difficulties and 14 healthy subjects. OD was evaluated by the 10-item screening questionnaire EAT-10 and the bedside method V-VST, videofluoroscopy (VFS) being the reference standard. The V-VST is an effort test that uses boluses of different volumes and viscosities to identify clinical signs of impaired efficacy (impaired labial seal, piecemeal deglutition, and residue) and impaired safety of swallow (cough, voice changes, and oxygen desaturation ≥3%). Discriminating ability was assessed by the AUC of the ROC curve and sensitivity and specificity values. Key Results According to VFS, prevalence of OD was 87%, 75.6% with impaired efficacy and 80.9% with impaired safety of swallow including 17.6% aspirations. The EAT-10 showed a ROC AUC of 0.89 for OD with an optimal cut-off at 2 (0.89 sensitivity and 0.82 specificity). The V-VST showed 0.94 sensitivity and 0.88 specificity for OD, 0.79 sensitivity and 0.75 specificity for impaired efficacy, 0.87 sensitivity and 0.81 specificity for impaired safety, and 0.91 sensitivity and 0.28 specificity for aspirations. Conclusions & Inferences Clinical methods for screening (EAT-10) and assessment (V-VST) of OD offer excellent psychometric proprieties that allow adequate management of OD. Their universal application among at-risk populations will improve the identification of patients with OD at risk for malnutrition and aspiration pneumonia. PMID:24909661

Immunogenicity of therapeutics: a matter of efficacy and safety.

PubMed

Nechansky, Andreas; Kircheis, Ralf

2010-11-01

The unwanted immunogenicity of therapeutic proteins is a major concern regarding patient safety. Furthermore, pharmacokinetic, pharmacodynamic and clinical efficacy can be seriously affected by the immunogenicity of therapeutic proteins. Authorities have fully recognized this issue and demand appropriate and well-characterized assays to detect anti-drug antibodies (ADAs). We provide an overview of the immunogenicity topic in general, the regulatory background and insight into underlying immunological mechanisms and the limited ability to predict clinical immunogenicity a priori. Furthermore, we comment on the analytical testing approach and the status-quo of appropriate method validation. The review provides insight regarding the analytical approach that is expected by regulatory authorities overseeing immunogenicity testing requirements. Additionally, the factors influencing immunogenicity are summarized and key references regarding immunogenicity testing approaches and method validation are discussed. The unwanted immunogenicity of protein therapeutics is of major concern because of its potential to affect patient safety and drug efficacy. Analytical testing is sophisticated and requires more than one assay. Because immunogenicity in humans is hardly predictable, assay development has to start in a timely fashion and for clinical studies immunogenicity assay validation is mandatory prior to analyzing patient serum samples. Regarding ADAs, the question remains as to when such antibodies are regarded of clinical relevance and what levels are, if at all, acceptable. In summary, the detection of ADAs should raise the awareness of the physician concerning patient safety and of the sponsor/manufacture concerning the immunogenic potential of the drug product.

The relationship between maternal self-efficacy and parenting practices: implications for parent training.

PubMed

Sanders, M R; Woolley, M L

2005-01-01

The present study examined the relationship between maternal self-efficacy, dysfunctional discipline practices and child conduct problems. Specifically, three levels of self-efficacy, global, domain and task-specific self-efficacy, were assessed in mothers of 2- to 8-year-old children with conduct problems (clinic group, n=45) and non-clinic mothers from the community (non-clinic group, n=79). Measures of global, domain and task-specific self-efficacy were completed by mothers. Clinic mothers reported significantly lower self-efficacy than non-clinic mothers for all but one of the parenting tasks assessed. Both groups of mothers reported lowest self-efficacy for similar parenting tasks. In the sample as a whole self-efficacy measures were significant predictors of maternal discipline style after controlling for other parent, child and risk factors. Of the self-efficacy variables behavioural self-efficacy was the best predictor of mothers discipline style. The findings support the importance of developing parenting strategies that enable parents to generalize their parenting skills to a diverse range of diverse parenting contexts both in the home and in the community.

[Accuracy of three methods for the rapid diagnosis of oral candidiasis].

PubMed

Lyu, X; Zhao, C; Yan, Z M; Hua, H

2016-10-09

Objective: To explore a simple, rapid and efficient method for the diagnosis of oral candidiasis in clinical practice. Methods: Totally 124 consecutive patients with suspected oral candidiasis were enrolled from Department of Oral Medicine, Peking University School and Hospital of Stomatology, Beijing, China. Exfoliated cells of oral mucosa and saliva or concentrated oral rinse) obtained from all participants were tested by three rapid smear methods(10% KOH smear, gram-stained smear, Congo red stained smear). The diagnostic efficacy(sensitivity, specificity, Youden's index, likelihood ratio, consistency, predictive value and area under curve(AUC) of each of the above mentioned three methods was assessed by comparing the results with the gold standard(combination of clinical diagnosis, laboratory diagnosis and expert opinion). Results: Gram-stained smear of saliva(or concentrated oral rinse) demonstrated highest sensitivity(82.3%). Test of 10%KOH smear of exfoliated cells showed highest specificity(93.5%). Congo red stained smear of saliva(or concentrated oral rinse) displayed highest diagnostic efficacy(79.0% sensitivity, 80.6% specificity, 0.60 Youden's index, 4.08 positive likelihood ratio, 0.26 negative likelihood ratio, 80% consistency, 80.3% positive predictive value, 79.4% negative predictive value and 0.80 AUC). Conclusions: Test of Congo red stained smear of saliva(or concentrated oral rinse) could be used as a point-of-care tool for the rapid diagnosis of oral candidiasis in clinical practice. Trial registration: Chinese Clinical Trial Registry, ChiCTR-DDD-16008118.

[From cradle to grave? Expectations from atypical antipsychotics].

PubMed

Frecska, Ede

2005-03-01

Clinical expectations are high toward atypical, second generation antipsychotics (SGAs). Controlled clinical trials supporting the superiority of SGAs over traditional agents are scarce. Meta-analysis of existing data may come for the rescue but that kind of method has its limitations. One of the most meticulous approaches (Davis et al. 2003) reached the conclusion that some, but not all, SGAs are more efficacious than traditional ones. Within the group of distinguished drugs, clozapine and amisulpride have the highest efficacy. The present paper critically overviews the study of the Davis group. Based on in vivo D2 receptor binding data of the new SGAs and the usual post marketing changes of clinical dosing, it is expected that some of the currently and most recently marketed SGAs may show similar superiority.

Effect of the dedicated education unit on nursing student self-efficacy: A quasi-experimental research study.

PubMed

George, Lynn E; Locasto, Lisa W; Pyo, Katrina A; W Cline, Thomas

2017-03-01

Although the Dedicated Education Unit (DEU) has shown initial promise related to satisfaction with the teaching/learning environment, few studies have examined student outcomes related to the use of the DEU as a clinical education model beyond student satisfaction. The purpose of this quantitative, quasi-experimental study was to compare student outcomes from the traditional clinical education (TCE) model with those from the DEU model. Participants were students enrolled in a four-year baccalaureate program in nursing (n = 193) who had clinical education activities in one of three clinical agencies. Participants were assigned to either the DEU or a TCE model. Pre-clinical and post-clinical self-efficacy scores were measured for each group using an adapted Generalized Self-Efficacy Scale (Schwarzer and Jerusalem, 1995). Both groups experienced a significant increase in self-efficacy scores post clinical education. The increase in self-efficacy for the DEU students was significantly greater than the increase in self-efficacy for the traditional students. Self-efficacy is considered an important outcome of nursing education because high self-efficacy has been linked to making an easier transition from student to nursing professional. This study supports the quality of the DEU as a clinical education model by examining student self-efficacy outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mesenchymal stromal cell-based therapy: Regulatory and translational aspects in gastroenterology.

PubMed

Dothel, Giovanni; Raschi, Emanuel; Rimondini, Roberto; De Ponti, Fabrizio

2016-11-07

The past decade has witnessed an outstanding scientific production focused towards the possible clinical applications of mesenchymal stromal cells (MSCs) in autoimmune and chronic inflammatory diseases. This raised the need of novel standards to adequately address quality, efficacy and safety issues of this advanced therapy. The development of a streamlined regulation is currently hampered by the complexity of analyzing dynamic biological entities rather than chemicals. Although numerous pieces of evidence show efficacy in reducing intestinal inflammation, some inconsistencies between the mechanisms of action of rodent vs human MSCs suggest caution before assigning translational value to preclinical studies. Preliminary evidence from clinical trials showed efficacy of MSCs in the treatment of fistulizing Crohn's disease (CD), and preparations of heterologous MSCs for CD treatment are currently tested in ongoing clinical trials. However, safety issues, especially in long-term treatment, still require solid clinical data. In this regard, standardized guidelines for appropriate dosing and methods of infusion could enhance the likelihood to predict more accurately the number of responders and the duration of remission periods. In addition, elucidating MSC mechanisms of action could lead to novel and more reliable formulations such as those derived from the MSCs themselves ( e.g ., supernatants).

Cell division inhibitors with efficacy equivalent to isoniazid in the acute murine Mycobacterium tuberculosis infection model

PubMed Central

Knudson, Susan E.; Awasthi, Divya; Kumar, Kunal; Carreau, Alexandra; Goullieux, Laurent; Lagrange, Sophie; Vermet, Hélène; Ojima, Iwao; Slayden, Richard A.

2015-01-01

Objectives The increasing number of clinical strains resistant to one or more of the front-line TB drugs complicates the management of this disease. To develop next-generation benzimidazole-based FtsZ inhibitors with improved efficacy, we employed iterative optimization strategies based on whole bacteria potency, bactericidal activity, plasma and metabolic stability and in vivo efficacy studies. Methods Candidate benzimidazoles were evaluated for potency against Mycobacterium tuberculosis H37Rv and select clinical strains, toxicity against Vero cells and compound stability in plasma and liver microsomes. The efficacy of lead compounds was assessed in the acute murine M. tuberculosis infection model via intraperitoneal and oral routes. Results MICs of SB-P17G-A33, SB-P17G-A38 and SB-P17G-A42 for M. tuberculosis H37Rv and select clinical strains were 0.18–0.39 mg/L. SB-P17G-A38 and SB-P17G-A42 delivered at 50 mg/kg twice daily intraperitoneally or orally demonstrated efficacy in reducing the bacterial load by 5.7–6.3 log10 cfu in the lungs and 3.9–5.0 log10 cfu in the spleen. SB-P17G-A33 delivered at 50 mg/kg twice daily intraperitoneally or orally also reduced the bacterial load by 1.7–2.1 log10 cfu in the lungs and 2.5–3.4 log10 cfu in the spleen. Conclusions Next-generation benzimidazoles with excellent potency and efficacy against M. tuberculosis have been developed. This is the first report on benzimidazole-based FtsZ inhibitors showing an equivalent level of efficacy to isoniazid in an acute murine M. tuberculosis infection model. PMID:26245639

Evaluation of trimethoprim-sulfamethoxazole based combination therapy against Stenotrophomonas maltophilia: in vitro effects and clinical efficacy in cancer patients.

PubMed

Araoka, Hideki; Baba, Masaru; Okada, Chikako; Abe, Masahiro; Kimura, Muneyoshi; Yoneyama, Akiko

2017-05-01

The aim of this study was to evaluate the in vitro effects and clinical efficacies of trimethoprim-sulfamethoxazole (SXT) combined with other antimicrobial agents against Stenotrophomonas maltophilia. In vitro analysis was conducted on 89 S. maltophilia strains isolated from blood and the respiratory tract between June 2012 and October 2014. Levofloxacin (LVX), ticarcillin-clavulanic acid (TIM), and minocycline (MIN) were selected for an examination of their effects when individually combined with SXT by the checkerboard method. In addition, 29 S. maltophilia bacteremia cases were reviewed and the clinical efficacies of SXT-based combination therapies were analyzed. SXT+LVX showed synergy in 21, no interactions in 61, and antagonism in 7. SXT+TIM showed synergy in 71, and no interactions in 18. SXT+MIN showed synergy in 10, and no interactions in 79. The review of clinical data indicated that a combination of SXT+fluoroquinolone was not associated with improved prognosis compared with monotherapy. The in vitro data indicated that SXT+TIM had beneficial microbiological effects and was not antagonistic. Our in vitro and clinical data analyses do not support the routine use of SXT+fluoroquinolone combination therapy for S. maltophilia infection. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Multidimensional outcome considerations in assessing the efficacy of medical educational programs.

PubMed

Blumberg, Phyllis

2003-01-01

To be accredited, schools must evaluate the effectiveness of their programs. Educators are looking for specific indicators beyond the traditional measures. Data from multiple methods, including indicators of student performance and of the institutional environment, can be used to determine if educational program goals are met. This article outlines specific ways to consider three types of efficacy outcomes that are consistent with accreditation guidelines: educational, clinical career, and environmental outcomes. Specific measurable outcomes for each of these categories are derived from higher education literature: for example, learning approaches and information acquisition for education; professional behaviors and interpersonal dimensions for clinical career, and scholarship of teaching and teaching itself as a shared and valued activity for environmental outcomes. These outcomes address student assessment and program evaluation. Data from problem-based learning programs illustrate these outcomes. Educators can determine if educational program innovations have met their goals by collecting efficacy outcome data.

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

Novel diagnostic procedure for determining metastasis to sentinel lymph nodes in breast cancer using a semi-dry dot-blot method.

PubMed

Otsubo, Ryota; Oikawa, Masahiro; Hirakawa, Hiroshi; Shibata, Kenichiro; Abe, Kuniko; Hayashi, Tomayoshi; Kinoshita, Naoe; Shigematsu, Kazuto; Hatachi, Toshiko; Yano, Hiroshi; Matsumoto, Megumi; Takagi, Katsunori; Tsuchiya, Tomoshi; Tomoshige, Koichi; Nakashima, Masahiro; Taniguchi, Hideki; Omagari, Takeyuki; Itoyanagi, Noriaki; Nagayasu, Takeshi

2014-02-15

We developed an easy, quick and cost-effective detection method for lymph node metastasis called the semi-dry dot-blot (SDB) method, which visualizes the presence of cancer cells with washing of sectioned lymph nodes by anti-pancytokeratin antibody, modifying dot-blot technology. We evaluated the validity and efficacy of the SDB method for the diagnosis of lymph node metastasis in a clinical setting (Trial 1). To evaluate the validity of the SDB method in clinical specimens, 180 dissected lymph nodes from 29 cases, including breast, gastric and colorectal cancer, were examined. Each lymph node was sliced at the maximum diameter and the sensitivity, specificity and accuracy of the SDB method were determined and compared with the final pathology report. Metastasis was detected in 32 lymph nodes (17.8%), and the sensitivity, specificity and accuracy of the SDB method were 100, 98.0 and 98.3%, respectively (Trial 2). To evaluate the efficacy of the SDB method in sentinel lymph node (SLN) biopsy, 174 SLNs from 100 cases of clinically node-negative breast cancer were analyzed. Each SLN was longitudinally sliced at 2-mm intervals and the sensitivity, specificity, accuracy and time required for the SDB method were determined and compared with the intraoperative pathology report. Metastasis was detected in 15 SLNs (8.6%), and the sensitivity, specificity, accuracy and mean required time of the SDB method were 93.3, 96.9, 96.6 and 43.3 min, respectively. The SDB method is a novel and reliable modality for the intraoperative diagnosis of SLN metastasis. © 2013 UICC.

A meta-analysis of mammographic screening with and without clinical breast examination

PubMed Central

Hamashima, Chisato; Ohta, Koji; Kasahara, Yoshio; Katayama, Takafumi; Nakayama, Tomio; Honjo, Satoshi; Ohnuki, Koji

2015-01-01

Mammographic screening with clinical breast examination has been recommended in Japan since 2000. Although mammographic screening without clinical breast examination has not been recommended, its introduction is anticipated. The efficacies of mammographic screening with and without clinical breast examination were evaluated based on the results of randomized controlled trials. PubMed and other databases for studies published between 1985 and 2014 were searched. The study design was limited to randomized controlled trials to evaluate mortality reduction from breast cancer. Five studies were eligible for meta-analysis of mammographic screening without clinical breast examination. The relative risk for women aged 40–74 years was 0.75 (95% confidence interval, 0.67–0.83). Three studies evaluated the efficacy of mammographic screening with clinical breast examination. The relative risk for women aged 40–64 years was 0.87 (95% confidence interval, 0.77–0.98). The number needed to invite was always lower in mammographic screening without clinical breast examination than in mammographic screening with clinical breast examination. In both screening methods, the number needed to invite was higher in women aged 40–49 years than in women aged 50–70 years. These results suggest that mammographic screening without clinical breast examination can afford higher benefits to women aged 50 years and over. Although evidence of the efficacy of mammographic screening without clinical breast examination was confirmed based on the results of the randomized controlled trials, a Japanese study is needed to resolve local problems. PMID:25959787

Complementary and Alternative Therapies for Chronic Constipation

PubMed Central

2015-01-01

Chronic constipation, an ancient disease, is prevalent, and costly in the general population. Complementary and alternative therapies are frequently used for constipation. This review introduces various methods of complementary and alternative therapies, including acupuncture, moxibustion, massage, and herbal medicine. Efficacy, safety, influence factors, sham control design, and mechanisms of these therapies are discussed and evaluated. Acupuncture or electroacupuncture was found to be most commonly used for constipation among these complementary and alternative therapies, followed by herbal medicine. Although only a small number of clinical studies are flawless, our review of the literature seems to suggest that acupuncture or electroacupuncture and herbal medicine are effective in treating constipation, whereas findings on massage and moxibustion are inconclusive. More well-designed clinical trials are needed to improve and prove the efficacy of the complementary and alternative therapies for constipation; mechanistic studies that would lead to wide spread use and improvement of the methods are also discussed in this review. PMID:26064163

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.

[Study on flomoxef in the perinatal period].

PubMed

Tamate, K; Sengoku, K; Ishikawa, M; Shimizu, T; Haga, H; Hasegawa, T; Takada, H; Mure, K; Kawamura, M; Torii, Y

1991-06-01

The placental passage and the the therapeutic efficacy of flomoxef (FMOX, 6315-S) were studied in patients in the perinatal period. A summary of the obtained results is as follows: 1. Concentrations of FMOX in maternal serum, umbilical cord serum and amniotic fluid obtained upon one-shot intravenous injections to 12 patients were compared with those obtained upon 1 hour drip infusions to 9 patients. It was found that the former means of administration gave higher concentrations that the latter. 2. Concentrations of FMOX in maternal serum, umbilical cord serum and amniotic fluid at 1 to 6 hours after administration through either method were all higher than MIC80's of recognized bacteria. 3. Clinical efficacies were evaluated in 10 patients with puerperal intrauterine infection, 7 patients with endometritis, 2 patients with pyelonephritis and 1 patient each with endo-cervicitis, amniotic fluid infection, mastitis and perineal wound infection. Clinical efficacies were excellent in 5 patients (21.7%), good in 17 patients (73.9%) and poor in 1 patient (4.4%), thus the overall efficacy rate was 95.7%. 4. Eradication of causative bacteria were obtained in all 8 cases tested, hence the eradication rate was 100%. 5. Mild diarrhea in 1 patient was the only side effect observed. No abnormal clinical laboratory test results were found in any patients.

Evaluating the Real-World Effectiveness of Cognitive-Behavior Therapy Efficacy Research on Eating Disorders: A Case Study from a Community-based Clinical Setting

PubMed Central

Lowe, Michael R.; Bunnell, Douglas W.; Neeren, Amy M.; Chernyak, Yelena; Greberman, Laurel

2009-01-01

Objective There is a growing consensus that there is a need to test the real-world effectiveness of eating disorder therapies that show promise in efficacy research. The current paper provides a narrative account of an NIMH-funded study that attempted to apply efficacy findings from CBT research to an Intensive Outpatient Program (IOP) at the largest community-based eating disorder program in the United States. Method We describe the study as originally envisioned as well as the various challenges that the researchers and the IOP staff encountered in implementing this study. Results The different training, assumptions, and “ways of knowing” of the research team and the treatment staff in regard to the nature of eating disorders and their treatment created multiple challenges for both groups during the study period. We describe valuable lessons learned about how to - and how not to -implement effectiveness designs in clinical settings that are relatively unfamiliar with empirically-based research findings. Discussion It is hoped that our experience in attempting to apply efficacy-based research findings on eating disorders treatment in a community-based clinical setting will prove helpful to other researchers and service providers engaging in such translational research. PMID:20063375

A Grading System To Evaluate Objectively the Strength of Pre-Clinical Data of Acute Neuroprotective Therapies for Clinical Translation in Spinal Cord Injury

PubMed Central

Okon, Elena B.; Tsai, Eve; Beattie, Michael S.; Bresnahan, Jacqueline C.; Magnuson, David K.; Reier, Paul J.; McTigue, Dana M.; Popovich, Phillip G.; Blight, Andrew R.; Oudega, Martin; Guest, James D.; Weaver, Lynne C.; Fehlings, Michael G.; Tetzlaff, Wolfram

2011-01-01

Abstract The past three decades have seen an explosion of research interest in spinal cord injury (SCI) and the development of hundreds of potential therapies that have demonstrated some promise in pre-clinical experimental animal models. A growing number of these treatments are seeking to be translated into human clinical trials. Conducting such a clinical trial, however, is extremely costly, not only for the time and money required to execute it, but also for the limited resources that will then no longer be available to evaluate other promising therapies. The decision about what therapies have sufficient pre-clinical evidence of efficacy to justify testing in humans is therefore of utmost importance. Here, we have developed a scoring system for objectively grading the body of pre-clinical literature on neuroprotective treatments for acute SCI. The components of the system include an evaluation of a number of factors that are thought to be important in considering the “robustness” of a therapy's efficacy, including the animal species and injury models that have been used to test it, the time window of efficacy, the types of functional improvements effected by it, and whether efficacy has been independently replicated. The selection of these factors was based on the results of a questionnaire that was performed within the SCI research community. A modified Delphi consensus-building exercise was then conducted with experts in pre-clinical SCI research to refine the criteria and decide upon how to score them. Finally, the grading system was applied to a series of potential neuroprotective treatments for acute SCI. This represents a systematic approach to developing an objective method of evaluating the extent to which the pre-clinical literature supports the translation of a particular experimental treatment into human trials. PMID:20507235

Chemophototherapy: An Emerging Treatment Option for Solid Tumors

PubMed Central

Luo, Dandan; Carter, Kevin A.; Miranda, Dyego

2016-01-01

Near infrared (NIR) light penetrates human tissues with limited depth, thereby providing a method to safely deliver non‐ionizing radiation to well‐defined target tissue volumes. Light‐based therapies including photodynamic therapy (PDT) and laser‐induced thermal therapy have been validated clinically for curative and palliative treatment of solid tumors. However, these monotherapies can suffer from incomplete tumor killing and have not displaced existing ablative modalities. The combination of phototherapy and chemotherapy (chemophototherapy, CPT), when carefully planned, has been shown to be an effective tumor treatment option preclinically and clinically. Chemotherapy can enhance the efficacy of PDT by targeting surviving cancer cells or by inhibiting regrowth of damaged tumor blood vessels. Alternatively, PDT‐mediated vascular permeabilization has been shown to enhance the deposition of nanoparticulate drugs into tumors for enhanced accumulation and efficacy. Integrated nanoparticles have been reported that combine photosensitizers and drugs into a single agent. More recently, light‐activated nanoparticles have been developed that release their payload in response to light irradiation to achieve improved drug bioavailability with superior efficacy. CPT can potently eradicate tumors with precise spatial control, and further clinical testing is warranted. PMID:28105389

Non-pharmacological biological treatment approaches to difficult-to-treat depression.

PubMed

Fitzgerald, Paul B

2013-09-16

There has been substantial recent interest in novel brain stimulation treatments for difficult-to-treat depression. Electroconvulsive therapy (ECT) is a well established, effective treatment for severe depression. ECT's problematic side-effect profile and questions regarding optimal administration methods continue to be investigated. Magnetic seizure therapy, although very early in development, shows promise, with potentially similar efficacy to ECT but fewer side effects. Vagus nerve stimulation (VNS) and repetitive transcranial magnetic stimulation (rTMS) are clinically available in some countries. Limited research suggests VNS has potentially long-lasting antidepressant effects in a small group of patients. Considerable research supports the efficacy of rTMS. Both techniques require further study of optimal treatment parameters. Transcranial direct current stimulation may provide a low-cost antidepressant option if its efficacy is substantiated in larger samples. Deep brain stimulation is likely to remain reserved for patients with the most severe and difficult-to-treat depression, requiring further exploration of administration methods and its role in depression therapy. New and innovative forms of brain stimulation, including low-intensity ultrasound, low-field magnetic stimulation and epidural stimulation of the cortical surface, are in early stages of exploration and are yet to move into the clinical domain. Ongoing work is required to define which brain stimulation treatments are likely to be most useful, and in which patient groups. Clinical service development of brain stimulation treatments will likely be inconsistent and variable.

Cognitive Behavioral Treatment of PTSD in Residents of Battered Women's Shelters: Results of a Randomized Clinical Trial

ERIC Educational Resources Information Center

Johnson, Dawn M.; Zlotnick, Caron; Perez, Sara

2011-01-01

Objective: This study was designed to explore the acceptability, feasibility, and initial efficacy of a new shelter-based treatment for victims of intimate partner violence (IPV; i.e., Helping to Overcome PTSD through Empowerment [HOPE]). Method: A Phase I randomized clinical trial comparing HOPE (n = 35) with standard shelter services (SSS) (n =…

Health economics in drug development: efficient research to inform healthcare funding decisions.

PubMed

Hall, Peter S; McCabe, Christopher; Brown, Julia M; Cameron, David A

2010-10-01

In order to decide whether a new treatment should be used in patients, a robust estimate of efficacy and toxicity is no longer sufficient. As a result of increasing healthcare costs across the globe healthcare payers and providers now seek estimates of cost-effectiveness as well. Most trials currently being designed still only consider the need for prospective efficacy and toxicity data during the development life-cycle of a new intervention. Hence the cost-effectiveness estimates are inevitably less precise than the clinical data on which they are based. Methods based on decision theory are being developed by health economists that can contribute to the design of clinical trials in such a way that they can more effectively lead to better informed drug funding decisions on the basis of cost-effectiveness in addition to clinical outcomes. There is an opportunity to apply these techniques prospectively in the design of future clinical trials. This article describes the problems encountered by those responsible for drug reimbursement decisions as a consequence of the current drug development pathway. The potential for decision theoretic methods to help overcome these problems is introduced and potential obstacles in implementation are highlighted. Copyright © 2010 Elsevier Ltd. All rights reserved.

Cognitive hypnotherapy for pain management.

PubMed

Elkins, Gary; Johnson, Aimee; Fisher, William

2012-04-01

Pain is a serious health care problem and there is growing evidence to support the use of hypnosis and cognitive-behavioral interventions for pain management. This article reviews clinical techniques and methods of cognitive hypnotherapy for pain management. Current research with emphasis given to randomized, controlled trials is presented and the efficacy of hypnotherapy for pain management is discussed. Evidence for cognitive hypnotherapy in the treatment in chronic pain, cancer, osteoarthritis, sickle cell disease, temporomandibular disorder, fibromyalgia, non-cardiac chest pain, and disability related chronic pains are identified. Implications for clinical practice and research are discussed in light of the accumulating evidence in support of the efficacy and effectiveness of cognitive hypnotherapy for pain management.

Clinical efficacy and safety of polyethylene glycol 3350 versus liquid paraffin in the treatment of pediatric functional constipation

PubMed Central

Rafati, MR.; Karami, H.; Salehifar, E.; Karimzadeh, A.

2011-01-01

Background and the purpose of the study Functional constipation is prevalent in children. Recently polyethylene glycol has been introduced as an effective and safe drug to treat chronic constipation. There are only a few clinical trials on comparison of PEG and liquid paraffin in childhood constipation. The purpose of this study was to evaluate clinical efficacy and safety of PEG 3350 solution and liquid paraffin in the treatment of children with functional constipation in Sari Toba clinic during the period of 2008–2009. Methods Children with a history of functional constipation were subjects of this study. One hundred and sixty children of 2–12 years old with functional constipation were randomized in two PEG and paraffin treatment groups. Patients received either 1.0–1.5 g/kg/day PEG 3350 or 1.0–1.5 ml/kg/day liquid paraffin for 4 months. Clinical efficacy was evaluated by stool and encopresis frequency/week and overall treatment success rate was compared in two groups. Results and major conclusion Compared with the baseline, defecation frequency/ week increased significantly and encopresis frequency meaningfully decreased in two groups during the period of the study. Patients using PEG 3350 had more success rate (mean: 95.3%±3.7) compared with the patients in paraffin group (mean: 87.2%±7.1) (p=0.087). Administration of PEG 3350 were associated with less adverse events than liquid paraffin. In conclusion in treatment of pediatric functional constipation, regarding clinical efficacy and safety, PEG 3350 were at least as effective as liquid paraffin and but less adverse drug events. PMID:22615652

A Field Trial to Assess a Blood-Stage Malaria Vaccine

PubMed Central

Thera, Mahamadou A.; Doumbo, Ogobara K.; Coulibaly, Drissa; Laurens, Matthew B.; Ouattara, Amed; Kone, Abdoulaye K.; Guindo, Ando B.; Traore, Karim; Traore, Idrissa; Kouriba, Bourema; Diallo, Dapa A.; Diarra, Issa; Daou, Modibo; Dolo, Amagana; Tolo, Youssouf; Sissoko, Mahamadou S.; Niangaly, Amadou; Sissoko, Mady; Takala-Harrison, Shannon; Lyke, Kirsten E.; Wu, Yukun; Blackwelder, William C.; Godeaux, Olivier; Vekemans, Johan; Dubois, Marie-Claude; Ballou, W. Ripley; Cohen, Joe; Thompson, Darby; Dube, Tina; Soisson, Lorraine; Diggs, Carter L.; House, Brent; Lanar, David E.; Dutta, Sheetij; Heppner, D. Gray; Plowe, Christopher V.

2011-01-01

BACKGROUND Blood-stage malaria vaccines are intended to prevent clinical disease. The malaria vaccine FMP2.1/AS02A, a recombinant protein based on apical membrane antigen 1 (AMA1) from the 3D7 strain of Plasmodium falciparum, has previously been shown to have immunogenicity and acceptable safety in Malian adults and children. METHODS In a double-blind, randomized trial, we immunized 400 Malian children with either the malaria vaccine or a control (rabies) vaccine and followed them for 6 months. The primary end point was clinical malaria, defined as fever and at least 2500 parasites per cubic millimeter of blood. A secondary end point was clinical malaria caused by parasites with the AMA1 DNA sequence found in the vaccine strain. RESULTS The cumulative incidence of the primary end point was 48.4% in the malaria-vaccine group and 54.4% in the control group; efficacy against the primary end point was 17.4% (hazard ratio for the primary end point, 0.83; 95% confidence interval [CI], 0.63 to 1.09; P = 0.18). Efficacy against the first and subsequent episodes of clinical malaria, as defined on the basis of various parasite-density thresholds, was approximately 20%. Efficacy against clinical malaria caused by parasites with AMA1 corresponding to that of the vaccine strain was 64.3% (hazard ratio, 0.36; 95% CI, 0.08 to 0.86; P = 0.03). Local reactions and fever after vaccination were more frequent with the malaria vaccine. CONCLUSIONS On the basis of the primary end point, the malaria vaccine did not provide significant protection against clinical malaria, but on the basis of secondary results, it may have strain-specific efficacy. If this finding is confirmed, AMA1 might be useful in a multicomponent malaria vaccine. PMID:21916638

A Comprehensive Review of mTOR-Inhibiting Pharmacotherapy for the Treatment of Non-Infectious Uveitis.

PubMed

Blair, Joshua; Barry, Robert; Moore, David J; Denniston, Alastair K

2017-01-01

Non-infectious uveitis is a sight-threatening inflammatory disease that often necessitates prolonged use of high-dose corticosteroids, resulting in significant systemic side effects. There is a need for efficacious steroid-sparing immunomodulatory therapy for these patients, and the mTOR inhibitors (sirolimus and everolimus) may be contenders for this role. A comprehensive review of preclinical and clinical research on mTOR inhibitors for non-infectious uveitis was performed. Articles were identified by a search of MEDLINE (PubMed/OVID) and EMBASE (OVID) the terms (uveitis OR non-infectious uveitis) AND (mTOR inhibitor OR sirolimus OR everolimus). Assessment of study aims, methods, efficacy outcomes and adverse events was performed. Seven pre-clinical and nine clinical studies were identified. One study in each group was on everolimus, the rest sirolimus. Preclinical studies have been performed in rabbit, rat, mouse and in-vitro models. Clinical studies range from comparative open-label trials to case reports, with reported clinical efficacy ranging from 40% to 100% depending on endpoint assessed. The overall rate of drug-related adverse events (such as ocular irritation, visual floaters, nausea and vomiting) was 0.640 events per patient-year with sirolimus, and 0.111 events per patient-year with everolimus. Published evidence suggests that sirolimus and everolimus may be useful in the management of noninfectious uveitis. Both appear to be well tolerated, especially when locally administered. Further high-quality RCTs adopting standardised end-points are required to definitively determine the efficacy of each agent. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Self-Efficacy as a Predictor of Self-Reported Physical, Cognitive and Social Functioning in Multiple Sclerosis

PubMed Central

Schmitt, Margaret M.; Goverover, Yael; DeLuca, John; Chiaravalloti, Nancy

2014-01-01

Objective Investigate whether self-efficacy is associated with physical, cognitive and social functioning in individuals with Multiple Sclerosis (MS) when controlling for disease-related characteristics and depressive symptomatology. Participants 81 individuals between the ages of 29 and 67 with a diagnosis of clinically definite MS. Method Hierarchical regression analysis was employed to examine the relationships between self-efficacy and self-reported physical, cognitive, and social functioning. Results Self-efficacy is a significant predictor of self-reported physical, cognitive and social functioning in MS after controlling for variance due to disease related factors and depressive symptomatology. Conclusions Self-efficacy plays a significant role in individual adjustment to MS across multiple areas of functional outcome, beyond that which is accounted for by disease related variables and symptoms of depression. PMID:24320946

Detoxification in Naturopathic Medicine: A Survey

PubMed Central

Montalto, Melissa; Lovejoy, Jennifer; Weber, Wendy

2011-01-01

Abstract Objectives This study sought to assess the use of clinical detoxification therapies used by licensed naturopathic doctors (NDs) in the United States. Design This was a qualitative, descriptive, online survey of a convenience sample of NDs. Methods An online survey was conducted of NDs who were licensed in the United States. Responses were analyzed descriptively regarding the use of clinical detoxification therapies. Respondents were recruited from a membership list provided by the American Association of Naturopathic Physicians, and from alumni e-mail lists of Council of Naturopathic Medical Education accredited naturopathic medical schools. Results Surveys were sent out to 1442 e-mail addresses (261 were returned to sender); a total of 196 respondents completed the survey (16.6%). Ninety-two percent (92%) of respondents reported using clinical detoxification therapies. Over 75% of respondents utilized detoxification therapies primarily to treat patients for environmental exposures, general cleansing/preventive medicine, gastrointestinal disorders, and autoimmune disease. Regarding methods used, >75% reported using dietary measures, reducing environmental exposures, and using botanicals as detoxification therapies. Eighty-three percent (83%) of NDs surveyed reported using follow-up measurements to determine efficacy of detoxification therapies. The most common were patient symptom questionnaires (66%), patient medical histories (54%), and urinary provocative challenge testing (53%). Conclusions The majority of NDs responding to this survey reported routine use of clinical detoxification therapies to treat a range of medical conditions utilizing multiple therapeutic approaches. Although the majority of NDs reported using some follow-up measurements after detoxification therapy, few of these are an objective means to determine treatment efficacy. Further research is needed in the field of complementary and alternative medicine clinical detoxification to determine the safety and efficacy of these approaches. PMID:22103982

Pharmacotherapy of anxiety disorders: a critical review

PubMed Central

Koen, Nastassja; Stein, Dan J.

2011-01-01

Given the enormous contribution of anxiety disorders to the burden of disease, it is key to optimize their prevention and treatment. In this critical review we assess advances in the pharmacotherapy of anxiety disorders, as well as remaining challenges, in recent decades, the field has seen rigorous clinical trial methods to quantify the efficacy and safety of serendipitously discovered agents, more focused development of medications with selective mechanisms of action, and the gradual translation of insights from laboratory research into proof-of-principle clinical trials. On the positive side, a considerable database of studies shows efficacy and relative tolerability of the selective serotonin reuptake inhibitors in the major anxiety disorders, and secondary analyses of such datasets have informed questions such as optimal definition of response and remission, optimal dose and duration, and comparative efficacy of different agents. Significant challenges in the field include barriers to appropriate diagnosis and treatment of anxiety disorders, failure of a significant proportion of patients to respond to first-line pharmacotherapy agents, and a limited database of efficacy or effectiveness studies to guide treatment in such cases. PMID:22275848

Contact lens disinfecting solutions antibacterial efficacy: comparison between clinical isolates and the standard ISO ATCC strains of Pseudomonas aeruginosa and Staphylococcus aureus

PubMed Central

Mohammadinia, M; Rahmani, S; Eslami, G; Ghassemi-Broumand, M; Aghazadh Amiri, M; Aghaie, Gh; Tabatabaee, S M; Taheri, S; Behgozin, A

2012-01-01

Purpose To evaluate the disinfectant properties of the three multipurpose contact lens disinfecting solutions available in Iran, against clinical isolates and the standard ISO ATCC strains of Pseudomonas aeruginosaand Staphylococcus aureus, based on the international organization for standardization (ISO) 14729 guidelines. Methods Three multipurpose solutions that were tested were ReNu Multiplus, Solo Care Aqua and All-Clean Soft. The test solutions were challenged with clinical isolates and the standard strains of P. aeruginosa(ATCC 9027) and S. aureus(ATCC 6538), based on the ISO Stand-alone procedure for disinfecting products. Solutions were sampled for surviving microorganisms at manufacturer's minimum recommended disinfection time. The number of viable organisms was determined and log reductions calculated. Results All of the three test solutions in this study provided a reduction greater than the required mean 3.0 logarithmic reduction against the recommended standard ATCC strains of P. aeruginosaand S. aureus. Antibacterial effectiveness of Solo Care Aqua and All-Clean Soft against clinical isolates of P. aeruginosaand S. aureuswere acceptable based on ISO 14729 Stand-alone test. ReNu MultiPlus showed a minimum acceptable efficacy against the clinical isolate of S. aureus, but did not reduce the clinical isolate by the same amount. Conclusions Although the contact lens disinfecting solutions meet/exceed the ISO 14729 Stand-alone primary acceptance criteria for standard strains of P. aeruginosaand S. aureus, their efficacy may be insufficient against clinical isolates of these organisms. PMID:22094301

[Virtual reality in the treatment of mental disorders].

PubMed

Malbos, Eric; Boyer, Laurent; Lançon, Christophe

2013-11-01

Virtual reality is a media allowing users to interact in real time with computerized virtual environments. The application of this immersive technology to cognitive behavioral therapies is increasingly exploited for the treatment of mental disorders. The present study is a review of literature spanning from 1992 to 2012. It depicts the utility of this new tool for assessment and therapy through the various clinical studies carried out on subjects exhibiting diverse mental disorders. Most of the studies conducted on tested subjects attest to the significant efficacy of the Virtual Reality Exposure Therapy (VRET) for the treatment of distinct mental disorders. Comparative studies of VRET with the treatment of reference (the in vivo exposure component of the cognitive behavioral therapy) document an equal efficacy of the two methods and in some cases a superior therapeutic effect in favor of the VRET. Even though clinical experiments set on a larger scale, extended follow-up and studies about factors influencing presence are needed, virtual reality exposure represents an efficacious, confidential, affordable, flexible, interactive therapeutic method which application will progressively widened in the field of mental health. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Convection-enhanced Delivery of Therapeutics for Malignant Gliomas.

PubMed

Saito, Ryuta; Tominaga, Teiji

2017-01-15

Convection-enhanced delivery (CED) circumvents the blood-brain barrier by delivering agents directly into the tumor and surrounding parenchyma. CED can achieve large volumes of distribution by continuous positive-pressure infusion. Although promising as an effective drug delivery method in concept, the administration of therapeutic agents via CED is not without challenges. Limitations of distribution remain a problem in large brains, such as those of humans. Accurate and consistent delivery of an agent is another challenge associated with CED. Similar to the difficulties caused by immunosuppressive environments associated with gliomas, there are several mechanisms that make effective local drug distribution difficult in malignant gliomas. In this review, methods for local drug application targeting gliomas are discussed with special emphasis on CED. Although early clinical trials have failed to demonstrate the efficacy of CED against gliomas, CED potentially can be a platform for translating the molecular understanding of glioblastomas achieved in the laboratory into effective clinical treatments. Several clinical studies using CED of chemotherapeutic agents are ongoing. Successful delivery of effective agents should prove the efficacy of CED in the near future.

Convection-enhanced Delivery of Therapeutics for Malignant Gliomas

PubMed Central

SAITO, Ryuta; TOMINAGA, Teiji

2017-01-01

Convection-enhanced delivery (CED) circumvents the blood–brain barrier by delivering agents directly into the tumor and surrounding parenchyma. CED can achieve large volumes of distribution by continuous positive-pressure infusion. Although promising as an effective drug delivery method in concept, the administration of therapeutic agents via CED is not without challenges. Limitations of distribution remain a problem in large brains, such as those of humans. Accurate and consistent delivery of an agent is another challenge associated with CED. Similar to the difficulties caused by immunosuppressive environments associated with gliomas, there are several mechanisms that make effective local drug distribution difficult in malignant gliomas. In this review, methods for local drug application targeting gliomas are discussed with special emphasis on CED. Although early clinical trials have failed to demonstrate the efficacy of CED against gliomas, CED potentially can be a platform for translating the molecular understanding of glioblastomas achieved in the laboratory into effective clinical treatments. Several clinical studies using CED of chemotherapeutic agents are ongoing. Successful delivery of effective agents should prove the efficacy of CED in the near future. PMID:27980285

The effect of berberine on insulin resistance in women with polycystic ovary syndrome: detailed statistical analysis plan (SAP) for a multicenter randomized controlled trial.

PubMed

Zhang, Ying; Sun, Jin; Zhang, Yun-Jiao; Chai, Qian-Yun; Zhang, Kang; Ma, Hong-Li; Wu, Xiao-Ke; Liu, Jian-Ping

2016-10-21

Although Traditional Chinese Medicine (TCM) has been widely used in clinical settings, a major challenge that remains in TCM is to evaluate its efficacy scientifically. This randomized controlled trial aims to evaluate the efficacy and safety of berberine in the treatment of patients with polycystic ovary syndrome. In order to improve the transparency and research quality of this clinical trial, we prepared this statistical analysis plan (SAP). The trial design, primary and secondary outcomes, and safety outcomes were declared to reduce selection biases in data analysis and result reporting. We specified detailed methods for data management and statistical analyses. Statistics in corresponding tables, listings, and graphs were outlined. The SAP provided more detailed information than trial protocol on data management and statistical analysis methods. Any post hoc analyses could be identified via referring to this SAP, and the possible selection bias and performance bias will be reduced in the trial. This study is registered at ClinicalTrials.gov, NCT01138930 , registered on 7 June 2010.

Development and validation of the Family Decision-Making Self-Efficacy Scale

PubMed Central

NOLAN, MARIE T.; HUGHES, MARK T.; KUB, JOAN; TERRY, PETER B.; ASTROW, ALAN; THOMPSON, RICHARD E.; CLAWSON, LORA; TEXEIRA, KENNETH; SULMASY, DANIEL P.

2010-01-01

Objective Several studies have reported high levels of distress in family members who have made health care decisions for loved ones at the end of life. A method is needed to assess the readiness of family members to take on this important role. Therefore, the purpose of this study was to develop and validate a scale to measure family member confidence in making decisions with (conscious patient scenario) and for (unconscious patient scenario) a terminally ill loved one. Methods On the basis of a survey of family members of patients with amyotrophic lateral sclerosis (ALS) enriched by in-depth interviews guided by Self-Efficacy Theory, we developed six themes within family decision making self-efficacy. We then created items reflecting these themes that were refined by a panel of end-of-life research experts. With 30 family members of patients in an outpatient ALS and a pancreatic cancer clinic, we tested the tool for internal consistency using Cronbach’s alpha and for consistency from one administration to another using the test–retest reliability assessment in a subset of 10 family members. Items with item to total scale score correlations of less than .40 were eliminated. Results A 26-item scale with two 13-item scenarios resulted, measuring family self-efficacy in decision making for a conscious or unconscious patient with a Cronbach’s alphas of .91 and .95, respectively. Test–retest reliability was r = .96, p = .002 in the conscious senario and r = .92, p = .009 in the unconscious scenario. Significance of results The Family Decision-Making Self-Efficacy Scale is valid, reliable, and easily completed in the clinic setting. It may be used in research and clinical care to assess the confidence of family members in their ability to make decisions with or for a terminally ill loved one. PMID:19788773

Safety and Efficacy of Methotrexate in Psoriasis: A Meta-Analysis of Published Trials

PubMed Central

West, Jonathan; Ogston, Simon; Foerster, John

2016-01-01

Background Methotrexate (MTX) has been used to treat psoriasis for over half a century. Even so, clinical data characterising its efficacy and safety are sparse. Objective In order to enhance the available evidence, we conducted two meta-analyses, one for efficacy and one for safety outcomes, respectively, according to PRISMA checklist. (Data sources, study criteria, and study synthesis methods are detailed in Methods). Results In terms of efficacy, only eleven studies met criteria for study design and passed a Cochrane risk of bias analysis. Based on this limited dataset, 45.2% [95% confidence interval 34.1–60.0] of patients achieve PASI75 at primary endpoint (12 or 16 weeks, respectively, n = 705 patients across all studies), compared to a calculated PASI75 of 4.4 [3.5–5.6] for placebo, yielding a relative risk of 10.2 [95% C.I. 7.1–14.7]. For safety outcomes, we extended the meta-analysis to include studies employing the same dose range of MTX for other chronic inflammatory conditions, e.g. rheumatoid arthritis, in order not to maximise capture of relevant safety data. Based on 2763 patient safety years, adverse events (AEs) were found treatment limiting in 6.9 ± 1.4% (mean ± s.e.) of patients treated for six months, with an adverse effect profile largely in line with that encountered in clinical practice. Finally, in order to facilitate prospective clinical audit and to help generate long-term treatment outcomes under real world conditions, we also developed an easy to use documentation form to be completed by patients without requirement for additional staff time. Limitations Meta-analyses for efficacy and safety, respectively, employed non-identical selection criteria. Conclusions These meta-analyses summarise currently available evidence on MTX in psoriasis and should be of use to gauge whether local results broadly fall within outcomes. PMID:27168193

Efficacy of Photodynamic Therapy in the Short and Medium Term in the Treatment of Actinic Keratosis, Basal Cell Carcinoma, Acne Vulgaris and Photoaging: Results from Four Clinical Trials

PubMed Central

Martínez-Carpio, PA; Alcolea-López, JM; Vélez, M

2012-01-01

Objective: To determine the clinical efficacy of methyl-aminolevulinate (MAL)-Photodynamic Therapy (PDT) in the treatment of actinic keratosis (AK), basal cell carcinoma (BCC), acne vulgaris (AV) and photoaging (PA), in the short and medium term. Subjects and methods: Four separate prospective studies were designed on patients with AK (n=25), BCC (n=20), AV (n=20) and PA (n=25). Two PDT protocols were applied, and different clinical efficacy criteria were established, including lesion count and size. Two semi-quantitative and four analogue visual scales were completed for the evaluation of results according to the therapist, the patient and two independent experts. Results: In the AK and BCC studies, full clinical remission was observed in 84.7% and 75.7% of lesions, respectively. In the AV study, the number of inflammatory and non-inflammatory lesions fell significantly (p<0.001, p<0.05). In the PA study a reduction in Dover scale scores (3.19 vs. 2.14, p<0.001) was proven. The percentages of satisfied or very satisfied patients were: AK=88%, BCC=90%, AV=89% and PA=80%. A year later, none of the AK or BCC lesions had reappeared, and the cases of AV and PA remained stable, with a tendency towards improvement. Conclusion: the MAL-PDT procedures used produced efficacious, safe and satisfactory results in KA, BCC, AV and PA in the short and medium term. PMID:24511190

Nurses' discourse in contraceptive prescribing: an analysis using Foucault's 'procedures of exclusion'.

PubMed

Hayter, Mark

2007-05-01

This paper is a report of an analysis of the discourse about contraceptive efficacy and side effects used by nurses when prescribing contraception. All women seeking contraception should be informed of the efficacy and potential adverse effects of the particular method they are considering. This information facilitates an informed choice. Women also require this information in order to monitor for any side effects. Paradoxically, side effects are also a key factor in reducing adherence with contraceptive regimens. However, there is no literature that explores specifically how this issue is addressed in clinical consultations, or places these practices in a theoretical context. Forty-nine consultations between nurses and women in sexual health clinics were audio-recorded during 2002. Data were subject to a discourse analysis using Foucault's 'procedures of exclusion' to explore the discursive construction of contraceptive efficacy and side effects The nurses employed specific discursive strategies when discussing contraception. When addressing efficacy, discourse centred on medico-statistical facts, but side effects were described in lay terms that minimized their severity. Nurses contextualized contraceptive side effects within potential problems that women might experience in pregnancy, and also attempted to 'normalize' contraceptive-related problems. Discourse and its deployment play a key role in practitioner-client relationships that sexual health nurses need to become more aware of how they discuss clinical issues about contraception with women. Clinical data on contraceptive side-effects are present in the literature, and it is important that sexual health nurses use this to help women make truly informed decisions.

Safety and Antioxidant Efficacy Profiles of Rutin-Loaded Ethosomes for Topical Application.

PubMed

Cândido, Thalita Marcílio; De Oliveira, Camila Areias; Ariede, Maíra Bueno; Velasco, Maria Valéria Robles; Rosado, Catarina; Baby, André Rolim

2018-05-01

Topical application of dermocosmetics containing antioxidant and/or the intake of antioxidants through diet or supplementation are remarkable tools in an attempt to slow down some of the harmful effects of free radicals. Rutin is a strong antioxidant compound used in food and pharmaceutical industries. It was established that rutin presents a low skin permeation rate, a property that could be considered an inconvenience to the satisfactory action for a dermocosmetic formulation to perform its antioxidant activity onto the skin. Therefore, it is indispensable to improve its delivery, aiming at increasing its antioxidant capacity in deeper layers of the epidermis, being a possibility to associate the rutin to liposomal vesicles, such as ethosomes. Thus, in this work, the pre-clinical safety of rutin-loaded ethosomes was investigated employing an in vitro method, and the clinical safety and efficacy were also assessed. Rutin-loaded ethosomes were efficaciously obtained in a nanoscale dimension with a relevant bioactive compound loading (80.2%) and provided antioxidant in vitro activity in comparison with the blank sample. Pre-clinical and clinical safety assays assured the innocuous profile of the rutin-loaded ethosomes. The ethosomes containing the bioactive compound accomplished a more functional delivery system profile, since in the tape stripping assay, the deeper layers presented higher rutin amounts than the active delivered in its free state. However, the ex vivo antioxidant efficacy test detected no positive antioxidant activity from the rutin-loaded ethosomes, even though the in vitro assay demonstrated an affirmative antioxidant action.

Simulation of cryolipolysis as a novel method for noninvasive fat layer reduction.

PubMed

Majdabadi, Abbas; Abazari, Mohammad

2016-12-20

Regarding previous problems in conventional liposuction methods, the need for development of new fat removal operations was appreciated. In this study we are going to simulate one of the novel methods, cryolipolysis, aimed to tackle those drawbacks. We think that simulation of clinical procedures contributes considerably in efficacious performance of the operations. To do this we have attempted to simulate temperature distribution in a sample fat of the human body. Using Abaqus software we have presented the graphical display of temperature-time variations within the medium. Findings of our simulation indicate that tissue temperature decreases after cold exposure of about 30 min. It can be seen that the minimum temperature of tissue occurs in shallow layers of the sample and the temperature in deeper layers of the sample remains nearly unchanged. It is clear that cold exposure time of more than the specific time (t > 30 min) does not result in considerable changes. Numerous clinical studies have proved the efficacy of cryolipolysis. This noninvasive technique has eliminated some of drawbacks of conventional methods. Findings of our simulation clearly prove the efficiency of this method, especially for superficial fat layers.

Characteristics of caring self-efficacy in pediatric nurses: a qualitative study.

PubMed

Alavi, Azam; Bahrami, Masoud; Zargham-Boroujeni, Ali; Yousefy, Alireza

2015-07-01

The present study was conducted to clarify pediatric nurses' characteristics of caring self-efficacy. This study was conducted using a qualitative content analysis approach. The participants included 27 pediatric nurses and clinical instructors, selected purposively. Data were collected using semi-structured interviews and were analyzed using the content analysis method. Data analysis generated four main themes as attributes of a self-efficient pediatric nurse including: (a) professional communications; (b) management of care; (c) altruism; and (d) proficiency. Nursing managers and instructors can use these results to help develop nurses' empowerment and self-efficacy, especially in pediatric care. © 2015, Wiley Periodicals, Inc.

The role of religiosity, coping strategies, self-efficacy and personality dimensions in the prediction of Iranian undergraduate rehabilitation interns' satisfaction with their clinical experience.

PubMed

Mirsaleh, Y R; Rezai, H; Kivi, S R; Ghorbani, R

2010-12-01

to investigate the relationship between religiosity, coping styles, self-efficacy and personality dimensions as predictors of satisfaction with clinical experience in rehabilitation interns during transition from academic study to clinical internship. a cross-sectional survey design. five rehabilitation faculties. three hundred and eighteen undergraduate rehabilitation interns, including physical therapy, occupational therapy and speech and language pathology students. Islamic Religiosity Scale, Ways of Coping Questionnaire, General Self-efficacy Scale, NEO Five Factor Inventory, and Satisfaction with Clinical Experiences Questionnaire. religiosity, problem-focused coping and general self-efficacy had significant positive correlation with satisfaction with clinical internship in rehabilitation students. Among personality dimensions, openness, agreement and consciousness had significant positive correlation with satisfaction with clinical experience and neuroticism had significant negative correlation with satisfaction with clinical experience. The results of regression analysis demonstrated that religiosity and self-efficacy had important roles in the prediction of satisfaction with clinical experience in all the rehabilitation intern students of three disciplines (physical therapy, occupational therapy, and speech and language pathology). religiosity, problem-focused coping and general self-efficacy seem to be good predictors of satisfaction with clinical internship in rehabilitation students.

Exposing Clinicians to Exposure: A Randomized Controlled Dissemination Trial of Exposure Therapy for Anxiety Disorders

PubMed Central

Harned, Melanie S.; Dimeff, Linda A.; Woodcock, Eric A.; Kelly, Tim; Zavertnik, Jake; Contreras, Ignacio; Danner, Sankirtana M.

2014-01-01

Objective The present study evaluated three technology-based methods of training mental health providers in exposure therapy (ET) for anxiety disorders. Training methods were designed to address common barriers to the dissemination of ET, including limited access to training, negative clinician attitudes toward ET, and lack of support during and following training. Method Clinicians naïve to ET (N=181, Mage = 37.4, 71.3% female, 72.1% Caucasian) were randomly assigned to: 1) an interactive, multimedia online training (OLT), 2) OLT plus a brief, computerized motivational enhancement intervention (OLT+ME), or 3) OLT + ME plus a web-based learning community (OLT+ME+LC). Assessments were completed at baseline, post-training, and 6 and 12 weeks following training. Outcomes include satisfaction, knowledge, self-efficacy, attitudes, self-reported clinical use, and observer-rated clinical proficiency. Results All three training methods led to large and comparable improvements in self-efficacy and clinical use of ET, indicating that OLT alone was sufficient for improving these outcomes. The addition of the ME intervention did not significantly improve outcomes in comparison to OLT alone. Supplementing the OLT with both the ME intervention and the LC significantly improved attitudes and clinical proficiency in comparison to OLT alone. The OLT+ME+LC condition was superior to both other conditions in increasing knowledge of ET. Conclusions Multi-component trainings that address multiple potential barriers to dissemination appear to be most effective in improving clinician outcomes. Technology-based training methods offer a satisfactory, effective, and scalable way to train mental health providers in evidence-based treatments such as ET. PMID:25311284

Clinical efficacy of gene-modified stem cells in adenosine deaminase–deficient immunodeficiency

PubMed Central

Shaw, Kit L.; Garabedian, Elizabeth; Mishra, Suparna; Barman, Provaboti; Davila, Alejandra; Carbonaro, Denise; Shupien, Sally; Silvin, Christopher; Geiger, Sabine; Nowicki, Barbara; Smogorzewska, E. Monika; Brown, Berkley; Wang, Xiaoyan; de Oliveira, Satiro; Choi, Yeong; Ikeda, Alan; Terrazas, Dayna; Fu, Pei-Yu; Yu, Allen; Fernandez, Beatriz Campo; Cooper, Aaron R.; Engel, Barbara; Podsakoff, Greg; Balamurugan, Arumugam; Anderson, Stacie; Muul, Linda; Jagadeesh, G. Jayashree; Kapoor, Neena; Tse, John; Moore, Theodore B.; Purdy, Ken; Rishi, Radha; Mohan, Kathey; Skoda-Smith, Suzanne; Buchbinder, David; Abraham, Roshini S.; Scharenberg, Andrew; Yang, Otto O.; Cornetta, Kenneth; Gjertson, David; Hershfield, Michael; Sokolic, Rob; Candotti, Fabio

2017-01-01

BACKGROUND. Autologous hematopoietic stem cell transplantation (HSCT) of gene-modified cells is an alternative to enzyme replacement therapy (ERT) and allogeneic HSCT that has shown clinical benefit for adenosine deaminase–deficient (ADA-deficient) SCID when combined with reduced intensity conditioning (RIC) and ERT cessation. Clinical safety and therapeutic efficacy were evaluated in a phase II study. METHODS. Ten subjects with confirmed ADA-deficient SCID and no available matched sibling or family donor were enrolled between 2009 and 2012 and received transplantation with autologous hematopoietic CD34+ cells that were modified with the human ADA cDNA (MND-ADA) γ-retroviral vector after conditioning with busulfan (90 mg/m2) and ERT cessation. Subjects were followed from 33 to 84 months at the time of data analysis. Safety of the procedure was assessed by recording the number of adverse events. Efficacy was assessed by measuring engraftment of gene-modified hematopoietic stem/progenitor cells, ADA gene expression, and immune reconstitution. RESULTS. With the exception of the oldest subject (15 years old at enrollment), all subjects remained off ERT with normalized peripheral blood mononuclear cell (PBMC) ADA activity, improved lymphocyte numbers, and normal proliferative responses to mitogens. Three of nine subjects were able to discontinue intravenous immunoglobulin replacement therapy. The MND-ADA vector was persistently detected in PBMCs (vector copy number [VCN] = 0.1–2.6) and granulocytes (VCN = 0.01–0.3) through the most recent visits at the time of this writing. No patient has developed a leukoproliferative disorder or other vector-related clinical complication since transplant. CONCLUSION. These results demonstrate clinical therapeutic efficacy from gene therapy for ADA-deficient SCID, with an excellent clinical safety profile. TRIAL REGISTRATION. ClinicalTrials.gov NCT00794508. FUNDING. Food and Drug Administration Office of Orphan Product Development award, RO1 FD003005; NHLBI awards, PO1 HL73104 and Z01 HG000122; UCLA Clinical and Translational Science Institute awards, UL1RR033176 and UL1TR000124. PMID:28346229

Postauthorization safety surveillance of ADVATE [antihaemophilic factor (recombinant), plasma/albumin-free method] demonstrates efficacy, safety and low-risk for immunogenicity in routine clinical practice.

PubMed

Oldenburg, J; Goudemand, J; Valentino, L; Richards, M; Luu, H; Kriukov, A; Gajek, H; Spotts, G; Ewenstein, B

2010-11-01

  Postauthorization safety surveillance of factor VIII (FVIII) concentrates is essential for assessing rare adverse event incidence. We determined safety and efficacy of ADVATE [antihaemophilic factor (recombinant), plasma/albumin-free method, (rAHF-PFM)] during routine clinical practice. Subjects with differing haemophilia A severities and medical histories were monitored during 12 months of prophylactic and/or on-demand therapy. Among 408 evaluable subjects, 386 (95%) received excellent/good efficacy ratings for all on-demand assessments; the corresponding number for subjects with previous FVIII inhibitors was 36/41 (88%). Among 276 evaluable subjects receiving prophylaxis continuously in the study, 255 (92%) had excellent/good ratings for all prophylactic assessments; the corresponding number for subjects with previous FVIII inhibitors was 41/46 (89%). Efficacy of surgical prophylaxis was excellent/good in 16/16 evaluable procedures. Among previously treated patients (PTPs) with >50 exposure days (EDs) and FVIII≤2%, three (0.75%) developed low-titre inhibitors. Two of these subjects had a positive inhibitor history; thus, the incidence of de novo inhibitor formation in PTPs with FVIII≤2% and no inhibitor history was 1/348 (0.29%; 95% CI, 0.01-1.59%). A PTP with moderate haemophilia developed a low-titre inhibitor. High-titre inhibitors were reported in a PTP with mild disease (following surgery), a previously untreated patient (PUP) with moderate disease (following surgery) and a PUP with severe disease. The favourable benefit/risk profile of rAHF-PFM previously documented in prospective clinical trials has been extended to include a broader range of haemophilia patients, many of whom would have been ineligible for registration studies. © 2010 Blackwell Publishing Ltd.

Primary outcome indices in illicit drug dependence treatment research: systematic approach to selection and measurement of drug use end-points in clinical trials

PubMed Central

Donovan, Dennis M.; Bigelow, George E.; Brigham, Gregory S.; Carroll, Kathleen M.; Cohen, Allan J.; Gardin, John G.; Hamilton, John A.; Huestis, Marilyn A.; Hughes, John R.; Lindblad, Robert; Marlatt, G. Alan; Preston, Kenzie L.; Selzer, Jeffrey A.; Somoza, Eugene C.; Wakim, Paul G.; Wells, Elizabeth A.

2012-01-01

Aims Clinical trials test the safety and efficacy of behavioral and pharmacological interventions in drug-dependent individuals. However, there is no consensus about the most appropriate outcome(s) to consider in determining treatment efficacy or on the most appropriate methods for assessing selected outcome(s). We summarize the discussion and recommendations of treatment and research experts, convened by the US National Institute on Drug Abuse, to select appropriate primary outcomes for drug dependence treatment clinical trials, and in particular the feasibility of selecting a common outcome to be included in all or most trials. Methods A brief history of outcomes employed in prior drug dependence treatment research, incorporating perspectives from tobacco and alcohol research, is included. The relative merits and limitations of focusing on drug-taking behavior, as measured by self-report and qualitative or quantitative biological markers, are evaluated. Results Drug-taking behavior, measured ideally by a combination of self-report and biological indicators, is seen as the most appropriate proximal primary outcome in drug dependence treatment clinical trials. Conclusions We conclude that the most appropriate outcome will vary as a function of salient variables inherent in the clinical trial, such as the type of intervention, its target, treatment goals (e.g. abstinence or reduction of use) and the perspective being taken (e.g. researcher, clinical program, patient, society). It is recommended that a decision process, based on such trial variables, be developed to guide the selection of primary and secondary outcomes as well as the methods to assess them. PMID:21781202

New quantitative method for evaluation of motor functions applicable to spinal muscular atrophy.

PubMed

Matsumaru, Naoki; Hattori, Ryo; Ichinomiya, Takashi; Tsukamoto, Katsura; Kato, Zenichiro

2018-03-01

The aim of this study was to develop and introduce new method to quantify motor functions of the upper extremity. The movement was recorded using a three-dimensional motion capture system, and the movement trajectory was analyzed using newly developed two indices, which measure precise repeatability and directional smoothness. Our target task was shoulder flexion repeated ten times. We applied our method to a healthy adult without and with a weight, simulating muscle impairment. We also applied our method to assess the efficacy of a drug therapy for amelioration of motor functions in a non-ambulatory patient with spinal muscular atrophy. Movement trajectories before and after thyrotropin-releasing hormone therapy were analyzed. In the healthy adult, we found the values of both indices increased significantly when holding a weight so that the weight-induced deterioration in motor function was successfully detected. From the efficacy assessment of drug therapy in the patient, the directional smoothness index successfully detected improvements in motor function, which were also clinically observed by the patient's doctors. We have developed a new quantitative evaluation method of motor functions of the upper extremity. Clinical usability of this method is also greatly enhanced by reducing the required number of body-attached markers to only one. This simple but universal approach to quantify motor functions will provide additional insights into the clinical phenotypes of various neuromuscular diseases and developmental disorders. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

A new dry-surface biofilm model: An essential tool for efficacy testing of hospital surface decontamination procedures.

PubMed

Almatroudi, Ahmad; Hu, Honghua; Deva, Anand; Gosbell, Iain B; Jacombs, Anita; Jensen, Slade O; Whiteley, Greg; Glasbey, Trevor; Vickery, Karen

2015-10-01

The environment has been shown to be a source of pathogens causing infections in hospitalised patients. Incorporation of pathogens into biofilms, contaminating dry hospital surfaces, prolongs their survival and renders them tolerant to normal hospital cleaning and disinfection procedures. Currently there is no standard method for testing efficacy of detergents and disinfectants against biofilm formed on dry surfaces. The aim of this study was to develop a reproducible method of producing Staphylococcus aureus biofilm with properties similar to those of biofilm obtained from dry hospital clinical surfaces, for use in efficacy testing of decontamination products. The properties (composition, architecture) of model biofilm and biofilm obtained from clinical dry surfaces within an intensive care unit were compared. The CDC Biofilm Reactor was adapted to create a dry surface biofilm model. S. aureus ATCC 25923 was grown on polycarbonate coupons. Alternating cycles of dehydration and hydration in tryptone soy broth (TSB) were performed over 12 days. Number of biofilm bacteria attached to individual coupons was determined by plate culture and the coefficient of variation (CV%) calculated. The DNA, glycoconjugates and protein content of the biofilm were determined by analysing biofilm stained with SYTO 60, Alexa-488-labelled Aleuria aurantia lectin and SyproOrange respectively using Image J and Imaris software. Biofilm architecture was analysed using live/dead staining and confocal microscopy (CM) and scanning electron microscopy (SEM). Model biofilm was compared to naturally formed biofilm containing S. aureus on dry clinical surfaces. The CDC Biofilm reactor reproducibly formed a multi-layered, biofilm containing about 10(7) CFU/coupon embedded in thick extracellular polymeric substances. Within run CV was 9.5% and the between run CV was 10.1%. Protein was the principal component of both the in vitro model biofilm and the biofilms found on clinical surfaces. Continued dehydration and ageing of the model biofilm for 30 days increased the % of protein, marginally decreased gylcoconjugate % but reduced extracellular DNA by 2/3. The surface of both model and clinical biofilms was rough reflecting the heterogeneous nature of biofilm formation. The average maximum thickness was 30.74±2.1 μm for the in vitro biofilm model and between 24 and 47 μm for the clinical biofilms examined. The laboratory developed biofilm was similar to clinical biofilms in architecture and composition. We propose that this method is suitable for evaluating the efficacy of surface cleaners and disinfectants in removing biofilm formed on dry clinical surfaces as both within run and between run variation was low, and the required equipment is easy to use, cheap and readily available. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

Last-observation-carried-forward imputation method in clinical efficacy trials: review of 352 antidepressant studies.

PubMed

Woolley, Stephen B; Cardoni, Alex A; Goethe, John W

2009-12-01

To determine the prevalence, over 40 years, of using the last-observation-carried-forward (LOCF) imputation method in clinical trials, the association between use of LOCF and how the trials were conducted, and the extent of information about attrition and LOCF use in published reports. Retrospective analysis of the reports of randomized antidepressant efficacy trials published over a 40-year period (1965-2004). MEDLINE database, Cochrane reviews, reference- and bibliography-based manual search, and publication list services. A total of 352 trials met the following criteria for analysis: antidepressant comparative efficacy trial, randomized design, patients with major depressive disorder, English-language article, published during 1965-2004, and first report of a trial. Design, attrition, and data analysis characteristics were recorded by investigators and trained assistants. Analyses included descriptive statistics of the trial size, duration, and number of patients who dropped out in LOCF versus non-LOCF studies, as well as the extent to which dropouts and the potential bias associated with attrition was discussed in the published report. The frequency of published antidepressant clinical trials increased from less than 1 trial/year (1965-1974) to 19 trials/year (1990-1994). Trials using the LOCF method were significantly larger than non-LOCF trials (p<0.01), and the proportion of subjects dropping out was significantly greater (p<0.05) in LOCF versus non-LOCF trials. The proportion of subjects dropping out remained relatively constant over time (approximately 30%) but was significantly greater among LOCF (30.9%) than non-LOCF (28.8%) trials (p<0.01). The LOCF study articles were more likely to report dropouts, but only 7% of these articles reported outcomes recorded for subjects before they dropped out. Less than 16% of articles discussed bias associated with dropouts, 6.8% discussed the direction of bias, and only about 2% suggested the magnitude of the bias. The percentage of clinical antidepressant trials using the LOCF method and the percentage of study subjects' data imputed by using LOCF increased many-fold during 1965-2004. Published reports of trials provided little information to allow readers to assess possible bias introduced by use of the LOCF method.

Coronary diet intervention with olive oil and cardiovascular prevention study (the CORDIOPREV study); rationale, methods, and baseline characteristics: a clinical trial comparing the efficacy of a Mediterranean diet rich...

USDA-ARS?s Scientific Manuscript database

Coronary heart disease (CHD) represents a major global health burden. However, despite the well-known influence that dietary habits exert over the progression of this disease, there are no well-established and scientifically sound dietary approaches to prevent the onset of clinical outcomes in secon...

The Effect of Cognitive-Behavioral Therapy versus Treatment as Usual for Anxiety in Children with Autism Spectrum Disorders: A Randomized, Controlled Trial

ERIC Educational Resources Information Center

Storch, Eric A.; Arnold, Elysse B.; Lewin, Adam B.; Nadeau, Josh M.; Jones, Anna M.; De Nadai, Alessandro S.; Mutch, P. Jane; Selles, Robert R.; Ung, Danielle; Murphy, Tanya K.

2013-01-01

Objective: To examine the efficacy of a modular cognitive-behavioral therapy (CBT) protocol relative to treatment as usual (TAU) among children with high-functioning autism spectrum disorders (ASD) and clinically significant anxiety. Method: A total of 45 children (7-11 years of age) with high-functioning ASD and clinically significant anxiety…

Depression and Cancer Survivorship: Importance of Coping Self-Efficacy in Post-Treatment Survivors

PubMed Central

Philip, Errol J.; Merluzzi, Thomas V.; Zhang, Zhiyong; Heitzmann, Carolyn A.

2012-01-01

Purpose An estimated 30% of cancer patients are expected to experience clinically significant psychological distress during the treatment phase of their disease. Despite significant attention being directed to the mental health needs of individuals undergoing and completing treatment, there is less known about the mental health needs of survivors and the role of potential protective factors in survivorship, such as coping self-efficacy and social support. Method One hundred and twenty-four post-treatment cancer survivors (mean age = 62.23 years, female = 70%, average 9.3 years post-treatment) were asked to complete measures of physical symptoms, coping self-efficacy, social support, and depression as part of a national convenience sample of cancer patients and survivors. Results About 20% of participants possessed scores on the CES-D indicative of clinically-relevant depression. Coping self-efficacy was not only a significant predictor of depression (43% VAC); it also partially mediated the relationship between symptoms and depression. Social support accounted for limited variance and was not a significant predictor of depression in a model containing both social support and coping self-efficacy as predictors. Conclusion A substantial minority of post-treatment survivors reported depression symptomatology. Coping self-efficacy may be an important component of patients’ adjustment and possible target for intervention. These results highlight the ongoing mental health and support needs of cancer survivors. PMID:22573371

The job self-efficacy and job involvement of clinical nursing teachers.

PubMed

Yang, Hui-Ling; Kao, Yu-Hsiu; Huang, Yi-Ching

2006-09-01

This paper explored the present status of self-efficacy and job involvement of clinical nursing teachers and investigated the predictive power of teachers' personal background variables on such, as well as the relationship between self-efficacy and job involvement. A total of 419 participants in the survey sample were chosen among clinical nursing teachers at 19 public and private institutes of technology and junior colleges in Taiwan in 2004. The self-developed structural questionnaire was categorized into three sections, including personal background data, job self-efficacy related to the clinical teaching inventory and job involvement related to clinical teaching inventory. Of the total 419 questionnaires distributed for this cross-sectional survey, 266 valid copies were registered, at a recovery rate of 63%. Findings indicated that both the job self-efficacy and job involvement of clinical nursing teachers are at a medium to high level and that significant differences exist in job self-efficacy and job involvement based on differences in age, marital status, teaching seniority, teacher qualifications, and job satisfaction. Second, samples have significantly different performance in self-efficacy due to differences in education level attained and the medical institution to which nursing teachers had been assigned. Self-efficacy and job involvement are significantly positively correlated. These results can serve as a reference for the cultivation of nursing teachers and reform of clinical nursing education in the future.

Exact tests using two correlated binomial variables in contemporary cancer clinical trials.

PubMed

Yu, Jihnhee; Kepner, James L; Iyer, Renuka

2009-12-01

New therapy strategies for the treatment of cancer are rapidly emerging because of recent technology advances in genetics and molecular biology. Although newer targeted therapies can improve survival without measurable changes in tumor size, clinical trial conduct has remained nearly unchanged. When potentially efficacious therapies are tested, current clinical trial design and analysis methods may not be suitable for detecting therapeutic effects. We propose an exact method with respect to testing cytostatic cancer treatment using correlated bivariate binomial random variables to simultaneously assess two primary outcomes. The method is easy to implement. It does not increase the sample size over that of the univariate exact test and in most cases reduces the sample size required. Sample size calculations are provided for selected designs.

Estimating the efficacy of medical abortion.

PubMed

Trussell, J; Ellertson, C

1999-09-01

Comparisons of the efficacy of different regimens of medical abortion are difficult because of the widely varying protocols (even for testing identical regimens), divergent definitions of success and failure, and lack of a standard method of analysis. In this article we review the current efficacy literature on medical abortion, highlighting some of the most important differences in the way that efficacy has been analyzed. We then propose a standard conceptual approach and the accompanying statistical methods for analyzing clinical trials of medical abortion and to explain how clinical investigators can implement this approach. Our review reveals that research on the efficacy of medical abortion has closely followed the conceptual model used for analysis of surgical abortion. The problem, however, is that, whereas surgical abortion is a discrete event occurring in the space of a few minutes or less, medical abortion is a process typically lasting from several days to several weeks. In this process, two events may occur that are not possible with surgical abortion. First, the woman can opt out of the process before a fair determination of efficacy can be made. Second, the process of medical abortion allows time for surgical interventions that may be convenient for the clinician but not strictly necessary from a medical perspective. Another difference from surgical abortions is that, for medical abortions, different medical abortion protocols specify different waiting periods, giving the drugs less time to work in some studies than in others before a determination of efficacy is made. We argue that, when analyzing efficacy of medical abortion, researchers should abandon their close reliance on the analogy to surgical abortion. In fact, medical abortion is more appropriately analyzed by life table procedures developed for the study of another fertility regulation technology; contraception. As with medical abortion, a woman initiating use of a contraceptive method can change her mind after some period of exposure and opt out. Also, as with medical abortion, a contraceptive can fail, usually with the risk of failure depending heavily on whether or not the woman follows the protocol for that method precisely. Finally, as with medical abortion, medical conditions may arise that necessitate discontinuing use of the contraceptive method. In both cases, these medical conditions are sometimes open to interpretation or subject to the skill, judgment, or experience of the clinician involved. The appropriate information to collect for a multiple decrement life table analysis of medical abortion includes data on compliance with the protocol, timing of the event of interest (abortion) when it is observable, and, because we argue that these should be regarded as events of interest, a typology of any surgical interventions that are conducted during the woman's participation in the study.

Adherence issues related to sublingual immunotherapy as perceived by allergists

PubMed Central

Scurati, Silvia; Frati, Franco; Passalacqua, Gianni; Puccinelli, Paola; Hilaire, Cecile; Incorvaia, Cristoforo

2010-01-01

Objectives: Sublingual immunotherapy (SLIT) is a viable alternative to subcutaneous immunotherapy to treat allergic rhinitis and asthma, and is widely used in clinical practice in many European countries. The clinical efficacy of SLIT has been established in a number of clinical trials and meta-analyses. However, because SLIT is self-administered by patients without medical supervision, the degree of patient adherence with treatment is still a concern. The objective of this study was to evaluate the perception by allergists of issues related to SLIT adherence. Methods: We performed a questionnaire-based survey of 296 Italian allergists, based on the adherence issues known from previous studies. The perception of importance of each item was assessed by a VAS scale ranging from 0 to 10. Results: Patient perception of clinical efficacy was considered the most important factor (ranked 1 by 54% of allergists), followed by the possibility of reimbursement (ranked 1 by 34%), and by the absence of side effects (ranked 1 by 21%). Patient education, regular follow-up, and ease of use of SLIT were ranked first by less than 20% of allergists. Conclusion: These findings indicate that clinical efficacy, cost, and side effects are perceived as the major issues influencing patient adherence to SLIT, and that further improvement of adherence is likely to be achieved by improving the patient information provided by prescribers. PMID:20622914

Emerging Applications of Stem Cell and Regenerative Medicine to Sports Injuries

PubMed Central

Ajibade, David A.; Vance, Danica D.; Hare, Joshua M.; Kaplan, Lee D.; Lesniak, Bryson P.

2014-01-01

Background: The treatment of sports-related musculoskeletal injuries with stem cells has become more publicized because of recent reports of high-profile athletes undergoing stem cell procedures. There has been increased interest in defining the parameters of safety and efficacy and the indications for potential use of stem cells in clinical practice. Purpose: To review the role of regenerative medicine in the treatment of sports-related injuries. Study Design: Review. Method: Relevant studies were identified through a PubMed search combining the terms stem cells and cartilage, ligament, tendon, muscle, and bone from January 2000 to August 2013. Studies and works cited in these studies were also reviewed. Results: Treatment of sports-related injuries with stem cells shows potential for clinical efficacy from the data available from basic science and animal studies. Conclusion: Cell-based therapies and regenerative medicine offer safe and potentially efficacious treatment for sports-related musculoskeletal injuries. Basic science and preclinical studies that support the possibility of enhanced recovery from sports injuries using cell-based therapies are accumulating; however, more clinical evidence is necessary to define the indications and parameters for their use. Accordingly, exposing patients to cell-based therapies could confer an unacceptable risk profile with minimal or no benefit. Continued clinical testing with animal models and clinical trials is necessary to determine the relative risks and benefits as well as the indications and methodology of treatment. PMID:26535296

PODCAST: From Lost in Translation to Paradise Found: Enabling Protein Biomarker Method Transfer by Mass Spectrometry | Office of Cancer Clinical Proteomics Research

Cancer.gov

Translation of novel biomarkers into clinical care for the evaluation of therapeutic safety and efficacy has been slow, partly attributable to the cost and complexity of immunoassay development.  The potential for liquid chromatography-tandem mass spectrometry (LC-MS/MS) to streamline the translation of novel protein biomarkers is profound.  Drs. Henry Rodriguez and Andrew Hoofnagle discuss what the future may be for clinical proteomics. This is an American Association for Clinical Chemistry (AACC) podcast.

Factors Related to Healthy Diet and Physical Activity in Hospital-Based Clinical Nurses.

PubMed

Albert, Nancy M; Butler, Robert; Sorrell, Jeanne

2014-09-30

Hospitals often promote healthy lifestyles, but little is known about nurses' actual diet and physical activity. Greater understanding about these lifestyle choices for clinical nurses may improve existing hospital-based programs and/or create desirable services. This article discusses a study that considered diet and physical activity of clinical nurses, using elements of Pender's self-care theory as a conceptual framework. Study methods included a cross-sectional, correlational design and a convenience sample of 278 nurses who worked on units with 24 hours/day and seven days-per-week responsibilities. Participants completed diet and exercise questionnaires about perceptions of attitudes and opinions, barriers, diet benefits/exercise motivators, self-efficacy, and locus of control, and personal and work characteristics. Diet and activity categories were created. Study results demonstrated that over 50% of nurses had moderately healthy diets but were insufficiently active. Healthy diet and physical activity levels were associated with higher self-efficacy, more diet benefits and physical activity motivators, fewer perceived barriers, and confidence in body image. The article discussion and conclusion sections note areas for future research and suggest that focused interventions that address benefits, motivators, and self-efficacy may increase participation in hospital-based programs and enhance healthy lifestyle for hospital-based clinical nurses.

Rhodiola rosea therapy for major depressive disorder: a study protocol for a randomized, double-blind, placebo- controlled trial

PubMed Central

Mao, Jun J; Li, Qing S.; Soeller, Irene; Xie, Sharon X; Amsterdam, Jay D.

2014-01-01

Background Rhodiola rosea (R. rosea), a botanical of both western and traditional Chinese medicine, has been used as a folk remedy for improving stamina and reducing stress. However, few controlled clinical trials have examined the safety and efficacy of R. rosea for the treatment of major depressive disorder (MDD). This study seeks to evaluate the safety and efficacy of R. rosea in a 12-week, randomized, double-blind, placebo-controlled, parallel group study design. Methods / Design Subjects with MDD not receiving antidepressant therapy will be randomized to either R. rosea extract 340–1,360 mg daily; sertraline 50–200 mg daily, or placebo for 12 weeks. The primary outcome measure will be change over time in the mean 17-item Hamilton Depression Rating score. Secondary outcome measures will include safety and quality of life ratings. Statistical procedures will include mixed-effects models to assess efficacy for primary and secondary outcomes. Discussion This study will provide valuable preliminary information on the safety and efficacy data of R. rosea versus conventional antidepressant therapy of MDD. It will also inform additional hypotheses and study design of future, fully powered, phase III clinical trials with R. rosea to determine its safety and efficacy in MDD. PMID:25610752

Gender Differences in the Efficacy and Safety of Chronic Nightly Zolpidem

PubMed Central

Roehrs, Timothy A.; Roth, Thomas

2016-01-01

Study Objectives: Studies have shown pharmacokinetic differences for hypnotics in women compared to men, but few studies have assessed either short-or long-term differences in efficacy and safety. Methods: To evaluate gender differences in the efficacy and safety of chronic nightly zolpidem (10 mg), we did a post hoc assessment of a large clinical trial. In the trial, participants with primary insomnia (n = 89), ages 23–70, meeting DSM-IV-TR criteria for primary insomnia were randomized, double blind, to nightly zolpidem, 10 mg (n = 47) or placebo (n = 42) 30 minutes before bedtime nightly for 12 months. Polysomnographic sleep on 2 nights in months 1 and 8 and likelihood of next-day sleepiness, rebound insomnia, and dose escalation were evaluated in months 1, 4, and 12. Results: Relative to placebo, zolpidem significantly increased sleep efficiency and reduced sleep latency and wake after sleep onset assessed at months 1 and 8, with no differences in efficacy between women and men and no diminution of efficacy over months. On a next-day multiple sleep latency test (MSLT), no residual sedation was observed for either women or men. No rebound insomnia or dose escalation was seen with no gender differences in either. Conclusions: In adults with primary insomnia, nightly zolpidem administration showed no gender differences in acute or chronic efficacy or in next-day sleepiness. Zolpidem remained efficacious and safe across 12 months. Clincial Trials Registration: ClinicalTrials.gov Identifier: NCT01006525; Trial Name: Safety and Efficacy of Chronic Hypnotic Use; http://clinicaltrials.gov/ct2/show/NCT01006525. Citation: Roehrs TA, Roth T. Gender differences in the efficacy and safety of chronic nightly zolpidem. J Clin Sleep Med 2016;12(3):319–325. PMID:26446253

Gender identity, research self-efficacy and research intention in trainee clinical psychologists in the UK.

PubMed

Wright, Anne B; Holttum, Sue

2012-01-01

This study tested, with a sample of United Kingdom (UK) trainee clinical psychologists, part of an existing model of factors that influence clinical psychologists' levels of research activity, in which gender identity is hypothesized to influence research self-efficacy and this in turn strength of intention to do research. A sample of 121 trainee clinical psychologists (56 men and 65 women) completed a measure of gender identity, research intention, and a research self-efficacy scale. Results indicated no differences in levels of research intention or research self-efficacy between the biological sexes or according to category-based gender identities (masculine and feminine). However, masculinity as a scale quantity was statistically significantly related to stronger research intention, preference for conducting quantitative research and research self-efficacy. Multiple regression analysis provided evidence that research self-efficacy may mediate between masculinity and strength of research intention. Research self-efficacy was the strongest predictor of intention to do research in the future. Findings have relevance for clinical psychology training as research activity directly impacts upon advances in the discipline of clinical psychology, implementation of research into practice, and evaluation of psychological therapies. Copyright © 2010 John Wiley & Sons, Ltd.

Impact of critical thinking disposition, general self-efficacy, and leadership on clinical competence in nursing students.

PubMed

Park, Jee Won; Kim, Chun Ja; Kim, Yong Soon; Yoo, Moon Sook; Yoo, Hyera; Chae, Sun Mi; Ahn, Jeong Ah

2012-09-01

The purpose of this study was to evaluate the relationships among critical thinking disposition, general self-efficacy, leadership and clinical competence, and identify the factors influencing clinical competence in nursing students. In this descriptive study, 153 nursing students (from 2nd to 4th school year) of a university in South Korea were enrolled in December 2010. The instruments for this study were the Korean versions of the Critical Thinking Disposition Scale, General Self-Efficacy Scale, Leadership Inventory, and Clinical Competence Scale. Data were analyzed by descriptive statistics, t-test, MANOVA, Pearson correlation, and multiple linear regression with PASW 18.0 software. The mean scores (ranging from 1 to 5) in nursing students for critical thinking disposition, general self-efficacy, leadership, and clinical competence were 3.44, 3.51, 3.55, and 3.42, respectively. Positive correlations were found for clinical competence with critical thinking disposition, general self-efficacy, and leadership. The strongest predictor of clinical competence was leadership. In addition, leadership, nursing school year, and subjective academic achievement accounted for 34.5% of variance in clinical competence. This study revealed that developing leadership, critical thinking disposition, and self-efficacy in undergraduate nursing education is important to improve clinical competence of nursing students.

The Influence of Big (Clinical) Data and Genomics on Precision Medicine and Drug Development.

PubMed

Denny, Joshua C; Van Driest, Sara L; Wei, Wei-Qi; Roden, Dan M

2018-03-01

Drug development continues to be costly and slow, with medications failing due to lack of efficacy or presence of toxicity. The promise of pharmacogenomic discovery includes tailoring therapeutics based on an individual's genetic makeup, rational drug development, and repurposing medications. Rapid growth of large research cohorts, linked to electronic health record (EHR) data, fuels discovery of new genetic variants predicting drug action, supports Mendelian randomization experiments to show drug efficacy, and suggests new indications for existing medications. New biomedical informatics and machine-learning approaches advance the ability to interpret clinical information, enabling identification of complex phenotypes and subpopulations of patients. We review the recent history of use of "big data" from EHR-based cohorts and biobanks supporting these activities. Future studies using EHR data, other information sources, and new methods will promote a foundation for discovery to more rapidly advance precision medicine. © 2017 American Society for Clinical Pharmacology and Therapeutics.

Evaluating Adaptation of a Cancer Clinical Trial Decision Aid for Rural Cancer Patients: A Mixed-Methods Approach.

PubMed

Pathak, Swati; George, Nerissa; Monti, Denise; Robinson, Kathy; Politi, Mary C

2018-06-03

Rural-residing cancer patients often do not participate in clinical trials. Many patients misunderstand cancer clinical trials and their rights as participant. The purpose of this study is to modify a previously developed cancer clinical trials decision aid (DA), incorporating the unique needs of rural populations, and test its impact on knowledge and decision outcomes. The study was conducted in two phases. Phase I recruited 15 rural-residing cancer survivors in a qualitative usability study. Participants navigated the original DA and provided feedback regarding usability and implementation in rural settings. Phase II recruited 31 newly diagnosed rural-residing cancer patients. Patients completed a survey before and after using the revised DA, R-CHOICES. Primary outcomes included decisional conflict, decision self-efficacy, knowledge, communication self-efficacy, and attitudes towards and willingness to consider joining a trial. In phase I, the DA was viewed positively by rural-residing cancer survivors. Participants provided important feedback about factors rural-residing patients consider when thinking about trial participation. In phase II, after using R-CHOICES, participants had higher certainty about their choice (mean post-test = 3.10 vs. pre-test = 2.67; P = 0.025) and higher trial knowledge (mean percentage correct at post-test = 73.58 vs. pre-test = 57.77; P < 0.001). There was no significant change in decision self-efficacy, communication self-efficacy, and attitudes towards or willingness to join trials. The R-CHOICES improved rural-residing patients' knowledge of cancer clinical trials and reduced conflict about making a trial decision. More research is needed on ways to further support decisions about trial participation among this population.

Clinical efficacy and effectiveness of 3D printing: a systematic review

PubMed Central

Diment, Laura E; Thompson, Mark S; Bergmann, Jeroen H M

2017-01-01

Objective To evaluate the clinical efficacy and effectiveness of using 3D printing to develop medical devices across all medical fields. Design Systematic review compliant with Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Data sources PubMed, Web of Science, OVID, IEEE Xplore and Google Scholar. Methods A double-blinded review method was used to select all abstracts up to January 2017 that reported on clinical trials of a three-dimensional (3D)-printed medical device. The studies were ranked according to their level of evidence, divided into medical fields based on the International Classification of Diseases chapter divisions and categorised into whether they were used for preoperative planning, aiding surgery or therapy. The Downs and Black Quality Index critical appraisal tool was used to assess the quality of reporting, external validity, risk of bias, risk of confounding and power of each study. Results Of the 3084 abstracts screened, 350 studies met the inclusion criteria. Oral and maxillofacial surgery contained 58.3% of studies, and 23.7% covered the musculoskeletal system. Only 21 studies were randomised controlled trials (RCTs), and all fitted within these two fields. The majority of RCTs were 3D-printed anatomical models for preoperative planning and guides for aiding surgery. The main benefits of these devices were decreased surgical operation times and increased surgical accuracy. Conclusions All medical fields that assessed 3D-printed devices concluded that they were clinically effective. The fields that most rigorously assessed 3D-printed devices were oral and maxillofacial surgery and the musculoskeletal system, both of which concluded that the 3D-printed devices outperformed their conventional comparators. However, the efficacy and effectiveness of 3D-printed devices remain undetermined for the majority of medical fields. 3D-printed devices can play an important role in healthcare, but more rigorous and long-term assessments are needed to determine if 3D-printed devices are clinically relevant before they become part of standard clinical practice. PMID:29273650

Use of FEV1 in Cystic Fibrosis Epidemiologic Studies and Clinical Trials: A Statistical Perspective for the Clinical Researcher

PubMed Central

Szczesniak, Rhonda; Heltshe, Sonya L.; Stanojevic, Sanja; Mayer-Hamblett, Nicole

2017-01-01

Background Forced expiratory volume in 1 second (FEV1) is an established marker of cystic fibrosis (CF) disease progression that is used to capture clinical course and evaluate therapeutic efficacy. The research community has established FEV1 surveillance data through a variety of observational data sources such as patient registries, and there is a growing pipeline of new CF therapies demonstrated to be efficacious in clinical trials by establishing improvements in FEV1. Results In this review, we summarize from a statistical perspective the clinical relevance of FEV1 based on its association with morbidity and mortality in CF, its role in epidemiologic studies of disease progression and comparative effectiveness, and its utility in clinical trials. In addition, we identify opportunities to advance epidemiologic research and the clinical development pipeline through further statistical considerations. Conclusions Our understanding of CF disease course, therapeutics, and clinical care has evolved immensely in the past decades, in large part due to the thoughtful application of rigorous research methods and meaningful clinical endpoints such as FEV1. A continued commitment to conduct research that minimizes the potential for bias, maximizes the limited patient population, and harmonizes approaches to FEV1 analysis while maintaining clinical relevance, will facilitate further opportunities to advance CF care. PMID:28117136

Altruism, the values dimension of caring self-efficacy concept in Iranian pediatric nurses.

PubMed

Alavi, Azam; Zargham-Boroujeni, Ali; Yousefy, Alireza; Bahrami, Masoud

2017-01-01

Self-efficacy is the most influential among factors affecting nurses' performance. Yet, understanding of the constituent elements of the caring self-efficacy concept was not considered. This study was to introduce altruism as one of the main aspects of caring self-efficacy in pediatric nurses. This is part of a larger study on the concept of caring self-efficacy conducted with qualitative content analysis approach in Iran. Participants included 27 clinical pediatric nurses and instructors, selected purposively. Data were collected using semi-structured interviews and analyzed using conventional content analysis method. Theme "altruism" as one of the main themes extracted from the analysis of the interviews in this study. This theme includes two main categories of "humanistic care" and "caring attitude." This paper introduces altruism as one of the values aspects of caring self-efficacy in pediatric nurses. Efficient nurse with features Humanistic care, through the provision of maternal care and family-centered care and caring attitudes resulting from religious beliefs and loving children to care for the children.

The efficacy-effectiveness distinction in trials of alcohol brief intervention

PubMed Central

2014-01-01

Three recent sets of null findings from trials of alcohol brief intervention (BI) have been disappointing to those who wish to see a reduction in alcohol-related harm through the widespread dissemination of BI. Saitz (7) has suggested that these null findings result from a failure to translate the effects of BI seen in efficacy trials, which are thought to contribute mainly to the beneficial effects of BI shown in meta-analyses, to effectiveness trials conducted in real-world clinical practice. The present article aims to: (i) clarify the meaning of the terms “efficacy” and “effectiveness” and other related concepts; (ii) review the method and findings on efficacy-effectiveness measurement in the 2007 Cochrane Review by Kaner and colleagues; and (iii) make suggestions for further research in this area. Conclusions are: 1) to avoid further confusion, terms such as “efficacy trial”, “effectiveness trial”, “clinical representativeness”, etc. should be clearly defined and carefully used; 2) applications of BI to novel settings should begin with foundational research and developmental studies, followed by efficacy trials, and political pressures for quick results from premature effectiveness trials should be resisted; 3) clear criteria are available in the literature to guide progress from efficacy research, through effectiveness research, to dissemination in practice; 4) to properly interpret null findings from effectiveness studies, it is necessary to ensure that interventions are delivered as intended; 5) in future meta-analyses of alcohol BI trials, more attention should be paid to the development and application of a psychometrically robust scale to measure efficacy-effectiveness or clinical representativeness; 6) the null findings under consideration cannot be firmly attributed to a failure to translate effects from efficacy trials to real-world practice, because it is possible that the majority of trials included in meta-analyses on which the evidence for the beneficial effects of alcohol BI was based tended to be effectiveness rather than efficacy trials; and 7) a hypothesis to explain the null findings in question is that they are due to lack of fidelity in the implementation of BI in large, organizationally complex, cluster randomized trials. PMID:25127717

Evaluating the Effectiveness of Text Messaging and Phone Call Reminders to Minimize No Show at Pediatric Outpatient Clinics in Pakistan: Protocol for a Mixed-Methods Study.

PubMed

Saeed, Sana; Somani, Noureen; Sharif, Fatima; Kazi, Abdul Momin

2018-04-10

Missing health care appointments without canceling in advance results in a no show, a vacant appointment slot that cannot be offered to others. No show can be reduced by reminding patients about their appointment in advance. In this regard, mobile health (mHealth) strategy is to use text messaging (short message service, SMS), which is available on all cellular phones, including cheap low-end handsets. Nonattendance for appointments in health care results in wasted resources and disturbs the planned work schedules. The purpose of this study is to evaluate the efficacy of the current text messaging (SMS) and call-based reminder system and further explore how to improve the attendance at the pediatric outpatient clinics. The primary objectives are to (1) determine the efficacy of the current clinic appointment reminder service at pediatric outpatient clinics at Aga Khan University Hospital, (2) assess the mobile phone access and usage among caregivers visiting pediatrics consultant clinics, and (3) explore the perception and barriers of parents regarding the current clinic appointment reminder service at the pediatric outpatient clinics at Aga Khan University Hospital. The study uses a mixed-method design that consists of 3 components: (1) retrospective study (component A) which aims to determine the efficacy of text messaging (SMS) and phone call-based reminder service on patient's clinic attendance during January to June 2017 (N=58,517); (2) quantitative (component B) in which a baseline survey will be conducted to assess the mobile phone access and usage among parents/caregivers of children visiting pediatrics consultant clinics (n=300); and (3) qualitative (component C) includes in-depth interviews and focus group discussion with parents/caregivers of children visiting the pediatric consultancy clinic and with health care providers and administrative staff. Main constructs will be to explore perceptions and barriers related to existing clinic appointment reminder service. Ethics approval has been obtained from the Ethical Review Committee, Aga Khan University, Pakistan (4770-Ped-ERC-17). Results will be disseminated to pediatric quality public health and mHealth communities through scientific meetings and through publications, nationally and internationally. This study will provide insight regarding efficacy of using mHealth-based reminder services for patient's appointments in low- and middle-income countries setup. The finding of this study will be used to recommend further enhanced mHealth-based solutions to improve patient appointments and decrease no show. ©Sana Saeed, Noureen Somani, Fatima Sharif, Abdul Momin Kazi. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 10.04.2018.

Controlled randomized clinical trial of spirituality integrated psychotherapy, cognitive-behavioral therapy and medication intervention on depressive symptoms and dysfunctional attitudes in patients with dysthymic disorder

PubMed Central

Ebrahimi, Amrollah; Neshatdoost, Hamid Taher; Mousavi, Seyed Ghafur; Asadollahi, Ghorban Ali; Nasiri, Hamid

2013-01-01

Background: Due to the controversy over efficacy of cognitive-behavioral therapy for chronic depression, recently, there has been an increasingly tendency toward therapeutic methods based on the cultural and spiritual approaches. The aim of this research was to compare efficacy of spiritual integrated psychotherapy (SIPT) and cognitive-behavioral therapy (CBT) on the intensity of depression symptoms and dysfunctional attitudes of patients with dysthymic disorder. Materials and Methods: This study had a mixed qualitative and quantitative design. In the first phase, SIPT model was prepared and, in the second phase, a double-blind random clinical trial was performed. Sixty-two patients with dysthymic disorder were selected from several centers include Nour and Alzahra Medical Center, Counseling Centers of Isfahan University of Medical Sciences and Goldis in Isfahan. The participants were randomly assigned to three experimental groups and one control group. The first group received 8 sessions treatment of SIPT, second groups also had 8 sessions of cognitive-behavioral therapy, which was specific to dysthymic disorder and third group were under antidepressant treatment. Beck depression inventory and dysfunctional attitudes scale were used to evaluate all the participants in four measurement stages. The data were analyzed using MANCOVA repeated measure method. Results: The results revealed that SIPT had more efficacy than medication based on both scales (P < 0.01); however, it was not different from CBT. SIPT was more effective on the modification of dysfunctional attitudes compared with CBT and medication (P < 0.05). Conclusion: These findings supported the efficacy of psychotherapy enriched with cultural capacities and religious teachings. PMID:24516853

Safety and efficacy evaluation of gelatin-based nanoparticles associated with UV filters.

PubMed

Oliveira, Camila Areias de; Dario, Michelli Ferrera; Sarruf, Fernanda Daud; Mariz, Inês Fátima Afonso; Velasco, Maria Valéria Robles; Rosado, Catarina; Baby, André Rolim

2016-04-01

The safety and efficacy assessment of nanomaterials is a major concern of industry and academia. These materials, due to their nanoscale size, can have chemical, physical, and biological properties that differ from those of their larger counterparts. The encapsulation of natural ingredients can provide marked improvements in sun protection efficacy. This strategy promotes solubility enhancement of flavonoids and yields an improved active ingredient with innovative physical, physicochemical and functional characteristics. Rutin, a flavonoid, has chemical and functional stability in topical vehicles exerting a synergistic effect in association with ultraviolet (UV) filters. However, the solubility of rutin is a limiting factor. Additionally, this bioactive compound does not have tendency to permeate across the stratum corneum. As an alternative to common synthetic based sunscreens, rutin-entrapped gelatin nanoparticles were designed. The present study investigated the pre-clinical safety of gelatin nanoparticles (GNPs) using an in vitro method and also assessed the clinical safety and efficacy of the association of GNPs with three commonly used chemical UV filters (ethylhexyl dimethyl PABA, ethylhexyl methoxycinnamate and methoxydibenzoylmethane). The non-irritant and adequate safety profile under sun-exposed skin conditions of the nanomaterials and the emulsions qualified the products for clinical efficacy assays. The in vivo results indicated that the GNPs increased the antioxidant protection of the emulsions developed. However, the presence of rutin in the nanosized material did not enhance performance on the SPF test. In conclusion, these findings characterized the nanomaterials as an innovative platform for multifunctional bioactive sunscreens. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

In-vivo efficacy of amodiaquine-artesunate in children with uncomplicated Plasmodium falciparum malaria in western Kenya

PubMed Central

Thwing, J. I.; Odero, C. O.; Odhiambo, F. O.; Otieno, K. O.; Kariuki, S.; Ord, R.; Roper, C.; McMorrow, M.; Vulule, J.; Slutsker, L.; Newman, R. D.; Hamel, M. J.; Desai, M.

2018-01-01

Summary OBJECTIVES To assess the efficacy of amodiaquine-artesunate in an area with high chloroquine resistance in western Kenya. METHODS Twenty-eight day in-vivo efficacy trial of amodiaquine-artesunate in 103 children aged 6–59 months in western Kenya with smear-confirmed uncomplicated Plasmodium falciparum malaria. RESULTS The 28-day uncorrected adequate clinical and parasitological response (ACPR) was 69.0%, with 15.5% Late Clinical Failure and 15.5% Late Parasitologic Failure rates. The PCR-corrected 28-day ACPR was 90.2%. Clinical risk factors for recurrent infection (recrudescences and reinfections) were lower axillary temperature at enrolment and low weight-for-age Z-score. The presence of single nucleotide polymorphisms pfcrt 76T and pfmdr1 86Y at baseline was associated with increased risk of recurrent infections, both reinfections and recrudescences. CONCLUSION Although artemether-lumefantrine (Coartem®) is the first line ACT in Kenya, amodiaquine-artesunate is registered as an option for treatment of uncomplicated P. falciparum and remains an effective alternative to Coartem® in western Kenya. Continued amodiaquine monotherapy in the private sector may jeopardise the future use of amodiaquine-artesunate as an alternative artemisinin-based combination therapy. PMID:19187521

Efficacy and safety of cross-cylinder photorefractive keratectomy versus single method in medium-high astigmatism: a randomized clinical trial.

PubMed

Sedghipour, Mohammad R; Lotfi, Afshin; Sadeghilar, Ayaz; Banan, Saeeid

2012-09-07

BACKGROUND: To compare efficacy and safety of photorefractive keratectomy (PRK) by cross-cylinder with single methods in medium-high astigmatism. DESIGN: Randomized clinical trial study PARTICIPANTS: Fifty patients with medium-high compound myopic astigmatism were enrolled between September 2007 and September 2008. METHODS: PRK was performed on 100 eyes of 50 patients with compound myopic astigmatism. Each patient underwent PRK by cross-cylinder approach in one eye and single method on the contralateral eye. Vector analysis was used to assess astigmatic results. MAIN OUTCOME MEASURES: Improvement of visual acuity (snelen chart), refraction, aberrometry. RESULTS: Uncorrected visual acuity (UCCA) equal to 20/40 or better after six months, was achieved in 98% of eyes in the cross-cylinder method versus 96% in single method.. Mean preoperative spherical equivalent(SE) was -5.2 ±2.1 D in the cross-cylinder method versus -5.1 ±0.5 D in the single method. At six months, the mean SE was - 0.5±0.4 D and -0.6±0.3 D, respectively. Mean IOS was 0.4±0.3 in the cross-cylinder group and 0.4±0.4 in the single group. Mean postoperative absolute change in total root-mean-square higher order aberrations in the cross-cylinder group and single group were 0.16 pm and 0.17 pm, respectively. Any of the mentioned differences didn't appear to be statistically significant. CONCLUSIONS: Both PRK methods appeared to be safe and effective in correcting medium-high astigmatism. © 2012 The Author. Clinical and Experimental Ophthalmology © 2012 Royal Australian and New Zealand College of Ophthalmologists.

Empiric transcatheter arterial embolization for massive bleeding from duodenal ulcers: efficacy and complications.

PubMed

Ichiro, Ikushima; Shushi, Higashi; Akihiko, Ishii; Yasuhiko, Iryo; Yasuyuki, Yamashita

2011-07-01

To evaluate the efficacy and safety of empiric transcatheter arterial embolization (TAE) for patients with massive bleeding from duodenal ulcers. During January 2000 and December 2009, 59 patients with duodenal ulcer bleeding in whom TAE was attempted after endoscopic therapy failed were retrospectively analyzed. The patients were divided into empiric TAE (n = 36) and identifiable TAE (n = 23) groups according to angiographic findings with or without identification of the bleeding sites. The technical and clinical success rate, recurrent bleeding rate, procedure-related complications, and clinical outcomes were evaluated. The technical and clinical success rates of TAE were 100% and 83%. The recurrent bleeding rate, clinical success, duodenal stenosis, and 30-day mortality after TAE were not significantly different between the empiric and identifiable TAE groups. A high rate of technical and clinical success was obtained with empiric TAE comparable to identifiable TAE in patients with massive bleeding from duodenal ulcers. There were no severe complications. Empiric TAE is an effective and safe method when a bleeding site cannot determined by angiography. Copyright © 2011 SIR. Published by Elsevier Inc. All rights reserved.

Diagnostic Efficacy of Cell Block Immunohistochemistry, Smear Cytology, and Liquid-Based Cytology in Endoscopic Ultrasound-Guided Fine-Needle Aspiration of Pancreatic Lesions: A Single-Institution Experience

PubMed Central

Qin, Shan-yu; Zhou, You; Li, Ping; Jiang, Hai-xing

2014-01-01

Background The diagnostic efficiency of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) cytology varies widely depending on the treatment method of the specimens. The present study aimed to evaluate the diagnostic efficacy of cell block (CB) immunohistochemistry, smear cytology (SC), and liquid-based cytology (LBC) in patients with pancreatic lesions without consulting an on-site cytopathologist. Methods This study prospectively enrolled 72 patients with pancreatic lesions. The EUS-FNA specimens were examined by SC, LBC, and CB immunohistochemistry. The diagnostic efficacy of the 3 methods was then compared. Patients’ final diagnosis was confirmed by surgical resection specimens, diagnostic imaging, and clinical follow-up. Results Our results included 60 malignant and 12 benign pancreatic lesions. The diagnostic sensitivity (90%), negative predictive value (66.7%), and accuracy (91.7%) of CB immunohistochemistry were significantly higher than those of SC (70.0%, 30.0%, and 75.0%, respectively) and LBC (73.3%, 31.6%, and 77.8%, respectively) (all P<0.05). The combination of CB and SC, or CB and LBC, did not significantly increase the efficacy compared to CB immunohistochemistry alone. Conclusion Our findings suggest that in the absence of an on-site cytopathologist, CB immunohistochemistry on EUS-FNA specimens offers a higher diagnostic efficacy in patients with pancreatic lesions than does SC and LBC. PMID:25259861

Preclinical Evidence for the Efficacy of Ischemic Postconditioning against Renal Ischemia-Reperfusion Injury, a Systematic Review and Meta-Analysis

PubMed Central

Jonker, Simone J.; Menting, Theo P.; Warlé, Michiel C.; Ritskes-Hoitinga, Merel; Wever, Kimberley E.

2016-01-01

Background Renal ischemia-reperfusion injury (IRI) is a major cause of kidney damage after e.g. renal surgery and transplantation. Ischemic postconditioning (IPoC) is a promising treatment strategy for renal IRI, but early clinical trials have not yet replicated the promising results found in animal studies. Method We present a systematic review, quality assessment and meta-analysis of the preclinical evidence for renal IPoC, and identify factors which modify its efficacy. Results We identified 39 publications studying >250 control animals undergoing renal IRI only and >290 animals undergoing renal IRI and IPoC. Healthy, male rats undergoing warm ischemia were used in the vast majority of studies. Four studies applied remote IPoC, all others used local IPoC. Meta-analysis showed that both local and remote IPoC ameliorated renal damage after IRI for the outcome measures serum creatinine, blood urea nitrogen and renal histology. Subgroup analysis indicated that IPoC efficacy increased with the duration of index ischemia. Measures to reduce bias were insufficiently reported. Conclusion High efficacy of IPoC is observed in animal models, but factors pertaining to the internal and external validity of these studies may hamper the translation of IPoC to the clinical setting. The external validity of future animal studies should be increased by including females, comorbid animals, and transplantation models, in order to better inform clinical trial design. The severity of renal damage should be taken into account in the design and analysis of future clinical trials. PMID:26963819

Sensitivity and specificity of the Eating Assessment Tool and the Volume-Viscosity Swallow Test for clinical evaluation of oropharyngeal dysphagia.

PubMed

Rofes, L; Arreola, V; Mukherjee, R; Clavé, P

2014-09-01

Oropharyngeal dysphagia (OD) is an underdiagnosed digestive disorder that causes severe nutritional and respiratory complications. Our aim was to determine the accuracy of the Eating Assessment Tool (EAT-10) and the Volume-Viscosity Swallow Test (V-VST) for clinical evaluation of OD. We studied 120 patients with swallowing difficulties and 14 healthy subjects. OD was evaluated by the 10-item screening questionnaire EAT-10 and the bedside method V-VST, videofluoroscopy (VFS) being the reference standard. The V-VST is an effort test that uses boluses of different volumes and viscosities to identify clinical signs of impaired efficacy (impaired labial seal, piecemeal deglutition, and residue) and impaired safety of swallow (cough, voice changes, and oxygen desaturation ≥3%). Discriminating ability was assessed by the AUC of the ROC curve and sensitivity and specificity values. According to VFS, prevalence of OD was 87%, 75.6% with impaired efficacy and 80.9% with impaired safety of swallow including 17.6% aspirations. The EAT-10 showed a ROC AUC of 0.89 for OD with an optimal cut-off at 2 (0.89 sensitivity and 0.82 specificity). The V-VST showed 0.94 sensitivity and 0.88 specificity for OD, 0.79 sensitivity and 0.75 specificity for impaired efficacy, 0.87 sensitivity and 0.81 specificity for impaired safety, and 0.91 sensitivity and 0.28 specificity for aspirations. Clinical methods for screening (EAT-10) and assessment (V-VST) of OD offer excellent psychometric proprieties that allow adequate management of OD. Their universal application among at-risk populations will improve the identification of patients with OD at risk for malnutrition and aspiration pneumonia. © 2014 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.

Comparison between Unilateral and Bilateral Ovarian Drilling in Clomiphene Citrate Resistance Polycystic Ovary Syndrome Patients: A Randomized Clinical Trial of Efficacy

PubMed Central

Zahiri Sorouri, Ziba; Sharami, Seyede Hajar; Tahersima, Zinab; Salamat, Fatemeh

2015-01-01

Background Laparoscopic ovarian drilling (LOD) is an alternative method to induce ovulation in polycystic ovary syndrome (PCOS) patients with clomiphene citrate (CC) resistant instead of gonadotropins. This study aimed to compare the efficacy of unilateral LOD (ULOD) versus bilateral LOD (BLOD) in CC resistance PCOS patients in terms of ovulation and pregnancy rates. Materials and Methods In a prospective randomized clinical trial study, we included 100 PCOS patients with CC resistance attending to Al-Zahra Hospital in Rasht, Guilan Province, Iran, from June 2011 to July 2012. Patients were randomly divided into two ULOD and BLOD groups with equal numbers. The clinical and biochemical responses on ovulation and pregnancy rates were assessed over a 6-month follow-up period. Results Differences in baseline characteristics of patients between two groups prior to laparoscopy were not significant (p>0.05). There were no significant differences between the two groups in terms of clinical and biochemical responses, spontaneous menstruation (66.1 vs. 71.1%), spontaneous ovulation rate (60 vs. 64.4%), and pregnancy rate (33.1 vs. 40%) (p>0.05). Following drilling, there was a significant decrease in mean serum concentrations of luteinizing hormone (LH) (p=0.001) and testosterone (p=0.001) in both the groups. Mean decrease in serum LH (p=0.322) and testosterone concentrations (p=0.079) were not statistically significant between two groups. Mean serum level of follicle stimulating hormone (FSH) did not change significantly in two groups after LOD (p>0.05). Conclusion Based on results of this study, ULOD seems to be equally efficacious as BLOD in terms of ovulation and pregnancy rates (Registration Number: IRCT138903291306N2). PMID:25918587

Postoperative self-efficacy and psychological morbidity in radical prostatectomy1

PubMed Central

da Mata, Luciana Regina Ferreira; de Carvalho, Emilia Campos; Gomes, Cássia Regina Gontijo; da Silva, Ana Cristina; Pereira, Maria da Graça

2015-01-01

Objective: evaluate the general and perceived self-efficacy, psychological morbidity, and knowledge about postoperative care of patients submitted to radical prostatectomy. Identify the relationships between the variables and know the predictors of self-efficacy. Method: descriptive, cross-sectional study, conducted with 76 hospitalized men. The scales used were the General and Perceived Self-efficacy Scale and the Hospital Anxiety and Depression Scale, in addition to sociodemographic, clinical and knowledge questionnaires. Results: a negative relationship was found for self-efficacy in relation to anxiety and depression. Psychological morbidity was a significant predictor variable for self-efficacy. An active professional situation and the waiting time for surgery also proved to be relevant variables for anxiety and knowledge, respectively. Conclusion: participants had a good level of general and perceived self-efficacy and small percentage of depression. With these findings, it is possible to produce the profile of patients about their psychological needs after radical prostatectomy and, thus, allow the nursing professionals to act holistically, considering not only the need for care of physical nature, but also of psychosocial nature. PMID:26487129

CD25 Preselective Anti-HIV Vectors for Improved HIV Gene Therapy

PubMed Central

Kalomoiris, Stefanos; Lawson, Je'Tai; Chen, Rachel X.; Bauer, Gerhard; Nolta, Jan A.

2012-01-01

Abstract As HIV continues to be a global public health problem with no effective vaccine available, new and innovative therapies, including HIV gene therapies, need to be developed. Due to low transduction efficiencies that lead to low in vivo gene marking, therapeutically relevant efficacy of HIV gene therapy has been difficult to achieve in a clinical setting. Methods to improve the transplantation of enriched populations of anti-HIV vector-transduced cells may greatly increase the in vivo efficacy of HIV gene therapies. Here we describe the development of preselective anti-HIV lentiviral vectors that allow for the purification of vector-transduced cells to achieve an enriched population of HIV-resistant cells. A selectable protein, human CD25, not normally found on CD34+ hematopoietic progenitor cells (HPCs), was incorporated into a triple combination anti-HIV lentiviral vector. Upon purification of cells transduced with the preselective anti-HIV vector, safety was demonstrated in CD34+ HPCs and in HPC-derived macrophages in vitro. Upon challenge with HIV-1, improved efficacy was observed in purified preselective anti-HIV vector-transduced macrophages compared to unpurified cells. These proof-of-concept results highlight the potential use of this method to improve HIV stem cell gene therapy for future clinical applications. PMID:23216020

Continuous infusion of antibiotics in critically ill patients.

PubMed

Smuszkiewicz, Piotr; Szałek, Edyta; Tomczak, Hanna; Grześkowiak, Edmund

2013-02-01

Antibiotics are the most commonly used drugs in intensive care unit patients and their supply should be based on pharmacokinetic/pharmacodynamic rules. The changes that occur in septic patients who are critically ill may be responsible for subtherapeutic antibiotic concentrations leading to poorer clinical outcomes. Evolving in time the disturbed pathophysiology in severe sepsis (high cardiac output, glomerular hyperfiltration) and therapeutic interventions (e.g. haemodynamically active drugs, mechanical ventilation, renal replacement therapy) alters antibiotic pharmacokinetics mainly through an increase in the volume of distribution and altered drug clearance. The lack of new and efficacious drugs and increased bacterial resistance are current problems of contemporary antibiotic therapy. Although intermittent administration is a standard clinical practice, alternative methods of antibiotic administration are sought, which may potentialise effects and reduce toxicity as well as contribute to inhibition of bacterial resistance. A wide range of studies prove that the application of continuous infusion of time-dependent antibiotics (beta-lactams, glycopeptides) is more rational than standard intermittent administration. However, there are also studies which do not confirm the advantage of one method over the other. In spite of controversy the continuous administration of this group of antibiotics is common practice, because the results of both studies point to the higher efficacy of this method in critically ill patients. Authors reviewed the literature to determine whether any clinical benefits exist for administration of time-dependent antibiotics by continuous infusion. Definite specification of the clinical advantage of administration this way over standard dosage requires a large-scale multi-centre randomised controlled trial.

Recommendations for the Design and Analysis of Treatment Trials for Alcohol Use Disorders

PubMed Central

Witkiewitz, Katie; Finney, John W.; Harris, Alex H.S; Kivlahan, Daniel R.; Kranzler, Henry R.

2015-01-01

Background Over the past 60 years the view that “alcoholism” is a disease for which the only acceptable goal of treatment is abstinence has given way to the recognition that alcohol use disorders (AUDs) occur on a continuum of severity, for which a variety of treatment options are appropriate. However, because the available treatments for AUDs are not effective for everyone, more research is needed to develop novel and more efficacious treatments to address the range of AUD severity in diverse populations. Here we offer recommendations for the design and analysis of alcohol treatment trials, with a specific focus on the careful conduct of randomized clinical trials of medications and non-pharmacological interventions for AUDs. Methods Narrative review of the quality of published clinical trials and recommendations for the optimal design and analysis of treatment trials for AUDs. Results Despite considerable improvements in the design of alcohol clinical trials over the past two decades, many studies of AUD treatments have used faulty design features and statistical methods that are known to produce biased estimates of treatment efficacy. Conclusions The published statistical and methodological literatures provide clear guidance on methods to improve clinical trial design and analysis. Consistent use of state-of-the-art design features and analytic approaches will enhance the internal and external validity of treatment trials for AUDs across the spectrum of severity. The ultimate result of this attention to methodological rigor is that better treatment options will be identified for patients with an AUD. PMID:26250333

Effects of Gait Self-Efficacy and Lower-Extremity Physical Function on Dual-Task Performance in Older Adults

PubMed Central

Banducci, Sarah E.; Daugherty, Ana M.; Fanning, Jason; Awick, Elizabeth A.; Porter, Gwenndolyn C.; Burzynska, Agnieszka; Shen, Sa; Kramer, Arthur F.; McAuley, Edward

2017-01-01

Objectives. Despite evidence of self-efficacy and physical function's influences on functional limitations in older adults, few studies have examined relationships in the context of complex, real-world tasks. The present study tested the roles of self-efficacy and physical function in predicting older adults' street-crossing performance in single- and dual-task simulations. Methods. Lower-extremity physical function, gait self-efficacy, and street-crossing success ratio were assessed in 195 older adults (60–79 years old) at baseline of a randomized exercise trial. During the street-crossing task, participants walked on a self-propelled treadmill in a virtual reality environment. Participants crossed the street without distraction (single-task trials) and conversed on a cell phone (dual-task trials). Structural equation modeling was used to test hypothesized associations independent of demographic and clinical covariates. Results. Street-crossing performance was better on single-task trials when compared with dual-task trials. Direct effects of self-efficacy and physical function on success ratio were observed in dual-task trials only. The total effect of self-efficacy was significant in both conditions. The indirect path through physical function was evident in the dual-task condition only. Conclusion. Physical function can predict older adults' performance on high fidelity simulations of complex, real-world tasks. Perceptions of function (i.e., self-efficacy) may play an even greater role. The trial is registered with United States National Institutes of Health ClinicalTrials.gov (ID: NCT01472744; Fit & Active Seniors Trial). PMID:28255557

Long-term efficacy and safety of certolizumab pegol in Japanese rheumatoid arthritis patients with an inadequate response to methotrexate: 52-week results from an open-label extension of the J-RAPID study

PubMed Central

Tanaka, Yoshiya; Yamamoto, Kazuhiko; Takeuchi, Tsutomu; Yamanaka, Hisashi; Ishiguro, Naoki; Eguchi, Katsumi; Watanabe, Akira; Origasa, Hideki; Shoji, Toshiharu; Miyasaka, Nobuyuki; Koike, Takao

2014-01-01

Abstract Objectives. To evaluate the long-term efficacy and safety of certolizumab pegol (CZP) plus methotrexate treatment and to assess the efficacy of two CZP maintenance dosing schedules in Japanese rheumatoid arthritis (RA) patients with an inadequate response to methotrexate. Methods. J-RAPID double-blind patients were entered into an open-label extension (OLE) study. Patients withdrawn due to lack of efficacy at 16 weeks and double-blind completers without a week-24 American College of Rheumatology (ACR) 20 response received CZP 200 mg every other week (Q2W) plus methotrexate. Double-blind completers with week-24 ACR20 responses were randomized to CZP 200 mg Q2W plus methotrexate or CZP 400 mg every 4 weeks plus methotrexate. Results. The ACR20/ACR50/ACR70 response rates of double-blind completers (n = 204) were 89.7%/67.2%/36.3% at OLE entry and 95.6%/84.8%/58.3% at 52 weeks, respectively. Other clinical, functional and radiographic outcomes were sustained with long-term CZP plus methotrexate. Long-term treatment with CZP was well-tolerated with no new unexpected adverse events observed. The efficacy and safety of CZP treatment were similar between the two dosing schedules. Conclusions. Continued CZP administration with methotrexate maintained efficacy over 52 weeks and was well-tolerated for Japanese RA patients. No obvious differences in clinical efficacy and safety were observed between the two dosing schedules, giving flexibility in maintenance administration schedules. PMID:24593170

Cryolipolysis for fat reduction and body contouring: safety and efficacy of current treatment paradigms.

PubMed

Ingargiola, Michael J; Motakef, Saba; Chung, Michael T; Vasconez, Henry C; Sasaki, Gordon H

2015-06-01

Cryolipolysis is a nonsurgical technique for localized fat reduction. With the increased risk of complications from more invasive methods such as liposuction, cryolipolysis presents a promising method for nonsurgical body contouring. This study presents a systematic review of the available clinical data, with an emphasis on the efficacy, methods, safety, and complications of cryolipolysis. To identify clinical studies that assessed outcomes of cryolipolysis, a systematic review of the MEDLINE and Cochrane databases was performed with the search algorithm cryolipolysis OR cool sculpting OR fat freezing OR lipocryolysis. The primary literature search returned 319 articles. After inclusion criteria were applied and additional articles were idenfied via manual review of article references, 19 studies were selected for review. Average reduction in caliper measurement ranged from 14.67 percent to 28.5 percent. Average reduction by ultrasound ranged from 10.3 percent to 25.5 percent. No significant impact on lipid levels or liver function tests after cryolipolysis treatments was noted in any study. Only mild, short-term side effects, such as erythema, swelling, and pain, were noted. Paradoxical adipose hyperplasia was described in one patient. Cryolipolysis is a promising procedure for nonsurgical fat reduction and body contouring and presents a compelling alternative to liposuction and other, more invasive methods. This procedure appears to be safe in the short term, with a limited side effect profile, and results in significant fat reduction when used for localized adiposities. It remains unclear whether posttreatment manual massage and multiple treatments in the same anatomic area enhance the efficacy of cryolipolysis.

Clinical assessment of a new 755 nm diode laser for hair removal: Efficacy, safety and practicality in 56 patients.

PubMed

Royo, Josefina; Moreno-Moraga, Javier; Trelles, Mario A

2017-04-01

Recently, the first diode laser with a wavelength of 755 nm for in-motion hair removal came on the market. The objective of this study was to check its efficacy, safety, and practicality under different options for its use. A prospective study in a heterogeneous group of 56 patients who had hair removed from various areas of their bodies using three different treatment methods. Four sessions were scheduled in all cases, with a gap of 3 months between each session. Efficacy was assessed by counting of hairs per cm 2 and the adverse effects in each session were recorded in detail in the patients' clinical histories. The three tested options achieved a significant reduction in the number of hairs (P < 0.0001). The average clearances achieved using the conventional method (HR), the in-motion method (SHR) and the stacking method were 75.5%, 70.1%, and 41.9%, respectively. The degree of satisfaction of the participants on a scale of 0-10 was 7.7, 8.1 and 6.8, respectively. Erythema and perifollicular edema, which are characteristic responses in laser hair removal, were observed. The incidence of burns was 1.33%. The 755-nm diode laser performed efficiently and safely in all the tested areas, using high total accumulated energy per surface unit. Based on our prior experience with other equipment, the results are promising. Lasers Surg. Med. 49:355-360, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Reliability of Chinese medicine diagnostic variables in the examination of patients with osteoarthritis of the knee.

PubMed

Hua, Bin; Abbas, Estelle; Hayes, Alan; Ryan, Peter; Nelson, Lisa; O'Brien, Kylie

2012-11-01

Chinese medicine (CM) has its own diagnostic indicators that are used as evidence of change in a patient's condition. The majority of studies investigating efficacy of Chinese herbal medicine (CHM) have utilized biomedical diagnostic endpoints. For CM clinical diagnostic variables to be incorporated into clinical trial designs, there would need to be evidence that these diagnostic variables are reliable. Previous studies have indicated that the reliability of CM syndrome diagnosis is variable. Little information is known about where the variability stems from--the basic data collection level or the synthesis of diagnostic data, or both. No previous studies have investigated systematically the reliability of all four diagnostic methods used in the CM diagnostic process (Inquiry, Inspection, Auscultation/Olfaction, and Palpation). The objective of this study was to assess the inter-rater reliability of data collected using the four diagnostic methods of CM in Australian patients with knee osteoarthritis (OA), in order to investigate if CM variables could be used with confidence as diagnostic endpoints in a clinical trial investigating the efficacy of a CHM in treating OA. An inter-rater reliability study was conducted as a substudy of a clinical trial investigating the treatment of knee OA with Chinese herbal medicine. Two (2) experienced CM practitioners conducted a CM examination separately, within 2 hours of each other, in 40 participants. A CM assessment form was utilized to record the diagnostic data. Cohen's κ coefficient was used as a measure of the level of agreement between 2 practitioners. There was a relatively good level of agreement for Inquiry and Auscultation variables, and, in general, a low level of agreement for (visual) Inspection and Palpation variables. There was variation in the level of agreement between 2 practitioners on clinical information collected using the Four Diagnostic Methods of a CM examination. Some aspects of CM diagnosis appear to be reliable, while others are not. Based on these results, it was inappropriate to use CM diagnostic variables as diagnostic endpoints in the main study, which was an investigation of efficacy of CHM treatment of knee OA.

[Efficacy of dynamic magnetotherapy with modulation frequency 10Hz in the complex of spa rehabilitation of children with cerebral palsy].

PubMed

Gurova, N Iu; Babina, L M

2007-01-01

Two groups of children with cerebral paralysis received combined therapy. Treatment of one of the groups included a course of magnetotherapy (AMO-ATOS unit, 10 Hz) according to the suboccipital-lumbar method, the other group was control (no magnetotherapy). The study of cliniconeurophysiological indices showed significantly higher efficacy of the therapeutic complex with a course of magnetotherapy. The highest beneficial effect was observed on bioelectrogenesis of the brain, rheoencephalographic parameters and clinical manifestation of muscular spasticity.

Designing clinical trials to test disease-modifying agents: application to the treatment trials of Alzheimer's disease.

PubMed

Xiong, Chengjie; van Belle, Gerald; Miller, J Philip; Morris, John C

2011-02-01

Therapeutic trials of disease-modifying agents on Alzheimer's disease (AD) require novel designs and analyses involving switch of treatments for at least a portion of subjects enrolled. Randomized start and randomized withdrawal designs are two examples of such designs. Crucial design parameters such as sample size and the time of treatment switch are important to understand in designing such clinical trials. The purpose of this article is to provide methods to determine sample sizes and time of treatment switch as well as optimum statistical tests of treatment efficacy for clinical trials of disease-modifying agents on AD. A general linear mixed effects model is proposed to test the disease-modifying efficacy of novel therapeutic agents on AD. This model links the longitudinal growth from both the placebo arm and the treatment arm at the time of treatment switch for these in the delayed treatment arm or early withdrawal arm and incorporates the potential correlation on the rate of cognitive change before and after the treatment switch. Sample sizes and the optimum time for treatment switch of such trials as well as optimum test statistic for the treatment efficacy are determined according to the model. Assuming an evenly spaced longitudinal design over a fixed duration, the optimum treatment switching time in a randomized start or a randomized withdrawal trial is half way through the trial. With the optimum test statistic for the treatment efficacy and over a wide spectrum of model parameters, the optimum sample size allocations are fairly close to the simplest design with a sample size ratio of 1:1:1 among the treatment arm, the delayed treatment or early withdrawal arm, and the placebo arm. The application of the proposed methodology to AD provides evidence that much larger sample sizes are required to adequately power disease-modifying trials when compared with those for symptomatic agents, even when the treatment switch time and efficacy test are optimally chosen. The proposed method assumes that the only and immediate effect of treatment switch is on the rate of cognitive change. Crucial design parameters for the clinical trials of disease-modifying agents on AD can be optimally chosen. Government and industry officials as well as academia researchers should consider the optimum use of the clinical trials design for disease-modifying agents on AD in their effort to search for the treatments with the potential to modify the underlying pathophysiology of AD.

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

A Contingency Management Intervention for Adolescent Marijuana Abuse and Conduct Problems.

ERIC Educational Resources Information Center

Kamon, Jody; Budney, Alan; Stanger, Catherine

2005-01-01

Objective: To describe an innovative treatment for adolescent marijuana abuse and provide initial information about its feasibility, acceptability, and potential efficacy. Method: Provided an intervention composed of (1) a clinic-administered, abstinence-based incentive program; (2) parent-directed contingency management targeting substance use…

Tablet-Based Education to Reduce Depression-Related Stigma

ERIC Educational Resources Information Center

Lu, Catherine; Winkelman, Megan; Wong, Shane Shucheng

2016-01-01

Objectives: This study investigated the efficacy of a tablet-based multimedia education application, the Project Not Alone Depression Module, in improving depression literacy and reducing depression stigma among a community-based mental health clinic population. Methods: A total of 93 participants completed either a tablet-based multimedia…

Bromfenac 0.09% bioavailability in aqueous humor, prophylactic effect on cystoid macular edema, and clinical signs of ocular inflammation after phacoemulsification in a Mexican population

PubMed Central

Palacio, Claudia; Fernández De Ortega, Lourdes; Bustos, Francisco R; Chávez, Eduardo; Oregon-Miranda, Aldo A; Mercado-Sesma, Arieh R

2016-01-01

Purpose The purpose of this study was to evaluate the aqueous humor bioavailability and clinical efficacy of bromfenac 0.09% vs nepafenac on the presence of cystoid macular edema (CME) after phacoemulsification. Material and methods A Phase II, double-blind, masked, active-controlled, multicenter, clinical trial of 139 subjects, randomized to either a bromfenac 0.09% ophthalmic solution (n=69) or nepafenac 0.1% (n=70). Subjects instilled a drop three times a day for a period of 30 days. Follow-up visits were on days 2, 7, 15, 30, and 60. Biomicroscopy, clinical ocular signs, and assessment of posterior segment were performed. The primary efficacy endpoints included the presence of CME evaluated by optical coherence tomography. Safety evaluation included intraocular pressure, transaminase enzymes, lissamine green, and fluorescein stain. Results The demographic and efficacy variables were similar between groups at baseline. The presence of pain, photophobia, conjunctival hyperemia, chemosis, cellularity, and corneal edema disappeared by day 30 in both groups. The central retinal thickness did not show significant changes after treatment when compared to baseline as follows: in the bromfenac group (247.2±32.9 vs 252.0±24.9 μm; P=0.958) and in nepafenac group (250.8±34 vs 264.0±34.1 μm; P=0.137), respectively. A statistically significant difference was observed between bromfenac and nepafenac group: (252.0±24.9 vs 264.0±34.1 μm; P=0.022), at day 30, respectively; even though there was no clinical relevance in the presentation of CME. There were no significant alterations in intraocular pressure, either lissamine green or fluorescein stains. The adverse events were not related to the interventions. Conclusion Bromfenac 0.09% ophthalmic solution showed similar clinical efficacy to reduce the presentation of CME after phacoemulsification compared to nepafenac 0.01%. PMID:26869758

Clinic-level introduction of medical abortion in Vietnam.

PubMed

Raghavan, Sheila; Ngoc, Nguyen thi Nhu; Shochet, Tara; Winikoff, Beverly

2012-10-01

To assess the efficacy of medical abortion and patient satisfaction in the clinic setting, in addition to determining healthcare providers' views. From 2006 to 2008, 2400 women were enrolled at 10 Vietnam Family Planning Association (VINAFPA) clinics in an operations research project. Participants took 200mg of oral mifepristone in the clinic and 400 μg of oral misoprostol 2 days later at home or in the clinic. Abortion status was assessed at follow-up. Furthermore, in 2006, 900 clinicians at 45 health facilities answered a knowledge, attitudes, and practices survey to capture providers' views. In total, 93.8% of participants had successful medical abortions. The majority (84.5%) administered misoprostol at home. Adverse effects included bleeding, pain/cramps, and nausea. Most women (92.6%) were satisfied/very satisfied with the method. Most providers who took the survey (85.6%) recommended that medical abortion be introduced at VINAFPA clinics. The operations research data demonstrate the safety, efficacy, and acceptability of medical abortion at VINAFPA clinics. The majority of surveyed providers endorsed adding medical abortion at their own facilities. Developing national guidelines for providing medical abortion at the clinic level is an important step in expanding access to services in Vietnam. Copyright © 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Efficacy of Conventional Laser Irradiation Versus a New Method for Gingival Depigmentation (Sieve Method): A Clinical Trial.

PubMed

Houshmand, Behzad; Janbakhsh, Noushin; Khalilian, Fatemeh; Talebi Ardakani, Mohammad Reza

2017-01-01

Introduction: Diode laser irradiation has recently shown promising results for treatment of gingival pigmentation. This study sought to compare the efficacy of 2 diode laser irradiation protocols for treatment of gingival pigmentations, namely the conventional method and the sieve method. Methods: In this split-mouth clinical trial, 15 patients with gingival pigmentation were selected and their pigmentation intensity was determined using Dummett's oral pigmentation index (DOPI) in different dental regions. Diode laser (980 nm wavelength and 2 W power) was irradiated through a stipple pattern (sieve method) and conventionally in the other side of the mouth. Level of pain and satisfaction with the outcome (both patient and periodontist) were measured using a 0-10 visual analog scale (VAS) for both methods. Patients were followed up at 2 weeks, one month and 3 months. Pigmentation levels were compared using repeated measures of analysis of variance (ANOVA). The difference in level of pain and satisfaction between the 2 groups was analyzed by sample t test and general estimate equation model. Results: No significant differences were found regarding the reduction of pigmentation scores and pain and scores between the 2 groups. The difference in satisfaction with the results at the three time points was significant in both conventional and sieve methods in patients ( P = 0.001) and periodontists ( P = 0.015). Conclusion: Diode laser irradiation in both methods successfully eliminated gingival pigmentations. The sieve method was comparable to conventional technique, offering no additional advantage.

Treatment efficacy and safety of ultrasound-guided percutaneous bipolar radiofrequency ablation for benign thyroid nodules

PubMed Central

Li, Xiao-long; Lu, Feng; Yue, Wen-wen; Sun, Li-ping; Bo, Xiao-wan; Guo, Le-hang; Xu, Jun-mei; Liu, Bo-ji; Li, Dan-dan; Qu, Shen

2016-01-01

Objective: To evaluate the therapeutic efficacy and safety of ultrasound-guided percutaneous bipolar radiofrequency ablation (BRFA) of benign thyroid nodules by comparison with a matched untreated control group. Methods: The therapeutic efficacy and safety in 35 patients who were subjected to a single session of ultrasound-guided percutaneous BRFA (Group A) for benign thyroid nodules were compared with those in 35 untreated patients (Group B) with benign nodules. The benign nature of all the nodules was confirmed by ultrasound-guided fine-needle aspiration biopsy (FNAB), and all the patients had normal thyroid functions. BRFA was performed with a bipolar electrode (CelonProSurge 150–T20) with an output power of 20 W. Nodule volume, thyroid function and clinical symptoms of all the patients were compared before treatment and during follow-up. Results: In Group A, the BRFA procedures were completed with a mean time of 10.02 ± 3.30 min (range, 5.47–16.03 min) and with a mean total energy deposition of 10.747 ± 3704 J (range, 5510–17.770 J). The procedures were tolerated well in all the patients without causing any major complications. At the 6-month follow-up, all of the nodule volume decreased significantly (from 8.81 ± 8.66 to 1.59 ± 1.55 ml, p < 0.001) in Group A, whereas the nodule volume increased from 6.90 ± 3.77 to 7.87 ± 3.95 ml in Group B (p < 0.001). All (100%) the 35 nodules in Group A had volume reduction ratios (VRRs) of >50%, among which 3 (8.57%) had VRRs >90%. In Group A, the clinical symptoms of the patients who had symptoms before BRFA disappeared, whereas in Group B, the patients had no resolution of clinical symptoms at the 6-month follow-up. Conclusion: Ultrasound-guided percutaneous BRFA seems to be an effective and safe method for the treatment of benign thyroid nodules. It may gain a wide use in clinical practice. Advances in knowledge: Based on the comparable efficacy and clinical symptoms between the BRFA and untreated groups, the technique of BRFA can be used as an effective and safe method for the treatment of benign thyroid nodules. PMID:26800232

Nursing self-efficacy of an integrated clinical and administrative information system.

PubMed

Dillon, Thomas W; Lending, Diane; Crews, Thaddeus R; Blankenship, Ray

2003-01-01

Self-efficacy is a user's confidence that he or she has the ability to use an information system. A survey gathered demographics, self-assessed computer skills, attitude and self-efficacy before installation of an integrated clinical and administrative information system. Results showed that higher levels of nursing education, home computer use, and average levels of self-assessed e-mail, Internet search, word processing, and general computer expertise predicted self-efficacy of the system. In addition, previous use of home and office electronics equipment, such as an answering machine, predicted self-efficacy. Implications for training and future adoption of clinical information systems are presented.

Guidelines for the Reporting of Treatment Trials for Alcohol Use Disorders

PubMed Central

Witkiewitz, Katie; Finney, John W.; Harris, Alex H.S; Kivlahan, Daniel R.; Kranzler, Henry R.

2015-01-01

Background The primary goals in conducting clinical trials of treatments for alcohol use disorders (AUDs) is to identify efficacious treatments and determine which treatments are most efficacious for which patients. Accurate reporting of study design features and results is imperative to enable readers of research reports to evaluate to what extent a study has achieved these goals. Guidance on quality of clinical trial reporting has evolved substantially over the past two decades, primarily through the publication and widespread adoption of the Consolidated Standards of Reporting Trials (CONSORT) statement. However, there is room to improve the adoption of those standards in reporting the design and findings of treatment trials for AUD. Methods Narrative review of guidance on reporting quality in AUD treatment trials. Results Despite improvements in the reporting of results of treatment trials for AUD over the past two decades, many published reports provide insufficient information on design or methods. Conclusions The reporting of alcohol treatment trial design, analysis, and results requires improvement in four primary areas: (1) trial registration, (2) procedures for recruitment and retention, (3) procedures for randomization and intervention design considerations, and (4) statistical methods used to assess treatment efficacy. Improvements in these areas and the adoption of reporting standards by authors, reviewers, and editors are critical to an accurate assessment of the reliability and validity of treatment effects. Continued developments in this area are needed to move AUD treatment research forward via systematic reviews and meta-analyses that maximize the utility of completed studies. PMID:26259958

Preliminary antifungal activity assay of selected chlorine-containing derivatives of xanthone and phenoxyethyl amines.

PubMed

Klesiewicz, Karolina; Żelaszczyk, Dorota; Trojanowska, Danuta; Bogusz, Bożena; Małek, Marianna; Waszkielewicz, Anna; Szkaradek, Natalia; Karczewska, Elżbieta; Marona, Henryk; Budak, Alicja

2018-06-20

The aim of this study was to preliminary evaluate antifungal activity diverse group of chlorine-containing xanthone and phenoxyethyl amine derivatives - and to select most promising compounds for further studies. The antifungal efficacy of 16 compounds was tested with qualitative and quantitative methods against both reference and clinical strains of dermatophytes, moulds and yeasts. The disc-diffusion method has demonstrated that from 16 tested compounds, 7 possess good antifungal activity against dermatophytes and/or moulds while none of them has shown good efficacy against yeasts or bacterial strains. The most active compounds (2, 4, 10, 11, 12, 15, 16) were tested quantitatively by broth dilution method to obtain MIC values. The MIC values against dermatophytes ranged from 8 to 64 μg/mL. Compound 2 was the most active one against dermatophytes (MIC 50 and MIC 90 were 8 μg/mL). The MIC values for moulds ranged from 16 to 256 μg/mL. Compound 4 was the most active one against moulds, with MIC 50 and MIC 90 values amounting to 32 μg/mL. Among the tested compounds, compound 4 (derivative of xanthone) was the most active one and expressed good antifungal efficacy against clinical strains of dermatophytes and moulds. However, another xanthone derivative (compound 2) was the most active and selective against dermatophytes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Randomized Controlled Trial of Antiseptic Hand Hygiene Methods in an Outpatient Surgery Clinic.

PubMed

Therattil, Paul J; Yueh, Janet H; Kordahi, Anthony M; Cherla, Deepa V; Lee, Edward S; Granick, Mark S

2015-12-01

Outpatient wound care plays an integral part in any plastic surgery practice. However, compliance with hand hygiene measures has shown to be low, due to skin irritation and lack of time. The objective of this trial was to determine whether single-use, long-acting antiseptics can be as effective as standard multiple-use hand hygiene methods in an outpatient surgical setting. A prospective, randomized controlled trial was performed in the authors' outpatient plastic surgery clinic at Rutgers New Jersey Medical School, Newark, NJ to compare the efficacy of an ethyl alcohol-based sanitizer (Avagard D Instant Hand Aniseptic, 3M Health Care, St. Paul, MN), a benzalkonium chloride-based sanitizer (Soft & Shield, Bioderm Technologies, Inc, Trenton, NJ, distributed by NAPP Technologies, Hackensack, NJ ), and soap and- water handwashing. Subjects included clinic personnel, who were followed throughout the course of a 3-hour clinic session with hourly hand bacterial counts taken. During the course of the trial, 95 subjects completed the clinic session utilizing 1 of the hand hygiene methods (36 ethyl alcohol-based sanitizer, 38 benzalkonium chloride-based sanitizer, and 21 soap-and-water handwashing). There was no difference between hand bacterial counts using the different methods at 4 hourly time points (P greater than 0.05). Hand bacterial counts increased significantly over the 3-hour clinic session with the ethyl alcohol-based sanitizer (9.24 to 21.90 CFU, P less than 0.05), benzalkonium chloride-based sanitizer (6.69 to 21.59 CFU, P less than 0.05), and soap-and-water handwashing (8.43 to 22.75 CFU, P less than 0.05). There does not appear to be any difference in efficacy between single-use, long-acting sanitizer, and standard multiple-use hand hygiene methods. Hand bacterial counts increased significantly over the course of the 3-hour clinic session regardless of the hand hygiene measure used. Hand condition of subjects was improved with the ethyl alcohol-based sanitizer and the benzalkonium chloride-based sanitizer compared with soap-and-water handwashing.

Efficacy of exposure versus cognitive therapy in anxiety disorders: systematic review and meta-analysis

PubMed Central

2011-01-01

Background There is growing evidence of the effectiveness of Cognitive Behavioural Therapy (CBT) for a wide range of psychological disorders. There is a continued controversy about whether challenging maladaptive thoughts rather than use of behavioural interventions alone is associated with the greatest efficacy. However little is known about the relative efficacy of various components of CBT. This review aims to compare the relative efficacy of Cognitive Therapy (CT) versus Exposure (E) for a range of anxiety disorders using the most clinically relevant outcome measures and estimating the summary relative efficacy by combining the studies in a meta-analysis. Methods Psych INFO, MEDLINE and EMBASE were searched from the first available year to May 2010. All randomised controlled studies comparing the efficacy of exposure with cognitive therapy were included. Odds ratios (OR) or standardised means' differences (Hedges' g) for the most clinically relevant primary outcomes were calculated. Outcomes of the studies were grouped according to specific disorders and were combined in meta-analyses exploring short-term and long-term outcomes. Results 20 Randomised Controlled Trials with (n = 1,308) directly comparing the efficacy of CT and E in anxiety disorders were included in the meta-analysis. No statistically significant difference in the relative efficacy of CT and E was revealed in Post Traumatic Stress Disorder (PTSD), in Obsessive Compulsive Disorder (OCD) and in Panic Disorder (PD). There was a statistically significant difference favouring CT versus E in Social Phobia both in the short-term (Z = 3.72, p = 0.0002) and the long-term (Z = 3.28, p = 0.001) outcomes. Conclusions On the basis of extant literature, there appears to be no evidence of differential efficacy between cognitive therapy and exposure in PD, PTSD and OCD and strong evidence of superior efficacy of cognitive therapy in social phobia PMID:22185596

[Applications of mathematical statistics methods on compatibility researches of traditional Chinese medicines formulae].

PubMed

Mai, Lan-Yin; Li, Yi-Xuan; Chen, Yong; Xie, Zhen; Li, Jie; Zhong, Ming-Yu

2014-05-01

The compatibility of traditional Chinese medicines (TCMs) formulae containing enormous information, is a complex component system. Applications of mathematical statistics methods on the compatibility researches of traditional Chinese medicines formulae have great significance for promoting the modernization of traditional Chinese medicines and improving clinical efficacies and optimizations of formulae. As a tool for quantitative analysis, data inference and exploring inherent rules of substances, the mathematical statistics method can be used to reveal the working mechanisms of the compatibility of traditional Chinese medicines formulae in qualitatively and quantitatively. By reviewing studies based on the applications of mathematical statistics methods, this paper were summarized from perspective of dosages optimization, efficacies and changes of chemical components as well as the rules of incompatibility and contraindication of formulae, will provide the references for further studying and revealing the working mechanisms and the connotations of traditional Chinese medicines.

Resveratrol Based Oral Nutritional Supplement Produces Long-Term Beneficial Effects on Structure and Visual Function in Human Patients

PubMed Central

Richer, Stuart; Patel, Shana; Sockanathan, Shivani; Ulanski, Lawrence J.; Miller, Luke; Podella, Carla

2014-01-01

Background: Longevinex® (L/RV) is a low dose hormetic over-the-counter (OTC) oral resveratrol (RV) based matrix of red wine solids, vitamin D3 and inositol hexaphosphate (IP6) with established bioavailability, safety, and short-term efficacy against the earliest signs of human atherosclerosis, murine cardiac reperfusion injury, clinical retinal neovascularization, and stem cell survival. We previously reported our short-term findings for dry and wet age-related macular degeneration (AMD) patients. Today we report long term (two to three year) clinical efficacy. Methods: We treated three patients including a patient with an AMD treatment resistant variant (polypoidal retinal vasculature disease). We evaluated two clinical measures of ocular structure (fundus autofluorescent imaging and spectral domain optical coherence extended depth choroidal imaging) and qualitatively appraised changes in macular pigment volume. We further evaluated three clinical measures of visual function (Snellen visual acuity, contrast sensitivity, and glare recovery to a cone photo-stress stimulus). Results: We observed broad bilateral improvements in ocular structure and function over a long time period, opposite to what might be expected due to aging and the natural progression of the patient’s pathophysiology. No side effects were observed. Conclusions: These three cases demonstrate that application of epigenetics has long-term efficacy against AMD retinal disease, when the retinal specialist has exhausted other therapeutic modalities. PMID:25329968

Comparative Clinical Efficacy between Electrodesiccation with Curettage and Application of 80% Phenol Solution in Treatment of Common Warts

PubMed Central

Dalimunthe, Dina Arwina; Siregar, Remenda; Tanjung, Chairiyah

2018-01-01

BACKGROUND: Common warts are skin diseases caused by human papillomavirus. Several treatment modalities available for common warts, two of them are electrodesiccation with curettage and application of 80% phenol solution. AIM: This study aims to compare clinical efficacy between these two modalities. MATERIAL AND METHODS: Open clinical trial was conducted at Dr Pirngadi General Hospital Medan and H. Adam Malik General Hospital Medan from February to June 2013 on 17 patients with multiple common warts. Both treatments began and applied simultaneously on the same day on each patient. RESULTS: Cure rate was higher in electrodesiccation with curettage (76.5%, 100%) compared to the application of 80% phenol solution (11.8%, 64.7%) on three weeks and six weeks of follow up. Statistical analysis showed a significant difference of common warts cure rate between electrodesiccation with curettage and application of 80% phenol solution after three weeks (p < 0.001) and six weeks (p = 0.018) of treatment. CONCLUSION: As a conclusion, electrodesiccation with curettage has higher cure rate than the application of 80% phenol solution on the treatment of common warts. Further study is needed to find out the best concentration and time interval for application of phenol solution to improve its clinical efficacy as an alternative treatment of choice for common warts. PMID:29531597

Randomised Clinical Efficacy Trial of Topiramate and Nitrazepam in Treatment of Infantile Spasms

PubMed Central

FALLAH, Razieh; SALOR, Fahimah; AKHAVAN KARBASI, Sedighah; MOTAGHIPISHEH, Hadi

2014-01-01

Objective Infantile spasms (IS) are among the most catastrophic epileptic syndromes of infancy. The purpose of this study was to compare efficacy and safety of topiramate (TPM) and nitrazepam (NZP) as first-line drugs in the treatment of IS. Materials & Methods In a parallel single-blinded randomized clinical trial, 50 patients with IS referred to Pediatric Neurology Clinic of Shahid Sadoughi University of Medical Sciences, Yazd, Iran, were evaluated from September 2008 to March 2010. Patients were randomly assigned to two groups to be treated with TPM or with NZP for 6 months. The primary endpoint was efficacy in cessation of all spasms or reduction of more than 50% in weekly seizure frequency, which was evaluated before and 6 months after the drug use. Secondary outcome was clinical sideeffects of the drugs. Results Twenty boys (40%) and 30 girls (60%) with the mean age of 9.4±3.8 months were evaluated. Cessation of all spasms occurred in 12 (48%) infants in TPM group and 4(16%) in NZP group. Eight (32%) children in TPM group and 7 (28%) in NZP group had more than 50% reduction in spasms frequency. So, TPM was more effective. Side effects were seen in 32% of TPM and in 36% of NZP groups. Conclusion Topiramate is an effective and safe drug, which might be considered as the firstline drug for the treatment of ISs. PMID:24665322

A Prospective, Randomized, Double-blind, Split-face Clinical Trial Comparing the Efficacy of Two Topical Human Growth Factors for the Rejuvenation of the Aging Face

PubMed Central

Goldman, Mitchel P.

2017-01-01

Background: Cosmeceutical products represent an increasingly important therapeutic option for anti-aging and rejuvenation, either used alone or in combination with dermatologic surgical procedures. Among this group of products, topical growth factors have demonstrated efficacy in randomized, controlled clinical trials. However, comparisons between different products remain uncommon. Objective: The objective of this randomized, double-blind, split-face clinical trial was to compare two different topical growth factor formulations derived from either human fibroblasts or human adipose tissue derived mesenchymal stem cells. Methods: This was an institutional review board-approved, randomized, double-blind, split-face clinical trial involving 20 healthy subjects with moderate-to-severe facial wrinkling secondary to photodamage. One half of the face was randomized to receive topical human fibroblast growth factors and the other topical human mesenchymal stem cell growth factors. Treatment was continued for three months, and evaluations were performed in a double-blind fashion. Results: Both growth factor formulations achieved significant improvement in facial wrinkling. Blinded investigator and subject evaluations did not detect any significant differences between the two formulations in terms of efficacy, safety, or tolerability. Conclusion: Both human fibroblast growth factors and human mesenchymal stem cell growth factors are effective at facial rejuvenation. Topical growth factors represent a useful therapeutic modality. PMID:28670356

The Clinical Efficacy of Yindanxinnaotong Soft Capsule in the Treatment of Stroke and Angina Pectoris: A Meta-Analysis

PubMed Central

Liu, Yue

2017-01-01

Objective. To systematically evaluate the clinical efficacy of Yindanxinnaotong (YD) soft capsule in adult patients with cardiovascular diseases (stroke and angina pectoris). Methods. We electronically searched databases including Medline, PubMed, Chinese National Knowledge Infrastructure (CNKI), Cqvip Database (VIP), and Wanfang Database for published articles of randomized controlled trials (RCTs) of YD capsule in treating stroke and angina pectoris. The meta-analysis was performed using RevMan 5.3 software. Results. 49 RCTs involving 6195 subjects with cardiovascular diseases (angina pectoris and stroke) were included. Compared with western conventional medicine (WCM) and/or other Chinese medicines, YD plus WCM therapeutic regimen could significantly improve the efficacy rate (RR = 1.21, 95% CI (1.17, 1.25), P < 0.00001 for angina pectoris, RR = 1.24, 95% CI (1.18, 1.31), P < 0.00001 for stroke), showing the clinical value. In addition, the therapeutic efficiency of WCM plus YD capsule regimen is better than that of WCM alone in improving CRP (MD = −2.07, 95% CI (−3.97, −0.17), P = 0.03 <0.05) and TG (MD = −0.37, 95% CI (−0.52, −0.23), P < 0.0001). Conclusion. YD is effective in the treatment of cardiovascular diseases (angina pectoris and stroke) in adults, and WCM plus YD therapeutic regimen can significantly improve the effective rate in the clinic. PMID:28539962

A Prospective, Randomized, Double-blind, Split-face Clinical Trial Comparing the Efficacy of Two Topical Human Growth Factors for the Rejuvenation of the Aging Face.

PubMed

Wu, Douglas C; Goldman, Mitchel P

2017-05-01

Background: Cosmeceutical products represent an increasingly important therapeutic option for anti-aging and rejuvenation, either used alone or in combination with dermatologic surgical procedures. Among this group of products, topical growth factors have demonstrated efficacy in randomized, controlled clinical trials. However, comparisons between different products remain uncommon. Objective: The objective of this randomized, double-blind, split-face clinical trial was to compare two different topical growth factor formulations derived from either human fibroblasts or human adipose tissue derived mesenchymal stem cells. Methods: This was an institutional review board-approved, randomized, double-blind, split-face clinical trial involving 20 healthy subjects with moderate-to-severe facial wrinkling secondary to photodamage. One half of the face was randomized to receive topical human fibroblast growth factors and the other topical human mesenchymal stem cell growth factors. Treatment was continued for three months, and evaluations were performed in a double-blind fashion. Results: Both growth factor formulations achieved significant improvement in facial wrinkling. Blinded investigator and subject evaluations did not detect any significant differences between the two formulations in terms of efficacy, safety, or tolerability. Conclusion: Both human fibroblast growth factors and human mesenchymal stem cell growth factors are effective at facial rejuvenation. Topical growth factors represent a useful therapeutic modality.

Evaluating the Effectiveness of Using a Progressive Muscle Relaxation Technique on the Self-Efficacy of Breastfeeding in Mothers With Preterm Infants.

PubMed

Karbandi, Soheila; Hosseini, Seyedeh Maryam; Hosseini, Seyedeh Asieh; Sadeghi, Farshad; Hesari, Maryam; Masoudi, Reza

2017-08-01

Breast milk is a God-given gift that conveys a mother's love and compassion and that is made according to the needs and age of the child. Mothers who are interested in the welfare of their newborns tend to breastfeed their children. Training programs have been shown to improve breastfeeding self-efficacy in terms of both duration and amount. The aim of this study was to evaluate the effect of using the progressive muscle relaxation (PMR) technique on the self-efficacy of breastfeeding in mothers with preterm infants. A clinical trial approach was used. Sixty mothers with preterm infants were randomly assigned to either the intervention or control group. The clinical trial ran for a period of 2 months for both groups. At 24-72 hours postpartum, the researcher used the Jacobson method to provide 30-45 minutes of individual training to the intervention group participants on PMR. Under the Jacobson method, mothers contract the 16 groups of muscles until they experience the feeling of pressure and then relax these muscles. The tools used in this study were the standard questionnaire of Dennis breastfeeding self-efficacy, which was completed by the participants at baseline, at the end of the fourth week, and during the eighth week. Data were analyzed using SPSS software. No significant difference was observed between the intervention and control groups in terms of demographic variables (p > .05). Independent t tests found no significant difference between the two groups (p = .45) in terms of mean score of maternal breastfeeding self-efficacy at pretest and significantly higher scores for the intervention group than the control group at both 4 (p = .001) and 8 (p < .001) weeks posttest. Furthermore, the analysis of variance test showed significant differences in the mean score of breastfeeding self-efficacy for the intervention group between pretest and the first posttest and between the first posttest and the second posttest, respectively (p < .001). Considering the effect of relaxation training on the breastfeeding self-efficacy of mothers with preterm infants, training and performing these exercises as an effective and low-cost method to improve the health of mothers, particularly mothers of preterm infants, are recommended. The PMR technique facilitates the self-efficacy of breastfeeding in mothers with preterm infants and should be considered as an effective strategy to improve nursing care and the provision of better support services for mothers who breastfeed their infants.

A systematic review and meta-analysis of online versus alternative methods for training licensed health care professionals to deliver clinical interventions.

PubMed

Richmond, Helen; Copsey, Bethan; Hall, Amanda M; Davies, David; Lamb, Sarah E

2017-11-23

Online training is growing in popularity and yet its effectiveness for training licensed health professionals (HCPs) in clinical interventions is not clear. We aimed to systematically review the literature on the effectiveness of online versus alternative training methods in clinical interventions for licensed Health Care Professionals (HCPs) on outcomes of knowledge acquisition, practical skills, clinical behaviour, self-efficacy and satisfaction. Seven databases were searched for randomised controlled trials (RCTs) from January 2000 to June 2015. Two independent reviewers rated trial quality and extracted trial data. Comparative effects were summarised as standardised mean differences (SMD) and 95% confidence intervals. Pooled effect sizes were calculated using a random-effects model for three contrasts of online versus (i) interactive workshops (ii) taught lectures and (iii) written/electronic manuals. We included 14 studies with a total of 1089 participants. Most trials studied medical professionals, used a workshop or lecture comparison, were of high risk of bias and had small sample sizes (range 21-183). Using the GRADE approach, we found low quality evidence that there was no difference between online training and an interactive workshop for clinical behaviour SMD 0.12 (95% CI -0.13 to 0.37). We found very low quality evidence of no difference between online methods and both a workshop and lecture for knowledge (workshop: SMD 0.04 (95% CI -0.28 to 0.36); lecture: SMD 0.22 (95% CI: -0.08, 0.51)). Lastly, compared to a manual (n = 3/14), we found very low quality evidence that online methods were superior for knowledge SMD 0.99 (95% CI 0.02 to 1.96). There were too few studies to draw any conclusions on the effects of online training for practical skills, self-efficacy, and satisfaction across all contrasts. It is likely that online methods may be as effective as alternative methods for training HCPs in clinical interventions for the outcomes of knowledge and clinical behaviour. However, the low quality of the evidence precludes drawing firm conclusions on the relative effectiveness of these training methods. Moreover, the confidence intervals around our effect sizes were large and could encompass important differences in effectiveness. More robust, adequately powered RCTs are needed.

Albendazole nanocrystals in experimental alveolar echinococcosis: Enhanced chemoprophylactic and clinical efficacy in infected mice.

PubMed

Pensel, Patricia; Paredes, Alejandro; Albani, Clara M; Allemandi, Daniel; Sanchez Bruni, Sergio; Palma, Santiago D; Elissondo, María C

2018-02-15

Human alveolar echinococcosis is caused by the fox tapeworm Echinococcus multilocularis and is usually fatal if left untreated. Medical treatment with albendazole (ABZ) remains an effective option. However, due to its low aqueous solubility, ABZ is poorly and erratically absorbed following oral administration resulting in low drug levels in plasma and liver distribution. Thus, there arises the need to find a simple, efficient and scalable method to produce new ABZ formulations with increased bioavailability. Bearing this in mind, ABZ nanocrystals (ABZ-NCs) appears to be a useful tool to achieve this goal. The aim of the current study was to investigate the chemoprophylactic and clinical efficacy of an ABZ-NC formulation on mice infected with E. multilocularis. In the chemoprophylactic efficacy study, mean weight of the cysts recovered from the ABZ-NC group was 50% lower than that recorded from untreated mice, whereas the treatment with ABZ suspension did not show preventive effect. The viability of protoscoleces isolated from ABZ-NC treated mice was significantly lower than control groups. In the clinical efficacy studies, both ABZ formulations resulted in a reduction in the mean weight of the cysts obtained from mice, however only the treatment with the nanosuspension revealed significant differences (P < 0.05) compared to the control groups. Treatment with ABZ-NCs reduced the weight of the cysts by 77% and the viability of their protoscoleces to 34%. All these results coincided with the tissue damage determined at the ultrastructural level. The enhanced chemoprophylactic and clinical efficacy of ABZ-NCs observed in this study could be attributed to an increase in the oral bioavailability of the drug. In a next step, we will characterize the cyst concentration profile after the administration of ABZ-NCs in mice infected with E. multilocularis. Copyright © 2017 Elsevier B.V. All rights reserved.

In Vivo Assessment of Drug Efficacy against Mycobacterium abscessus Using the Embryonic Zebrafish Test System

PubMed Central

Bernut, Audrey; Le Moigne, Vincent; Lesne, Tiffany; Lutfalla, Georges; Herrmann, Jean-Louis

2014-01-01

Mycobacterium abscessus is responsible for a wide spectrum of clinical syndromes and is one of the most intrinsically drug-resistant mycobacterial species. Recent evaluation of the in vivo therapeutic efficacy of the few potentially active antibiotics against M. abscessus was essentially performed using immunocompromised mice. Herein, we assessed the feasibility and sensitivity of fluorescence imaging for monitoring the in vivo activity of drugs against acute M. abscessus infection using zebrafish embryos. A protocol was developed where clarithromycin and imipenem were directly added to water containing fluorescent M. abscessus-infected embryos in a 96-well plate format. The status of the infection with increasing drug concentrations was visualized on a spatiotemporal level. Drug efficacy was assessed quantitatively by measuring the index of protection, the bacterial burden (CFU), and the number of abscesses through fluorescence measurements. Both drugs were active in infected embryos and were capable of significantly increasing embryo survival in a dose-dependent manner. Protection from bacterial killing correlated with restricted mycobacterial growth in the drug-treated larvae and with reduced pathophysiological symptoms, such as the number of abscesses within the brain. In conclusion, we present here a new and efficient method for testing and compare the in vivo activity of two clinically relevant drugs based on a fluorescent reporter strain in zebrafish embryos. This approach could be used for rapid determination of the in vivo drug susceptibility profile of clinical isolates and to assess the preclinical efficacy of new compounds against M. abscessus. PMID:24798271

A new cognitive evaluation battery for Down syndrome and its relevance for clinical trials

PubMed Central

de Sola, Susana; de la Torre, Rafael; Sánchez-Benavides, Gonzalo; Benejam, Bessy; Cuenca-Royo, Aida; del Hoyo, Laura; Rodríguez, Joan; Catuara-Solarz, Silvina; Sanchez-Gutierrez, Judit; Dueñas-Espin, Ivan; Hernandez, Gimena; Peña-Casanova, Jordi; Langohr, Klaus; Videla, Sebastia; Blehaut, Henry; Farre, Magi; Dierssen, Mara; Cuenca-Royo, Aida

2015-01-01

The recent prospect of pharmaceutical interventions for cognitive impairment of Down syndrome (DS) has boosted a number of clinical trials in this population. However, running the trials has raised some methodological challenges and questioned the prevailing methodology used to evaluate cognitive functioning of DS individuals. This is usually achieved by comparing DS individuals to matched healthy controls of the same mental age. We propose a new tool, the TESDAD Battery that uses comparison with age-matched typically developed adults. This is an advantageous method for probing the clinical efficacy of DS therapies, allowing the interpretation and prediction of functional outcomes in clinical trials. In our DS population the TESDAD battery permitted a quantitative assessment of cognitive defects, which indicated language dysfunction and deficits in executive function, as the most important contributors to other cognitive and adaptive behavior outcomes as predictors of functional change in DS. Concretely, auditory comprehension and functional academics showed the highest potential as end-point measures of therapeutic intervention for clinical trials: the former as a cognitive key target for therapeutic intervention, and the latter as a primary functional outcome measure of clinical efficacy. Our results also emphasize the need to explore the modulating effects of IQ, gender and age on cognitive enhancing treatments. Noticeably, women performed significantly better than men of the same age and IQ in most cognitive tests, with the most consistent differences occurring in memory and executive functioning and negative trends rarely emerged on quality of life linked to the effect of age after adjusting for IQ and gender. In sum, the TESDAD battery is a useful neurocognitive tool for probing the clinical efficacy of experimental therapies in interventional studies in the DS population suggesting that age-matched controls are advantageous for determining normalization of DS. PMID:26089807

The Mechanisms Linking Health Literacy to Behavior and Health Status

PubMed Central

Osborn, Chandra Y.; Paasche-Orlow, Michael K.; Bailey, Stacy Cooper; Wolf, Michael S.

2011-01-01

Objective To examine the mechanisms linking health literacy to physical activity and self-reported health. Methods From 2005–2007, patients (N=330) with hypertension were recruited from safety net clinics. Path analytic models tested the pathways linking health literacy to physical activity and self-reported health. Results There were significant paths from health literacy to knowledge (r=0.22, P<0.001), knowledge to self-efficacy (r=0.13, P<0.01), self-efficacy to physical activity (r=0.17, P<0.01), and physical activity to health status (r=0.17, P<0.01). Conclusions Health education interventions should be literacy sensitive and aim to enhance patient health knowledge and self-efficacy to promote self-care behavior and desirable health outcomes. PMID:20950164

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

Experimental Evaluation of the Training Structure of the Picture Exchange Communication System (PECS)

ERIC Educational Resources Information Center

Cummings, Anne R.; Carr, James E.; LeBlanc, Linda A.

2012-01-01

The Picture Exchange Communication System (PECS) is a picture-based alternative communication method that is widely accepted and utilized with individuals with disabilities. Although prior studies have examined the clinical efficacy of PECS, none have experimentally evaluated its manualized training structure. We experimentally evaluated the…

Available Resources | Division of Cancer Prevention

Cancer.gov

Preclinical pharmacology and efficacy studies Identification and evaluation of intermediate biomarkers Formulation optimization for enhanced bioavailability and clinical usefulness Analytical method development for investigational agents in bulk form and in biological fluids and tissues PK and PK-PD modeling to optimize dosing regimen Scale-up non-cGMP and cGMP production of

Pharmaceutical Technology Clerkship: A Professional Elective Course at the University of Kentucky

ERIC Educational Resources Information Center

Im, Sophann; DeLuca, Patrick P.

1978-01-01

Three objectives are described: (1) teach methods for applying the principles of pharmaceutical technology to institutional services involving drug safety, efficacy, and administration; (2) develop student skills in drug-delivery systems within hospitals; and (3) encourage technology application within a clinical setting for better patient care.…

[Efficacy and Safety Evaluation of Bushen Shuji Granule in Treating Ankylosing Spondylitis Patients: a Clinical Study].

PubMed

Kong, Wei-ping; Tao, Qing-wen; Zhang, Ying-ze; Yang, Shu; Xu, Yuan; Zhu, Xiao-xia; Jin, Yue; Yang, Wen-xue; Yan, Xiao-ping

2015-06-01

To evaluate the short-term efficacy and safety of Bushen Shuji Granule (BSG) in treating ankylosing spondylitis (AS) patients. A prospective randomized controlled clinical trial was carried out in 62 active stage AS patients with Shen deficiency Du-channel cold syndrome (SDDCS), who were randomly assigned to the BSG group (treated with BSG) and the control group (treated with Celecoxib Capsule). Twelve weeks consisted of one therapeutic course. Therapeutic effects were evaluated by ASAS20 and ASAS40 (set by Assessments in Ankylosing Spondylitis working group) , BASDA150, Chinese medical (CM) syndrome efficacy evaluation standards. BASDAI, the Bath Ankylosing Spondylitis Functional Index (BASFI), the Bath AS Metrology Index (BASMI), scores for spine pain, scores for pain at night, patient global assessment (PGA) , erythrocyte sedimentation rate (ESR) , and C reactive protein (CRP) were observed before and after treatment. After three-month treatment by BSG, ASAS20 standard rate was 63. 33% (19/30 cases) in the BSG group and 66.67% (20/30 cases) in the control group with no significant difference between the two groups (χ2 = 0.073, P > 0.05). The efficacy for CM syndromes was 70.00% (21/30 cases) in the BSG group, higher than that in the control group [40.00% (12/30 cases), χ2 = 5.455, P < 0.05]. Scores for CM syndromes, BASDAI, night pain index, spinal pain index, PGA, CRP were improved in the BSG group (P < 0.05, P < 0.01). The incidence of adverse events in the BSG group was lower than that of the control group. BSG based on Shen supplementing, Du-channel strengthening, blood activating, and channels dredging method had good short-term clinical efficacy and safety in treating AS.

A Model of Parental Distress and Factors that Mediate its Link with Parental Monitoring of Youth Diabetes Care, Adherence, and Glycemic Control

PubMed Central

Robinson, Elizabeth M.; Weaver, Patrick; Chen, Rusan; Streisand, Randi; Holmes, Clarissa S.

2016-01-01

Objective Parental monitoring of adolescents’ diabetes self-care is associated with better adherence and glycemic control (A1c). A number of parent-level factors are associated with higher levels of parental monitoring, including lower levels of parental distress (depressive symptoms, stress, anxiety), as well as higher levels of parental self-efficacy for diabetes management and authoritative parenting. Often studied in isolation, these factors may be best considered simultaneously as they are interrelated and are associated with parental monitoring and youth adherence. Methods Structural equation modeling with a cross-sectional sample of 257 parent/youth (aged 11-14) dyads: 1) examined a broad model of parental factors (i.e., parental distress, parental diabetes self-efficacy, authoritative parenting) and 2) assessed their relation to parental monitoring, youth adherence, and A1c. Post-hoc ANOVAs evaluated clinical implications of daily parental monitoring. Results Parental distress was not related directly to parental monitoring. Instead less distress related indirectly to more monitoring via higher parental self-efficacy and more authoritative parenting which in turn related to better adherence and A1c. Higher parental self-efficacy also related directly to better youth adherence and then to better A1c. Clinically, more parental monitoring related to more daily blood glucose checks and to better A1c (8.48% v. 9.17%). Conclusions A broad model of parent-level factors revealed more parental distress was linked only indirectly to less monitoring via lower parental self-efficacy and less authoritative parenting. Behaviorally, more parental monitoring related to better adherence and to clinically better A1c in adolescents. Further study of parent-level factors that relate to parental distress and monitoring of adherence appears warranted. PMID:27513476

Safety and Efficacy of Catheter Direct Thrombolysis in Management of Acute Iliofemoral Deep Vein Thrombosis: A Systematic Review

PubMed Central

Elbasty, Ahmed; Metcalf, James

2017-01-01

Purpose Catheter direct thrombolysis (CDT) has been shown to be an effective treatment for deep venous thrombosis. The objective of the review is to improve safety and efficacy of the CDT by using ward based protocol, better able to predict complications and treatment outcome through monitoring of haemostatic parameters and clinical observation during thrombolysis procedure. Materials and Methods MEDLINE, EMBASE, CENTRAL and Web of Science were searched for all articles on deep venous thrombosis, thrombolysis and correlations of clinical events (bleeding, successful thrombolysis) during thrombolysis with hemostatic parameters to March 2016. The risk of bias in included studies was assessed by Cochrane Collaboration’s tool and Cochrane Risk of Bias Assessment Tool: for Non-Randomized Studies of Interventions. Results Twenty-four studies were included in the review and we found that improving safety and efficacy of CDT by using ward based protocol depending on eight factors; strict patient selection criteria, types of fibrinolytic drugs, mode of fibrinolytic drug injection, biochemical markers monitoring (fibrinogen, D-dimer, activated partial thromboplastin time, plasminogen activator inhibitor-1), timing of intervention, usage of intermittent pneumatic calf, ward monitoring and thrombolysis imaging assessment (intravascular ultrasound). These factors may help to improve safety and efficacy by reducing total thrombolytic drug dosage and at the same time ensure successful lysis. There is a marked lack of randomized controlled trials discussing the safety and efficacy of catheter direct thrombolysis. Conclusion CDT can be performed safely and efficiently in clinical ward, providing that careful nursing, biochemical monitoring, proper selection and mode of infusion of fibrinolytic drugs, usage of Intermittent pneumatic calf and adequate thrombolysis imaging assessment are ensured. PMID:29354622

A Flexible-Dose Study of Paliperidone ER in Patients With Nonacute Schizophrenia Previously Treated Unsuccessfully With Oral Olanzapine

PubMed Central

KOTLER, MOSHE; DILBAZ, NESRIN; ROSA, FERNANDA; PATERAKIS, PERIKLIS; MILANOVA, VIHRA; SMULEVICH, ANATOLY B.; LAHAYE, MARJOLEIN

2016-01-01

Objective: The goal of this study was to explore the tolerability, safety, and treatment response of switching from oral olanzapine to paliperidone extended release (ER). Methods: Adult patients with nonacute schizophrenia who had been treated unsuccessfully with oral olanzapine were switched to flexible doses of paliperidone ER (3 to 12 mg/d). The primary efficacy outcome was a ≥20% improvement in Positive and Negative Syndrome Scale (PANSS) total scores from baseline to endpoint for patients who switched medications because of lack of efficacy with olanzapine and noninferiority versus previous olanzapine treatment (mean endpoint change in PANSS total scores vs. baseline of ≤5 points) for patients who switched for reasons other than lack of efficacy. Safety and tolerability were assessed by monitoring adverse events, extrapyramidal symptoms, and weight change. Results: Of 396 patients, 65.2% were men, mean age was 40.0±12.0 years, and 75.5% had paranoid schizophrenia. Among the patients whose main reason for switching was lack of efficacy, an improvement in the PANSS total score of ≥20% occurred in 57.4% of patients. Noninferiority was confirmed for each subgroup of patients whose main reason for switching was something other than lack of efficacy. Paliperidone ER was generally well tolerated. Extrapyramidal symptoms as measured by total Extrapyramidal Symptom Rating Scale scores showed statistically significant and clinically relevant improvements at endpoint, the average weight decreased by 0.8±5.2 kg at endpoint, and a clinically relevant weight gain of ≥7% occurred in 8.0% of patients. Conclusion: Paliperidone ER flexibly-dosed over 6 months was well tolerated and associated with a meaningful clinical response in patients with nonacute schizophrenia who had previously been unsuccessfully treated with oral olanzapine. PMID:26813484

Efficacy and safety of topical diquafosol ophthalmic solution for treatment of dry eye: a systematic review of randomized clinical trials.

PubMed

Wu, Di; Chen, Wang Qi; Li, Ryan; Wang, Yan

2015-06-01

To evaluate the efficacy and safety of topical diquafosol ophthalmic solution for treatment of dry eye. Randomized clinical trials (RCTs) from MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) were identified to evaluate the efficacy and safety of topical administration of diquafosol to patients with dry eyes. Data evaluation was based on endpoints including Schirmer test, tear film break-up time, ocular surface staining score, subjective symptom score, and adverse events. A total of 8 RCTs involving 1516 patients were selected based on the prespecified criteria. Significant improvement of Schirmer test values and tear film break-up time were reported in 40% (2 of 5) and 80% (4 of 5) studies, respectively. Ocular surface staining scores significantly decreased in 100% (fluorescein corneal staining, 6 of 6; Rose Bengal corneal and conjunctival staining, 4 of 4) RCTs. Symptoms significantly improved in 75% (6 of 8) RCTs in patients with dry eyes. No severe adverse events were reported with the concentration of diquafosol from 0.5% to 5%. Heterogeneity in study design prevented meta-analysis from statistical integration and summarization. Topical diquafosol seems to be a safe therapeutic option for the treatment of dry eye. The high variability of the selected RCTs compromised the strength of evidence and limits the determination of efficacy. However, the topical administration of diquafosol seems to be beneficial in improving the integrity of the epithelial cell layer of the ocular surface and mucin secretion in patients with dry eyes. This review indicates a need for standardized criteria and methods for evaluation to assess the efficacy of diquafosol in the future clinical trials.

RESULTS OF THE MEGAVERTEBRATE ANALGESIA SURVEY: ELEPHANTS AND RHINO.

PubMed

Kottwitz, Jack; Boothe, Matthew; Harmon, Roy; Citino, Scott B; Zuba, Jeffery R; Boothe, Dawn M

2016-03-01

An online survey utilizing Survey Monkey linked through the American Association of Zoo Veterinarians listserve examined current practices in megavertebrate analgesia. Data collected included drugs administered, dosing regimens, ease of administration, efficacy, and adverse events. Fifty-nine facilities (38 housing elephants, 33 housing rhinoceroses) responded. All facilities administered nonsteroidal anti-inflammatory drugs (NSAIDs), with phenylbutazone (0.25-10 mg/kg) and flunixin meglumine (0.2-4 mg/kg) being most common. Efficacy was reported as "good" to "excellent" for these medications. Opioids were administered to elephants (11 of 38) and rhinoceroses (7 of 33), with tramadol (0.5-3.0 mg/kg) and butorphanol (0.05-1.0 mg/kg) being most common. Tramadol efficacy scores were highly variable in both elephants and rhinoceroses. While drug choices were similar among institutions, substantial variability in dosing regimens and reported efficacy between and within facilities indicates the need for pharmacokinetic studies and standardized methods of analyzing response to treatment to establish dosing regimens and clinical trials to establish efficacy and safety.

An analysis of redactions in Canada’s Common Drug Review Clinical Review Reports and how they relate to the patients’ voice

PubMed Central

Soprovich, Allison; El Kurdi, Sylvia; Eurich, Dean T

2017-01-01

Importance Canada’s Common Drug Review (CDR) evaluates drug data from published and unpublished research, as well as input from patient groups, to recommend provincial coverage. Currently, the CDR process gives manufacturers the opportunity to redact information in the final publicly available report. Patients often have strong feelings regarding the efficacy, harms, health-related quality of life (HRQL), and cost associated with the drugs under review and their redacted data. Highlighting Canada’s approach will hopefully build on the growing international concern regarding transparency of clinical study data. Objective The purpose was to objectively examine and classify completed, publicly available CDR-Clinical Review Reports (CRR) for redactions, and compare them to the patients’ reported interests as patient-centred outcomes. Methods Two independent reviewers searched for and examined publicly available CDR-CRR from November 2013-September 2016 through the Canadian Agency for Drugs and Technologies in Health (CADTH) on-line database. Both reviewers separately classified the redactions and patient-reported interests into the following categories: efficacy, harms, HRQL and costs. All discrepancies were rectified by consensus involving a third reviewer. Results Fifty-two completed CDR-CRR were reviewed. 48 (92%) included patient-reported interests and 40 (77%) had redactions classified in the following categories: efficacy (75%), costs (48%), harms (38%), HRQL (23%). 89% of redactions were outcomes identified as patient-reported interests (69% efficacy, 42% harms, 36% cost, 33% HRQL). When examining drug characteristics, biological agents were statistically associated with increased odds of redactions with respect to either efficacy (OR 3.4, 95% CI 1.0 to 11.6) or harms (OR 3.5, 95% CI 1.02 to 12.4) compared with non-biological agents. Conclusions Whether data from the CDR-CRR used in the decision-making should be fully disclosed to the public is controversial. Our findings suggest clinical data (efficacy, harms, HRQL) matters to patients and should be publicly available within the CDR-CRR. Canada trails Europe and the USA regarding the transparency of clinical study data. This lack of transparency relates to the patient voice, and limits movement towards patient-centred care and patient-engaged research, restricting real-world value measurement. PMID:28893743

Controlled randomized clinical trial of spirituality integrated psychotherapy, cognitive-behavioral therapy and medication intervention on depressive symptoms and dysfunctional attitudes in patients with dysthymic disorder.

PubMed

Ebrahimi, Amrollah; Neshatdoost, Hamid Taher; Mousavi, Seyed Ghafur; Asadollahi, Ghorban Ali; Nasiri, Hamid

2013-01-01

Due to the controversy over efficacy of cognitive-behavioral therapy for chronic depression, recently, there has been an increasingly tendency toward therapeutic methods based on the cultural and spiritual approaches. The aim of this research was to compare efficacy of spiritual integrated psychotherapy (SIPT) and cognitive-behavioral therapy (CBT) on the intensity of depression symptoms and dysfunctional attitudes of patients with dysthymic disorder. This study had a mixed qualitative and quantitative design. In the first phase, SIPT model was prepared and, in the second phase, a double-blind random clinical trial was performed. Sixty-two patients with dysthymic disorder were selected from several centers include Nour and Alzahra Medical Center, Counseling Centers of Isfahan University of Medical Sciences and Goldis in Isfahan. The participants were randomly assigned to three experimental groups and one control group. The first group received 8 sessions treatment of SIPT, second groups also had 8 sessions of cognitive-behavioral therapy, which was specific to dysthymic disorder and third group were under antidepressant treatment. Beck depression inventory and dysfunctional attitudes scale were used to evaluate all the participants in four measurement stages. The data were analyzed using MANCOVA repeated measure method. The results revealed that SIPT had more efficacy than medication based on both scales (P < 0.01); however, it was not different from CBT. SIPT was more effective on the modification of dysfunctional attitudes compared with CBT and medication (P < 0.05). These findings supported the efficacy of psychotherapy enriched with cultural capacities and religious teachings.

Efficacy of surface disinfectant cleaners against emerging highly resistant gram-negative bacteria

PubMed Central

2014-01-01

Background Worldwide, the emergence of multidrug-resistant gram-negative bacteria is a clinical problem. Surface disinfectant cleaners (SDCs) that are effective against these bacteria are needed for use in high risk areas around patients and on multi-touch surfaces. We determined the efficacy of several SDCs against clinically relevant bacterial species with and without common types of multidrug resistance. Methods Bacteria species used were ATCC strains; clinical isolates classified as antibiotic-susceptible; and multi-resistant clinical isolates from Klebsiella oxytoca, Klebsiella pneumoniae, and Serratia marcescens (all OXA-48 and KPC-2); Acinetobacter baumannii (OXA-23); Pseudomonas aeruginosa (VIM-1); and Achromobacter xylosoxidans (ATCC strain). Experiments were carried out according to EN 13727:2012 in quadruplicate under dirty conditions. The five evaluated SDCs were based on alcohol and an amphoteric substance (AAS), an oxygen-releaser (OR), surface-active substances (SAS), or surface-active-substances plus aldehydes (SASA; two formulations). Bactericidal concentrations of SDCs were determined at two different contact times. Efficacy was defined as a log10 ≥ 5 reduction in bacterial cell count. Results SDCs based on AAS, OR, and SAS were effective against all six species irrespective of the degree of multi-resistance. The SASA formulations were effective against the bacteria irrespective of degree of multi-resistance except for one of the four P. aeruginosa isolates (VIM-1). We found no general correlation between SDC efficacy and degree of antibiotic resistance. Conclusions SDCs were generally effective against gram-negative bacteria with and without multidrug resistance. SDCs are therefore suitable for surface disinfection in the immediate proximity of patients. Single bacterial isolates, however, might have reduced susceptibility to selected biocidal agents. PMID:24885029

Comparison of Intravenous/Oral Ciprofloxacin Plus Metronidazole Versus Piperacillin/Tazobactam in the Treatment of Complicated Intraabdominal Infections

PubMed Central

Cohn, Stephen M.; Lipsett, Pamela A.; Buchman, Timothy G.; Cheadle, William G.; Milsom, Jeffery W.; O’Marro, Steven; Yellin, Albert E.; Jungerwirth, Steven; Rochefort, Estela V.; Haverstock, Daniel C.; Kowalsky, Steven F.

2000-01-01

Objective To compare the safety and efficacy of intravenous (IV) ciprofloxacin plus IV metronidazole (CIP+MET) with that of IV piperacillin/tazobactam (PIP/TAZO) in adults with complicated intraabdominal infections, and to compare the efficacy of sequential IV-to-oral CIP+MET therapy with that of the IV CIP-only regimen. Summary Background Data Treatment of intraabdominal infections remains a challenge, mainly because of their polymicrobial etiology and attendant death and complications. Antimicrobial regimens using sequential IV-to-oral therapy may reduce the length of hospital stay. Methods In this multicenter, randomized, double-blind trial involving 459 patients, clinically improved IV-treated patients were switched to oral therapy after 48 hours. Overall clinical response was the primary efficacy measurement. Results A total of 282 patients (151 CIP+MET, 131 PIP/TAZO) were valid for efficacy. Of these patients, 64% CIP+MET and 57% PIP/TAZO patients were considered candidates for oral therapy. Patients had a mean APACHE II score of 9.6. The most common diagnoses were appendicitis (33%), other intraabdominal infection (29%), and abscess (25%). Overall clinical resolution rates were statistically superior for CIP+MET (74%) compared with PIP/TAZO (63%). Corresponding rates in the subgroup suitable for oral therapy were 85% for CIP+MET and 70% for PIP/TAZO. Postsurgical wound infection rates were significantly lower in CIP+MET (11%) versus PIP/TAZO patients (19%). Mean length of stay was 14 days for CIP+MET and 17 days for PIP/TAZO patients. Conclusion CIP+MET, initially administered IV and followed by CIP+MET oral therapy, was clinically more effective than IV PIP/TAZO for the treatment of patients with complicated intraabdominal infections. PMID:10903605

Cervical Interlaminar Epidural Steroid Injection for Unilateral Cervical Radiculopathy: Comparison of Midline and Paramedian Approaches for Efficacy

PubMed Central

Yoon, Ji Young; Yoon, Young Cheol; Lee, Jongseok

2015-01-01

Objective The objective of this study was to compare the clinical outcomes of the cervical interlaminar epidural steroid injection (CIESI) for unilateral radiculopathy by the midline or paramedian approaches and to determine the prognostic factors of CIESI. Materials and Methods We retrospectively analyzed 182 patients who underwent CIESI from January 2009 to December 2012. Inclusion criteria were no previous spinal steroid injection, presence of a cross-sectional image, and presence of follow-up records. Exclusion criteria were patients with bilateral cervical radiculopathy and/or dominant cervical axial pain, combined peripheral neuropathy, and previous cervical spine surgery. Short-term clinical outcomes were evaluated at the first follow-up after CIESI. We compared the clinical outcomes between the midline and paramedian approaches. Possible prognostic factors for the outcome, such as age, gender, duration of radiculopathy, and cause of radiculopathy were also analyzed. Results Cervical interlaminar epidural steroid injections were effective in 124 of 182 patients (68.1%) at the first follow-up. There was no significant difference in the clinical outcomes of CIESI, between midline (69.6%) and paramedian (63.7%) approaches (p = 0.723). Cause of radiculopathy was the only significant factor affecting the efficacy of CIESI. Patients with disc herniation had significantly better results than patients with neural foraminal stenosis (82.9% vs. 56.0%) (p < 0.001). Conclusion There is no significant difference in treatment efficacy between the midline and paramedian approaches in CIESI, for unilateral radiculopathy. The cause of the radiculopathy is significantly associated with the treatment efficacy; patients with disc herniation experience better pain relief than those with neural foraminal stenosis. PMID:25995690

Do Published Data in Trials Assessing Cancer Drugs Reflect the Real Picture of Efficacy and Safety?

PubMed

Lv, Jia-Wei; Chen, Yu-Pei; Zhou, Guan-Qun; Liu, Xu; Guo, Ying; Mao, Yan-Ping; Ma, Jun; Sun, Ying

2017-11-01

Background: The reporting quality of publications is of vital importance to ensure accurate evidence dissemination. This study aimed to compare the consistency of results reporting between the ClinicalTrials.gov results database and the respective matching publications. Methods: We identified 323 phase III/IV cancer drug trials with a randomized controlled design and searched PubMed for publications in a 50% random sample (n=160). Data were extracted independently from ClinicalTrials.gov and publications. A scoring system was applied to determine characteristics associated with reporting quality. Results: Of 117 reviewed trials with publications, result reporting was significantly more complete in ClinicalTrials.gov for efficacy measurement (92.3% vs 90.6%), serious adverse events (SAEs; 100% vs 43.6%), and other adverse events (OAEs; 100% vs 62.4%). For trials with both posted and published results for design information (n=117), efficacy measurements (n=98), SAEs (n=51), and OAEs (n=73), discrepancies were found in 16 (13.7%), 38 (38.8%), 26 (51.0%), and 54 (74.0%) trials, respectively. Overreporting of treatment effects (7 trials) and alteration of primary end points favoring statistically significant outcomes (11 trials) were the major discrepancies in efficacy reporting; incomplete (66 trials) and underreporting (20 trials) of SAEs were the predominant issues in benefit/risk reporting. Median quality score was 21 (range, 14-28). Trials that had parallel assignment, were phase IV, had primary funding by industry, were completed after 2009, and had earlier results posted possessed better reporting quality. Conclusions: Although most trials showed reasonable completeness and consistency, some discrepancies are prevalent and persistent, jeopardizing evidence-based decision-making. Our findings highlight the need to consult results systematically from both ClinicalTrials.gov and publications. Copyright © 2017 by the National Comprehensive Cancer Network.

Students’ Perception of Self-Efficacy Following Medicinal Chemistry Skills Laboratory Exercises

PubMed Central

Roche, Victoria F.; Qi, Yongyue

2016-01-01

Objective. To analyze student perceptions of self-efficacy in meeting medicinal chemistry course related educational outcomes and skills following a medicinal chemistry skills laboratory. Methods. Four activities were implemented in a pharmacy skills laboratory (PSL) for second-year pharmacy students. Students (n=121) worked individually on exercises for three of the four activities. Pre/post-laboratory surveys on self-efficacy were administered. The McNemar test was performed to evaluate students’ self-efficacy above 70% related to course outcomes before and after the exercises in each activity. An independent t test was conducted to compare the mean of students’ responses on meeting course outcomes based on the 70% anchor for the perspective confidence on meeting course outcomes. Results. The post-PSL scores on all self-efficacy questions improved. The majority of students reported skill development in all exercises. Students and clinical faculty qualitative responses indicated they felt exercises were effective. Conclusion. A PSL can serve as a valuable opportunity to address course related educational outcomes and specific skill development and can help students assess their self-efficacy in meeting them. PMID:27402979

Students' Perception of Self-Efficacy Following Medicinal Chemistry Skills Laboratory Exercises.

PubMed

Alsharif, Naser Z; Roche, Victoria F; Qi, Yongyue

2016-06-25

Objective. To analyze student perceptions of self-efficacy in meeting medicinal chemistry course related educational outcomes and skills following a medicinal chemistry skills laboratory. Methods. Four activities were implemented in a pharmacy skills laboratory (PSL) for second-year pharmacy students. Students (n=121) worked individually on exercises for three of the four activities. Pre/post-laboratory surveys on self-efficacy were administered. The McNemar test was performed to evaluate students' self-efficacy above 70% related to course outcomes before and after the exercises in each activity. An independent t test was conducted to compare the mean of students' responses on meeting course outcomes based on the 70% anchor for the perspective confidence on meeting course outcomes. Results. The post-PSL scores on all self-efficacy questions improved. The majority of students reported skill development in all exercises. Students and clinical faculty qualitative responses indicated they felt exercises were effective. Conclusion. A PSL can serve as a valuable opportunity to address course related educational outcomes and specific skill development and can help students assess their self-efficacy in meeting them.

Mobile Technology Interventions for Asthma Self-Management: Systematic Review and Meta-Analysis

PubMed Central

Schüz, Benjamin; Walters, Julia; Walters, E Haydn

2017-01-01

Background Mobile technology interventions (MTI) are becoming increasingly popular in the management of chronic health behaviors. Most MTI allow individuals to monitor medication use, record symptoms, or store and activate disease-management action plans. Therefore, MTI may have the potential to improve low adherence to medication and action plans for individuals with asthma, which is associated with poor clinical outcomes. Objective A systematic review and meta-analysis were conducted to evaluate the efficacy of MTI on clinical outcomes as well as adherence in individuals with asthma. As the use of evidence-based behavior change techniques (BCT) has been shown to improve intervention effects, we also conducted exploratory analyses to determine the role of BCT and engagement with MTI as moderators of MTI efficacy. Methods We searched electronic databases for randomized controlled trials up until June 2016. Random effect models were used to assess the effect of MTI on clinical outcomes as well as adherence to preventer medication or symptom monitoring. Mixed effects models assessed whether the features of the MTI (ie, use of BCT) and how often a person engaged with MTI moderated the effects of MTI. Results The literature search located 11 studies meeting the inclusion criteria, with 9 providing satisfactory data for meta-analysis. Compared with standard treatment, MTI had moderate to large effect sizes (Hedges g) on medication adherence and clinical outcomes. MTI had no additional effects on adherence or clinical outcomes when compared with paper-based monitoring. No moderator effects were found, and the number of studies was small. A narrative review of the two studies, which are not included in the meta-analysis, found similar results. Conclusions This review indicated the efficacy of MTI for self-management in individuals with asthma and also indicated that MTI appears to be as efficacious as paper-based monitoring. This review also suggested a need for robust studies to examine the effects of BCT use and engagement on MTI efficacy to inform the evidence base for MTI in individuals with asthma. PMID:28465281

Evaluation of the efficacy of 100% Type-I collagen membrane of bovine origin in the treatment of human gingival recession: A clinical study

PubMed Central

Soni, Nitin; Sikri, Poonam; Kapoor, Daljit; Soni, Bhavita Wadhwa; Jain, Rachna

2014-01-01

Background: Various treatment modalities have been devised for gingival recession, which is one of the most common signs of periodontal disease. The present study evaluates the efficacy of bioresorbable 100% type I collagen membrane of bovine origin in the treatment of human gingival recession. Materials and Methods: Twenty cases of Miller's class I or class II localized gingival recession defects on the facial surface were treated with 100% type I collagen membrane of bovine origin in conjunction with coronally positioned flap. Pre-operative and post-operative assessments were performed with respect to probing pocket depth, clinical attachment level and clinical recession at 12, 24 and 36 weeks. The data thus collected were analyzed statistically. Results: Statistically significant improvement based on Student's t test was found in all the three clinical parameters. Conclusion: Bioresorbable 100% type I collagen membrane of bovine origin has given inspiring results in the treatment of human gingival recession defects, thereby justifying the use of this material wherever indicated. PMID:25565742

Evaluating principal surrogate endpoints with time-to-event data accounting for time-varying treatment efficacy

PubMed Central

Gabriel, Erin E.; Gilbert, Peter B.

2014-01-01

Principal surrogate (PS) endpoints are relatively inexpensive and easy to measure study outcomes that can be used to reliably predict treatment effects on clinical endpoints of interest. Few statistical methods for assessing the validity of potential PSs utilize time-to-event clinical endpoint information and to our knowledge none allow for the characterization of time-varying treatment effects. We introduce the time-dependent and surrogate-dependent treatment efficacy curve, \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}${\\mathrm {TE}}(t|s)$\\end{document}, and a new augmented trial design for assessing the quality of a biomarker as a PS. We propose a novel Weibull model and an estimated maximum likelihood method for estimation of the \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}${\\mathrm {TE}}(t|s)$\\end{document} curve. We describe the operating characteristics of our methods via simulations. We analyze data from the Diabetes Control and Complications Trial, in which we find evidence of a biomarker with value as a PS. PMID:24337534

Feasibility trial of a Spanish-language multimedia educational intervention.

PubMed

Wells, Kristen J; McIntyre, Jessica; Gonzalez, Luis E; Lee, Ji-Hyun; Fisher, Kate J; Jacobsen, Paul B; Meade, Cathy; Muñoz-Antonia, Teresita; Quinn, Gwendolyn P

2013-10-01

Hispanic cancer patients are underrepresented in clinical trials; research suggests lack of knowledge and language barriers contribute to low accrual. Multimedia materials offer advantages to Hispanic populations because they have high acceptability, are easy to disseminate, and can be viewed with family. Hispanic cancer patients and caregivers participated in focus groups to aid in developing a Spanish-language multimedia intervention to educate Hispanic cancer patients about clinical trials. We explored the feasibility of delivering the intervention in medical oncology clinics. A total of 35 patients were randomized to either the multimedia intervention group (n = 18) or a control group (n = 17) who were asked to read the National Cancer Institute's Spanish-language clinical trials brochure. Self-reported data on knowledge about and attitudes toward clinical trials, self-efficacy for participating in a clinical trial, intention to participate in a clinical trial if asked, and receptivity to information about a clinical trial were collected at baseline and 10 days later. Delivery of the multimedia presentation in oncology clinics was feasible. The intervention group had more knowledge about clinical trials at follow-up than the control group; scores for intention to participate in a clinical trial by participants in the intervention group increased from 3.8 to 4.0 of a possible 5, but declined in the control group from 4.5 to 4.1. No statistically significant difference was detected between groups in scores for attitudes or self-efficacy for making a decision to participate in a clinical trial. Our sample size was inadequate to identify differences between the informational methods. Although all patients were asked about their willingness to participate in a clinical trial, this decision was hypothetical. In addition, the study was conducted with a sample of Spanish-speaking Hispanic cancer patients at a comprehensive cancer center in Florida. Thus, the results may not generalize to other Hispanic populations. In the pilot project, we demonstrated the feasibility of delivering multimedia information to patients in medical oncology clinics. Because delivery in a clinical setting was found to be feasible, a larger study should be conducted to evaluate the efficacy of the multimedia intervention with respect to promoting accrual of Hispanic patients to clinical trials.

The Perceived Value and Efficacy of Traditional Face-to-Face versus Hybrid Methods of Clinical Instruction among Physical Therapy Educators and Students in Doctoral Level Programs: A Qualitative Case Study

ERIC Educational Resources Information Center

Eddow, Christine

2017-01-01

Physical therapy is a branch of healthcare that has advanced from an ancillary support role to an autonomous doctoral level profession in only two decades. Enrollment in physical therapy programs is increasing while resources and program length remain limited, leaving academic leaders challenged to identify instructional methods to manage…

One Year Follow-up of Outcomes from the Randomized Clinical Trial of the Building on Family Strengths Program.

PubMed

Churchill, Shervin S; Kieckhefer, Gail M

2018-06-01

Objectives Test the 12-month efficacy of an inclusive non-diagnosis-specific, parent education program with seven in-person sessions. Methods Parents of 110 children, 2-11 years old, with a variety of special health care conditions, were recruited to participate in a randomized clinical trial. At twelve months data from 104 parents were available for longitudinal analysis. Linear mixed models, with the interaction term of group by time, were used to assess the efficacy of the intervention over 12 months using data from 3 time points: baseline, 6 and 12 months. The outcome measures were self-efficacy, parent and child shared management of chronic condition, coping skills, parental depressive symptoms and quality of life. Results All of the outcomes improved within the intervention group over 12 months. Self-efficacy was the strongest outcome which remained significantly different from the control group 12 months post intervention, without any statistical adjustment (p = 0.045). The coefficient of the interaction term for study group (intervention or control) by time, quantifying the intervention effect, was statistically significant for four of five pre-specified study outcomes, favorably so toward the intervention group (p < 0.05, with the 5th outcome, parental depression, p = 0.052). Conclusions for Practice The Building on Family Strengths intervention was efficacious in improving self-efficacy, shared management, coping skills, and quality of life and decreasing depressive symptoms in parents, in particular for parents who were most impacted by the lack of these strengths and skills at baseline. These results are encouraging and future studies to investigate the efficacy of this intervention in an Internet-based setting or other modalities are encouraged.

Specific expectancies are associated with symptomatic outcomes and side effect burden in a trial of chamomile extract for Generalized Anxiety Disorder

PubMed Central

Keefe, John R.; Amsterdam, Jay; Li, Qing S; Soeller, Irene; DeRubeis, Robert; Mao, Jun J

2017-01-01

Objective Patient expectancies are hypothesized to contribute to the efficacy and side effects of psychiatric treatments, but little research has investigated this hypothesis in the context of psychopharmacological therapies for anxiety. We prospectively investigated whether expectancies predicted efficacy and adverse events in oral therapy for Generalized Anxiety Disorder (GAD), controlling for confounding patient characteristics correlating with outcomes. Methods Expectancies regarding treatment efficacy and side effects were assessed at baseline of an eight week open-label phase of a trial of chamomile for Generalized Anxiety Disorder (GAD). The primary outcome was patient-reported GAD-7 scores, with clinical response and treatment-emergent side-effects as secondary outcomes. Expectancies were used to predict symptomatic and side-effect outcomes. Results Very few baseline patient characteristics predicted either type of expectancy. Controlling for a patient’s predicted recovery based on their baseline characteristics, higher efficacy expectancies at baseline predicted greater change on the GAD-7 (adjusted β = −0.19, p = 0.011). Efficacy expectancies also predicted a higher likelihood of attaining clinical response (adjusted odds ratio = 1.69, p = 0.002). Patients with higher side effect expectancies reported more side effects (adjusted log expected count = 0.26, p = 0.038). Efficacy expectancies were unrelated to side effect reports (log expected count = −0.05, p = 0.680), and side effect expectancies were unrelated to treatment efficacy (β = 0.08, p = 0.306). Conclusions Patients entering chamomile treatment for GAD with more favorable self-generated expectancies for the treatment experience greater improvement and fewer adverse events. Aligning patient expectancies with treatment selections may optimize outcomes. PMID:27716513

Efficacy of Crest Herbal Toothpaste in “Clearing Internal Heat”: A Randomized, Double-Blind Clinical Study

PubMed Central

Chen, Jia-Xu; Liu, Yue-Yun; Wang, Shao-Xian; Li, Xiao-Hong

2013-01-01

Objective. Evaluation of the efficacy of Crest Herbal Crystal Toothpaste in “clearing internal heat.” Methods. This was a randomized, double-blind, controlled parallel design clinical test of a product that was already on the market. 72 subjects were randomly assigned to control group (group A with Colgate Herbal Salty Toothpaste) or treatment group (group B with Crest Herbal Crystal Toothpaste) with ratio of 1 : 2. Subjects were instructed to brush with 1g toothpaste for 2 minutes each time, 2 times per day in a 4-aweek test period; measurement with the rating scale on the efficacy of “clearing internal heat” for the herbal toothpaste was done at baseline, 2 weeks, and 4 weeks of toothpaste usage. Results. The rating scale on efficacy of “clearing internal heat” for the herbal toothpaste reveals that the primitive points of 72-case intention-to-treat (ITT) analysis and 67-case per-protocol (PP) analysis for subjects in group A and subjects in group B were found to be reduced progressively with statistical significance (P < 0.05). The overall effective rates for group A and group B were, respectively, 62.50%, 56.25% (ITT) and 62.50%, 60.64% (PP). The statistical results indicated that the symptoms of fire-heat for both groups of subjects have been improved after application of toothpaste. Conclusion. The efficacy of Crest Herbal Crystal Toothpaste in “clearing internal heat” was confirmed by the trial as compared to Colgate Herbal Salty Toothpaste. And its efficacy was objectively evaluated by the rating scale on efficacy of “clearing internal heat.” PMID:24228064

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

PubMed

Gupta, Aditya K; Drummond-Main, Chris

2013-01-01

Two oral antifungal agents, griseofulvin and terbinafine, have regulatory approval in the United States, but it is unknown whether one has superior overall efficacy. Genus-specific differences in efficacy are believed to exist for the two agents. It is not clear at what doses and durations of treatment these differences apply. The goals of this meta-analysis were to determine whether a statistically significant difference in efficacy exists between these agents at a given dose and duration of each in tinea capitis infections overall and to determine whether a genus-specific difference in efficacy exists for these two treatments at a given dose and duration of each. We performed a literature search for clinically and methodologically similar randomized controlled trials comparing 8 weeks of griseofulvin (6.25-12.5 mg/kg/day) to 4 weeks of terbinafine (3.125-6.25 mg/kg/day) in the treatment of tinea capitis. A meta-analysis was performed using the Mantel-Haenszel method and random effects model; results were expressed as odds ratios with 95% confidence intervals. Meta-analysis of randomized controlled trials did not show a significant difference in the overall efficacy of the two drugs at the doses specified, but specific efficacy differences were observed based on the infectious species. For tinea capitis caused by Microsporum spp., griseofulvin is superior (p = 0.04), whereas terbinafine is superior for Trichophyton spp. infection (p = 0.04). Our results support species-specific differences in treatment efficacy between griseofulvin and terbinafine and provide a clinical context in which this knowledge may be applied. © 2012 Wiley Periodicals, Inc.

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.

Systematic Review of Chinese Medicine for Miscarriage during Early Pregnancy

PubMed Central

Leung, Ping Chung; Chung, Tony Kwok Hung; Wang, Chi Chiu

2014-01-01

Background. Miscarriage is a very common complication during early pregnancy. So far, clinical therapies have limitation in preventing the early pregnancy loss. Chinese Medicine, regarded as gentle, effective, and safe, has become popular and common as a complementary and alternative treatment for miscarriages. However, the evidence to support its therapeutic efficacy and safety is still very limited. Objectives and Methods. To summarize the clinical application of Chinese Medicine for pregnancy and provide scientific evidence on the efficacy and safety of Chinese medicines for miscarriage, we located all the relevant pieces of literature on the clinical applications of Chinese Medicine for miscarriage and worked out this systematic review. Results. 339,792 pieces of literature were identified, but no placebo was included and only few studies were selected for systematic review and conducted for meta-analysis. A combination of Chinese medicines and Western medicines was more effective than Chinese medicines alone. No specific safety problem was reported, but potential adverse events by certain medicines were identified. Conclusions. Studies vary considerably in design, interventions, and outcome measures; therefore conclusive results remain elusive. Large scales of randomized controlled trials and more scientific evidences are still necessary to confirm the efficacy and safety of Chinese medicines during early pregnancy. PMID:24648851

Efficacy and mechanisms of action of traditional Chinese medicines for treating asthma and allergy

PubMed Central

Li, Xiu-Min; Brown, Laverne

2009-01-01

Background While corticosteroids and β-2 agonists are effective in managing asthma symptoms, a curative therapy for asthma is lacking. Traditional Chinese medicine (TCM), used in Asia for centuries, is beginning to play a role in Western health care as a complementary and alternative medicine (CAM) modality. There is increasing scientific evidence supporting the use of TCM for asthma treatment. Objective This review article discusses promising TCM interventions for asthma and explores their possible mechanisms of action. Methods We first reviewed five clinical studies of “anti-asthma” TCM herbal remedies published between 2005–2007. We then summarized possible mechanisms underlying their effects based on data in the original articles, published abstracts, and available data bases. Possible mechanisms include anti-inflammation, inhibition of airway smooth muscle contraction, and immunomodulation. Research on TCM herbal therapy for food allergy is rare, and we therefore focused on the effect and mechanism of action of Food Allergy Herbal Formula-2 (FAHF-2) on a murine model of peanut allergy and preliminary clinical study results. Conclusion Evidence from clinical studies supports beneficial effects of TCM herbal therapy on asthma. A number of mechanisms may be responsible for efficacy of these agents. Strong preclinical study data suggest potential efficacy of FAHF-2 for food allergy. PMID:19203653

Treatment of Chronic Migraine with OnabotulinumtoxinA: Mode of Action, Efficacy and Safety

PubMed Central

Szok, Délia; Csáti, Anett; Vécsei, László; Tajti, János

2015-01-01

Background: Chronic migraine is a common, highly disabling, underdiagnosed and undertreated entity of migraine. It affects 0.9%–2.2% of the general adult population. The present paper overviews the preclinical and clinical data regarding the therapeutic effect of onabotulinumtoxinA in chronic migraineurs. Methods: A literature search was conducted in the database of PubMed up to 20 May 2015 for articles related to the pathomechanism of chronic migraine, the mode of action, and the efficacy, safety and tolerability of onabotulinumtoxinA for the preventive treatment of chronic migraine. Results: The pathomechanism of chronic migraine has not been fully elucidated. The mode of action of onabotulinumtoxinA in the treatment of chronic migraine is suggested to be related to the inhibition of the release of calcitonin gene-related peptide and substance P in the trigeminovascular system. Randomized clinical trials demonstrated that long-term onabotulinumtoxinA fixed-site and fixed-dose (155–195 U) intramuscular injection therapy was effective and well tolerated for the prophylactic treatment of chronic migraine. Conclusions: Chronic migraine is a highly devastating entity of migraine. Its exact pathomechanism is unrevealed. Two-third of chronic migraineurs do not receive proper preventive medication. Recent clinical studies revealed that onabotulinumtoxinA was an efficacious and safe treatment for chronic migraine. PMID:26193319

Assessment and Treatment of Cognition and Communication Skills in Adults With Acquired Brain Injury via Telepractice: A Systematic Review.

PubMed

Coleman, Jaumeiko J; Frymark, Tobi; Franceschini, Nicole M; Theodoros, Deborah G

2015-05-01

This is a systematic review of assessment and treatment of cognitive and communicative abilities of individuals with acquired brain injury via telepractice versus in person. The a priori clinical questions were informed by previous research that highlights the importance of considering any functional implications of outcomes, determining disorder- and setting-specific concerns, and measuring the potential impact of diagnostic accuracy and treatment efficacy data on interpretation of findings. A literature search of multiple databases (e.g., PubMed) was conducted using key words and study inclusion criteria associated with the clinical questions. Ten group studies were accepted that addressed assessment of motor speech, language, and cognitive impairments; assessment of motor speech and language activity limitations/participation restrictions; and treatment of cognitive impairments and activity limitations/participation restrictions. In most cases, equivalence of outcomes was noted across service delivery methods. Limited findings, lack of diagnostic accuracy and treatment efficacy data, and heterogeneity of assessments and interventions precluded robust evaluation of clinical implications for telepractice equivalence and the broader area of telepractice efficacy. Future research is needed that will build upon current knowledge through replication. In addition, further evaluation at the impairment and activity limitation/participation restriction levels is needed.

Meta-analysis in clinical trials revisited.

PubMed

DerSimonian, Rebecca; Laird, Nan

2015-11-01

In this paper, we revisit a 1986 article we published in this Journal, Meta-Analysis in Clinical Trials, where we introduced a random-effects model to summarize the evidence about treatment efficacy from a number of related clinical trials. Because of its simplicity and ease of implementation, our approach has been widely used (with more than 12,000 citations to date) and the "DerSimonian and Laird method" is now often referred to as the 'standard approach' or a 'popular' method for meta-analysis in medical and clinical research. The method is especially useful for providing an overall effect estimate and for characterizing the heterogeneity of effects across a series of studies. Here, we review the background that led to the original 1986 article, briefly describe the random-effects approach for meta-analysis, explore its use in various settings and trends over time and recommend a refinement to the method using a robust variance estimator for testing overall effect. We conclude with a discussion of repurposing the method for Big Data meta-analysis and Genome Wide Association Studies for studying the importance of genetic variants in complex diseases. Published by Elsevier Inc.

Response of falciparum malaria to different antimalarials in Myanmar.

PubMed Central

Ejov, M. N.; Tun, T.; Aung, S.; Sein, K.

1999-01-01

The purpose of the study was to ascertain the therapeutic efficacy of different treatments for uncomplicated falciparum malaria in the hospitals in Sagaing, northern and eastern Shan, to facilitate updating the existing national antimalarial drug policy. The proposed 14-day trial for monitoring the efficacy of treatments of uncomplicated falciparum malaria is an efficient method for identifying treatment failure patterns at the intermediate level (township hospital) in the Union of Myanmar. Minimal clinical and parasitological data for days 0-14 were required to classify treatment failure and success. Clinical and parasitiological responses on day 3 and days 4-14 were used as clear examples of early and late treatment failure, respectively. Mefloquine is five times more likely to be effective than chloroquine and sulfadoxine pyrimethamine (S-P), whereas chloroquine and S-P treatments have nearly identical failure patterns. The alarming frequency of clinical and parasitological failure (failure rate > 50%) following chloroquine treatment was reported in Sagaing and following S-P treatment in Sagaing and eastern Shan. PMID:10212515

Efficacy and safety of selective glucocorticoid receptor modulators in comparison to glucocorticoids in arthritis, a systematic review.

PubMed

Safy, M; de Hair, M J H; Jacobs, J W G; Buttgereit, F; Kraan, M C; van Laar, J M

2017-01-01

Long-term treatment with glucocorticoids (GCs) plays an important role in the management of arthritis patients, although the efficacy/safety balance is unfavorable. Alternatives with less (severe) adverse effects but with good efficacy are needed. Selective GC receptor modulators (SGRMs) are designed to engage the GC receptor with dissociative characteristics: transactivation of genes, which is mainly responsible for unwanted effects, is less strong while trans-repression of genes, reducing inflammation, is maintained. It is expected that SGRMs thus have a better efficacy/safety balance than GCs. A systematic review providing an overview of the evidence in arthritis is lacking. To systematically review the current literature on efficacy and safety of oral SGRMs in comparison to GCs in arthritis. A search was performed in Medline, Embase and the Cochrane Library, from inception dates of databases until May 2017. Experimental studies involving animal arthritis models or human material of arthritis patients, as well as clinical studies in arthritis patients were included, provided they reported original data. All types of arthritis were included. Data was extracted on the SGRM studied and on the GC used as reference standard; the design or setting of the study was extracted as well as the efficacy and safety results. A total of 207 articles was retrieved of which 17 articles were eligible for our analysis. Two studies concerned randomized controlled trials (RCT), five studies were pre-clinical studies using human material, and 10 studies involved pre-clinical animal models (acute and/or chronic arthritis induced in mice or rats). PF-04171327, the only compound investigated in a clinical trial setting, had a better efficacy/safety balance compared to GCs: better clinical anti-inflammatory efficacy and similar safety. Studies assessing both efficacy and safety of SGRMs are scarce. There is limited evidence for dissociation of anti-inflammatory and metabolic effects of the SGRMs studied. Development of many SGRMs is haltered in a preclinical phase. One SGRM showed a better clinical efficacy/safety balance.

Improving glycaemic control self-efficacy and glycaemic control behaviour in Chinese patients with type 2 diabetes mellitus: randomised controlled trial.

PubMed

Shi, Qifang; Ostwald, Sharon K; Wang, Shaopeng

2010-02-01

To examine the effect of a hospital-based clinic intervention on glycaemic control self-efficacy and glycaemic control behaviour of Chinese patients with type 2 diabetes mellitus (DM). Self-efficacy expectations are related to self-management of diabetes and, in conjunction with environmental support, are better predictors of behaviour than are knowledge and skills. Enhancing self-efficacy in patients with DM has been shown to have a positive effect on behavioural change and positively influence long-term glycaemic control. A randomised controlled trial study consisting of two-group pretest-post-test. One hundred and fifty-seven patients with type 2 DM were randomly divided into two groups: (1) the experimental group (77 patients) receiving one-month hospital-based clinic intervention and (2) the control group (80 patients) receiving usual care. Data collection instruments used in this study were Diabetes Management Self-Efficacy Scale and Summary of Diabetes Self-Care Activities Measure. Outcomes were determined by changes in glycaemic control self-efficacy and glycaemic control behaviour of patients with type 2 DM. The findings revealed that the experimental group showed statistically significant improvement in glycaemic control self-efficacy and glycaemic control behaviour immediately and four months after the intervention (F = 26.888, df = 1, 155, p < 0.05 and F = 18.619, df = 1, 155, p < 0.05, respectively). One-month hospital-based clinic intervention could be useful in improving glycaemic control self-efficacy and glycaemic control behaviour. Nurses can learn and use the sources of self-efficacy to enhance patients' self-efficacy on their glycaemic control in clinical care. The health education is most important in nursing care and should be considered while organising the hospital-based clinic intervention.

Systematic Review of Breastfeeding and Herbs

PubMed Central

Budzynska, Katarzyna; Gardner, Zoë E.; Dugoua, Jean-Jacques; Low Dog, Tieraona

2012-01-01

Abstract Objectives Despite popular and historical use, there has been little modern research conducted to determine the safety and efficacy of herb use during breastfeeding. The purpose of this study was to systematically review the clinical literature on herbal medicine and lactation. Methods The databases PubMed, CAB Abstracts, Cochrane Central Register of Controlled Trials, HealthSTAR, Cumulative Index to Nursing and Allied Health Literature, and Reprotox were systematically searched for human trials from 1970 until 2010. Reference lists from relevant articles were hand-searched. Results Thirty-two studies met the inclusion criteria. Clinical studies were divided into three categories: survey studies (n=11), safety studies (n=8), and efficacy studies (n=13). Six studies were randomized controlled trials. The most common herbs studied were St. John's wort (Hypericum perforatum L.) (n=3), garlic (Allium sativum L.) extract (n=2), and senna (Cassia senna L.) (n=2). Studies were very heterogeneous with regard to study design, herbal intervention, and outcome measures. Overall, poor methodological quality predominated among the studies. Conclusions Our review concludes that further research is needed to assess the prevalence, efficacy, and safety of commonly used herbs during breastfeeding. PMID:22686865

Correction of stain variations in nuclear refractive index of clinical histology specimens

PubMed Central

Uttam, Shikhar; Bista, Rajan K.; Hartman, Douglas J.; Brand, Randall E.; Liu, Yang

2011-01-01

For any technique to be adopted into a clinical setting, it is imperative that it seamlessly integrates with well-established clinical diagnostic workflow. We recently developed an optical microscopy technique—spatial-domain low-coherence quantitative phase microscopy (SL-QPM) that can extract the refractive index of the cell nucleus from the standard histology specimens on glass slides prepared via standard clinical protocols. This technique has shown great potential in detecting cancer with a better sensitivity than conventional pathology. A major hurdle in the clinical translation of this technique is the intrinsic variation among staining agents used in histology specimens, which limits the accuracy of refractive index measurements of clinical samples. In this paper, we present a simple and easily generalizable method to remove the effect of variations in staining levels on nuclear refractive index obtained with SL-QPM. We illustrate the efficacy of our correction method by applying it to variously stained histology samples from animal model and clinical specimens. PMID:22112118

Efficacy and safety of Ginkgo biloba standardized extract in the treatment of vascular cognitive impairment: a randomized, double-blind, placebo-controlled clinical trial

PubMed Central

Demarin, Vida; Bašić Kes, Vanja; Trkanjec, Zlatko; Budišić, Mislav; Bošnjak Pašić, Marija; Črnac, Petra; Budinčević, Hrvoje

2017-01-01

Objectives The aim of this randomized, double-blind, placebo-controlled trial was to determine the efficacy and safety of Ginkgo biloba extract in patients diagnosed with vascular cognitive impairment (VCI). Methods A total of 90 patients (aged 67.1±8.0 years; 59 women) were randomly allocated (1:1:1) to receive G. biloba 120 mg, G. biloba 60 mg, or placebo during a 6-month period. Assessment was made for efficacy indicators, including neuropsychological tests scores (Sandoz Clinical Assessment Geriatric Scale, Folstein Mini-Mental State Examination, Mattis Dementia Rating Scale, and Clinical Global Impression) and transcranial Doppler ultrasound findings. Safety indicators included laboratory findings, reported adverse reactions, and clinical examination. Results At the end of 6-month study period, G. biloba 120 and 60 mg showed a statistically significant positive effect in comparison with placebo only on the Clinical Global Impression score (2.6±0.8 vs 3.1±0.7 vs 2.8±0.7, respectively; P=0.038). The Clinical Global Impression score showed a significant deterioration from the baseline values in the placebo group (−0.3±0.5; P=0.021) as opposed to G. biloba groups. No significant differences were found in the transcranial Doppler ultrasound findings. Adverse reactions were significantly more common and serious in the placebo group (16 subjects) than in either of the two G. biloba extract groups (eight and nine subjects, respectively), whereas laboratory findings and clinical examinations revealed no differences between the groups receiving G. biloba extract and placebo. Conclusion According to our results, G. biloba seemed to slow down the cognitive deterioration in patients with VCI, but the effect was shown in only one of the four neuropsychological tests administered. However, because of this mild effect in combination with a few adverse reactions, we cannot say that it is ineffective or unsafe either. Further studies are still needed to provide unambiguous evidence on the efficacy and safety of G. biloba extract. PMID:28243101

Evidence-Based Psychosocial Treatments for Adolescents with Disruptive Behavior

PubMed Central

McCart, Michael R.; Sheidow, Ashli J.

2016-01-01

Objective This article updates the earlier reviews of evidence-based psychosocial treatments for disruptive behavior in adolescents (Brestan & Eyberg, 1998; Eyberg, Nelson, & Boggs, 2008), focusing primarily on the treatment literature published from 2007 to 2014. Method Studies were identified through an extensive literature search and evaluated using Journal of Clinical Child and Adolescent Psychology (JCCAP) level of support criteria, which classify studies as well established, probably efficacious, possibly efficacious, experimental, or of questionable efficacy based on existing evidence. The JCCAP criteria have undergone modest changes in recent years. Thus, in addition to evaluating new studies from 2007–2014 for this update, all adolescent-focused articles that had been included in the 1998 and 2008 reviews were re-examined. In total, 86 empirical papers published over a 48-year period and covering 50 unique treatment protocols were identified and coded. Results Two multicomponent treatments that integrate strategies from family, behavioral, and cognitive-behavioral therapy met criteria as well established. Summaries are provided for those treatments, as well as for two additional multicomponent treatments and two cognitive-behavioral treatments that met criteria as probably efficacious. Treatments designated as possibly efficacious, experimental, or of questionable efficacy are listed. Additionally, moderator/mediator research is summarized. Conclusions Results indicate that since the prior reviews, there has been a noteworthy expansion of research on treatments for adolescent disruptive behavior, particularly treatments that are multicomponent in nature. Despite these advances, more research is needed to address key gaps in the field. Implications of the findings for future science and clinical practice are discussed. PMID:27152911

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.

Gold-nanoparticle-based theranostic agents for radiotherapy of malignant solid tumors

NASA Astrophysics Data System (ADS)

Moeendarbari, Sina

Radiation therapy is one of the three major methods of cancer treatment. The fundamental goal of radiotherapy is to deliver high radiation doses to targets while simultaneously minimizing doses to critical structures and healthy normal tissues. The aim of this study is to develop a general, practical, and facile method to prepare nanoscale theranostic agents for more efficacious radiation therapy with less adverse side effects. First, a novel type of gold nanoparticle, hollow Au nanoparticles (HAuNPs) which was synthesized using the unique bubble template synthesis method developed in our lab, are studied in vitro and in vivo to investigate their effect as radiosensitizing agents to enhance the radiation dose during external radiotherapy. The results showed the promising potential of using HAuNPs as radiosensitization agents for efficacious treatment of breast cancer. Second, a novel radiolabeling method is developed to incorporate medical radioisotopes to gold nanoparticles. We incorporate palladium-103 (103Pd), a radioisotope currently in clinical brachytherapy, into a hollow gold nanoparticle. The resulting 103Pd Au nanoparticles in the form of a colloidal suspension can be administered by direct injection into tumors, serving as internal radiation sources (nanoseeds) for radiation therapy. The size of the nanoseed, 150nm in diameter, is large enough to prevent nanoseeds from diffusing into other areas while still small enough to allow them to homogeneously distribute inside the tumor. The therapeutic efficacy of 103Pd Au nanoseeds have been tested when intratumorally injected into a prostate cancer xenograft model. The findings showed that this nanoseed-based brachytherapy has the potential to provide a theranostic solution to unresectable solid tumors. Finally, to make real clinical application more plausible, multi-functional magnetic nanoseeds nanoparticles for imaging-guided radiotherapy are synthesized and characterized.

Efficacy of Pregabalin in Childhood Refractory Partial Seizure

PubMed Central

Zamani, Gholamreza; Tavasoli, Alireza; Zare-Shahabadi, Ameneh; Rezaei, Nima; Ahmadvand, Alireza

2014-01-01

Objective: About one third of partial seizures are refractory to treatment. Several anticonvulsant drugs have entered the market in recent decades but concerns about intolerance, drug interactions, and the safety of the drug are notable. One of these new anticonvulsants is pregabalin, a safe drug with almost no interaction with other antiepileptic drugs. Methods: In this open label clinical trial study, pregabalin was used for evaluation of its efficacy on reducing seizure frequency in 29 children suffering from refractory partial seizures. Average daily and weekly seizure frequency of the patients was recorded during a 6-week period (baseline period). Then, during a period of 2 weeks (titration period), pregabalin was started with a dose of 25-75 mg/d, using method of flexible dose, and was brought to maximum dose of drug that was intended in this study (450 mg/d) based on clinical response of the patients and seizure frequency. Then the patients were given the drug for 12 weeks and the average frequency of daily and weekly seizures were recorded again (treatment period). Findings : Reduction in seizure frequency in this study was 36% and the responder rate or number of patients who gained more than 50% reduction in seizure frequency was 51.7%. Conclusion: This study showed that pregabalin can be used with safety and an acceptable efficacy in treatment of childhood refractory partial seizures. PMID:25793053

Characterization of Change and Significance for Clinical Findings in Radiology Reports Through Natural Language Processing.

PubMed

Hassanpour, Saeed; Bay, Graham; Langlotz, Curtis P

2017-06-01

We built a natural language processing (NLP) method to automatically extract clinical findings in radiology reports and characterize their level of change and significance according to a radiology-specific information model. We utilized a combination of machine learning and rule-based approaches for this purpose. Our method is unique in capturing different features and levels of abstractions at surface, entity, and discourse levels in text analysis. This combination has enabled us to recognize the underlying semantics of radiology report narratives for this task. We evaluated our method on radiology reports from four major healthcare organizations. Our evaluation showed the efficacy of our method in highlighting important changes (accuracy 99.2%, precision 96.3%, recall 93.5%, and F1 score 94.7%) and identifying significant observations (accuracy 75.8%, precision 75.2%, recall 75.7%, and F1 score 75.3%) to characterize radiology reports. This method can help clinicians quickly understand the key observations in radiology reports and facilitate clinical decision support, review prioritization, and disease surveillance.

Efficacy of terbinafine compared to lanoconazole and luliconazole in the topical treatment of dermatophytosis in a guinea pig model.

PubMed

Ghannoum, M A; Long, L; Kim, H G; Cirino, A J; Miller, A R; Mallefet, P

2010-05-01

The in vivo efficacy of terbinafine was compared to lanoconazole and luliconazole in the topical treatment of dermatophytosis caused by Trichophyton mentagrophytes using a guinea pig model. Topical antifungal treatment commenced three days post-infection, and each agent was applied once daily for seven consecutive days. Upon completion of the treatment period, evaluations of clinical and mycological efficacies were performed, as was scanning electron microscopy (SEM) analyses. Data showed that while all tested antifungals demonstrated significant mycological efficacy in terms of eradicating the fungi over untreated control, terbinafine and luliconazole showed superior clinical efficacy compared to lanoconazole (P-values < 0.001 & 0.003, respectively). Terbinafine demonstrated the highest clinical percent efficacy. SEM analysis revealed hairs from terbinafine and lanoconazole-treated animals had near complete clearance of fungi, while samples from luliconazole-treated animals were covered with debris and few conidia. This study demonstrates that, in general, terbinafine possessed similar efficacy to lanoconazole and luliconazole in the treatment of dermatophytosis. Terbinafine tended to have superior clinical efficacy compared to the azoles tested, although this difference was not statistically significant against luliconazole. This apparent superiority may be due to the fungicidal activity of terbinafine compared to the fungistatic effect of the other two drugs.

Introduction: the goals of antimicrobial therapy.

PubMed

Song, Jae-Hoon

2003-03-01

Antimicrobial agents are generally evaluated in preclinical studies assessing in vitro activity, animal models demonstrating in vivo bacteriologic efficacy, and clinical trials primarily investigating safety and clinical efficacy. However, large sample sizes are required to detect any differences in outcomes between antimicrobials in clinical trials, and, generally, studies are powered to show only clinical equivalence. In addition, diagnosis is often based on clinical symptoms, rather than microbiological evidence of bacterial infection, and the patients most likely to have resistant pathogens are often excluded. Clinical efficacy can be achieved in some bacterial infections in which antimicrobials are suboptimal or even not prescribed. However, bacterial eradication maximizes clinical efficacy and may also reduce the development and spread of resistant organisms. The goal of antimicrobial therapy is, therefore, to eradicate bacteria at the site of infection. Bacterial eradication is not usually assessed as a primary endpoint within the limits of currently recommended clinical trial design. However, pharmacokinetic (PK) (serum concentration profiles, penetration to site of infection) and pharmacodynamic (PD) (susceptibility, concentration- versus time-dependent killing, post-antimicrobial effects) criteria can be used to predict bacteriologic efficacy. PK/PD predictions should be confirmed during all phases of antimicrobial development and throughout clinical use in response to changing patterns of resistance. A clear rationale for dose recommendations can be determined preclinically based on PK/PD parameters, and correlated with efficacy, safety and resistance endpoints in clinical trials. The duration of treatment and dose should be the shortest that will reliably eradicate the pathogen(s), and that is safe and well tolerated. Currently available agents vary significantly in their ability to achieve PK/PD parameters necessary for bacteriologic eradication. Recommendations for appropriate antimicrobial therapy should be based on PK/PD parameters, with the aim of achieving the maximum potential for eradication of both existing and emerging resistant pathogens.

Thrombolysis research--new objectives after a shift of accent.

PubMed

Maksimenko, Alexander V

2002-01-01

The methods of increasing the efficacy of thrombolysis under clinical and experimental conditions are have been discussed in the light of analysis of current tendencies in the investigation and development of thrombolytic and adjunctive therapy. Analysis of the data obtained in the search for novel plasminogen activators for thrombolytic enzyme therapy has shown a decrease and depletion of this search. The reserves for further increase in thrombolysis efficiency have been notified. Special attention is paid to the purposes, realms and problems of adjunctive therapy, which is a promising breakthrough area in the effort of increasing the efficacy of thrombolysis.

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

An evaluation of the efficacy of a topical gel with Triester Glycerol Oxide (TGO) in the treatment of minor recurrent aphthous stomatitis in a Turkish cohort: A randomized, double-blind, placebo-controlled clinical trial

PubMed Central

Ergun, Sertan; Warnakulasuriya, Saman; Namdar-Pekiner, Filiz; Tanyeri, Hakkı

2017-01-01

Background Triester glycerol oxide gel (Protefix® Queisser Pharma, Germany) is a new topical agent that has the property of adherence to the oral mucosa by forming a lipid film which protects against mechanical trauma and may help to reduce oral tissue moisture loss and inflammation. The aim of this clinical trial was to determine the efficacy of a topical TGO gel and to also compare it with triamcinolone acetonide pomade in the treatment of minor recurrent aphthous stomatitis. Material and Methods This study was a randomized, double-blind, placebo-controlled clinical trial and 180 patients with the complaint of minor aphthous ulcers were enrolled in this study. The sociodemographic data and clinical characteristics of the ulcer were collected by questionnaire. Ulcer size and pain level measurements were performed and the efficacy indices for ulcer pain and size were calculated at day 0,2,4,6 by the same investigator. Results Significant differences were not detected among the demographics and ulcer histories including age, gender, onset of ulcer, mean healing time, family RAS history and ulcer localization between three groups. The pain score in TGO group was found statistically lower at day 2,4, and 6. Efficacy index and improvement rate of TGO group, regarding pain score, was higher than the other two groups at day 2 and 4. The reduction in ulcer size was statistically higher in TGO group than the other two groups at day 4 and 6. Conclusions Topical application of TGO gel could decrease pain intensity, accelerate ulcer healing without any side effects, utilizing an easy appliable and accessible procedure. Therefore TGO gel could be a well-tolerated, safe, topical therapeutic agent in the clinical practice of RAS treatment. Key words:Topical therapy, triester glycerol oxide, triamcinolone acetonide, minor recurrent aphthous stomatitis. PMID:28160585

Using Outcomes to Analyze Patients Rather than Patients to Analyze Outcomes: A Step toward Pragmatism in Benefit:risk Evaluation.

PubMed

Evans, Scott R; Follmann, Dean

2016-01-01

In the future, clinical trials will have an increased emphasis on pragmatism, providing a practical description of the effects of new treatments in realistic clinical settings. Accomplishing pragmatism requires better summaries of the totality of the evidence in ways that clinical trials consumers---patients, physicians, insurers---find transparent and allow for informed benefit:risk decision-making. The current approach to the analysis of clinical trials is to analyze efficacy and safety separately and then combine these analyses into a benefit:risk assessment. Many assume that this will effectively describe the impact on patients. But this approach is suboptimal for evaluating the totality of effects on patients. We discuss methods for benefit:risk assessment that have greater pragmatism than methods that separately analyze efficacy and safety. These include the concepts of within-patient analyses and composite benefit:risk endpoints with a goal of understanding how to analyze one patient before trying to figure out how to analyze many. We discuss the desirability of outcome ranking (DOOR) and introduce the partial credit strategy using an example in a clinical trial evaluating the effects of a new antibiotic. As part of the example we introduce a strategy to engage patients as a resource to inform benefit:risk analyses consistent with the goal of measuring and weighing outcomes that are most important from the patient's perspective. We describe a broad vision for the future of clinical trials consistent with increased pragmatism. Greater focus on using endpoints to analyze patients rather than patients to analyze endpoints particularly in late-phase/stage clinical trials is an important part of this vision.

[Personalized cell therapy for early postoperative bullous keratopathy (experimental proof and clinical results)].

PubMed

Kasparov, A A; Kasparova, Evg A; Fadeeva, L L; Subbot, A M; Borodina, N V; Kasparova, E A; Kobzova, M V; Musaeva, G M; Pavliuk, A S

2013-01-01

The article presents the results of a long-term research on development and clinical application of personalized cell therapy (PCT) for treatment of early postoperative (manifesting within the first 3 months after surgery) bullous keratopathy (BK). The method of intracameral PCT implies in vitro incubation of the patient's blood sample with poly(A:U) stimulator, separation of the serum with activated leukocytes, and injection of the final cell preparation into the anterior chamber. The fundamental part of the research was aimed at a detailed description of the cell preparation and investigation of its possible mechanisms of action. Cytokine and growth factor level in the cell preparation suggested that its high clinical efficacy might be due to its ability to improve regeneration of damaged corneal endothelium. The clinical study was conducted on a group of 52 patients with early BK. A significant effect (smoothing of the Descement's membrane folds, complete resorption of corneal edema, improvement of corneal transparency, reduction of corneal thickness and increase of visual acuity by 0.49 +/- 0.27) was achieved in 44.2% of patients, while partial effect was seen in 21.1% of patients. There was no clinical effect in 34.6% of patients. In those patients who developed significant or partial clinical effect after the PCT, many endotheliocytes appeared to have multiple nuclei (2 and more). In some patients polyploid nuclei persisted for 3-5 years after the treatment. Polyploidy results from incomplete mitosis which might be due to regenerative processes in the endothelium stimulated by the PCT. Obviously, high efficacy and relative simplicity of the method should promote its further clinical introduction.

Using Outcomes to Analyze Patients Rather than Patients to Analyze Outcomes: A Step toward Pragmatism in Benefit:risk Evaluation

PubMed Central

Evans, Scott R.; Follmann, Dean

2016-01-01

In the future, clinical trials will have an increased emphasis on pragmatism, providing a practical description of the effects of new treatments in realistic clinical settings. Accomplishing pragmatism requires better summaries of the totality of the evidence in ways that clinical trials consumers---patients, physicians, insurers---find transparent and allow for informed benefit:risk decision-making. The current approach to the analysis of clinical trials is to analyze efficacy and safety separately and then combine these analyses into a benefit:risk assessment. Many assume that this will effectively describe the impact on patients. But this approach is suboptimal for evaluating the totality of effects on patients. We discuss methods for benefit:risk assessment that have greater pragmatism than methods that separately analyze efficacy and safety. These include the concepts of within-patient analyses and composite benefit:risk endpoints with a goal of understanding how to analyze one patient before trying to figure out how to analyze many. We discuss the desirability of outcome ranking (DOOR) and introduce the partial credit strategy using an example in a clinical trial evaluating the effects of a new antibiotic. As part of the example we introduce a strategy to engage patients as a resource to inform benefit:risk analyses consistent with the goal of measuring and weighing outcomes that are most important from the patient’s perspective. We describe a broad vision for the future of clinical trials consistent with increased pragmatism. Greater focus on using endpoints to analyze patients rather than patients to analyze endpoints particularly in late-phase/stage clinical trials is an important part of this vision. PMID:28435515

painACTION-back pain: a self-management website for people with chronic back pain.

PubMed

Chiauzzi, Emil; Pujol, Lynette A; Wood, Mollie; Bond, Kathleen; Black, Ryan; Yiu, Elizabeth; Zacharoff, Kevin

2010-07-01

To determine whether an interactive self-management Website for people with chronic back pain would significantly improve emotional management, coping, self-efficacy to manage pain, pain levels, and physical functioning compared with standard text-based materials. The study utilized a pretest-posttest randomized controlled design comparing Website (painACTION-Back Pain) and control (text-based material) conditions at baseline and at 1-, 3, and 6-month follow-ups. Two hundred and nine people with chronic back pain were recruited through dissemination of study information online and at a pain treatment clinic. The 6-month follow-up rates for the Website and control groups were 73% and 84%, respectively. Measures were based on the recommendations of the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials and included measures of pain intensity, physical functioning, emotional functioning, coping, self-efficacy, fear-avoidance, perceived improvement with treatment, self-efficacy, and catastrophizing. Compared with controls, painACTION-Back Pain participants reported significantly: 1) lower stress; 2) increased coping self-statements; and 3) greater use of social support. Comparisons between groups suggested clinically significant differences in current pain intensity, depression, anxiety, stress, and global ratings of improvement. Among participants recruited online, those using the Website reported significantly: 1) lower "worst" pain; 2) lower "average" pain; and 3) increased coping self-statements, compared with controls. Participants recruited through the pain clinic evidenced no such differences. An online self-management program for people with chronic back pain can lead to improvements in stress, coping, and social support, and produce clinically significant differences in pain, depression, anxiety, and global rates of improvement.

Concept mapping to promote meaningful learning, help relate theory to practice and improve learning self-efficacy in Asian mental health nursing students: A mixed-methods pilot study.

PubMed

Bressington, Daniel T; Wong, Wai-Kit; Lam, Kar Kei Claire; Chien, Wai Tong

2018-01-01

Student nurses are provided with a great deal of knowledge within university, but they can find it difficult to relate theory to nursing practice. This study aimed to test the appropriateness and feasibility of assessing Novak's concept mapping as an educational strategy to strengthen the theory-practice link, encourage meaningful learning and enhance learning self-efficacy in nursing students. This pilot study utilised a mixed-methods quasi-experimental design. The study was conducted in a University school of Nursing in Hong Kong. A total of 40 third-year pre-registration Asian mental health nursing students completed the study; 12 in the concept mapping (CM) group and 28 in the usual teaching methods (UTM) group. The impact of concept mapping was evaluated thorough analysis of quantitative changes in students' learning self-efficacy, analysis of the structure and contents of the concept maps (CM group), a quantitative measure of students' opinions about their reflective learning activities and content analysis of qualitative data from reflective written accounts (CM group). There were no significant differences in self-reported learning self-efficacy between the two groups (p=0.38). The concept mapping helped students identify their current level of understanding, but the increased awareness may cause an initial drop in learning self-efficacy. The results highlight that most CM students were able to demonstrate meaningful learning and perceived that concept mapping was a useful reflective learning strategy to help them to link theory and practice. The results provide preliminary evidence that the concept mapping approach can be useful to help mental health nursing students visualise their learning progress and encourage the integration of theoretical knowledge with clinical knowledge. Combining concept mapping data with quantitative measures and qualitative reflective journal data appears to be a useful way of assessing and understanding the effectiveness of concept mapping. Future studies should utilise a larger sample size and consider using the approach as a targeted intervention immediately before and during clinical learning placements. Copyright © 2017 Elsevier Ltd. All rights reserved.

Simple and Complex Post-Traumatic Stress Disorder: Strategies for Comprehensive Treatment in Clinical Practice.

ERIC Educational Resources Information Center

Williams, Mary Beth; Sommer, John F., Jr.

This book delivers state-of-the-art techniques and information for practitioners to help individuals, groups, families, and communities suffering from post-traumatic stress disorder (PTSD). It addresses concerns about the efficacy of critical incident stress debriefing, examines the value of a variety of innovative treatment methods, and explores…

Within-Group Effect-Size Benchmarks for Trauma-Focused Cognitive Behavioral Therapy with Children and Adolescents

ERIC Educational Resources Information Center

Rubin, Allen; Washburn, Micki; Schieszler, Christine

2017-01-01

Purpose: This article provides benchmark data on within-group effect sizes from published randomized clinical trials (RCTs) supporting the efficacy of trauma-focused cognitive behavioral therapy (TF-CBT) for traumatized children. Methods: Within-group effect-size benchmarks for symptoms of trauma, anxiety, and depression were calculated via the…

“In vitro” antifungal activity of ozonized sunflower oil on yeasts from onychomycosis

PubMed Central

Guerrer, L.V.; Cunha, K. C.; Nogueira, M. C. L.; Cardoso, C. C.; Soares, M. M. C. N.; Almeida, M. T. G.

2012-01-01

The “in vitro” antifungal activity of ozonized sunflower oil (Bioperoxoil®) was tested on 101 samples of yeasts originating from onychomycosis using the disk diffusion method. The oil was efficacious against several clinical fungal strains: Candida parapsilosis, Candida albicans, Trichosporon asahii, Candida tropicalis and Candida guilliermondii. PMID:24031958

Citalopram Treatment of Pediatric Recurrent Abdominal Pain and Comorbid Internalizing Disorders: An Exploratory Study

ERIC Educational Resources Information Center

Campo, John V.; Perel, James; Lucas, Amanda; Bridge, Jeff; Ehmann, Mary; Kalas, Catherine; Monk, Kelly; Axelson, David; Birmaher, Boris; Ryan, Neal; Di Lorenzo, Carlo; Brent, David A.

2004-01-01

Objective: To assess the potential efficacy, tolerability, and safety of citalopram in the treatment of functional pediatric recurrent abdominal pain and comorbid internalizing disorders. Method: Twenty-five clinically referred children and adolescents with recurrent abdominal pain aged 7 to 18 years, inclusive, participated in a 12-week,…

Sequential Pharmacotherapy for Children with Comorbid Attention-Deficit/hyperactivity and Anxiety Disorders.

ERIC Educational Resources Information Center

Abikoff, Howard; McGough, James; Vitiello, Benedetto; McCracken, James; Davies, Mark; Walkup, John; Riddle, Mark; Oatis, Melvin; Greenhill, Laurence; Skrobala, Anne; March, John; Gammon, Pat; Robinson, James; Lazell, Robert; McMahon, Donald J.; Ritz, Louise

2005-01-01

Objective: Attention-deficit/hyperactivity disorder (ADHD) is often accompanied by clinically significant anxiety, but few empirical data guide treatment of children meeting full DSM-IV criteria for ADHD and anxiety disorders (ADHD/ANX). This study examined the efficacy of sequential pharmacotherapy for ADHD/ANX children. Method: Children, age 6…

Understanding the Effect Size of Lisdexamfetamine Dimesylate for Treating ADHD in Children and Adults

ERIC Educational Resources Information Center

Faraone, Stephen V.

2012-01-01

Objective: An earlier meta-analysis of pediatric clinical trials indicated that lisdexamfetamine dimesylate (LDX) had a greater effect size than other stimulant medications. This work tested the hypothesis that the apparent increased efficacy was artifactual. Method: The authors assessed two potential artifacts: an unusually high precision of…

The efficacy of an intraosseous injection system of delivering local anesthetic.

PubMed

Leonard, M S

1995-01-01

This article describes the clinical testing of a new system for the intraosseous delivery of local anesthesia. The author concluded that the system delivered local anesthetic very effectively (in some situations more effectively than the traditional delivery method), thus offering a great potential advantage to both dentists and patients.

Functional Magnetic Resonance Imaging Clinical Trial of a Dual-Processing Treatment Protocol for Substance-Dependent Adults

ERIC Educational Resources Information Center

Matto, Holly C.; Hadjiyane, Maria C.; Kost, Michelle; Marshall, Jennifer; Wiley, Joseph; Strolin-Goltzman, Jessica; Khatiwada, Manish; VanMeter, John W.

2014-01-01

Objectives: Empirical evidence suggests substance dependence creates stress system dysregulation which, in turn, may limit the efficacy of verbal-based treatment interventions, as the recovering brain may not be functionally capable of executive level processing. Treatment models that target implicit functioning are necessary. Methods: An RCT was…

Anesthetic Efficacy of Meperidine in Teeth With Symptomatic Irreversible Pulpitis

PubMed Central

Mohajeri, Ladan; Salehi, Farnaz; Mehrvarzfar, Payman; Arfaee, Hamide; Bohluli, Behnam; Hamedy, Reza

2015-01-01

Achieving adequate pulpal anesthesia in mandibular teeth is always a challenge. Supplementary injections and using drugs in combination are some methods implemented to overcome this hurdle. In this randomized clinical trial, use of meperidine in conjunction with lidocaine in intraligamentary injection did not exhibit significant improvement in anesthesia. PMID:25849469

Correlation between Students’ Self-Efficacy and Teachers’ Educational Leadership Style in Iranian Midwifery Students

PubMed Central

Sohrabi, Zohreh; Kheirkhah, Masoomeh; Sahebzad, Elahe Sadegi; Rasoulighasemlouei, Seyedehsahel; Khavandi, Siamak

2016-01-01

Background: Self-efficacy is believe in and feeling of ability to complete work. One of these factors is educational teachers’ role. This study aimed to determine relationship between teachers’ leadership style and students’ self-efficacy in midwifery students. Method: This Study is a cross sectional correlation study. Sampling was conducted in midwifery students in Bachelor Science degree in 2013. Data collection tools were multi leadership questionnaire and self-efficacy clinical performance. After explaining the goals of study, 97 students completed the questionnaire. Scoring the questionnaire was based on a Liker’s scale (0-5). Data were analyzed by SPSS 16. Correlation coefficient test was adopted to investigate the relationship and p value was considered 0.05. Result: Mean of self-efficacy scores were 116.12 (24.66.). In 53.3% of the cases, self-efficacy was good, in 42.2% moderate and in 4.3%, it was bad. The majority of the students (88.9%) reported that their teachers had an idealized style in leadership. About 94.6% of the students with good self- efficacy believed that their teachers’ leadership style was transformational style. There was a significant correlation between self- efficacy and leadership style (p<0.05). Conclusions: Results showed that transformational style is appropriate for midwifery teachers. PMID:26925916

In vivo and in vitro hyperspectral imaging of cervical neoplasia

NASA Astrophysics Data System (ADS)

Wang, Chaojian; Zheng, Wenli; Bu, Yanggao; Chang, Shufang; Tong, Qingping; Zhang, Shiwu; Xu, Ronald X.

2014-02-01

Cervical cancer is a prevalent disease in many developing countries. Colposcopy is the most common approach for screening cervical intraepithelial neoplasia (CIN). However, its clinical efficacy heavily relies on the examiner's experience. Spectroscopy is a potentially effective method for noninvasive diagnosis of cervical neoplasia. In this paper, we introduce a hyperspectral imaging technique for noninvasive detection and quantitative analysis of cervical neoplasia. A hyperspectral camera is used to collect the reflectance images of the entire cervix under xenon lamp illumination, followed by standard colposcopy examination and cervical tissue biopsy at both normal and abnormal sites in different quadrants. The collected reflectance data are calibrated and the hyperspectral signals are extracted. Further spectral analysis and image processing works are carried out to classify tissue into different types based on the spectral characteristics at different stages of cervical intraepithelial neoplasia. The hyperspectral camera is also coupled with a lab microscope to acquire the hyperspectral transmittance images of the pathological slides. The in vivo and the in vitro imaging results are compared with clinical findings to assess the accuracy and efficacy of the method.

Neurobehavioral testing in subarachnoid hemorrhage: A review of methods and current findings in rodents.

PubMed

Turan, Nefize; Miller, Brandon A; Heider, Robert A; Nadeem, Maheen; Sayeed, Iqbal; Stein, Donald G; Pradilla, Gustavo

2017-11-01

The most important aspect of a preclinical study seeking to develop a novel therapy for neurological diseases is whether the therapy produces any clinically relevant functional recovery. For this purpose, neurobehavioral tests are commonly used to evaluate the neuroprotective efficacy of treatments in a wide array of cerebrovascular diseases and neurotrauma. Their use, however, has been limited in experimental subarachnoid hemorrhage studies. After several randomized, double-blinded, controlled clinical trials repeatedly failed to produce a benefit in functional outcome despite some improvement in angiographic vasospasm, more rigorous methods of neurobehavioral testing became critical to provide a more comprehensive evaluation of the functional efficacy of proposed treatments. While several subarachnoid hemorrhage studies have incorporated an array of neurobehavioral assays, a standardized methodology has not been agreed upon. Here, we review neurobehavioral tests for rodents and their potential application to subarachnoid hemorrhage studies. Developing a standardized neurobehavioral testing regimen in rodent studies of subarachnoid hemorrhage would allow for better comparison of results between laboratories and a better prediction of what interventions would produce functional benefits in humans.

Unravelling intrinsic efficacy and ligand bias at G protein coupled receptors: A practical guide to assessing functional data.

PubMed

Stott, Lisa A; Hall, David A; Holliday, Nicholas D

2016-02-01

Stephenson's empirical definition of an agonist, as a ligand with binding affinity and intrinsic efficacy (the ability to activate the receptor once bound), underpins classical receptor pharmacology. Quantifying intrinsic efficacy using functional concentration response relationships has always presented an experimental challenge. The requirement for realistic determination of efficacy is emphasised by recent developments in our understanding of G protein coupled receptor (GPCR) agonists, with recognition that some ligands stabilise different active conformations of the receptor, leading to pathway-selective, or biased agonism. Biased ligands have potential as therapeutics with improved selectivity and clinical efficacy, but there are also pitfalls to the identification of pathway selective effects. Here we explore the basics of concentration response curve analysis, beginning with the need to distinguish ligand bias from other influences of the functional system under study. We consider the different approaches that have been used to quantify and compare biased ligands, many of which are based on the Black and Leff operational model of agonism. Some of the practical issues that accompany these analyses are highlighted, with opportunities to improve estimates in future, particularly in the separation of true agonist intrinsic efficacy from the contributions of system dependent coupling efficiency. Such methods are by their nature practical approaches, and all rely on Stephenson's separation of affinity and efficacy parameters, which are interdependent at the mechanistic level. Nevertheless, operational analysis methods can be justified by mechanistic models of GPCR activation, and if used wisely are key elements to biased ligand identification. Copyright © 2015 Elsevier Inc. All rights reserved.

Clinical Efficacy and Immune Regulation With Peanut Oral Immunotherapy

PubMed Central

Jones, Stacie M.; Pons, Laurent; Roberts, Joseph L.; Scurlock, Amy M.; Perry, Tamara T.; Kulis, Mike; Shreffler, Wayne G.; Steele, Pamela; Henry, Karen A.; Adair, Margaret; Francis, James M.; Durham, Stephen; Vickery, Brian P.; Zhong, Xiaoping; Burks, A. Wesley

2009-01-01

Background Oral immunotherapy (OIT) has been thought to induce clinical desensitization to allergenic foods, but trials coupling the clinical response and immunologic effects of peanut OIT have not been reported. Objective The study objective was to investigate the clinical efficacy and immunologic changes associated with OIT. Methods Peanut-allergic children underwent an OIT protocol including initial day escalation, build-up, and maintenance phases, and then oral food challenge. Clinical response and immunologic changes were evaluated. Results Of 29 subjects who completed the protocol, 27 ingested 3.9 g peanut protein during food challenge. Most symptoms noted during OIT resolved spontaneously or with antihistamines. By 6 months, titrated skin prick tests and activation of basophils significantly declined. Peanut-specific IgE decreased by 12–18 months, while IgG4 increased significantly. Serum factors inhibited IgE–peanut complex formation in an IgE-facilitated allergen binding assay. Secretion of IL-10, IL-5, IFN-γ, and TNF-α from PBMCs increased over 6–12 months. Peanut-specific FoxP3 T cells increased until 12 months and then decreased thereafter. Additionally, T cell microarrays showed downregulation of genes in apoptotic pathways. Conclusion OIT induces clinical desensitization to peanut, with significant longer term humoral and cellular changes. Microarray data suggest a novel role for apoptosis in OIT. PMID:19577283

Study on the Absorbed Fingerprint-Efficacy of Yuanhu Zhitong Tablet Based on Chemical Analysis, Vasorelaxation Evaluation and Data Mining

PubMed Central

Chen, Yanjun; Zhang, Yingchun; Tang, Shihuan; Wang, Shanshan; Shen, Dan; Wang, Xuguang; Lei, Yun; Li, Defeng; Zhang, Yi; Jin, Lan; Yang, Hongjun; Huang, Luqi

2013-01-01

Yuanhu Zhitong Tablet (YZT) is an example of a typical and relatively simple clinical herb formula that is widely used in clinics. It is generally believed that YZT play a therapeutical effect in vivo by the synergism of multiple constituents. Thus, it is necessary to build the relationship between the absorbed fingerprints and bioactivity so as to ensure the quality, safety and efficacy. In this study, a new combinative method, an intestinal absorption test coupled with a vasorelaxation bioactivity experiment in vitro, was a simple, sensitive, and feasible technique to study on the absorbed fingerprint-efficacy of YZT based on chemical analysis, vasorelaxation evaluation and data mining. As part of this method, an everted intestinal sac method was performed to determine the intestinal absorption of YZT solutions. YZT were dissolved in solution (n = 12), and the portion of the solution that was absorbed into intestinal sacs was analyzed using rapid-resolution liquid chromatography coupled with quadruple time-of-flight mass spectrometry (RRLC-Q-TOF/MS). Semi-quantitative analysis indicated the presence of 34 compounds. The effect of the intestinally absorbed solution on vasorelaxation of rat aortic rings with endothelium attached was then evaluated in vitro. The results showed that samples grouped by HCA from chemical profiles have similar bioactivity while samples in different groups displayed very different. Moreover, it established a relationship between the absorbed fingerprints and their bioactivity to identify important components by grey relational analysis, which could predict bioactive values based on chemical profiles and provide an evidence for the quantification of multi-constituents. PMID:24339904

Chronic Pain and Cognitive Behavioral Therapy: An Integrative Review.

PubMed

Knoerl, Robert; Lavoie Smith, Ellen M; Weisberg, James

2016-05-01

Cognitive behavioral therapy (CBT) is often used to treat chronic pain; however, more information is needed about what are the most efficacious dose and delivery methods. The aims of this review were to determine (a) which CBT doses, delivery methods, strategies, and follow-up periods have been explored in recent intervention studies of individuals with chronic pain and (b) whether the outcomes described in the selected studies were consistent with recommendations by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials. The CINAHL, EMBASE, PubMed, PsycInfo, and SCOPUS databases were searched for randomized controlled trials published from 2009 to 2015 testing CBT for adults with chronic pain. Thirty-five studies were included in this review. Results revealed that CBT reduced pain intensity in 43% of trials, the efficacy of online and in-person formats were comparable, and military veterans and individuals with cancer-related chronic pain were understudied. © The Author(s) 2015.

Noninvasive clinical assessment of port-wine stain birthmarks using current and future optical imaging technology: A review

PubMed Central

Sharif, S.A.; Taydas, E.; Mazhar, A.; Rahimian, R.; Kelly, K.M.; Choi, B.; Durkin, A.J.

2012-01-01

Port wine stain (PWS) birthmarks are one class of benign congenital vascular malformation. Laser therapy is the most successful treatment modality of PWS. Unfortunately, this approach has limited efficacy, with only 10% of patients experiencing complete blanching of the PWS. To address this problem, several research groups have developed technologies and methods designed to study treatment outcome and improve treatment efficacy. This paper reviews seven optical imaging techniques currently in use or under development to assess treatment efficacy, focusing on: Reflectance spectrophotometers/tristimulus colorimeters, Laser Doppler flowmetry (LDF) and Laser Doppler imaging (LDI), Cross-polarized diffuse reflectance color imaging system (CDR), Reflectance Confocal Microscopy (RCM), Optical Coherence Tomography (OCT), Spatial Frequency Domain Imaging (SFDI), and Laser Speckle Imaging (LSI). PMID:22804872

Evaluation of the Frails' Fall Efficacy by Comparing Treatments (EFFECT) on reducing fall and fear of fall in moderately frail older adults: study protocol for a randomised control trial

PubMed Central

2011-01-01

Background Falls are common in frail older adults and often result in injuries and hospitalisation. The Nintendo® Wii™ is an easily available exercise modality in the community which has been shown to improve lower limb strength and balance. However, not much is known on the effectiveness of the Nintendo® Wii™ to improve fall efficacy and reduce falls in a moderately frail older adult. Fall efficacy is the measure of fear of falling in performing various daily activities. Fear contributes to avoidance of activities and functional decline. Methods This randomised active-control trial is a comparison between the Nintendo WiiActive programme against standard gym-based rehabilitation of the older population. Eighty subjects aged above 60, fallers and non-fallers, will be recruited from the hospital outpatient clinic. The primary outcome measure is the Modified Falls Efficacy Scale and the secondary outcome measures are self-reported falls, quadriceps strength, walking agility, dynamic balance and quality of life assessments. Discussions The study is the first randomised control trial using the Nintendo Wii as a rehabilitation modality investigating a change in fall efficacy and self-reported falls. Longitudinally, the study will investigate if the interventions can successfully reduce falls and analyse the cost-effectiveness of the programme. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12610000576022 PMID:21682909

Effects of high-fidelity patient simulation led clinical reasoning course: Focused on nursing core competencies, problem solving, and academic self-efficacy.

PubMed

Lee, JuHee; Lee, Yoonju; Lee, Senah; Bae, Juyeon

2016-01-01

To examine the effects of high-fidelity patient simulation (HFPS) led clinical reasoning course among undergraduate nursing students. A quasi-experimental study of non-equivalent control group pretest-post test design was applied. A total of 49 senior nursing students participated in this study. The experimental group consisted of the students who took the "clinical reasoning" course (n = 23) while the control group consisted of students who did not (n = 26). Self-administered scales including the nursing core competencies, problem solving, academic self-efficacy, and Kolb learning style inventory were analyzed quantitatively using SPSS version 20.0. Data analysis was conducted using one-way ancova due to a significant difference in nursing core competencies between the experimental group and control group. There was a significant improvement in nursing core competencies in the experimental group (F = 7.747, P = 0.008). The scores of problem solving and academic self-efficacy were higher in the experimental group after the HFPS led clinical reasoning course without statistical difference. There is a need for the development of effective instructional methods to improve learning outcomes in nursing education. Future research is needed related to simulation education as well as management strategies so that learning outcomes can be achieved within different students' learning style. © 2015 The Authors. Japan Journal of Nursing Science © 2015 Japan Academy of Nursing Science.

Once-daily USL255 as adjunctive treatment of partial-onset seizures: Randomized phase III study

PubMed Central

Chung, Steve S; Fakhoury, Toufic A; Hogan, R Edward; Nagaraddi, Venkatesh N; Blatt, Ilan; Lawson, Balduin; Arnold, Stephan; Anders, Bob; Clark, Annie M; Laine, Dawn; Meadows, R Shawn; Halvorsen, Mark B

2014-01-01

Objective To evaluate the efficacy and safety of USL255, Qudexy™ XR (topiramate) extended-release capsules, as an adjunctive treatment for refractory partial-onset seizures (POS) in adults taking one to three concomitant antiepileptic drugs. Methods In this global phase III study (PREVAIL; NCT01142193), 249 adults with POS were randomized 1:1 to once-daily USL255 (200 mg/day) or placebo. The primary and key secondary efficacy endpoints were median percent reduction in weekly POS frequency and responder rate (proportion of patients with ≥50% reduction in seizure frequency). Seizure freedom was also assessed. Safety (adverse events, clinical and laboratory findings), as well as treatment effects on quality of life (QOLIE-31-P) and clinical global impression of change (CGI-C), were evaluated. Results Across the entire 11-week treatment phase, USL255 significantly reduced the median percent seizure frequency and significantly improved responder rate compared with placebo. Efficacy over placebo was observed early in treatment, in patients with highly refractory POS, and in those with the most debilitating seizure types (i.e., complex partial, partial secondarily generalized). USL255 was safe and generally well tolerated with a low incidence of neurocognitive adverse events. USL255 was associated with significant clinical improvement without adversely affecting quality of life. Significance The PREVAIL phase III clinical study demonstrated that once-daily USL255 (200 mg/day) significantly improved seizure control and was safe and generally well tolerated with few neurocognitive side effects. PMID:24902983

Comparison between pathogen directed antibiotic treatment and empirical broad spectrum antibiotic treatment in patients with community acquired pneumonia: a prospective randomised study

PubMed Central

van der Eerden, M M; Vlaspolder, F; de Graaff, C S; Groot, T; Bronsveld, W; Jansen, H; Boersma, W

2005-01-01

Background: There is much controversy about the ideal approach to the management of community acquired pneumonia (CAP). Recommendations differ from a pathogen directed approach to an empirical strategy with broad spectrum antibiotics. Methods: In a prospective randomised open study performed between 1998 and 2000, a pathogen directed treatment (PDT) approach was compared with an empirical broad spectrum antibiotic treatment (EAT) strategy according to the ATS guidelines of 1993 in 262 hospitalised patients with CAP. Clinical efficacy was primarily determined by the length of hospital stay (LOS). Secondary outcome parameters for clinical efficacy were assessment of therapeutic failure on antibiotics, 30 day mortality, duration of antibiotic treatment, resolution of fever, side effects, and quality of life. Results: Three hundred and three patients were enrolled in the study; 41 were excluded, leaving 262 with results available for analysis. No significant differences were found between the two treatment groups in LOS, 30 day mortality, clinical failure, or resolution of fever. Side effects, although they did not have a significant influence on the outcome parameters, occurred more frequently in patients in the EAT group than in those in the PDT group (60% v 17%, 95% CI –0.5 to –0.3; p<0.001). Conclusions: An EAT strategy with broad spectrum antibiotics for the management of hospitalised patients with CAP has comparable clinical efficacy to a PDT approach. PMID:16061709

The Traditional Chinese Medicine and Relevant Treatment for the Efficacy and Safety of Atopic Dermatitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

PubMed Central

Shi, Zhao-feng; Song, Tie-bing; Xie, Juan; Yan, Yi-quan

2017-01-01

Background Atopic dermatitis (AD) has become a common skin disease that requires systematic and comprehensive treatment to achieve adequate clinical control. Traditional Chinese medicines and related treatments have shown clinical effects for AD in many studies. But the systematic reviews and meta-analyses for them are lacking. Objective The systematic review and meta-analysis based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement were conducted to evaluate the efficacy and safety of traditional Chinese medicines and related treatments for AD treatment. Methods Randomized controlled trials (RCTs) were searched based on standardized searching rules in eight medical databases from the inception up to December 2016 and a total of 24 articles with 1,618 patients were enrolled in this meta-analysis. Results The results revealed that traditional Chinese medicines and related treatments did not show statistical differences in clinical effectiveness, SCORAD amelioration, and SSRI amelioration for AD treatment compared with control group. However, EASI amelioration of traditional Chinese medicines and related treatments for AD was superior to control group. Conclusion We need to make conclusion cautiously for the efficacy and safety of traditional Chinese medicine and related treatment on AD therapy. More standard, multicenter, double-blind randomized controlled trials (RCTs) of traditional Chinese medicine and related treatment for AD were required to be conducted for more clinical evidences providing in the future. PMID:28713436

Biomedical, translational and clinical research on PDT of TMJ

NASA Astrophysics Data System (ADS)

Kamenoff, J.

2017-02-01

Electromagnetic energy of laser light has some typical properties which are found to be a premise for discussions on laser irradiation abilities to control the severe and chronic disorders in TMJ. In world literature PDT application is recommended when soft tissues in TMJ are damaged, in cases of degenerative diseases of discus articularis, medial and lateral distensions of joint ligaments, chronic inflammatory processes in TMJ, occlusion trauma, etc. The aim of our clinical study was to analyze the theoretical achievements up to now in depth and basing on our clinic al observations suggest new methods guaranteeing high therapeutic efficacy of Photodynamic therapy.

Points to consider: efficacy and safety evaluations in the clinical development of ultra-orphan drugs.

PubMed

Maeda, Kojiro; Kaneko, Masayuki; Narukawa, Mamoru; Arato, Teruyo

2017-08-23

The unmet medical needs of individuals with very rare diseases are high. The clinical trial designs and evaluation methods used for 'regular' drugs are not applicable in the clinical development of ultra-orphan drugs (<1000 patients) in many cases. In order to improve the clinical development of ultra-orphan drugs, we examined several points regarding the efficient evaluations of drug efficacy and safety that could be conducted even with very small sample sizes, based on the review reports of orphan drugs approved in Japan. The clinical data packages of 43 ultra-orphan drugs approved in Japan from January 2001 to December 2014 were investigated. Japanese clinical trial data were not included in the clinical data package for eight ultra-orphan drugs, and non-Japanese clinical trial data were included for six of these eight drug. Japanese supportive data that included retrospective studies, published literature, clinical research and Japanese survey results were clinical data package attachments in 22 of the 43 ultra-orphan drugs. Multinational trials were conducted for three ultra-orphan drugs. More than two randomized controlled trials (RCTs) were conducted for only 11 of the 43 ultra-orphan drugs. The smaller the number of patients, the greater the proportion of forced titration and optional titration trials were conducted. Extension trials were carried out for enzyme preparations and monoclonal antibodies with high ratio. Post-marketing surveillance of all patients was required in 36 of the 43 ultra-orphan drugs. For ultra-orphan drugs, clinical endpoints were used as the primary efficacy endpoint of the pivotal trial only for two drugs. The control groups in RCTs were classified as follows: placebo groups different dosage groups, and active controls groups. Sample sizes have been determined on the basis of feasibility for some ultra-orphan drugs. We provide "Draft Guidance on the Clinical Development of Ultra-Orphan Drugs" based on this research. The development of ultra-orphan drugs requires various arrangements regarding evidence collection, data sources and the clinical trial design. We expect that this draft guidance is useful for ultra-orphan drugs developments in future.

Nursing students' viewpoints toward two methods of clinical conference and clinical nursing round.

PubMed

Gheidanzadeh, Maryam; Baghersad, Zahra; Abazari, Parvaneh

2017-01-01

Clinical education provides a chance to combine theoretical knowledge and clinical skills. Students are the key elements in the evaluation of clinical education efficacy. The present study was aimed to define nursing students' viewpoints concerning conformity to the characteristics of clinical conference and clinical round. This descriptive analytical study was conducted on the bachelor's students of the 4 th -6 th semester of nursing. Sampling was conducted using census sampling method during the 2 nd semester of 2014-2015 school year. Data collection tool was a three-section researcher-made questionnaire containing demographic, nursing round, and clinical conference characteristics. Descriptive and inferential statistical tests (independent t -test, ANOVA, and Spearman and Pearson correlation coefficients) were used for data analysis. Participants were 134 bachelor's students of the 4 th -6 th semester of nursing. According to half of the participants, conformity to the characteristics of clinical conference (45.5%, 53%) and clinical round (44%, 51.5%) were poor and medium, respectively. Paired t -test showed a significant difference between students' viewpoints toward the planning of clinical conference and clinical nursing round ( P = 0.006, t = 2.77). According to the results of the present study on students' viewpoints, clinical education faces a serious challenge with regard to clinical education methods. Considering the necessity and importance of clinical education, more investigation should be conducted to detect its relevant factors and plan for its improvement.

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.

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 assessment of infrasonic phonophoresis efficacy in the treatment of bacterial keratitis].

PubMed

Sidorenko, E I; Filatov, V V; Alimova, Iu M

1999-01-01

Therapeutic efficacy of infrasonic phonophoresis is studied in 30 patients with bacterial keratitis. Control group consisted of 87 patients with the same diagnosis. Clinical studies included comparative evaluation of the therapeutic efficacy of infrasonic phonophoresis and traditional local instillations of the same drugs. Before treatment, visual acuity was the same in both groups, while after regression of inflammation after treatment it was 0.13 higher in the phonophoresis group. Results of clinical studies indicate a higher efficacy of infrasonic therapy of patients with keratitis. The duration of therapy was decreased, number of bed-days decreased, and visual acuity after treatment improved.

[Professor HE Tianyou's clinical experience of acupuncture and medicine on intractable facial paralysis].

PubMed

Yan, Fenghua; Yao, Xuhong; Yan, Xingke; Zhang, Yongkui; Jing, Xiaohui; He, Tianyou

2015-02-01

Professor HE Tianyou's unique understanding and treatment characteristics for intractahle facial paralysis are introduced. In clinical practice professor HE highly values acupoint selection and manipulation application, and integrates Chinese and western medicine to flexibly choose acupoints and formulate prescriptions according to syndrome differentiation and location differentiation, besides, he creates several specialized manipulation methods including "tug-of war opposite acupuncture method" and "tractive flash cupping". Based on strengthening body and dredging collaterals. more attention is given on stimulation to local paralyzed facial nerves; meanwhile acupuncture and medication are combined to improve clinical efficacy. During the treatment, the important role of psychological counseling on patient's anxiety is emphasized, and comprehensive treatment is given physically and psychologically in order to achieve the purpose of total rehabilitation.

Rapid phenotypic antimicrobial susceptibility testing using nanoliter arrays.

PubMed

Avesar, Jonathan; Rosenfeld, Dekel; Truman-Rosentsvit, Marianna; Ben-Arye, Tom; Geffen, Yuval; Bercovici, Moran; Levenberg, Shulamit

2017-07-18

Antibiotic resistance is a major global health concern that requires action across all sectors of society. In particular, to allow conservative and effective use of antibiotics clinical settings require better diagnostic tools that provide rapid determination of antimicrobial susceptibility. We present a method for rapid and scalable antimicrobial susceptibility testing using stationary nanoliter droplet arrays that is capable of delivering results in approximately half the time of conventional methods, allowing its results to be used the same working day. In addition, we present an algorithm for automated data analysis and a multiplexing system promoting practicality and translatability for clinical settings. We test the efficacy of our approach on numerous clinical isolates and demonstrate a 2-d reduction in diagnostic time when testing bacteria isolated directly from urine samples.

Development and validation of the French-Canadian Chronic Pain Self-efficacy Scale

PubMed Central

Lacasse, Anaïs; Bourgault, Patricia; Tousignant-Laflamme, Yannick; Courtemanche-Harel, Roxanne; Choinière, Manon

2015-01-01

BACKGROUND: Perceived self-efficacy is a non-negligible outcome when measuring the impact of self-management interventions for chronic pain patients. However, no validated, chronic pain-specific self-efficacy scales exist for studies conducted with French-speaking populations. OBJECTIVES: To establish the validity of the use of the French-Canadian Chronic Pain Self-efficacy Scale (FC-CPSES) among chronic pain patients. METHODS: The Chronic Disease Self-Efficacy Scale is a validated 33-item self-administered questionnaire that measures perceived self-efficacy to perform self-management behaviours, manage chronic disease in general and achieve outcomes (a six-item version is also available). This scale was adapted to the context of chronic pain patients following cross-cultural adaptation guidelines. The FC-CPSES was administered to 109 fibromyalgia and 34 chronic low back pain patients (n=143) who participated in an evidence-based self-management intervention (the PASSAGE program) offered in 10 health care centres across the province of Quebec. Cronbach’s alpha coefficients (α) were calculated to determine the internal consistency of the 33- and six-item versions of the FC-CPSES. With regard to convergent construct validity, the association between the FC-CPSES baseline scores and related clinical outcomes was examined. With regard to the scale’s sensitivity to change, pre- and postintervention FC-CPSES scores were compared. RESULTS: Internal consistency was high for both versions of the FC-CPSES (α=0.86 to α=0.96). Higher self-efficacy was significantly associated with higher mental health-related quality of life and lower pain intensity and catastrophizing (P<0.05), supporting convergent validity of the scale. There was a statistically significant increase in FC-CPSES scores between pre- and postintervention measures for both versions of the FC-CPSES (P<0.003), which supports their sensitivity to clinical change during an intervention. CONCLUSIONS: These data suggest that both versions of the FC-CPSES are reliable and valid for the measurement of pain management self-efficacy among chronic pain patients. PMID:25848845

Meta-Analysis in Clinical Trials Revisited

PubMed Central

Laird, Nan

2015-01-01

In this paper, we revisit a 1986 article we published in this Journal, Meta-Analysis in Clinical Trials, where we introduced a random-effect model to summarize the evidence about treatment efficacy from a number of related clinical trials. Because of its simplicity and ease of implementation, our approach has been widely used (with more than 12,000 citations to date) and the “DerSimonian and Laird method” is now often referred to as the ‘standard approach’ or a ‘popular’ method for meta-analysis in medical and clinical research. The method is especially useful for providing an overall effect estimate and for characterizing the heterogeneity of effects across a series of studies. Here, we review the background that led to the original 1986 article, briefly describe the random-effects approach for meta-analysis, explore its use in various settings and trends over time and recommend a refinement to the method using a robust variance estimator for testing overall effect. We conclude with a discussion of repurposing the method for Big Data meta-analysis and Genome Wide Association Studies for studying the importance of genetic variants in complex diseases. PMID:26343745

[Establishment of biological assess for quality control of Fuzi based on determination of premature ventricular contractions in rats].

PubMed

Zhao, Zhi-Hao; Zhang, Ding-Kun; Wu, Ming-Quan; Li, Chun-Yu; Cao, Li-Juan; Zhang, Ping; Liu, Cui-Zhe; Wang, Jia-Bo; Xiao, Xiao-He

2016-10-01

Aconiti Lateralis Radix (Fuzi) is a toxic traditional Chinese medicine with definite efficacy. In order to improve the quality control of its different prepared products and ensure the security in clinic, it is significant to establish a method of quality evaluation related to clinic adverse effects. Aiming at the important biological marker of early cardiac toxicity reaction, there was no method to detect it. In this manuscript, a novel approach for measuring the minimal toxic dose (MTD) of premature ventricular contractions (PVC) poisoning of rats was established. Then, the determination methodology and conditions were optimized to meet the needs of the quality and biological assessment, including animal sex, weight, stability of standards and test solutions. Using this method, the MTD value of different Fuzi products were determined, such as Heishunpian, Baifupian, Zhengfupian, Baofupian, and Paotianxiong. The results showed that the MTD of Fuzi was significantly decreased after detoxification processed (P<0.05) and the MTD of Heishunpian, Zhengfupian, Baofupian and Baifupian was as much as 15.76, 22.36, 19.65 and 20.97 times to that of unprocessed Shengfuzi. In addition, Paotianxiong could not induce PVC in rats, which indicated that Paotianxiong was nontoxic and safe.This method could appropriately reflects the cardiotoxity of Fuzi and its prepared samples. Together with the chemical composition analysis, the contents of diester alkaloids were explored including aconitine, mesaconitine and hypaconitine as well as monoester alkaloids in Fuzi and its prepared products were significantly associated with PVC. Furthermore, there may be some components undetermined facilitating arrhythmia to be worth exploring. This research provides an overall and comprehensive approach to diagnose early clinical cardiotoxity and control the quality of Fuzi, which could not only be a complementary solution for the chemical evaluation, but a new method to ensure its efficacy and security of clinical application. Copyright© by the Chinese Pharmaceutical Association.

Reproducibility of clinical research in critical care: a scoping review.

PubMed

Niven, Daniel J; McCormick, T Jared; Straus, Sharon E; Hemmelgarn, Brenda R; Jeffs, Lianne; Barnes, Tavish R M; Stelfox, Henry T

2018-02-21

The ability to reproduce experiments is a defining principle of science. Reproducibility of clinical research has received relatively little scientific attention. However, it is important as it may inform clinical practice, research agendas, and the design of future studies. We used scoping review methods to examine reproducibility within a cohort of randomized trials examining clinical critical care research and published in the top general medical and critical care journals. To identify relevant clinical practices, we searched the New England Journal of Medicine, The Lancet, and JAMA for randomized trials published up to April 2016. To identify a comprehensive set of studies for these practices, included articles informed secondary searches within other high-impact medical and specialty journals. We included late-phase randomized controlled trials examining therapeutic clinical practices in adults admitted to general medical-surgical or specialty intensive care units (ICUs). Included articles were classified using a reproducibility framework. An original study was the first to evaluate a clinical practice. A reproduction attempt re-evaluated that practice in a new set of participants. Overall, 158 practices were examined in 275 included articles. A reproduction attempt was identified for 66 practices (42%, 95% CI 33-50%). Original studies reported larger effects than reproduction attempts (primary endpoint, risk difference 16.0%, 95% CI 11.6-20.5% vs. 8.4%, 95% CI 6.0-10.8%, P = 0.003). More than half of clinical practices with a reproduction attempt demonstrated effects that were inconsistent with the original study (56%, 95% CI 42-68%), among which a large number were reported to be efficacious in the original study and to lack efficacy in the reproduction attempt (34%, 95% CI 19-52%). Two practices reported to be efficacious in the original study were found to be harmful in the reproduction attempt. A minority of critical care practices with research published in high-profile journals were evaluated for reproducibility; less than half had reproducible effects.

Evaluation of Automated and Semi-Automated Scoring of Polysomnographic Recordings from a Clinical Trial Using Zolpidem in the Treatment of Insomnia

PubMed Central

Svetnik, Vladimir; Ma, Junshui; Soper, Keith A.; Doran, Scott; Renger, John J.; Deacon, Steve; Koblan, Ken S.

2007-01-01

Objective: To evaluate the performance of 2 automated systems, Morpheus and Somnolyzer24X7, with various levels of human review/editing, in scoring polysomnographic (PSG) recordings from a clinical trial using zolpidem in a model of transient insomnia. Methods: 164 all-night PSG recordings from 82 subjects collected during 2 nights of sleep, one under placebo and one under zolpidem (10 mg) treatment were used. For each recording, 6 different methods were used to provide sleep stage scores based on Rechtschaffen & Kales criteria: 1) full manual scoring, 2) automated scoring by Morpheus 3) automated scoring by Somnolyzer24X7, 4) automated scoring by Morpheus with full manual review, 5) automated scoring by Morpheus with partial manual review, 6) automated scoring by Somnolyzer24X7 with partial manual review. Ten traditional clinical efficacy measures of sleep initiation, maintenance, and architecture were calculated. Results: Pair-wise epoch-by-epoch agreements between fully automated and manual scores were in the range of intersite manual scoring agreements reported in the literature (70%-72%). Pair-wise epoch-by-epoch agreements between automated scores manually reviewed were higher (73%-76%). The direction and statistical significance of treatment effect sizes using traditional efficacy endpoints were essentially the same whichever method was used. As the degree of manual review increased, the magnitude of the effect size approached those estimated with fully manual scoring. Conclusion: Automated or semi-automated sleep PSG scoring offers valuable alternatives to costly, time consuming, and intrasite and intersite variable manual scoring, especially in large multicenter clinical trials. Reduction in scoring variability may also reduce the sample size of a clinical trial. Citation: Svetnik V; Ma J; Soper KA; Doran S; Renger JJ; Deacon S; Koblan KS. Evaluation of automated and semi-automated scoring of polysomnographic recordings from a clinical trial using zolpidem in the treatment of insomnia. SLEEP 2007;30(11):1562-1574. PMID:18041489

Stimuli-responsive magnetic nanoparticles for tumor-targeted bimodal imaging and photodynamic/hyperthermia combination therapy

NASA Astrophysics Data System (ADS)

Kim, Kyoung Sub; Kim, Jiyoung; Lee, Joo Young; Matsuda, Shofu; Hideshima, Sho; Mori, Yasurou; Osaka, Tetsuya; Na, Kun

2016-06-01

Despite magnetic nanoparticles having shown great potential in cancer treatment, tremendous challenges related to diagnostic sensitivity and treatment efficacy for clinical application remain. Herein, we designed optimized multifunctional magnetite nanoparticles (AHP@MNPs), composed of Fe3O4 nanoparticles and photosensitizer conjugated hyaluronic acid (AHP), to achieve enhanced tumor diagnosis and therapy. Fe3O4 nanoparticles (MNPs) were synthesized by a facile hydrolysis method. MNPs have higher biocompatibility, controllable particle sizes, and desirable magnetic properties. The fabricated AHP@MNPs have enhanced water solubility (average size: 108.13 +/- 1.08 nm), heat generation properties, and singlet oxygen generation properties upon magnetic and laser irradiation. The AHP@MNPs can target tumors via CD44 receptor-mediated endocytosis, which have enhanced tumor therapeutic effects through photodynamic/hyperthermia-combined treatment without any drugs. We successfully detected tumors implanted in mice via magnetic resonance imaging and optical imaging. Furthermore, we demonstrated the photodynamic/hyperthermia-combined therapeutic efficacy of AHP@MNPs with synergistically enhanced efficacy against cancer.Despite magnetic nanoparticles having shown great potential in cancer treatment, tremendous challenges related to diagnostic sensitivity and treatment efficacy for clinical application remain. Herein, we designed optimized multifunctional magnetite nanoparticles (AHP@MNPs), composed of Fe3O4 nanoparticles and photosensitizer conjugated hyaluronic acid (AHP), to achieve enhanced tumor diagnosis and therapy. Fe3O4 nanoparticles (MNPs) were synthesized by a facile hydrolysis method. MNPs have higher biocompatibility, controllable particle sizes, and desirable magnetic properties. The fabricated AHP@MNPs have enhanced water solubility (average size: 108.13 +/- 1.08 nm), heat generation properties, and singlet oxygen generation properties upon magnetic and laser irradiation. The AHP@MNPs can target tumors via CD44 receptor-mediated endocytosis, which have enhanced tumor therapeutic effects through photodynamic/hyperthermia-combined treatment without any drugs. We successfully detected tumors implanted in mice via magnetic resonance imaging and optical imaging. Furthermore, we demonstrated the photodynamic/hyperthermia-combined therapeutic efficacy of AHP@MNPs with synergistically enhanced efficacy against cancer. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr02273a

Reliability and Validity of a Turkish version of the Prenatal Breastfeeding Self-Efficacy Scale.

PubMed

Aydin, Ayse; Pasinlioglu, Turkan

2018-05-18

This study aims to conduct reliability and validity study of the Turkish version of the "Prenatal Breastfeeding Self-Efficacy Scale", which determines pregnant women's perception of breastfeeding self-efficacy in the prenatal period. This methodological research was carried out between December 2014 and May 2016 in maternity clinics of the Erzurum Nene Hatun Maternity Hospital and Atatürk University Research Hospital. The study population consisted of pregnant women, admitted to the specified clinics for prenatal controls. The study was carried out with 326 pregnant women, who met the inclusion criteria and agreed to participate in the research without any sample selection. "Personal Information Form" and "Prenatal Breastfeeding Self-Efficacy Scale - Turkish Form" were used for data collection. The data were collected by the face-to-face interview method, and analyzed by SPSS 18 software. In the validity-reliability analysis of the scale, language and content validity, explanatory factor analysis, Cronbach's Alpha coefficient, item-total score correlation, and testretest methods were used. Linguistic validity was verified by the translation-backtranslation of the Prenatal Breastfeeding Self-Efficacy Scale, then the necessary corrections were made according to the recommendations of the expert opinions, to ensure the content validity. As a result of the explanatory factor analysis, performed to determine the construct validity of the scale, a single factor structure was found, having factor loadings in the appropriate range (0.30-0.76). In the internal consistency analysis of the scale, Cronbach's Alpha was 0.86, and the item-total score correlations were between 0.23 and 0.65, and no item was removed from the scale. In order to test the time-invariance of the scale, the test-retest correlation value was found to be 0.94. The relationship between the two applications were determined to be statistically significant (p < 0.001). Turkish version of the Prenatal Breastfeeding Self-Efficacy Scale was evaluated in Turkish women and found to be a valid and reliable measurement instrument. Copyright © 2018 Elsevier Ltd. All rights reserved.

Human Patient Simulations: Evaluation of Self-Efficacy and Anxiety in Clinical Skills Performance

ERIC Educational Resources Information Center

Onovo, Grace N.

2013-01-01

The relationship between self-efficacy (self-confidence) and anxiety levels, and the use of Human Patient Simulations (HPS) as a teaching-learning strategy, has not been sufficiently studied in the area of clinical nursing education. Despite the evidence in the literature indicating that HPS increases self-efficacy/self-confidence and decreases…

Efficacy and Safety of Ceftazidime-Avibactam Plus Metronidazole Versus Meropenem in the Treatment of Complicated Intra-abdominal Infection: Results From a Randomized, Controlled, Double-Blind, Phase 3 Program

PubMed Central

Mazuski, John E.; Gasink, Leanne B.; Armstrong, Jon; Broadhurst, Helen; Stone, Greg G.; Rank, Douglas; Llorens, Lily; Newell, Paul; Pachl, Jan

2016-01-01

Background. When combined with ceftazidime, the novel non–β-lactam β-lactamase inhibitor avibactam provides a carbapenem alternative against multidrug-resistant infections. Efficacy and safety of ceftazidime-avibactam plus metronidazole were compared with meropenem in 1066 men and women with complicated intra-abdominal infections from 2 identical, randomized, double-blind phase 3 studies (NCT01499290 and NCT01500239). Methods. The primary end point was clinical cure at test-of-cure visit 28–35 days after randomization, assessed by noninferiority of ceftazidime-avibactam plus metronidazole to meropenem in the microbiologically modified intention-to-treat (mMITT) population (in accordance with US Food and Drug Administration guidance), and the modified intention-to-treat and clinically evaluable populations (European Medicines Agency guidance). Noninferiority was considered met if the lower limit of the 95% confidence interval for between-group difference was greater than the prespecified noninferiority margin of −12.5%. Results. Ceftazidime-avibactam plus metronidazole was noninferior to meropenem across all primary analysis populations. Clinical cure rates with ceftazidime-avibactam plus metronidazole and meropenem, respectively, were as follows: mMITT population, 81.6% and 85.1% (between-group difference, −3.5%; 95% confidence interval −8.64 to 1.58); modified intention-to-treat, 82.5% and 84.9% (−2.4%; −6.90 to 2.10); and clinically evaluable, 91.7% and 92.5% (−0.8%; −4.61 to 2.89). The clinical cure rate with ceftazidime-avibactam plus metronidazole for ceftazidime-resistant infections was comparable to that with meropenem (mMITT population, 83.0% and 85.9%, respectively) and similar to the regimen's own efficacy against ceftazidime-susceptible infections (82.0%). Adverse events were similar between groups. Conclusions. Ceftazidime-avibactam plus metronidazole was noninferior to meropenem in the treatment of complicated intra-abdominal infections. Efficacy was similar against infections caused by ceftazidime-susceptible and ceftazidime-resistant pathogens. The safety profile of ceftazidime-avibactam plus metronidazole was consistent with that previously observed with ceftazidime alone. Clinical Trials Registration. NCT01499290 and NCT01500239. PMID:26962078

Role of Omega-3 Fatty Acids in the Treatment of Depressive Disorders: A Comprehensive Meta-Analysis of Randomized Clinical Trials

PubMed Central

Grosso, Giuseppe; Pajak, Andrzej; Marventano, Stefano; Castellano, Sabrina; Galvano, Fabio; Bucolo, Claudio; Drago, Filippo; Caraci, Filippo

2014-01-01

Background Despite omega-3 polyunsaturated fatty acids (PUFA) supplementation in depressed patients have been suggested to improve depressive symptomatology, previous findings are not univocal. Objectives To conduct an updated meta-analysis of randomized controlled trials (RCTs) of omega-3 PUFA treatment of depressive disorders, taking into account the clinical differences among patients included in the studies. Methods A search on MEDLINE, EMBASE, PsycInfo, and the Cochrane Database of RCTs using omega-3 PUFA on patients with depressive symptoms published up to August 2013 was performed. Standardized mean difference in clinical measure of depression severity was primary outcome. Type of omega-3 used (particularly eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) and omega-3 as mono- or adjuvant therapy was also examined. Meta-regression analyses assessed the effects of study size, baseline depression severity, trial duration, dose of omega-3, and age of patients. Results Meta-analysis of 11 and 8 trials conducted respectively on patients with a DSM-defined diagnosis of major depressive disorder (MDD) and patients with depressive symptomatology but no diagnosis of MDD demonstrated significant clinical benefit of omega-3 PUFA treatment compared to placebo (standardized difference in random-effects model 0.56 SD [95% CI: 0.20, 0.92] and 0.22 SD [95% CI: 0.01, 0.43], respectively; pooled analysis was 0.38 SD [95% CI: 0.18, 0.59]). Use of mainly EPA within the preparation, rather than DHA, influenced final clinical efficacy. Significant clinical efficacy had the use of omega-3 PUFA as adjuvant rather than mono-therapy. No relation between efficacy and study size, baseline depression severity, trial duration, age of patients, and study quality was found. Omega-3 PUFA resulted effective in RCTs on patients with bipolar disorder, whereas no evidence was found for those exploring their efficacy on depressive symptoms in young populations, perinatal depression, primary disease other than depression and healthy subjects. Conclusions The use of omega-3 PUFA is effective in patients with diagnosis of MDD and on depressive patients without diagnosis of MDD. PMID:24805797

Parkinson's Disease Gene Therapy: Success by Design Meets Failure by Efficacy

PubMed Central

Bartus, Raymond T; Weinberg, Marc S; Samulski, R. Jude

2014-01-01

Over the past decade, nine gene therapy clinical trials for Parkinson's disease (PD) have been initiated and completed. Starting with considerable optimism at the initiation of each trial, none of the programs has yet borne sufficiently robust clinical efficacy or found a clear path toward regulatory approval. Despite the immediately disappointing nature of the efficacy outcomes in these trials, the clinical data garnered from the individual studies nonetheless represent tangible and significant progress for the gene therapy field. Collectively, the clinical trials demonstrate that we have overcome the major safety hurdles previously suppressing central nervous system (CNS) gene therapy, for none produced any evidence of untoward risk or harm after administration of various vector-delivery systems. More importantly, these studies also demonstrated controlled, highly persistent generation of biologically active proteins targeted to structures deep in the human brain. Therefore, a renewed, focused emphasis must be placed on advancing clinical efficacy by improving clinical trial design, patient selection and outcome measures, developing more predictive animal models to support clinical testing, carefully performing retrospective analyses, and most importantly moving forward—beyond our past limits. PMID:24356252

Clinical Evaluation of Efficacy and Performance of All-Poly Tibial Freedom® Total Knee System for Treating Osteoarthritis Patients: Three-Year Follow Up Study

PubMed Central

Singh, Kanwar Kulwinder

2017-01-01

Introduction Advancement in technology in terms of design and building materials has made Total Knee Replacement (TKR) a highly effective, safe, and predictable orthopedic procedure. Aim To review the clinical outcomes for efficacy and performance of Freedom Total Knee System for the management of Osteoarthritis (OA), at a minimum of three years follow up. Materials and Methods For this retrospective, post-marketing study, clinical data of patients treated with Freedom Total Knee System was retrieved from the clinical records after approval from the Institutional Ethics Committee . All the patients above the age of 18 years who completed at least three years after TKR were observed for the study purpose. Patients treated for OA were included while the patients who received the implant for treatment of rheumatoid arthritis and traumatic injury were excluded. Factors such as aseptic loosening, implant failure, and need for revision surgery were observed to evaluate implant performance. Cases were recruited for clinical assessment of primary efficacy endpoint in terms of post-surgery maximun range of motion. Secondary efficacy endpoint was to determine the clinical and social quality of life as per the American Knee Society Score (AKSS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and stiffness scores. Results A total of 158 patients who had 191 TKR were observed for performance. The mean age of the patients was 67.67 years; mean BMI was 28.97±3.33, and the group comprised of 43% men and 57% women. Telephonic follow up at three years of 158 patients identified that none of them required revision surgery or had aseptic loosening suggesting excellent performance. Final clinical follow up at three years was available for only 35 patients (41 knee implants). The range of motion significantly improved from preoperative 104°±5.67° (range, 85°-119°) to 119.8°±11.05° (98°-123°) at follow-up (p<0.05). There was a significant improvement in clinical and functional AKSS score and WOMAC score at follow-up. Conclusion The evaluation of Freedom Total Knee System for TKR in treating OA, at a minimum of three years follow up showed excellent outcomes in terms of performance, range of motion, reduced postoperative stiffness and pain, and improved functionality. PMID:29207792

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

Kanasaki, Shuzo; Furukawa, Akira; Kane, Teruyuki

Purpose: To evaluate the clinical efficacy of the polyure-thane-covered Nitinol Strecker stent in the treatment of patients with malignant biliary obstruction.Methods: Twenty-three covered stents produced by us were placed in 18 patients with malignant biliary obstruction. Jaundice was caused by cholangiocarcinoma (n=5), pancreatic Cancer (n=6), gallbladder Cancer (n=4), metastatic lymph nodes (n=2), and tumor of the papilla (n=1).Resulrs: The mean patency period of the Stents was 37.5 weeks (5-106 weeks). Recurrent obstructive jaundice occurred in two patients (11%). Adequate biliary drainage over 50 weeks or until death was achieved in 17 of 18 patients (94.4%). Late cholangitis was observed inmore » two patients whose stents bridged the ampulla of Vater. Other late severe complications were not encountered.Conclusion: Although more study is necessary, our results suggest the clinical efficacy of our covered Nitinol Strecker stent in the management of obstructive jaundice caused by malignant diseases.« less

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

Kanasaki, Shuzo; Furukawa, Akira; Kane, Teruyuki

Purpose: To evaluate the clinical efficacy of the polyurethane-covered Nitinol Strecker stent in the treatment of patients with malignant biliary obstruction.Methods: Twenty-three covered stents produced by us were placed in 18 patients with malignant biliary obstruction. Jaundice was caused by cholangiocarcinoma (n = 5), pancreatic cancer (n = 6), gallbladder cancer (n = 4), metastatic lymph nodes (n = 2), and tumor of the papilla (n 1).Results: The mean patency period of the stents was 37.5 weeks (5-106 weeks). Recurrent obstructive jaundice occurred in two patients (11%). Adequate biliary drainage over 50 weeks or until death was achieved in 17more » of 18 patients (94.4%). Late cholangitis was observed in two patients whose stents bridged the ampulla of Vater. Other late severe complications were not encountered.Conclusion: Although more study is necessary, our results suggest the clinical efficacy of our covered Nitinol Strecker stent in the management of obstructive jaundice caused by malignant diseases.« less

Bioanalysis of antibody-drug conjugates: American Association of Pharmaceutical Scientists Antibody-Drug Conjugate Working Group position paper.

PubMed

Gorovits, Boris; Alley, Stephen C; Bilic, Sanela; Booth, Brian; Kaur, Surinder; Oldfield, Phillip; Purushothama, Shobha; Rao, Chetana; Shord, Stacy; Siguenza, Patricia

2013-05-01

Antibody-drug conjugates (ADCs) typically consist of a cytotoxic drug covalently bound to an antibody by a linker. These conjugates have the potential to substantially improve efficacy and reduce toxicity compared with cytotoxic small-molecule drugs. Since ADCs are generally complex heterogeneous mixtures of multiple species, these novel therapeutic products present unique bioanalytical challenges. The growing number of ADCs being developed across the industry suggests the need for alignment of the bioanalytical methods or approaches used to assess the multiple species and facilitate consistent interpretation of the bioanalytical data. With limited clinical data, the current strategies that can be used to provide insight into the relationship between the multiple species and the observed clinical safety and efficacy are still evolving. Considerations of the bioanalytical strategies for ADCs based on the current industry practices that take into account the complexity and heterogeneity of ADCs are discussed.

Adjustment Disorder: epidemiology, diagnosis and treatment

PubMed Central

2009-01-01

Background Adjustment Disorder is a condition strongly tied to acute and chronic stress. Despite clinical suggestion of a large prevalence in the general population and the high frequency of its diagnosis in the clinical settings, there has been relatively little research reported and, consequently, very few hints about its treatments. Methods the authors gathered old and current information on the epidemiology, clinical features, comorbidity, treatment and outcome of adjustment disorder by a systematic review of essays published on PUBMED. Results After a first glance at its historical definition and its definition in the DSM and ICD systems, the problem of distinguishing AD from other mood and anxiety disorders, the difficulty in the definition of stress and the implied concept of 'vulnerability' are considered. Comorbidity of AD with other conditions, and outcome of AD are then analyzed. This review also highlights recent data about trends in the use of antidepressant drugs, evidence on their efficacy and the use of psychotherapies. Conclusion AD is a very common diagnosis in clinical practice, but we still lack data about its rightful clinical entity. This may be caused by a difficulty in facing, with a purely descriptive methods, a "pathogenic label", based on a stressful event, for which a subjective impact has to be considered. We lack efficacy surveys concerning treatment. The use of psychotropic drugs such as antidepressants, in AD with anxious or depressed mood is not properly supported and should be avoided, while the usefulness of psychotherapies is more solidly supported by clinical evidence. To better determine the correct course of therapy, randomized-controlled trials, even for the combined use of drugs and psychotherapies, are needed vitally, especially for the resistant forms of AD. PMID:19558652

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…

[Application of magnetic therapy in acute paraproctitis].

PubMed

Kondratenko, P G; Elin, F E; Avraimov, S L; Sobolev, D V

2003-09-01

There were studied the possibilities and perspectives of application of the magnetically liquefied layer as an instrument for better purulent and putrefactive wounds clearance after intervention for an acute paraproctitis. Together with clinical signs the results of bacteriological investigation were controlled as well. There was established high efficacy of the method proposed and expedience of its application.

Efficacy of Adjunct In-Home Coaching to Improve Outcomes in Parent-Child Interaction Therapy

ERIC Educational Resources Information Center

Timmer, Susan G.; Zebell, Nancy M.; Culver, Michelle A.; Urquiza, Anthony J.

2010-01-01

Objectives: The purpose of this study is to test whether increasing the exposure to coaching by adding an in-home component to clinic-delivered Parent-Child Interaction Therapy (PCIT) will increase the speed of parenting skill acquisition and show greater improvements in children's behaviors and parental stress. Methods: Seventy-three parent-child…

Atomoxetine for Hyperactivity in Autism Spectrum Disorders: Placebo-Controlled Crossover Pilot Trial

ERIC Educational Resources Information Center

Arnold, L. Eugene; Aman, Michael G.; Cook, Amelia M.; Witwer, Andrea N.; Hall, Kristy L.; Thompson, Susan; Ramadan, Yaser

2006-01-01

Objective: To explore placebo-controlled efficacy and safety of atomoxetine (ATX) for attention-deficit/hyperactivity disorder (ADHD) symptoms in children with autism spectrum disorders (ASD). Method: Children ages 5 to 15 with ASD and prominent ADHD symptoms were randomly assigned to order in a crossover of clinically titrated ATX and placebo, 6…

Melatonin and Sleep Disorders Associated with Intellectual Disability: A Clinical Review

ERIC Educational Resources Information Center

Sajith, S. G.; Clarke, D.

2007-01-01

Background: Melatonin is used to treat sleep disorders in both children and adults with intellectual disability (ID), although it has no product license for such use. The evidence for its efficacy, potential adverse effects and drug interactions are reviewed in the context of prescribing to people with ID. Methods: A literature search was…

Evaluating Group Therapy for Aphasia: What Is the Evidence? EBP Briefs. Volume 7, Issue 5

ERIC Educational Resources Information Center

Layfield, Claire A.; Ballard, Kirrie J.; Robin, Donald A.

2013-01-01

Clinical Question: For people with aphasia following a stroke, is group therapy shown to be more effective on communication outcome measures reflecting impairment, activity, and/or participation than individual therapy or no therapy? Method: Review of treatment efficacy research for group intervention in aphasia Study Sources: Cochrane Database of…

[INTERVENTIONAL AND SURGICAL TREATMENT OF THE ANGINA PECTORIS RECURRENCE AFTER CORONARY SHUNTING OPERATION].

PubMed

Fanta, S M

2015-12-01

There were examined 134 patients, in whom in the clinic in 2005-2014 yrs a coronary shunting operation was performed. In patients with the angina pectoris recurrence a reoperation is indicated. The data of repeated coronaroventriculography and shuntography were analyzed. Efficacy of the surgical and interventional methods application in the patients was proved.

The Effect of Mindfulness-Based Therapy on Anxiety and Depression: A Meta-Analytic Review

ERIC Educational Resources Information Center

Hofmann, Stefan G.; Sawyer, Alice T.; Witt, Ashley A.; Oh, Diana

2010-01-01

Objective: Although mindfulness-based therapy has become a popular treatment, little is known about its efficacy. Therefore, our objective was to conduct an effect size analysis of this popular intervention for anxiety and mood symptoms in clinical samples. Method: We conducted a literature search using PubMed, PsycINFO, the Cochrane Library, and…

Do Anxiety-Disordered Children Need to Come into the Clinic for Efficacious Treatment?

ERIC Educational Resources Information Center

Cobham, Vanessa E.

2012-01-01

Objective: This study compared 3 experimental conditions: wait-list, therapist-supported bibliotherapy, and individual therapy, in the treatment of child anxiety. Method: Participants were 55 children (25 girls and 30 boys), aged 7 to 14 years diagnosed with an anxiety disorder, and their parents. Families were assigned using a modified random…

Cognitive Behavioral Therapy for 4- to 7-Year-Old Children with Anxiety Disorders: A Randomized Clinical Trial

ERIC Educational Resources Information Center

Hirshfeld-Becker, Dina R.; Masek, Bruce; Henin, Aude; Blakely, Lauren Raezer; Pollock-Wurman, Rachel A.; McQuade, Julia; DePetrillo, Lillian; Briesch, Jacquelyn; Ollendick, Thomas H.; Rosenbaum, Jerrold F.; Biederman, Joseph

2010-01-01

Objective: To examine the efficacy of a developmentally appropriate parent-child cognitive behavioral therapy (CBT) protocol for anxiety disorders in children ages 4-7 years. Method: Design: Randomized wait-list controlled trial. Conduct: Sixty-four children (53% female, mean age 5.4 years, 80% European American) with anxiety disorders were…

Exploring the Link between Self-Efficacy, Workplace Learning and Clinical Practice

ERIC Educational Resources Information Center

Cox, Jennifer; Simpson, Maree Donna

2016-01-01

Pre-registration nurse education includes both conceptual and practical elements to prepare graduates for the transition to clinical practice. Workplace learning plays an important role in developing students' confidence, clinical skills and competency. This paper explores the, perhaps overlooked, centrality of self-efficacy to all areas of…

Expectancies for the Effectiveness of Different Tobacco Interventions Account for Racial and Gender Differences in Motivation to Quit and Abstinence Self-Efficacy

PubMed Central

Leventhal, Adam M.; Stevens, Erin N.; Trent, Lindsay R.; Clark, C. Brendan; Lahti, Adrienne C.; Hendricks, Peter S.

2014-01-01

Introduction: Racial and gender disparities for smoking cessation might be accounted for by differences in expectancies for tobacco interventions, but few studies have investigated such differences or their relationships with motivation to quit and abstinence self-efficacy. Methods: In this cross-sectional study, 673 smokers (African American: n = 443, 65.8%; women: n = 222, 33.0%) under criminal justice supervision who enrolled in a clinical smoking cessation trial in which all received bupropion and half received counseling. All participants completed pretreatment measures of expectancies for different tobacco interventions, motivation to quit, and abstinence self-efficacy. The indirect effects of race and gender on motivation to quit and abstinence self-efficacy through expectancies for different tobacco interventions were evaluated. Results: African Americans’ stronger expectancies that behavioral interventions would be effective accounted for their greater motivation to quit and abstinence self-efficacy. Women’s stronger expectancies for the effectiveness of pharmacotherapy accounted for their greater motivation to quit, whereas their stronger expectancies for the effectiveness of behavioral treatments accounted for their greater abstinence self-efficacy. Conclusions: Findings point to the mediating role of expectancies for treatment effectiveness and suggest the importance of exploring expectancies among African Americans and women as a way to augment motivation and self-efficacy. PMID:24719492

Efficacy of chemomechanical caries removal in reducing cariogenic microbiota: a randomized clinical trial.

PubMed

Ammari, Michelle Mikhael; Moliterno, Luiz Flávio Martins; Hirata Júnior, Raphael; Séllos, Mariana Canano; Soviero, Vera Mendes; Coutinho Filho, Wagner Pereira

2014-01-01

The aim of this study was to compare the efficacy of chemochemical methods (Carisolv™ and Papacárie®) versus the manual method (excavators) in reducing the cariogenic microbiota in dentine caries of primary teeth. Forty-six healthy children (5 to 9 years old) having at least one primary tooth with a cavitated dentine carious lesion were included in the study. The teeth presented no clinical or radiographic signs of pulpal involvement. The sample of 74 teeth was randomly divided into three different groups: Papacárie® (n = 25), Carisolv™ (n = 27) and Manual (n = 22). Samples of carious and sound dentine were collected with sterile excavators before and after caries removal in the three groups. The dentine samples were transferred to glass tubes containing a 1mL thioglycollate medium used as a carrier and enriched for microbiological detection of mutans streptococci and Lactobacillus spp, after incubation for 6h at room temperature. The minimum detection value for colony forming units (CFU) was 3.3 x 102 CFU/ml, and the results were converted into scores from 0 to 4. A significant difference was observed in relation to the microbiological scores before and after caries removal for all methods (Wilcoxon test; p < 0.001). The use of chemomechanical methods for caries removal did not improve the reduction of cariogenic microorganisms in dentine caries lesions, in comparison with manual excavation.

Perceptions on efficacy and side effects of conventional depot antipsychotics (CDA) and atypical depot antipsychotics (ADA): Psychiatrists versus patients in Hong Kong.

PubMed

Tsang, Hector W H; Fong, Mandy W M; Fung, Kelvin M T; Chung, Raymond C K

2010-03-01

Abstract Objectives. We compared the satisfaction level of psychiatrists and psychiatric patients towards conventional (CDA) and atypical (ADA) depot antipsychotics on symptom management, role functioning, and side effects. Method. Patients from an out-patient clinic of a public hospital and psychiatrists from public hospitals participated in the survey in 2007-2008. A total of 153 patients were interviewed by a tailor-made questionnaire and 72 psychiatrists self-administered a similar questionnaire. Results. Both groups shared similar attitudes towards clinical effectiveness and treatment efficacy of ADA and CDA. More patients were ambivalent towards relapse prevention of CDA than psychiatrists (30.7 vs. 16.7%, P<0.044) and three quarters of psychiatrists believed that ADA are associated with less side effects. More than half of the patients showed negative attitudes towards the effectiveness of CDA on improving quality of life (52.40%), work (57.50%), and recreation (55.50%). Psychiatrists were more aware of the limitation of CDA and severity of side effects of CDA. They did not, however, seem to incorporate patients' opinions and research findings into their clinical practice. Conclusion. Evidence-based practice and shared decision-making model between clinicians and mental patients should be advocated. More investigations should be devoted to examine the efficacy of ADA as the alternative to CDA.

Systematic review of stimulant and nonstimulant laxatives for the treatment of functional constipation

PubMed Central

Paré, Pierre; Fedorak, Richard N

2014-01-01

BACKGROUND: Constipation is an uncomfortable and common condition that affects many, irrespective of age. Since 1500 BC and before, health care practitioners have provided treatments and prevention strategies to patients for chronic constipation despite the significant variation in both medical and personal perceptions of the condition. OBJECTIVE: To review relevant research evidence from clinical studies investigating the efficacy and safety of commercially available pharmacological laxatives in Canada, with emphasis on studies adopting the Rome criteria for defining functional constipation. SEARCH METHODS: PubMed, Medline, Embase and Evidence-Based Medicine Reviews databases were searched for blinded or randomized clinical trials and meta-analyses assessing the efficacy of nonstimulant and stimulant laxatives for the treatment of functional constipation. RESULTS: A total of 19 clinical studies and four meta-analyses were retrieved and abstracted regarding study design, participants, interventions and outcomes. The majority of studies focused on polyethylene glycol compared with placebo. Both nonstimulant and stimulant laxatives provided better relief of constipation symptoms than placebo according to both objective and subjective measures. Only one study compared the efficacy of a nonstimulant versus a stimulant laxative, while only two reported changes in quality of life. All studies reported minor side effects due to laxative use, regardless of treatment duration, which ranged from one week to one year. Laxatives were well tolerated by both adults and children. PMID:25390617

Fentanyl Buccal Tablet for the Treatment of Breakthrough Pain: Pharmacokinetics of Buccal Mucosa Delivery and Clinical Efficacy

PubMed Central

Darwish, Mona; Hamed, Ehab; Messina, John

2010-01-01

The treatment of breakthrough pain (BTP), a transitory exacerbation of pain that occurs on a background of otherwise-controlled, persistent pain, requires an opioid formulation and/or method of administration that can provide rapid and extensive systemic exposure. Fentanyl buccal tablet (FBT; FENTORA®, Cephalon, Inc.) employs OraVescent® drug delivery technology, which enhances the rate and extent of fentanyl absorption. OraVescent technology enhances the oral dissolution and buccal absorption of fentanyl, which facilitates rapid uptake of fentanyl into the bloodstream, reducing gastrointestinal absorption and minimizing extensive first-pass metabolism. The resulting pharmacokinetic profile of FBT is characterized by greater bioavailability and a higher early systemic exposure compared with the earlier oral transmucosal fentanyl citrate formulation. In clinical studies of opioid-tolerant patients with cancer-related and noncancer-related BTP, FBT has provided consistent and clinically relevant improvements in pain intensity and pain relief relative to placebo, with a safety and tolerability profile that is generally typical of that observed with other potent opioids. The pharmacokinetic properties of FBT allow for meaningful clinical efficacy, with an onset of action that closely matches the onset of BTP. PMID:20634985

[Controversies in the conduction and evaluation of clinical trials results for the treatment in vasovagal syncope].

PubMed

Gajek, Jacek; Zyśko, Dorota; Halawa, Bogumił

2003-05-01

The vasovagal syncope is a reflex reaction to various stimuli leading to the marked hypotension with or without bradycardia with loss of consciousness and fall of postural muscle tone. The vast majority of the patients recover spontaneously but if the syncope occurs frequently and causes injury of the patients body it worsens the quality of life and needs appropriate treatment. The injuries requiring hospitalization occur approximately in 10% of the patients with vasovagal syncope. The aim of the therapy of affected patients is to diminish the syncope prevalence, to brake the neurocardiogenic reaction on an early stage or to prolong the duration of the presyncope phase to enable the patient prevention of the injury. The lack of clear diagnostic criteria and difficulties with estimation the efficacy of any particular therapeutic intervention in many clinical studies of different authors, inclusion to the studies patients with different clinical presentation stages of the disease contribute to different conclusions, which automatic use in the clinical practice is inappropriate. There is an urgent need to clear the methodological discrepancies and to conduct good planed, large, randomized, multicentre studies to assess the efficacy of different therapeutic methods in the treatment of vasovagal syncope.

Idiopathic club foot treated with the Ponseti method. Clinical and sonographic evaluation of Achilles tendon tenotomy. A review of 221 club feet.

PubMed

Marleix, S; Chapuis, M; Fraisse, B; Tréguier, C; Darnault, P; Rozel, C; Rayar, M; Violas, P

2012-06-01

The Ponseti method applied to treating idiopathic club foot consists in placing successive corrective casts, possibly an Achilles tendon tenotomy, then derotation braces, a method that has proven its efficacy. This study compared 221 cases of club foot treated with this method between 2002 and 2007 divided into two groups, based on whether or not Achilles tendon tenotomy was performed. Assessment was both clinical and sonographic. We observed clear improvement of the results in the group that underwent Achilles tendon tenotomy and a significant difference in the rate of secondary surgery. The sonographic evaluation also showed improvement of the morphological results. We now systematically propose Achilles tendon tenotomy however severe club foot may be. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Large-scale exploration and analysis of drug combinations.

PubMed

Li, Peng; Huang, Chao; Fu, Yingxue; Wang, Jinan; Wu, Ziyin; Ru, Jinlong; Zheng, Chunli; Guo, Zihu; Chen, Xuetong; Zhou, Wei; Zhang, Wenjuan; Li, Yan; Chen, Jianxin; Lu, Aiping; Wang, Yonghua

2015-06-15

Drug combinations are a promising strategy for combating complex diseases by improving the efficacy and reducing corresponding side effects. Currently, a widely studied problem in pharmacology is to predict effective drug combinations, either through empirically screening in clinic or pure experimental trials. However, the large-scale prediction of drug combination by a systems method is rarely considered. We report a systems pharmacology framework to predict drug combinations (PreDCs) on a computational model, termed probability ensemble approach (PEA), for analysis of both the efficacy and adverse effects of drug combinations. First, a Bayesian network integrating with a similarity algorithm is developed to model the combinations from drug molecular and pharmacological phenotypes, and the predictions are then assessed with both clinical efficacy and adverse effects. It is illustrated that PEA can predict the combination efficacy of drugs spanning different therapeutic classes with high specificity and sensitivity (AUC = 0.90), which was further validated by independent data or new experimental assays. PEA also evaluates the adverse effects (AUC = 0.95) quantitatively and detects the therapeutic indications for drug combinations. Finally, the PreDC database includes 1571 known and 3269 predicted optimal combinations as well as their potential side effects and therapeutic indications. The PreDC database is available at http://sm.nwsuaf.edu.cn/lsp/predc.php. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Efficacy of Slimming Cream Containing 3.5% Water-Soluble Caffeine and Xanthenes for the Treatment of Cellulite: Clinical Study and Literature Review

PubMed Central

Byun, Sang-Young; Kwon, Soon-Hyo; Heo, Su-Hak; Shim, Jae-Seong; Du, Mi-Hee

2015-01-01

Background Cellulite is a 'cottage cheese-like' cutaneous change caused by subcutaneous fat bulging into the dermis that usually leads to cosmetic problems. Slimming cream containing 3.5% water-soluble caffeine and xanthenes exhibits a lipolytic effect with penetration into the dermis. Objective To evaluate the efficacy and safety of slimming cream for the treatment of cellulite. Methods Fifteen subjects with cellulite applied slimming cream to the thighs and inner side of the upper arms twice daily for 6 weeks. Efficacy was assessed using a standard visual scale, changes in the circumferences of the thighs and upper arms, and patient satisfaction by a questionnaire at baseline, week 3, and week 6. Safety was assessed by inquiring about adverse events through questionnaires. Results The standard visual scale score improved significantly by 0.49 points (19.8%) at week 6. Thigh and upper-arm circumferences decreased by 0.7 cm (1.7%) and 0.8 cm (2.3%), respectively, at week 6. Slight itching and transient flushing were commonly reported, but no serious adverse event occurred. Conclusion The slimming cream tested appears to be effective for the treatment of cellulitis without serious adverse effects. However, additional large clinical trials are required to confirm the efficacy and safety of slimming cream for the treatment of cellulitis. PMID:26082579

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.

Efficacy of a DVD-Based Smoking Cessation Intervention for African Americans

PubMed Central

Baker, Elizabeth A.; Robinson, Robert G.

2014-01-01

Introduction: Previous research suggests that African American smokers may have improved outcomes if interventions are culturally specific. However, few interventions sufficiently address the unique needs of this population in a format with large reach potential. The purpose of this study was to test the efficacy of a newly developed digital video disc (DVD)-based cessation intervention targeting African Americans. Methods: In a 2-arm randomized trial, smokers (N = 140) were randomly assigned to view either the new Pathways to Freedom (PTF) DVD or a standard control DVD. Participants were assessed at baseline, immediately postviewing the DVD, and at a 1-month follow-up. The primary outcomes were feasibility and process variables, including intervention evaluations, readiness to quit, and risk perceptions, and smoking-related behavior changes were examined as secondary outcomes. Results: Findings demonstrated the hypothesized positive effects of the PTF DVD compared with the control DVD on content evaluations, risk perceptions, and readiness to quit at follow-up. Conclusions: We found initial evidence for the efficacy of the PTF DVD as a stand-alone intervention. Future research will test the efficacy of the DVD for smoking cessation in a larger randomized trial. The ultimate goal of this research is to validate a new intervention for an underserved community of smokers that can be used in multiple settings, such as community health clinics, primary care, quitlines, cessation clinics, and seminars/workshops. PMID:24838844

Application of paclitaxel as adjuvant treatment for benign cicatricial airway stenosis.

PubMed

Qiu, Xiao-Jian; Zhang, Jie; Wang, Juan; Wang, Yu-Ling; Xu, Min

2016-12-01

Benign cicatricial airway stenosis (BCAS) is a potentially life-threatening disease. Recurrence occurs frequently after endoscopic treatment. Paclitaxel is known to prevent restenosis, but its clinical efficacy and safety is undetermined. Therefore, in this study, we investigated the efficacy and associated complications of paclitaxel as adjuvant treatment for BCAS of different etiologies. The study cohort included 28 patients with BCAS resulting from tuberculosis, intubation, tracheotomy, and other etiologies. All patients were treated at the Department of Respiratory Diseases, Beijing Tian Tan Hospital, Capital Medical University, China, between January 2010 and August 2014. After primary treatment by balloon dilation, cryotherapy, and/or high-frequency needle-knife treatment, paclitaxel was applied to the airway mucosa at the site of stenosis using a newly developed local instillation catheter. The primary outcome measures were the therapeutic efficacy of paclitaxel as adjuvant treatment, and the incidence of complications was observed as well. According to our criteria for evaluating the clinical effects on BCAS, 24 of the 28 cases achieved durable remission, three cases had remission, and one case showed no remission. Thus, the durable remission rate was 85.7%, and the combined effective rate was 96.4%. No differences in outcomes were observed among the different BCAS etiologies (P=0.144), and few complications were observed. Our results indicated that paclitaxel as an adjuvant treatment has greater efficacy than previously reported BCAS treatment methods.

Stroke awareness among inpatient nursing staff at an academic medical center

PubMed Central

Adelman, Eric E.; Meurer, William J.; Nance, Dorinda K.; Kocan, Mary Jo; Maddox, Kate E.; Morgenstern, Lewis B.; Skolarus, Lesli E.

2015-01-01

Background and Purpose Since 10% of strokes occur in hospitalized patients, we sought to evaluate stroke knowledge and predictors of stroke knowledge among inpatient and emergency department nursing staff. Methods Nursing staff completed an on-line stroke survey. The survey queried outcome expectations (the importance of rapid stroke identification), self-efficacy in recognizing stroke, and stroke knowledge (name three stroke warning signs/symptoms). Adequate stroke knowledge was defined as the ability to name two or more stroke warning signs. Logistic regression was used to identify the association between stroke symptom knowledge and staff characteristics (education, clinical experience, and nursing unit), stroke self-efficacy, and outcome expectations. Results A total of 875 respondents (84% response rate) completed the survey and most of the respondents were nurses. More than 85% of respondents correctly reported 2 or more stroke warning signs or symptoms. Greater self-efficacy in identifying stroke symptoms (OR 1.13, 95% CI 1.01–1.27) and higher ratings for the importance of rapid identification of stroke symptoms (OR 1.23, 95% CI 1.002–1.51) were associated with stroke knowledge. Clinical experience, educational experience, nursing unit, and personal knowledge of a stroke patient were not associated with stroke knowledge. Conclusions Stroke outcome expectations and self-efficacy are associated with stroke knowledge and should be included in nursing education about stroke. PMID:24135928

Latinos with obsessive-compulsive disorder: Mental healthcare utilization and inclusion in clinical trials.

PubMed

Wetterneck, Chad T; Little, Tannah E; Rinehart, Kimberly L; Cervantes, Maritza E; Hyde, Emma; Williams, Monnica

2012-04-01

Previous research has documented that ethnic minorities, particularly Latinos, obtain fewer mental health services than Caucasians (Kearney, Draper, & Baron 2005; Sue, Fujino, Hu, Takeuchi, & Zane, 1991). Conceivably, this may be due to a wide array of cultural issues (e.g., negative stigma attached to mental health, and language, socio-economic, and acculturation barriers), symptom disparities across Caucasian and Latino groups, or lack of effective outreach methods by clinicians and researchers. However, research is limited. As a result, Latinos may be insufficiently represented in clinical studies for OCD, making it unclear whether evidence-based treatments demonstrate the same efficacy and effectiveness for Latinos as has been demonstrated for Caucasians. The current study takes an in-depth analysis of 98 efficacy and effectiveness studies for OCD from across the Western hemisphere and reports the rates of Latino inclusion from each sample. Ninety clinical studies in the US and Canada, as well as eight clinical studies in Mexico and Central America were reviewed. Findings showed that only 11 (24%) US and Canadian studies included Latino participants, illustrating an overwhelming underrepresentation of Latinos in clinical studies for OCD. Further explanation of the results and their implications are discussed, along with suggestions for effectively improving access to mental health research and appropriate treatments.

Latinos with obsessive-compulsive disorder: Mental healthcare utilization and inclusion in clinical trials

PubMed Central

Wetterneck, Chad T.; Little, Tannah E.; Rinehart, Kimberly L.; Cervantes, Maritza E.; Hyde, Emma; Williams, Monnica

2014-01-01

Previous research has documented that ethnic minorities, particularly Latinos, obtain fewer mental health services than Caucasians (Kearney, Draper, & Baron 2005; Sue, Fujino, Hu, Takeuchi, & Zane, 1991). Conceivably, this may be due to a wide array of cultural issues (e.g., negative stigma attached to mental health, and language, socio-economic, and acculturation barriers), symptom disparities across Caucasian and Latino groups, or lack of effective outreach methods by clinicians and researchers. However, research is limited. As a result, Latinos may be insufficiently represented in clinical studies for OCD, making it unclear whether evidence-based treatments demonstrate the same efficacy and effectiveness for Latinos as has been demonstrated for Caucasians. The current study takes an in-depth analysis of 98 efficacy and effectiveness studies for OCD from across the Western hemisphere and reports the rates of Latino inclusion from each sample. Ninety clinical studies in the US and Canada, as well as eight clinical studies in Mexico and Central America were reviewed. Findings showed that only 11 (24%) US and Canadian studies included Latino participants, illustrating an overwhelming underrepresentation of Latinos in clinical studies for OCD. Further explanation of the results and their implications are discussed, along with suggestions for effectively improving access to mental health research and appropriate treatments. PMID:29057210

An emerging playbook for antibody-drug conjugates: lessons from the laboratory and clinic suggest a strategy for improving efficacy and safety.

PubMed

Drake, Penelope M; Rabuka, David

2015-10-01

Antibody-drug conjugates (ADCs) have become de rigueur for pharmaceutical oncology drug development pipelines. There are more than 40 ADCs undergoing clinical trials and many more in preclinical development. The field has rushed to follow the initial successes of Kadcyla™ and Adcetris™, and moved forward with new targets without much pause for optimization. In some respects, the ADC space has become divided into the clinical realm-where the proven technologies continue to represent the bulk of clinical candidates with a few exceptions-and the research realm-where innovations in conjugation chemistry and linker technologies have suggested that there is much room for improvement in the conventional methods. Now, two and four years after the approvals of Kadcyla™ and Adcetris™, respectively, consensus may at last be building that these two drugs rely on rather unique target antigens that enable their success. It is becoming increasingly clear that future target antigens will require additional innovative approaches. Next-generation ADCs have begun to move out of the lab and into the clinic, where there is a pressing need for continued innovation to overcome the twin challenges of safety and efficacy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Efficacy and safety of biosimilar insulins compared to their reference products: A systematic review.

PubMed

Tieu, Carolyn; Lucas, Eleanor J; DePaola, Mindi; Rosman, Lori; Alexander, G Caleb

2018-01-01

For nearly a century, no generic form of insulin has been available in the United States. However, the first biosimilar insulin, Basaglar, was approved by the U.S. Food and Drug Administration in 2015, and subsequently Admelog and Lusduna in 2017. To summarize the scientific evidence comparing the safety, efficacy, pharmacokinetics, and pharmacodynamics of biosimilar and reference insulin products. We conducted a systematic review using PubMed, Cochrane, Embase, Latin America and Caribbean Health Sciences, South Asian Database of Controlled Clinical Trials, and IndiaMED from their inception through January 14, 2018. We included randomized controlled trials (RCTs) comparing safety, clinical efficacy, pharmacokinetics and pharmacodynamics of any biosimilar insulin with a reference product in adults regardless of sample size and location. Two researchers independently reviewed all titles, abstracts and text; extracted data; and performed quality assessments. Efficacy, safety, pharmacokinetics, and pharmacodynamics of biosimilar and reference insulin products. Of 6945 articles screened, 11 studies were included in the data synthesis. LY2963016, Basalog, Basalin, and MK-1293 were compared to Lantus while SAR342434 was compared to Humalog. Three trials enrolled healthy volunteers, five enrolled type 1 diabetics, and two enrolled type 2 diabetics. One study enrolled both healthy and type 1 diabetics. Of the eleven studies, six examined pharmacokinetic and/or pharmacodynamic parameters and five examined clinical efficacy and immunogenicity. All studies included adverse events. All PK and/or PD studies showed that comparable parameters of biosimilar and reference products were within the pre-specified equivalence margins. Clinical studies suggested similar clinical efficacy and immunogenicity. Adverse events were similar between the groups across all studies. Few published studies have compared biosimilar and reference insulins, though those that did suggest that the biosimilars have comparable safety and clinical efficacy as its reference product.

Clinical efficacy of open reduction and semirigid internal fixation in management of displaced pediatric mandibular fractures: a series of 10 cases and surgical guidelines.

PubMed

Joshi, Samir; Kshirsagar, Rajesh; Mishra, Akshay; Shah, Rahul

2015-01-01

To evaluate the efficacy of open reduction and semirigid internal fixation in the management of displaced pediatric mandibular fractures. Ten patients with displaced mandibular fractures treated with 1.5 mm four holed titanium mini-plate and 4 mm screws which were removed within four month after surgery. All cases showed satisfactory bone healing without any growth disturbance. Open reduction and rigid internal fixation (ORIF) with 1.5 mm titanium mini- plates and 4 mm screws is a reliable and safe method in treatment of displaced paediatric mandibular fractures.

Predictive validity of behavioural animal models for chronic pain

PubMed Central

Berge, Odd-Geir

2011-01-01

Rodent models of chronic pain may elucidate pathophysiological mechanisms and identify potential drug targets, but whether they predict clinical efficacy of novel compounds is controversial. Several potential analgesics have failed in clinical trials, in spite of strong animal modelling support for efficacy, but there are also examples of successful modelling. Significant differences in how methods are implemented and results are reported means that a literature-based comparison between preclinical data and clinical trials will not reveal whether a particular model is generally predictive. Limited reports on negative outcomes prevents reliable estimate of specificity of any model. Animal models tend to be validated with standard analgesics and may be biased towards tractable pain mechanisms. But preclinical publications rarely contain drug exposure data, and drugs are usually given in high doses and as a single administration, which may lead to drug distribution and exposure deviating significantly from clinical conditions. The greatest challenge for predictive modelling is, however, the heterogeneity of the target patient populations, in terms of both symptoms and pharmacology, probably reflecting differences in pathophysiology. In well-controlled clinical trials, a majority of patients shows less than 50% reduction in pain. A model that responds well to current analgesics should therefore predict efficacy only in a subset of patients within a diagnostic group. It follows that successful translation requires several models for each indication, reflecting critical pathophysiological processes, combined with data linking exposure levels with effect on target. LINKED ARTICLES This article is part of a themed issue on Translational Neuropharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.164.issue-4 PMID:21371010

Novel ocular antihypertensive compounds in clinical trials

PubMed Central

Chen, June; Runyan, Stephen A; Robinson, Michael R

2011-01-01

Introduction: Glaucoma is a multifactorial disease characterized by progressive optic nerve injury and visual field defects. Elevated intraocular pressure (IOP) is the most widely recognized risk factor for the onset and progression of open-angle glaucoma, and IOP-lowering medications comprise the primary treatment strategy. IOP elevation in glaucoma is associated with diminished or obstructed aqueous humor outflow. Pharmacotherapy reduces IOP by suppressing aqueous inflow and/or increasing aqueous outflow. Purpose: This review focuses on novel non-FDA approved ocular antihypertensive compounds being investigated for IOP reduction in ocular hypertensive and glaucoma patients in active clinical trials within approximately the past 2 years. Methods: The mode of IOP reduction, pharmacology, efficacy, and safety of these new agents were assessed. Relevant drug efficacy and safety trials were identified from searches of various scientific literature databases and clinical trial registries. Compounds with no specified drug class, insufficient background information, reformulations, and fixed-combinations of marketed drugs were not considered. Results: The investigational agents identified comprise those that act on the same targets of established drug classes approved by the FDA (ie, prostaglandin analogs and β-adrenergic blockers) as well as agents belonging to novel drug classes with unique mechanisms of action. Novel targets and compounds evaluated in clinical trials include an actin polymerization inhibitor (ie, latrunculin), Rho-associated protein kinase inhibitors, adenosine receptor analogs, an angiotensin II type 1 receptor antagonist, cannabinoid receptor agonists, and a serotonin receptor antagonist. Conclusion: The clinical value of novel compounds for the treatment of glaucoma will depend ultimately on demonstrating favorable efficacy and benefit-to-risk ratios relative to currently approved prostaglandin analogs and β-blockers and/or having complementary modes of action. PMID:21629573

Efficacy and Safety of Adalimumab in Moderately to Severely Active Cases of Ulcerative Colitis: A Meta-Analysis of Published Placebo-Controlled Trials

PubMed Central

Zhang, Zong Mei; Li, Wei; Jiang, Xue Liang

2016-01-01

Background/Aims To evaluate the efficacy and safety of adalimumab (ADA) in moderately to severely active ulcerative colitis (UC) patients who are unresponsive to traditional therapy. Methods Electronic databases, including the PubMed, Embase, and Cochrane databases, were searched to April 20, 2014. UC-related randomized controlled trials (RCTs) that compared ADA with placebo were eligible. Review Manager 5.1 was used for data analysis. Results This meta-analysis included three RCTs. ADA was considerably more effective compared with a placebo, and it increased the ratio of patients with clinical remission, clinical responses, mucosal healing and inflammatory bowel disease questionnaire responses in the induction and maintenance phases (p<0.05), as well as patients with steroid-free remission (p<0.05) during the maintenance phase. Clinical remission was achieved in a greater number of UC cases in the ADA 160/80/40 mg groups (0/2/4 week, every other week) compared with the placebo group at week 8 (p=0.006) and week 52 (p=0.0002), whereas the week 8 clinical remission rate was equivalent between the ADA 80/40 mg groups and the placebo group. Among the patients who received immunomodulators (IMM) at baseline, ADA was superior to the placebo in terms of inducing clinical remission (p=0.01). Between-group differences were not observed in terms of serious adverse events (p=0.61). Conclusions ADA, particularly at doses of 160/80/40 mg (0/2/4 week, every other week), is effective and safe in patients with moderate-to-severe UC who are unresponsive to traditional treatment. Concomitant IMM therapy may improve the short-term therapeutic efficacy of ADA. PMID:26780088

Clinical and Antiviral Efficacy of an Ophthalmic Formulation of Dexamethasone Povidone-Iodine in a Rabbit Model of Adenoviral Keratoconjunctivitis

PubMed Central

Clement, Christian; Capriotti, Joseph A.; Kumar, Manish; Hobden, Jeffery A.; Foster, Timothy P.; Bhattacharjee, Partha S.; Thompson, Hilary W.; Mahmud, Rashed; Liang, Bo

2011-01-01

Purpose. To determine the efficacy of a new formulation of topical dexamethasone 0.1%/povidone-iodine 0.4% (FST-100) in reducing clinical symptoms and infectious viral titers in a rabbit model of adenoviral keratoconjunctivitis. Methods. Rabbit corneas were inoculated bilaterally with 2 × 106 plaque-forming-units (PFU) of adenovirus type 5 (Ad5) after corneal scarification. Animals were randomized 1:1:1:1 (five rabbits per group) to FST-100, 0.5% cidofovir, tobramycin/dexamethasone (Tobradex; Alcon Laboratories, Fort Worth, TX) ophthalmic suspension, and balanced salt solution (BSS; Alcon Laboratories). Treatment began 12 hours after viral inoculation and continued for 7 consecutive days. The eyes were clinically scored daily for scleral inflammation (injection), ocular neovascularization, eyelid inflammation (redness), friability of vasculature, inflammatory discharge (pus), and epiphora (excessive tearing). Eye swabs were collected daily before treatment for the duration of the study. Virus was eluted from the swabs and PFU determined by titration on human A549 cells, according to standard procedures. Results. The FST-100 treatment resulted in significantly lower clinical scores (P < 0.05) than did the other treatments. The 0.5% cidofovir exhibited the most ocular toxicity compared with FST-100, tobramycin/dexamethasone, and balanced salt solution treatments. FST-100 and 0.5% cidofovir significantly (P < 0.05) reduced viral titers compared with tobramycin/dexamethasone or balanced salt solution. Conclusions. FST-100 was the most efficacious in minimizing the clinical symptoms of adenovirus infection in rabbit eyes. FST-100 and 0.5% cidofovir were both equally effective in reducing viral titers and decreasing the duration of viral shedding. By providing symptomatic relief in addition to reducing infectious virus titers, FST-100 should be a valuable addition to treatment of epidemic adenoviral keratoconjunctivitis. PMID:20702820

Clinical pharmacology of analgesics assessed with human experimental pain models: bridging basic and clinical research

PubMed Central

Oertel, Bruno Georg; Lötsch, Jörn

2013-01-01

The medical impact of pain is such that much effort is being applied to develop novel analgesic drugs directed towards new targets and to investigate the analgesic efficacy of known drugs. Ongoing research requires cost-saving tools to translate basic science knowledge into clinically effective analgesic compounds. In this review we have re-examined the prediction of clinical analgesia by human experimental pain models as a basis for model selection in phase I studies. The overall prediction of analgesic efficacy or failure of a drug correlated well between experimental and clinical settings. However, correct model selection requires more detailed information about which model predicts a particular clinical pain condition. We hypothesized that if an analgesic drug was effective in an experimental pain model and also a specific clinical pain condition, then that model might be predictive for that particular condition and should be selected for development as an analgesic for that condition. The validity of the prediction increases with an increase in the numbers of analgesic drug classes for which this agreement was shown. From available evidence, only five clinical pain conditions were correctly predicted by seven different pain models for at least three different drugs. Most of these models combine a sensitization method. The analysis also identified several models with low impact with respect to their clinical translation. Thus, the presently identified agreements and non-agreements between analgesic effects on experimental and on clinical pain may serve as a solid basis to identify complex sets of human pain models that bridge basic science with clinical pain research. PMID:23082949

Efficacy of 8- and 4-Session Mindfulness-Based Interventions in a Non-clinical Population: A Controlled Study.

PubMed

Demarzo, Marcelo; Montero-Marin, Jesus; Puebla-Guedea, Marta; Navarro-Gil, Mayte; Herrera-Mercadal, Paola; Moreno-González, Sergio; Calvo-Carrión, Sandra; Bafaluy-Franch, Laura; Garcia-Campayo, Javier

2017-01-01

Background: Many attempts have been made to abbreviate mindfulness programmes in order to make them more accessible for general and clinical populations while maintaining their therapeutic components and efficacy. The aim of this study was to assess the efficacy of an 8-week mindfulness-based intervention (MBI) programme and a 4-week abbreviated version for the improvement of well-being in a non-clinical population. Method: A quasi-experimental, controlled, pilot study was conducted with pre-post and 6-month follow-up measurements and three study conditions (8- and 4-session MBI programmes and a matched no-treatment control group, with a sample of 48, 46, and 47 participants in each condition, respectively). Undergraduate students were recruited, and mindfulness, positive and negative affect, self-compassion, resilience, anxiety, and depression were assessed. Mixed-effects multi-level analyses for repeated measures were performed. Results: The intervention groups showed significant improvements compared to controls in mindfulness and positive affect at the 2- and 6-month follow-ups, with no differences between 8- vs. 4-session programmes. The only difference between the abbreviated MBI vs. the standard MBI was found in self-kindness at 6 months, favoring the standard MBI. There were marginal differences in anxiety between the controls vs. the abbreviated MBI, but there were differences between the controls vs. the standard MBI at 2- and 6-months, with higher levels in the controls. There were no differences in depression between the controls vs. the abbreviated MBI, but differences were found between the controls vs. the standard MBI at 2- and 6-months, favoring the standard MBI. There were no differences with regard to negative affect and resilience. Conclusion: To our knowledge, this is the first study to directly investigate the efficacy of a standard 8-week MBI and a 4-week abbreviated protocol in the same population. Based on our findings, both programmes performed better than controls, with similar effect size (ES). The efficacy of abbreviated mindfulness programmes may be similar to that of a standard MBI programme, making them potentially more accessible for a larger number of populations. Nevertheless, further studies with more powerful designs to compare the non-inferiority of the abbreviated protocol and addressing clinical populations are warranted. Clinical Trials.gov Registration ID: NCT02643927.

The Clinical Efficacy and Safety of the Sahastara Remedy versus Diclofenac in the Treatment of Osteoarthritis of the Knee: A Double-Blind, Randomized, and Controlled Trial

PubMed Central

Pinsornsak, Piya; Kanokkangsadal, Puritat; Itharat, Arunporn

2015-01-01

Introduction. The Sahastara (SHT) remedy is a Thai traditional medicine that has been acknowledged in the Thai National List of Essential Medicine and has been used as an alternative medicine to treat knee osteoarthritis. Although SHT remedies have been used in Thai traditional medical practices for a long period of time, there are few reports on their clinical trials. Aim of the Study. To investigate the clinical efficacy and safety of the SHT remedy in treating OA of the knee when compared to diclofenac. Methods. A phase 2, double-blind, randomized, and controlled trial study with a purpose to determine the clinical efficacy and safety of SHT in comparison with diclofenac for the treatment of knee osteoarthritis. Sixty-six patients, ages between 45 and 80 years of age, were randomly allocated into 2 groups. The SHT group received 1,000 mg of SHT powdered capsules 3 times per day, orally before meals, while another group received 25 mg of diclofenac sodium capsules 3 times a day, orally after meals for 28 days. All patients were followed up at 14 and 28 days for the evaluation of the efficacy and safety by using clinical examinations, blood tests, a visual analogue scale (VAS) for pain, and the 100-meter walktime test. Improvement on the quality of life was also assessed by the WOMAC index. Results. There were 31 and 30 patients in SHT and diclofenac groups, respectively, who had completed the study. Both medications have shown to significantly reduce the VAS for pain, and significantly improve the 100-meter walktime test and the WOMAC index score. However, there were no differences in the efficacy between the two groups. The blood chemistry showed no toxicity on renal and/or liver functions after taking SHT for 28 days but the patients who took diclofenac showed significant increases in their AST, ALT, and ALP. Systolic and diastolic blood pressure slightly increased in the diclofenac group but the SHT group did not effect on blood pressure. Conclusions. The SHT remedy is similar to diclofenac in all evaluating symptoms of OA knee. However, the SHT remedy has shown to be a good alternative treatment for OA knee with less systemic side effects when it was compared with diclofenac. PMID:25784944

Efficacy of 8- and 4-Session Mindfulness-Based Interventions in a Non-clinical Population: A Controlled Study

PubMed Central

Demarzo, Marcelo; Montero-Marin, Jesus; Puebla-Guedea, Marta; Navarro-Gil, Mayte; Herrera-Mercadal, Paola; Moreno-González, Sergio; Calvo-Carrión, Sandra; Bafaluy-Franch, Laura; Garcia-Campayo, Javier

2017-01-01

Background: Many attempts have been made to abbreviate mindfulness programmes in order to make them more accessible for general and clinical populations while maintaining their therapeutic components and efficacy. The aim of this study was to assess the efficacy of an 8-week mindfulness-based intervention (MBI) programme and a 4-week abbreviated version for the improvement of well-being in a non-clinical population. Method: A quasi-experimental, controlled, pilot study was conducted with pre-post and 6-month follow-up measurements and three study conditions (8- and 4-session MBI programmes and a matched no-treatment control group, with a sample of 48, 46, and 47 participants in each condition, respectively). Undergraduate students were recruited, and mindfulness, positive and negative affect, self-compassion, resilience, anxiety, and depression were assessed. Mixed-effects multi-level analyses for repeated measures were performed. Results: The intervention groups showed significant improvements compared to controls in mindfulness and positive affect at the 2- and 6-month follow-ups, with no differences between 8- vs. 4-session programmes. The only difference between the abbreviated MBI vs. the standard MBI was found in self-kindness at 6 months, favoring the standard MBI. There were marginal differences in anxiety between the controls vs. the abbreviated MBI, but there were differences between the controls vs. the standard MBI at 2- and 6-months, with higher levels in the controls. There were no differences in depression between the controls vs. the abbreviated MBI, but differences were found between the controls vs. the standard MBI at 2- and 6-months, favoring the standard MBI. There were no differences with regard to negative affect and resilience. Conclusion: To our knowledge, this is the first study to directly investigate the efficacy of a standard 8-week MBI and a 4-week abbreviated protocol in the same population. Based on our findings, both programmes performed better than controls, with similar effect size (ES). The efficacy of abbreviated mindfulness programmes may be similar to that of a standard MBI programme, making them potentially more accessible for a larger number of populations. Nevertheless, further studies with more powerful designs to compare the non-inferiority of the abbreviated protocol and addressing clinical populations are warranted. Clinical Trials.gov Registration ID: NCT02643927 PMID:28848465

Role of self-efficacy and anxiety among pre-clinically disabled older adults when using compensatory strategies to complete daily tasks

PubMed Central

Higgins, Torrance J.; Janelle, Christopher M.; Naugle, Kelly M.; Knaggs, Jeffrey; Hoover, Brian M.; Marsiske, Michael; Manini, Todd M.

2012-01-01

Classic developmental theory suggests that aging is associated with using compensatory strategies to prolong independence. While compensatory strategies are typically considered positive adaptations, they also signify an early phase in the disablement process — commonly known as pre-clinical disability. To build a better understanding of psychological constructs related to these early signs of disability, we examined the contribution of self-efficacy and state anxiety on using compensatory strategies among pre-clinically disabled older adults. Compensatory strategies were observed during performance of daily activities in 257 pre-clinically disabled older adults (67.6 ± 7.04), and self-efficacy and state anxiety were evaluated prior to performing each task. In univariate models, lower self-efficacy and higher anxiety were associated with more compensation (Spearman correlations: 0.15-0.48, p < 0.05). Multivariate logistic regression indicated that low self-efficacy [Odds Ratio (OR): 1.70; 95% Confidence Interval (CI): 1.40-2.08) and high anxiety (OR: 1.34; 95% CI: 1.10-1.63) were positively associated with using ≥ 6 compensatory strategies – a level signifying substantial compensation. When considered jointly with self-efficacy, the association with anxiety was reversed— higher anxiety demonstrated a lower likelihood of using compensation (OR: 0.70-0.73; 95% CI: 0.50-0.99). The addition of self-efficacy might remove the self-defeating cognitions characterizing anxiety allowing the remaining arousal component to appear beneficial. In conclusion, lower self-efficacy and higher anxiety are associated with using compensation to complete daily tasks among pre-clinically disabled older adults. Such psychological constructs may contribute to the use of compensatory strategies and represent future intervention targets to help reduce early signs of disability. PMID:22770713

Mathematical modeling of efficacy and safety for anticancer drugs clinical development.

PubMed

Lavezzi, Silvia Maria; Borella, Elisa; Carrara, Letizia; De Nicolao, Giuseppe; Magni, Paolo; Poggesi, Italo

2018-01-01

Drug attrition in oncology clinical development is higher than in other therapeutic areas. In this context, pharmacometric modeling represents a useful tool to explore drug efficacy in earlier phases of clinical development, anticipating overall survival using quantitative model-based metrics. Furthermore, modeling approaches can be used to characterize earlier the safety and tolerability profile of drug candidates, and, thus, the risk-benefit ratio and the therapeutic index, supporting the design of optimal treatment regimens and accelerating the whole process of clinical drug development. Areas covered: Herein, the most relevant mathematical models used in clinical anticancer drug development during the last decade are described. Less recent models were considered in the review if they represent a standard for the analysis of certain types of efficacy or safety measures. Expert opinion: Several mathematical models have been proposed to predict overall survival from earlier endpoints and validate their surrogacy in demonstrating drug efficacy in place of overall survival. An increasing number of mathematical models have also been developed to describe the safety findings. Modeling has been extensively used in anticancer drug development to individualize dosing strategies based on patient characteristics, and design optimal dosing regimens balancing efficacy and safety.

The evolution and rise of stereotactic body radiotherapy (SBRT) for spinal metastases.

PubMed

Vellayappan, Balamurugan A; Chao, Samuel T; Foote, Matthew; Guckenberger, Matthias; Redmond, Kristin J; Chang, Eric L; Mayr, Nina A; Sahgal, Arjun; Lo, Simon S

2018-06-25

Owing to improvements in clinical care and systemic therapy, more patients are being diagnosed with, and living longer with, spinal metastases (SM). In parallel, tremendous technological progress has been made in the field of radiation oncology. Advances in both software and hardware are able to integrate three- (and four-) dimensional body imaging with spatially accurate treatment delivery methods. This is able to improve the efficacy, shorten the overall treatment schedule and potentially reduce treatment-related toxicity. Areas covered: In this review, we will look at the progress made by stereotactic body radiotherapy (SBRT) in the management of SM. We will review the technological factors which have enabled the widespread use of SBRT. The efficacy of SBRT, in various clinical scenarios, and associated toxicities will be reviewed. Lastly, we will discuss about patient selection, and provide a five-year roadmap. Expert commentary: Spine SBRT is a safe and efficacious treatment option. Practice guidelines recommend the use of SBRT in oligo-metastatic patients especially those with radio-resistant cancer types, and in scenarios involving re-irradiation. SBRT offers patients dose-intensification over a short schedule which may allow less time off systemic therapy. The results of the phase III trials are eagerly awaited.

[Therapeutic efficacy of levofloxacin against a model of replicable Legionella pneumophila lung infection in DBA/2 mice].

PubMed

Kashimoto, Yoshinori; Kurosaka, Yuichi; Karibe, Yukie; Uoyama, Saori; Fujikawa, Katsuko; Namba, Kenji; Otani, Tsuyoshi; Yamaguchi, Keizo

2009-10-01

The in vitro and in vivo antibacterial activities of levofloxacin (LVFX), a quinolone antibacterial, against clinically isolated Legionella pneumophila were investigated in comparison with those of existing antimicrobial agents approved for legionnaires disease. The minimum inhibitory concentrations (MICs) of the agents against 42 strains of L. pneumophila isolated in Japan were determined using agar dilution methods with buffered starch yeast extract agar. MIC90 of LVFX was 0.03 microg/ml and this activity was similar to ciprofloxacin and pazufloxacin, and higher than telithromycin and minocycline. Therapeutic efficacy of LVFX was studied against a pneumonia model induced by intranasal of L. pneumophila strain suzuki serogoup 1 in DBA/2 mice. Therapeutic doses in mice were selected that would closely match human exposure profile, area under the concentration-time curve (AUC) for a human oral dose of LVFX at 500 mg once a day. LVFX decreased significantly the bacterial burden in the lungs from the next day of commencing treatment. These results, including in vitro antibacterial activity against clinical isolates and therapeutic efficacy of a humanized dosing regimen, provide good evidence to support the use of LVFX at 500 mg once a day for treating patient with legionnaires disease.

How health-related quality of life assessment should be used in advanced colorectal cancer clinical trials.

PubMed

Bonnetain, F; Borg, C; Adams, R R; Ajani, J A; Benson, A; Bleiberg, H; Chibaudel, B; Diaz-Rubio, E; Douillard, J Y; Fuchs, C S; Giantonio, B J; Goldberg, R; Heinemann, V; Koopman, M; Labianca, R; Larsen, A K; Maughan, T; Mitchell, E; Peeters, M; Punt, C J A; Schmoll, H J; Tournigand, C; de Gramont, A

2017-09-01

Traditionally, the efficacy of cancer treatment in patients with advance or metastatic disease in clinical studies has been studied using overall survival and more recently tumor-based end points such as progression-free survival, measurements of response to treatment. However, these seem not to be the relevant clinical end points in current situation if such end points were no validated as surrogate of overall survival to demonstrate the clinical efficacy. Appropriate, meaningful, primary patient-oriented and patient-reported end points that adequately measure the effects of new therapeutic interventions are then crucial for the advancement of clinical research in metastatic colorectal cancer to complement the results of tumor-based end points. Health-related quality of life (HRQoL) is effectively an evaluation of quality of life and its relationship with health over time. HRQoL includes the patient report at least of the way a disease or its treatment affects its physical, emotional and social well-being. Over the past few years, several phase III trials in a variety of solid cancers have assessed the incremental value of HRQoL in addition to the traditional end points of tumor response and survival results. HRQoL could provide not only complementary clinical data to the primary outcomes, but also more precise predictive and prognostic value. This end point is useful for both clinicians and patients in order to achieve the dogma of precision medicine. The present article examines the use of HRQoL in phase III metastatic colorectal cancer clinical trials, outlines the importance of HRQoL assessment methods, analysis, and results presentation. Moreover, it discusses the relevance of including HRQoL as a primary/co-primary end point to support the progression-free survival results and to assess efficacy of treatment in the advanced disease setting. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Earlier Detection of Tumor Treatment Response Using Magnetic Resonance Diffusion Imaging with Oscillating Gradients

PubMed Central

Colvin, Daniel C.; Loveless, Mary E.; Does, Mark D.; Yue, Zou; Yankeelov, Thomas E.; Gore, John C.

2011-01-01

An improved method for detecting early changes in tumors in response to treatment, based on a modification of diffusion-weighted magnetic resonance imaging, has been demonstrated in an animal model. Early detection of therapeutic response in tumors is important both clinically and in pre-clinical assessments of novel treatments. Non-invasive imaging methods that can detect and assess tumor response early in the course of treatment, and before frank changes in tumor morphology are evident, are of considerable interest as potential biomarkers of treatment efficacy. Diffusion-weighted magnetic resonance imaging is sensitive to changes in water diffusion rates in tissues that result from structural variations in the local cellular environment, but conventional methods mainly reflect changes in tissue cellularity and do not convey information specific to micro-structural variations at sub-cellular scales. We implemented a modified imaging technique using oscillating gradients of the magnetic field for evaluating water diffusion rates over very short spatial scales that are more specific for detecting changes in intracellular structure that may precede changes in cellularity. Results from a study of orthotopic 9L gliomas in rat brains indicate that this method can detect changes as early as 24 hours following treatment with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), when conventional approaches do not find significant effects. These studies suggest that diffusion imaging using oscillating gradients may be used to obtain an earlier indication of treatment efficacy than previous magnetic resonance imaging methods. PMID:21190804

LBH589, A Hydroxamic Acid-Derived HDAC Inhibitor, is Neuroprotective in Mouse Models of Huntington’s Disease

PubMed Central

Chopra, Vanita; Quinti, Luisa; Khanna, Prarthana; Paganetti, Paolo; Kuhn, Rainer; Young, Anne B.; Kazantsev, Aleksey G.; Hersch, Steven

2016-01-01

Background: Modulation of gene transcription by HDAC inhibitors has been shown repeatedly to be neuroprotective in cellular, invertebrate, and rodent models of Huntington’s disease (HD). It has been difficult to translate these treatments to the clinic, however, because existing compounds have limited potency or brain bioavailability. Objective: In the present study, we assessed the therapeutic potential of LBH589, an orally bioavailable hydroxamic acid-derived nonselective HDAC inhibitor in mouse models of HD. Method: The efficacy of LBH589 is tested in two HD mouse models using various biochemical, behavioral and neuropathological outcome measures. Results: We show that LBH589 crosses the blood brain barrier; induces histone hyperacetylation and prevents striatal neuronal shrinkage in R6/2 HD mice. In full-length knock-in HD mice LBH589-treatment improves motor performance and reduces neuronal atrophy. Conclusions: Our efficacious results of LBH589 in fragment and full-length mouse models of HD suggest that LBH589 is a promising candidate for clinical assessment in HD patients and provides confirmation that non-selective HDAC inhibitors can be viable clinical candidates. PMID:27983565

Recognizing and managing a deteriorating patient: a randomized controlled trial investigating the effectiveness of clinical simulation in improving clinical performance in undergraduate nursing students.

PubMed

Stayt, Louise Caroline; Merriman, Clair; Ricketts, Barry; Morton, Sean; Simpson, Trevor

2015-11-01

To report the results of a randomized controlled trial which explored the effectiveness of clinical simulation in improving the clinical performance of recognizing and managing an adult deteriorating patient in hospital. There is evidence that final year undergraduate nurses may lack knowledge, clinical skills and situation awareness required to manage a deteriorating patient competently. The effectiveness of clinical simulation as a strategy to teach the skills required to recognize and manage the early signs of deterioration needs to be evaluated. This study was a two centre phase II single, randomized, controlled trial with single blinded assessments. Data were collected in July 2013. Ninety-eight first year nursing students were randomized either into a control group, where they received a traditional lecture, or an intervention group where they received simulation. Participants completed a pre- and postintervention objective structured clinical examination. General Perceived Self Efficacy and Self-Reported Competency scores were measured before and after the intervention. Student satisfaction with teaching was also surveyed. The intervention group performed significantly better in the post-objective structured clinical examination. There was no significant difference in the postintervention General Perceived Self Efficacy and Self-Reported Competency scores between the control and intervention group. The intervention group was significantly more satisfied with their teaching method. Simulation-based education may be an effective educational strategy to teach nurses the skills to effectively recognize and manage a deteriorating patient. © 2015 John Wiley & Sons Ltd.

Infliximab is superior to other biological agents for treatment of active ulcerative colitis: A meta-analysis

PubMed Central

Mei, Wei-Qun; Hu, Hui-Zhen; Liu, Ying; Li, Zhi-Chen; Wang, Wei-Guo

2015-01-01

AIM: To compare the efficacy and safety of biological agents for the treatment of active ulcerative colitis (UC). METHODS: PubMed, MEDLINE, EMBASE and the Cochrane library were searched to screen relevant articles from January 1996 to August 2014. The mixed treatment comparison meta-analysis within a Bayesian framework was performed using WinBUGS14 software. The proportions of patients reaching clinical response, clinical remission and mucosal healing in induction and maintenance phases were analyzed as efficacy indicators. Serious adverse events in maintenance phase were analyzed as safety indicators. RESULTS: The meta-analysis results showed that biological agents achieved better clinical response, clinical remission and mucosal healing than placebo. Indirect comparison indicated that in induction phase, infliximab was more effective than adalimumab in inducing clinical response (OR = 0.41, 95%CI: 0.29-0.57), clinical remission (OR = 0.33, 95%CI: 0.19-0.56) and mucosal healing (OR = 0.33, 95%CI: 0.19-0.56), and golimumab in inducing clinical response (OR = 0.66, 95%CI: 0.39-2.33) and mucosal healing (OR = 2.15, 95%CI: 1.18-4.22). No significant difference was found between placebo and biological agents regarding their safety. CONCLUSION: All biological agents were superior to placebo for UC treatment in both induction and maintenance phases with a similar safety profile, and infliximab had a better clinical effect than the other biological agents. PMID:26019471

Impact of peer teaching on nursing students: perceptions of learning environment, self-efficacy, and knowledge.

PubMed

Brannagan, Kim B; Dellinger, Amy; Thomas, Jan; Mitchell, Denise; Lewis-Trabeaux, Shirleen; Dupre, Susan

2013-11-01

Peer teaching has been shown to enhance student learning and levels of self efficacy. The purpose of the current study was to examine the impact of peer-teaching learning experiences on nursing students in roles of tutee and tutor in a clinical lab environment. This study was conducted over a three-semester period at a South Central University that provides baccalaureate nursing education. Over three semesters, 179 first year nursing students and 51 third year nursing students participated in the study. This mixed methods study, through concurrent use of a quantitative intervention design and qualitative survey data, examined differences during three semesters in perceptions of a clinical lab experience, self-efficacy beliefs, and clinical knowledge for two groups: those who received peer teaching-learning in addition to faculty instruction (intervention group) and those who received faculty instruction only (control group). Additionally, peer teachers' perceptions of the peer teaching learning experience were examined. Results indicated positive response from the peer tutors with no statistically significant differences for knowledge acquisition and self-efficacy beliefs between the tutee intervention and control groups. In contrast to previous research, students receiving peer tutoring in conjunction with faculty instruction were statistically more anxious about performing lab skills with their peer tutor than with their instructors. Additionally, some students found instructors' feedback moderately more helpful than their peers and increased gains in knowledge and responsibility for preparation and practice with instructors than with peer tutors. The findings in this study differ from previous research in that the use of peer tutors did not decrease anxiety in first year students, and no differences were found between the intervention and control groups related to self efficacy or cognitive improvement. These findings may indicate the need to better prepare peer tutors, and research should be conducted using more complex skills. Copyright © 2012 Elsevier Ltd. All rights reserved.

Efficacy and safety of metformin or oral contraceptives, or both in polycystic ovary syndrome

PubMed Central

Yang, Young-Mo; Choi, Eun Joo

2015-01-01

Background Polycystic ovary syndrome (PCOS) is an endocrinopathy that affects approximately 10% of reproductive-aged women throughout their lives. Women with PCOS present with heterogeneous symptoms including ovulatory dysfunction, hyperandrogenism, and polycystic ovaries. Therefore, lifelong individualized management should be considered. Pharmacological agents commonly used to manage the symptoms are metformin and oral contraceptive pills. Although these medications have been beneficial in treating PCOS symptoms, their efficacy and safety are still not entirely elucidated. This study aimed to report the efficacy and safety of metformin, oral contraceptives, or their combination in the treatment of PCOS and to define their specific individual roles. Methods A literature search of original studies published in PubMed and Scopus was conducted to identify studies comparing metformin with oral contraceptives or evaluating the combination of both in PCOS. Results Eight clinical trials involving 313 patients were examined in the review. The intervention dosage of metformin ranged from 1,000 to 2,000 mg/d and that of oral contraceptives was ethinylestradiol 35 µg and cyproterone acetate 2 mg. Lower body mass index was observed with regimens including metformin, but increased body mass index was observed in monotherapy with oral contraceptives. Administration of metformin or oral contraceptives, especially as monotherapy, had a negative effect on lipid profiles. In addition, there are still uncertainties surrounding the effects of metformin or oral contraceptives in the management of insulin level, although they improved total testosterone and sex hormone-binding globulin levels. In the included studies, significant side effects due to metformin or oral contraceptives were not reported. Conclusion The clinical trials suggest that metformin or oral contraceptives are at least patient convenient, efficacious, and safe for the treatment of PCOS. However, well-designed, prospective, long-term, large-scale, randomized clinical trials are necessary to elucidate the efficacy and safety of metformin, oral contraceptives, or both in the treatment of PCOS, and to elucidate their individual roles in the treatment of this condition. PMID:26366087

Efficacy of nystatin for the treatment of oral candidiasis: a systematic review and meta-analysis

PubMed Central

Lyu, Xin; Zhao, Chen; Yan, Zhi-min; Hua, Hong

2016-01-01

Objective To systematically review and assess the efficacy, different treatment protocols (formulation, dosage, and duration), and safety of nystatin for treating oral candidiasis. Methods Four electronic databases were searched for trials published in English till July 1, 2015. Randomized controlled trials comparing nystatin with other antifungal therapies or a placebo were included. Clinical and/or mycological cure was the outcome evaluation. A meta-analysis or descriptive study on the efficacy, treatment protocols, and safety of nystatin was conducted. Results The meta-analysis showed that nystatin pastille was significantly superior to placebo in treating denture stomatitis. Nystatin suspension was not superior to fluconazole in treating oral candidiasis in infants, children, or HIV/AIDS patients. The descriptive investigations showed that administration of nystatin suspension and pastilles in combination for 2 weeks might achieve a higher clinical and mycological cure rate, and using the nystatin pastilles alone might have a higher mycological cure rate, when compared with using nystatin suspensions alone. Nystatin pastilles at a dose of 400,000 IU resulted in a significantly higher mycological cure rate than that administrated at a dose of 200,000 IU. Furthermore, treatment with nystatin pastilles for 4 weeks seemed to have better clinical efficacy than treatment for 2 weeks. Descriptive safety assessment showed that poor taste and gastrointestinal adverse reaction are the most common adverse effects of nystatin. Conclusion Nystatin pastille was significantly superior to placebo in treating denture stomatitis, while nystatin suspension was not superior to fluconazole in treating oral candidiasis in infants, children, or HIV/AIDS patients. Indirect evidence from a descriptive study demonstrated that administration of nystatin pastille alone or pastille and suspension in combination is more effective than that of suspension alone; prolonged treatment duration for up to 4 weeks can increase the efficacy of nystatin. More well designed and high quality randomized control studies are needed to confirm these findings. PMID:27042008

The efficacy of fractional carbon dioxide (CO2) laser combined with terbinafine hydrochloride 1% cream for the treatment of onychomycosis.

PubMed

Shi, Jian; Li, Jin; Huang, He; Permatasari, Felicia; Liu, Juan; Xu, Yang; Wu, Di; Zhou, Bing-Rong; Luo, Dan

2017-10-01

Although systemic and topical antifungal agents are widely used to treat onychomycosis, oral medications can cause adverse effects and the efficacy of topical agents is not satisfying. Currently, laser treatment has been studied for its efficacy in the treatment of onychomycosis. Our study was aimed to evaluate the efficacy of fractional carbon dioxide (CO 2 ) laser treatment combined with terbinafine cream for 6 months in the treatment of onychomycosis and to analyze the influencing factors. A total of 30 participants (124 nails) with clinical and mycological diagnosis of onychomycosis received fractional CO 2 laser treatment at 2-week interval combined with terbinafine cream once daily for 6 months. The clinical efficacy rate (CER) was assessed from the percentage of fully normal-appearing nails or nails with ≤5% abnormal appearance, and the mycological clearance rate (MCR) was assessed from the percentage of nails with negative fungal microscopy. The CER was evaluated at 3 time points: at the end of treatment (58.9%), at 1 month after the last treatment (63.5%), and at 3 months after the last treatment (68.5%). The MCRs at 1 month and 3 months after the last treatment were 77.4 and 74.2%, respectively. The evaluation of influencing factors showed significantly higher CER (p < 0.05) in nails of participants with age <50 years, distal lateral subungual onychomycosis (DLSO), superficial white onychomycosis (SWO), nail thickness <2 mm, affected first-to-fourth finger/toenails, Trichophyton rubrum, and Trichophyton mentagrophytes. All participants experienced tolerable mild burning sensation during laser treatment, but there were no other adverse reactions reported. Fractional CO 2 laser treatment combined with terbinafine cream for 6 months was an effective and safe method for the treatment of onychomycosis. There were 5 factors that positively influenced the treatment outcome: age, clinical type of onychomycosis, nail thickness, involved nail, and species of fungus.

[Research progress of needles with knife-edge for carotid cardiac syndrome].

PubMed

Tan, Lingqiong; Zhao, Yanling

2015-04-01

According to topographic anatomy, pathogenesis and by retrieving, summarizing and analyzing literature regarding needle-knife and needles with knife-edge for carotid cardiac syndrome, it is found out that clinical misdiagnosis rate of carotid cardiac syndrome is considerably high. Needle-knife and needles with knife-edge could significantly improve the clinical symptoms of carotid cardiac syndrome, showing characteristic and advantage in treatment, but it is deficient in technique standard and efficacy criteria that should be united and authoritative. Researches regarding pathogenesis of carotid cardiac syndrome are not systematic. Clinical observation regarding long-term efficacy and relapse of needle-knife and needles with knife-edge treatment is rare. It is believed that the awareness on carotid cardiac syndrome should be increased to reduce misdiagnosis; scientific and standardized technique standard and efficacy criteria should be established; systematic and comprehensive researches regarding mechanism of needle-knife and needles with knife-edge for carotid cardiac syndrome should be launched; besides, clinical discussion regarding its long-term efficacy should start to provide a better clinical guideline.

Global measurement of coagulation in plasma from normal and haemophilia dogs using a novel modified thrombin generation test – Demonstrated in vitro and ex vivo

PubMed Central

Madsen, Daniel Elenius; Nichols, Timothy C.; Merricks, Elizabeth P.; Waters, Emily K.; Wiinberg, Bo

2017-01-01

Introduction Canine models of severe haemophilia resemble their human equivalents both regarding clinical bleeding phenotype and response to treatment. Therefore pre-clinical studies in haemophilia dogs have allowed researchers to make valuable translational predictions regarding the potency and efficacy of new anti-haemophilia drugs (AHDs) in humans. To refine in vivo experiments and reduce number of animals, such translational studies are ideally preceded by in vitro prediction of compound efficacy using a plasma based global coagulation method. One such widely used method is the thrombin generation test (TGT). Unfortunately, commercially available TGTs are incapable of distinguishing between normal and haemophilia canine plasma, and therefore in vitro prediction using TGT has so far not been possible in canine plasma material. Aim Establish a modified TGT capable of: 1) distinguishing between normal and haemophilia canine plasma, 2) monitoring correlation between canine plasma levels of coagulation factor VIII (FVIII) and IX (FIX) and thrombin generation, 3) assessing for agreement between compound activity and thrombin generation in ex vivo samples. Methods A modified TGT assay was established where coagulation was triggered using a commercially available activated partial thromboplastin time reagent. Results With the modified TGT a significant difference was observed in thrombin generation between normal and haemophilia canine plasma. A dose dependent thrombin generation was observed when assessing haemophilia A and B plasma spiked with dilution series of FVIII and FIX, respectively. Correlation between FVIII activity and thrombin generation was observed when analyzing samples from haemophilia A dogs dosed with canine FVIII. Limit of detection was 0.1% (v/v) FVIII or FIX. Conclusion A novel modified TGT suitable for monitoring and prediction of replacement therapy efficacy in plasma from haemophilia A and B dogs was established. PMID:28384182

The importance of exercise self-efficacy for clinical outcomes in pulmonary rehabilitation.

PubMed

Selzler, Anne-Marie; Rodgers, Wendy M; Berry, Tanya R; Stickland, Michael K

2016-11-01

Pulmonary rehabilitation (PR) improves functional exercise capacity and health status in people with chronic obstructive pulmonary disease (COPD), although these outcomes are often not maintained following PR. Self-efficacy is a precursor to outcomes achievement, yet few studies have examined the importance of self-efficacy to outcome improvement during PR, or how it develops over time. Further, the contribution of exercise-specific self-efficacy to outcomes in PR is unknown. The aims of this study were to determine (a) whether baseline exercise self-efficacy predicts PR attendance and change in functional exercise capacity and health status over PR, and (b) if exercise self-efficacy changes with PR. Fifty-eight out of 64 patients with COPD completed PR and assessments of exercise self-efficacy (task, coping, scheduling), the 6-minute walk test (6MWT), and St. George's Respiratory Questionnaire (SGRQ) at the beginning and end of PR. Analyses were conducted to predict attendance, and change in 6MWT and SGRQ, while controlling for baseline demographic and clinical indicators. Change in 6MWT, SGRQ, and self-efficacy with PR was also examined. Clinically significant increases in the 6MWT and SGRQ were achieved with PR. Stronger task self-efficacy predicted better attendance, while stronger coping self-efficacy predicted greater 6MWT improvement. No variables predicted SGRQ change. Scheduling self-efficacy significantly improved with PR, whereas task and coping self-efficacy did not. Baseline exercise self-efficacy appears to be a determinant of rehabilitation attendance and functional exercise improvement with PR. Clinicians should evaluate and target exercise self-efficacy to maximize adherence and health outcome improvement with PR. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

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

Prediction of the Efficacy of Antihistamines in Chronic Spontaneous Urticaria Based on Initial Suppression of the Histamine- Induced Wheal.

PubMed

Sánchez, J; Zakzuk, J; Cardona, R

2016-01-01

Antihistamines are the first line of treatment for chronic spontaneous urticaria. However, there is no effective method to predict whether an antihistamine will have a beneficial clinical effect or not. To assess whether the change in histamine-induced wheal and flare measurements 24 hours after administration of antihistamine can predict the efficacy of treatment. We performed a multicenter, triple-blind, randomized study. Patients received a daily oral dose of cetirizine, fexofenadine, bilastine, desloratadine, or ebastine over 8 weeks. After 4 weeks, a higher dose of antihistamine was administered to patients who did not experience a clinical response. A histamine skin prick test was carried out at baseline and 24 hours after the first dose of antihistamine. Disease severity (Urticaria Activity Score [UAS]), response to the histamine skin prick test, and impact on the patient's quality of life (Dermatology Life Quality Index [DLQI]) were determined every 2 weeks. The study population comprised 150 patients (30 per group) and 30 controls. Twenty-four hours after administration of antihistamine, inhibition of the histamine wheal by >75% was significantly associated with better UAS and DLQI scores. The safety and efficacy of the 5 antihistamines were similar. After updosing, rates of disease control (DLQI score <5) increased from 58.7% to 76.7%. Measurement of the histamine-induced wheal can predict which patients will have a strong clinical response to antihistamines but has limited utility for identifying nonresponders. The clinical significance of these data could be relevant in the search for new urticaria treatment regimens.

Relationship between haemagglutination-inhibiting antibody titres and clinical protection against influenza: development and application of a bayesian random-effects model

PubMed Central

2010-01-01

Background Antibodies directed against haemagglutinin, measured by the haemagglutination inhibition (HI) assay are essential to protective immunity against influenza infection. An HI titre of 1:40 is generally accepted to correspond to a 50% reduction in the risk of contracting influenza in a susceptible population, but limited attempts have been made to further quantify the association between HI titre and protective efficacy. Methods We present a model, using a meta-analytical approach, that estimates the level of clinical protection against influenza at any HI titre level. Source data were derived from a systematic literature review that identified 15 studies, representing a total of 5899 adult subjects and 1304 influenza cases with interval-censored information on HI titre. The parameters of the relationship between HI titre and clinical protection were estimated using Bayesian inference with a consideration of random effects and censorship in the available information. Results A significant and positive relationship between HI titre and clinical protection against influenza was observed in all tested models. This relationship was found to be similar irrespective of the type of viral strain (A or B) and the vaccination status of the individuals. Conclusion Although limitations in the data used should not be overlooked, the relationship derived in this analysis provides a means to predict the efficacy of inactivated influenza vaccines when only immunogenicity data are available. This relationship can also be useful for comparing the efficacy of different influenza vaccines based on their immunological profile. PMID:20210985

Comparative efficacy of photo-activated disinfection and calcium hydroxide for disinfection of remaining carious dentin in deep cavities: a clinical study

PubMed Central

Sharma, Sidhartha; Shah, Naseem

2014-01-01

Objectives To comparatively evaluate the efficacy of photo-activated disinfection (PAD), calcium hydroxide (CH) and their combination on the treatment outcome of indirect pulp treatment (IPT). Materials and Methods Institutional ethical clearance and informed consent of the patients were taken. The study was also registered with clinical registry of India. Sixty permanent molars exhibiting deep occlusal carious lesion in patients with the age range of 18 - 22 yr were included. Clinical and radiographic evaluation and set inclusion and exclusion criteria's were followed. Gross caries excavation was accomplished. In group I (n = 20) PAD was applied for sixty seconds. In group II (n = 20), CH was applied to the remaining carious dentin, while in group III (n = 20), PAD application was followed by CH placement. The teeth were permanently restored. They were clinically and radiographically followed-up at 45 day, 6 mon and 12 mon. Relative density of the remaining affected dentin was measured by 'Radiovisiography (RVG) densitometric' analysis. Results Successful outcome with an increase in radiographic grey values were observed in all three groups. However, on inter-group comparison, this change was not significant (p > 0.05). Conclusions PAD and CH both have equal disinfection efficacy in the treatment of deep carious dentin. PAD alone is as effective for treatment of deep carious lesion as calcium hydroxide and hence can be used as an alternative to CH. They can be used independently in IPT, since combining both does not offer any additional therapeutic benefits. PMID:25110643

Preliminary application of hybrid operation in the treatment of carotid artery stenosis in patients with complex ischemic cerebrovascular diseases

PubMed Central

Zhang, Liyong; Xing, Tao; Geng, Fenyang; Du, Lixin; Wang, Jiyue

2014-01-01

Along with the recent development of intraluminal interventional techniques and correlated imaging methods, one-stop hybrid operation has become a new focus in clinical settings. The aim of this study is to discuss the clinical significance of the one-stop hybrid endarterectomy surgery in the treatment of complex ischemic cerebrovascular diseases. In this study, clinical data from 10 patients with complex ischemic cerebrovascular diseases (including multi-vessel severe stenosis of the internal extracranial carotid artery, single vessel series stenosis of the internal extracranial carotid artery, in-stent restenosis, complete occlusion of the common carotid or the internal carotid artery) admitted to Beijing Xuanwu Hospital and Liaocheng Brain Hospital, were retrospectively analyzed. All enrolled subjects underwent three types of hybrid operations. The clinical efficacy of this surgery was subsequently assessed in this clinical trial. The results indicated that no related surgical complications were noted during the perioperative period. Intraoperative and postoperative imaging revealed no signs of vascular stenosis, the blood supply recovered, and clinical symptoms were alleviated. The follow-up lasted for 6 to 12 months. Imaging re-examination showed no evidence of re-stenosis and good blood circulation was present in the recanalized blood vessels. Favorable treatment efficacy was achieved. The intracranial blood supply was significantly improved postoperatively. In conclusion, one-stop hybrid operation plays an important role in treating complex stenosis cerebrovascular diseases. PMID:25197423

Efficacy and safety of tofacitinib following inadequate response to conventional synthetic or biological disease-modifying antirheumatic drugs

PubMed Central

Charles-Schoeman, Christina; Burmester, Gerd; Nash, Peter; Zerbini, Cristiano A F; Soma, Koshika; Kwok, Kenneth; Hendrikx, Thijs; Bananis, Eustratios; Fleischmann, Roy

2016-01-01

Objectives Biological disease-modifying antirheumatic drugs (bDMARDs) have shown diminished clinical response following an inadequate response (IR) to ≥1 previous bDMARD. Here, tofacitinib was compared with placebo in patients with an IR to conventional synthetic DMARDs (csDMARDs; bDMARD-naive) and in patients with an IR to bDMARDs (bDMARD-IR). Methods Data were taken from phase II and phase III studies of tofacitinib in patients with rheumatoid arthritis (RA). Patients received tofacitinib 5 or 10 mg twice daily, or placebo, as monotherapy or with background methotrexate or other csDMARDs. Efficacy endpoints and incidence rates of adverse events (AEs) of special interest were assessed. Results 2812 bDMARD-naive and 705 bDMARD-IR patients were analysed. Baseline demographics and disease characteristics were generally similar between treatment groups within subpopulations. Across subpopulations, improvements in efficacy parameters at month 3 were generally significantly greater for both tofacitinib doses versus placebo. Clinical response was numerically greater with bDMARD-naive versus bDMARD-IR patients (overlapping 95% CIs). Rates of safety events of special interest were generally similar between tofacitinib doses and subpopulations; however, patients receiving glucocorticoids had more serious AEs, discontinuations due to AEs, serious infection events and herpes zoster. Numerically greater clinical responses and incidence rates of AEs of special interest were generally reported for tofacitinib 10 mg twice daily versus tofacitinib 5 mg twice daily (overlapping 95% CIs). Conclusions Tofacitinib demonstrated efficacy in both bDMARD-naive and bDMARD-IR patients with RA. Clinical response to tofacitinib was generally numerically greater in bDMARD-naive than bDMARD-IR patients. The safety profile appeared similar between subpopulations. Trial registration numbers (NCT00413660, NCT0050446, NCT00603512, NCT00687193, NCT00960440, NCT00847613, NCT00814307, NCT00856544, NCT00853385). PMID:26275429

Safety and Efficacy of Memantine in Children with Autism: Randomized, Placebo-Controlled Study and Open-Label Extension

PubMed Central

Findling, Robert L.; Hardan, Antonio Y.; Hendren, Robert L.; Melmed, Raun D.; Kehinde-Nelson, Ola; Hsu, Hai-An; Trugman, Joel M.; Palmer, Robert H.; Graham, Stephen M.; Gage, Allyson T.; Perhach, James L.; Katz, Ephraim

2017-01-01

Abstract Objective: Abnormal glutamatergic neurotransmission is implicated in the pathophysiology of autism spectrum disorder (ASD). In this study, the safety, tolerability, and efficacy of the glutamatergic N-methyl-d-aspartate (NMDA) receptor antagonist memantine (once-daily extended-release [ER]) were investigated in children with autism in a randomized, placebo-controlled, 12 week trial and a 48 week open-label extension. Methods: A total of 121 children 6–12 years of age with Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR)-defined autistic disorder were randomized (1:1) to placebo or memantine ER for 12 weeks; 104 children entered the subsequent extension trial. Maximum memantine doses were determined by body weight and ranged from 3 to 15 mg/day. Results: There was one serious adverse event (SAE) (affective disorder, with memantine) in the 12 week study and one SAE (lobar pneumonia) in the 48 week extension; both were deemed unrelated to treatment. Other AEs were considered mild or moderate and most were deemed not related to treatment. No clinically significant changes occurred in clinical laboratory values, vital signs, or electrocardiogram (ECG). There was no significant between-group difference on the primary efficacy outcome of caregiver/parent ratings on the Social Responsiveness Scale (SRS), although an improvement over baseline at Week 12 was observed in both groups. A trend for improvement at the end of the 48 week extension was observed. No improvements in the active group were observed on any of the secondary end-points, with one communication measure showing significant worsening with memantine compared with placebo (p = 0.02) after 12 weeks. Conclusions: This trial did not demonstrate clinical efficacy of memantine ER in autism; however, the tolerability and safety data were reassuring. Our results could inform future trial design in this population and may facilitate the investigation of memantine ER for other clinical applications. PMID:26978327

Comparing biosimilar SB2 with reference infliximab after 54 weeks of a double-blind trial: clinical, structural and safety results

PubMed Central

Smolen, Josef S.; Choe, Jung-Yoon; Prodanovic, Nenad; Niebrzydowski, Jaroslaw; Staykov, Ivan; Dokoupilova, Eva; Baranauskaite, Asta; Yatsyshyn, Roman; Mekic, Mevludin; Porawska, Wieskawa; Ciferska, Hana; Jedrychowicz-Rosiak, Krystyna; Zielinska, Agnieszka; Choi, Jasmine; Rho, Young Hee

2017-01-01

Abstract Objectives SB2 is a biosimilar to the reference infliximab (INF). Similar efficacy, safety and immunogenicity between SB2 and INF up to 30 weeks were previously reported. This report investigates such clinical similarity up to 54 weeks, including structural joint damage. Methods In this phase III, double-blind, parallel-group, multicentre study, patients with moderate to severe RA despite MTX were randomized (1:1) to receive 3 mg/kg of either SB2 or INF at 0, 2, 6 and every 8 weeks thereafter. Dose escalation by 1.5 mg/kg up to a maximum dose of 7.5 mg/kg was allowed after week 30. Efficacy, safety and immunogenicity were measured at each visit up to week 54. Radiographic damage evaluated by modified total Sharp score was measured at baseline and week 54. Results A total of 584 patients were randomized to receive SB2 (n = 291) or INF (n = 293). The rate of radiographic progression was comparable between SB2 and INF (mean modified total Sharp score difference: SB2, 0.38; INF, 0.37) at 1 year. ACR responses, 28-joint DAS, Clinical Disease Activity Index and Simplified Disease Activity Index were comparable between SB2 and INF up to week 54. The incidence of treatment-emergent adverse events and anti-drug antibodies were comparable between treatment groups. Such comparable trends of efficacy, safety and immunogenicity were consistent from baseline up to 54 weeks. The pattern of dose increment was also comparable between SB2 and INF. Conclusion SB2 maintained similar efficacy, safety and immunogenicity with INF up to 54 weeks in patients with moderate to severe RA. Radiographic progression was comparable at 1 year. Trial registration ClinicalTrials.gov (http://clinicaltrials.gov; NCT01936181) and EudraCT (https://www.clinicaltrialsregister.eu; 2012-005733-37) PMID:28957563

The Efficacy and Clinical Safety of Various Analgesic Combinations for Post-Operative Pain after Third Molar Surgery: A Systematic Review and Meta-Analysis

PubMed Central

Au, Alvin Ho Yeung; Choi, Siu Wai; Cheung, Chi Wai; Leung, Yiu Yan

2015-01-01

Objectives To run a systematic review and meta-analysis of randomized clinical trials aiming to answer the clinical question “which analgesic combination and dosage is potentially the most effective and safe for acute post-operative pain control after third molar surgery?”. Materials and Methods A systematic search of computer databases and journals was performed. The search and the evaluations of articles were performed by 2 independent reviewers in 3 rounds. Randomized clinical trials related to analgesic combinations for acute post-operative pain control after lower third molar surgery that matched the selection criteria were evaluated to enter in the final review. Results Fourteen studies with 3521 subjects, with 10 groups (17 dosages) of analgesic combinations were included in the final review. The analgesic efficacy were presented by the objective pain measurements including sum of pain intensity at 6 hours (SPID6) and total pain relief at 6 hours (TOTPAR6). The SPID6 scores and TOTPAR6 scores of the reported analgesic combinations were ranged from 1.46 to 6.44 and 3.24 – 10.3, respectively. Ibuprofen 400mg with oxycodone HCL 5mg had superior efficacy (SPID6: 6.44, TOTPAR6: 9.31). Nausea was the most common adverse effect, with prevalence ranging from 0-55%. Ibuprofen 200mg with caffeine 100mg or 200mg had a reasonable analgesic effect with fewer side effects. Conclusion This systematic review and meta-analysis may help clinicians in their choices of prescribing an analgesic combination for acute post-operative pain control after lower third molar surgery. It was found in this systematic review Ibuprofen 400mg combined with oxycodone HCL 5mg has superior analgesic efficacy when compared to the other analgesic combinations included in this study. PMID:26053953

Compliant flooring to prevent fall-related injuries in older adults: A scoping review of biomechanical efficacy, clinical effectiveness, cost-effectiveness, and workplace safety

PubMed Central

Jurkowski, Michal P.; Dymarz, Ania C.; Robinovitch, Stephen N.; Feldman, Fabio; Laing, Andrew C.; Mackey, Dawn C.

2017-01-01

Background Compliant flooring, broadly defined as flooring systems or floor coverings with some level of shock absorbency, may reduce the incidence and severity of fall-related injuries in older adults; however, a lack of synthesized evidence may be limiting widespread uptake. Methods Informed by the Arksey and O’Malley framework and guided by a Research Advisory Panel of knowledge users, we conducted a scoping review to answer: what is presented about the biomechanical efficacy, clinical effectiveness, cost-effectiveness, and workplace safety associated with compliant flooring systems that aim to prevent fall-related injuries in healthcare settings? We searched academic and grey literature databases. Any record that discussed a compliant flooring system and at least one of biomechanical efficacy, clinical effectiveness, cost-effectiveness, or workplace safety was eligible for inclusion. Two independent reviewers screened and abstracted records, charted data, and summarized results. Results After screening 3611 titles and abstracts and 166 full-text articles, we included 84 records plus 56 companion (supplementary) reports. Biomechanical efficacy records (n = 50) demonstrate compliant flooring can reduce fall-related impact forces with minimal effects on standing and walking balance. Clinical effectiveness records (n = 20) suggest that compliant flooring may reduce injuries, but may increase risk for falls. Preliminary evidence suggests that compliant flooring may be a cost-effective strategy (n = 12), but may also result in increased physical demands for healthcare workers (n = 17). Conclusions In summary, compliant flooring is a promising strategy for preventing fall-related injuries from a biomechanical perspective. Additional research is warranted to confirm whether compliant flooring (i) prevents fall-related injuries in real-world settings, (ii) is a cost-effective intervention strategy, and (iii) can be installed without negatively impacting workplace safety. Avenues for future research are provided, which will help to determine whether compliant flooring is recommended in healthcare environments. PMID:28166265

Efficacy of commercial formulas in comparison with home-made formulas for enteral feeding: A critical review.

PubMed

Hassan-Ghomi, Majid; Nikooyeh, Bahareh; Motamed, Soudabeh; R Neyestani, Tirang

2017-01-01

Background: In several disease conditions, patients must inevitably be nourished by enteral feeding (EF). Though in many countries, commercial formulas are routinely used for EF, in Iran still home-made formulas are commonly employed as commercial formulas are not covered by insurance. This may pose patients to malnutrition and bring about further costs. The aim of this study was to evaluate the efficacy of EF commercial formulas in comparison with home-made formulas and thus to make further evidence for insurance policy-making Methods: Medline, Cochrane, Embass and Center for Review & Dissemination (CRD) as well as IranDoc and SID databases were searched. Keywords included formula, ICU, and enteral nutrition or tube feeding. No clinical trial study on the efficacy of EF formulas was found. Therefore, the compositions of available formulas and their cost-effectiveness were evaluated based on the clinical guidelines of scientific bodies such as American Society for Parenteral and Enteral Nutrition (ASPEN), European Society for Parenteral and Enteral Nutrition (ESPEN) and relative articles available in PubMed. In addition, the expert opinions were also taken into consideration. Results: Domestic commercial formulas seemed to less merit dietary recommended intakes, i.e. the amount of some nutrients were much higher, and some others were much lower than the recommended values. The amount of several micronutrients including vitamins B1, B6, C, D and K, as well as iron, calcium and magnesium were not sufficient to meet the body needs in most commercial formulas upon receiving 2000 kilocalories and less. Conclusion: Clinical studies on the efficacy of commercial formulas in comparison with home-made formulas are needed. Meanwhile, making suitable conditions for increasing the diversity of artificial nutrition products in the market would help clinical nutritionists to make better choices according to their patients conditions and to reduce the costs, as well.

Clinical efficacy of formula-based bifrontal versus right unilateral electroconvulsive therapy (ECT) in the treatment of major depression among elderly patients: a pragmatic, randomized, assessor-blinded, controlled trial.

PubMed

Bjølseth, Tor Magne; Engedal, Knut; Benth, Jūratė Šaltytė; Dybedal, Gro Strømnes; Gaarden, Torfinn Lødøen; Tanum, Lars

2015-04-01

No prior study has compared the efficacy of bifrontal (BF) vs right unilateral (RUL) electroconvulsive therapy (ECT) by including the subgroup that is most likely to receive it: only elderly patients with major depression (MD). This single-site, randomized, assessor-blinded, controlled trial was conducted from 2009 to 2013. Seventy-three elderly patients with MD, unipolar and bipolar, were treated with a course of formula-based BF ECT or RUL ECT. The 17-item Hamilton Rating Scale for Depression (HRSD17) was used to measure efficacy. Safety was assessed with the Mini Mental State Examination (MMSE). Both electrode placements resulted in highly significant downward trends in symptom severity (all p<0.001), with a non-significant difference between methods (p=0.703). At the end of the ECT course, response rates for the BF and RUL group were 63.9% and 67.6%, respectively. Short-term remission, defined as an HRSD17 score≤7, was achieved in 14 (38.9%) patients in the BF group and 19 (51.4%) patients in the RUL group. Global cognitive function, as measured by the MMSE, did not deteriorate in the two treatment groups. The small number of subjects may have led to reduced power to detect real differences. The MMSE is not sufficient to ascertain the negative effect of ECT on cognition. This study indicates that formula-based BF and RUL ECT are equally efficacious, and that remission rates of formula-based dosing are lower than those previously reported for titrated dosing, in a clinical sample of elderly patients with MD. ClinicalTrials.gov NCT01559324. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Budesonide Multimatrix Is Efficacious for Mesalamine-refractory, Mild to Moderate Ulcerative Colitis: A Randomised, Placebo-controlled Trial

PubMed Central

Cohen, Russell D.; Sandborn, William J.; Lichtenstein, Gary R.; Axler, Jeffrey; Riddell, Robert H.; Zhu, Cindy; Barrett, Andrew C.; Bortey, Enoch; Forbes, William P.

2017-01-01

Abstract Background and Aims: Safety and efficacy of budesonide multimatrix, an oral extended-release second-generation corticosteroid designed for targeted delivery throughout the colon, were examined for induction of remission in patients with mild to moderate ulcerative colitis refractory to baseline mesalamine therapy. Methods: A randomised, double-blind, placebo-controlled, multicentre trial evaluated efficacy and safety of budesonide multimatrix for induction of remission [ulcerative colitis disease activity index score ≥ 4 and ≤ 10] in 510 adults randomised to once-daily oral budesonide multimatrix 9 mg or placebo for 8 weeks. Patients continued baseline treatment with oral mesalamine ≥ 2.4 g/day. Results: Combined clinical and endoscopic remission at Week 8 was achieved by 13.0% and 7.5% of patients receiving budesonide multimatrix [n = 230] or placebo [n = 228], respectively, in the modified intention-to-treat population [p = 0.049]. Clinical remission [ulcerative colitis disease activity index rectal bleeding and stool frequency subscale scores of 0] was similar in both groups [p = 0.70]. More patients receiving budesonide multimatrix vs placebo achieved endoscopic remission [ulcerative colitis disease activity index mucosal appearance subscale score of 0; 20.0% vs 12.3%; p = 0.02] and histological healing [27.0% vs 17.5%; p = 0.02]. Adverse event rates were similar [budesonide multimatrix, 31.8%; placebo, 27.1%]. Mean morning cortisol concentrations decreased at Weeks 2, 4, and 8 with budesonide multimatrix but remained within the normal range. Conclusion: Budesonide multimatrix was safe and efficacious for inducing clinical and endoscopic remission for mild to moderate ulcerative colitis refractory to oral mesalamine therapy. PMID:28333362

Self-efficacy in weight management.

PubMed

Clark, M M; Abrams, D B; Niaura, R S; Eaton, C A; Rossi, J S

1991-10-01

Self-efficacy is an important mediating mechanism in advancing understanding of the treatment of obesity. This study developed and validated the Weight Efficacy Life-Style Questionnaire (WEL), improving on previous studies by the use of clinical populations, cross-validation of the initial factor analysis, exploration of the best fitting theoretical model of self-efficacy, and examination of change in treatment. The resulting 20-item WEL consists of five situational factors: Negative Emotions, Availability, Social Pressure, Physical Discomfort, and Positive Activities. A hierarchical model was found to provide the best fit to the data. Results from two separate clinical treatment studies (total N = 382) show that the WEL is sensitive to changes in global scores as well as to a subset of the five situational factor scores. Treatment programs may be incomplete if they change only a subset of the situational dimensions of self-efficacy. Theoretical and clinical implications are discussed.

Genital herpes simplex virus infections in adults.

PubMed

Mertz, G; Corey, L

1984-02-01

With the decline in prevalence of childhood-acquired oral-labial herpes simplex type 1 infections in some populations and the increasing incidence of genital herpes infections in adults, clinicians are more likely to see patients with severe primary, first-episode genital herpes infections. Complications of these primary infections may include aseptic meningitis and urine retention secondary to sacral radiculopathy or autonomic dysfunction. Presented are the clinical course of first-episode and recurrent infections, complications, diagnostic laboratory methods, and results of controlled clinical trials evaluating the efficacy of topical, intravenous, and oral preparations of acyclovir.

An overview of targeted alpha therapy with 225Actinium and 213Bismuth.

PubMed

Morgenstern, Alfred; Apostolidis, Christos; Kratochwil, Clemens; Sathekge, Mike; Krolicki, Leszek; Bruchertseifer, Frank

2018-05-01

Recent reports of the remarkable therapeutic efficacy of 225Ac-labeled PSMA-617 for therapy of metastatic castration-resistant prostate cancer have underlined the clinical potential of targeted alpha therapy. This review describes methods for the production of 225Ac and its daughter nuclide 213Bi and summarizes the current clinical experience with both alpha emitters with particular focus on recent studies of targeted alpha therapy of bladder cancer, brain tumors, neuroendocrine tumors and prostate cancer. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Container-Based Clinical Solutions for Portable and Reproducible Image Analysis.

PubMed

Matelsky, Jordan; Kiar, Gregory; Johnson, Erik; Rivera, Corban; Toma, Michael; Gray-Roncal, William

2018-05-08

Medical imaging analysis depends on the reproducibility of complex computation. Linux containers enable the abstraction, installation, and configuration of environments so that software can be both distributed in self-contained images and used repeatably by tool consumers. While several initiatives in neuroimaging have adopted approaches for creating and sharing more reliable scientific methods and findings, Linux containers are not yet mainstream in clinical settings. We explore related technologies and their efficacy in this setting, highlight important shortcomings, demonstrate a simple use-case, and endorse the use of Linux containers for medical image analysis.

Deodorant effects of a supercritical hops extract: antibacterial activity against Corynebacterium xerosis and Staphylococcus epidermidis and efficacy testing of a hops/zinc ricinoleate stick in humans through the sensory evaluation of axillary deodorancy.

PubMed

Dumas, Elizabeth R; Michaud, Amy E; Bergeron, Chantal; Lafrance, Jennifer L; Mortillo, Susan; Gafner, Stefan

2009-09-01

There is little scientific evidence to support the efficacy of natural deodorants and therefore, such products may be perceived as inefficacious. The evaluation of the in vitro antibacterial activity of a hop extract and the evaluation of the odor-reducing capacity of a hops/zinc ricinoleate-containing product by a sensory evaluation panel is employed to verify deodorant performance. The goal of this study was to evaluate the in vitro antibacterial activity of a hop extract against Corynebacterium xerosis and Staphylococcus epidermidis and to verify in vivo deodorant performance of a hops/zinc ricinoleate-containing product. The hops extract was evaluated on a culture of an armpit swab from six volunteers. Furthermore, the extract was submitted to a zone of inhibition test and an agar-dilution assay against two major odor-causing bacteria. The clinical evaluation of the finished product was carried out according to a standard method for substantiating deodorant efficacy using trained odor judges for the assessment of axillary malodor (ASTM method E 1207-87 Standard Practice for the Sensory Evaluation of Axillary Deodorancy). The supercritical hops extract showed good antibacterial activities in all three tests. Minimum inhibitory concentration values of 6.25 and 25 mug/mL against C. xerosis and S. aureus, respectively, were obtained in the agar-dilution assay. In the clinical underarm odor-reduction evaluation, the mean malodor score dropped from 6.28 (+/-0.70) to 1.80 (+/-0.71) after 8 h of application. There was still a noticeable effect at both 12 and 24 h after the application, with a score of 1.82 (+/-0.74) and 2.24 (+/-0.77), respectively. The hops extract has good in vitro antibacterial properties and, in combination with zinc ricinoleate in an appropriate base, delivers in vivo odor reduction. The clinical efficacy is likely due to a combination of the base ingredients and the antibacterial actives.

Exploring psychological mechanisms of clinical response to an internet-delivered psychological pain management program.

PubMed

Gandy, M; Karin, E; Jones, M P; McDonald, S; Sharpe, L; Titov, N; Dear, B F

2018-05-13

The evidence for Internet-delivered pain management programs for chronic pain is growing, but there is little empirical understanding of how they effect change. Understanding mechanisms of clinical response to these programs could inform their effective development and delivery. A large sample (n = 396) from a previous randomized controlled trial of a validated internet-delivered psychological pain management program, the Pain Course, was used to examine the influence of three potential psychological mechanisms (pain acceptance, pain self-efficacy, fear of movement/re-injury) on treatment-related change in disability, depression, anxiety and average pain. Analyses involved generalized estimating equation models for clinical outcomes that adjusted for co-occurring change in psychological variables. This was paired with cross-lagged analysis to assess for evidence of causality. Analyses involved two time points, pre-treatment and post-treatment. Changes in pain-acceptance were strongly associated with changes in three (depression, anxiety and average pain) of the four clinical outcomes. Changes in self-efficacy were also strongly associated with two (anxiety and average pain) clinical outcomes. These findings suggest that participants were unlikely to improve in these clinical outcomes without also experiencing increases in their pain self-efficacy and pain acceptance. However, there was no clear evidence from cross-lagged analyses to currently support these psychological variables as direct mechanisms of clinical improvements. There was only statistical evidence to suggest higher levels of self-efficacy moderated improvements in depression. The findings suggest that, while clinical improvements are closely associated with improvements in pain acceptance and self-efficacy, these psychological variables may not drive the treatment effects observed. This study employed robust statistical techniques to assess the psychological mechanisms of an established internet-delivered pain management program. While clinical improvements (e.g. depression, anxiety, pain) were closely associated with improvements in psychological variables (e.g. pain self-efficacy and pain acceptance), these variables do not appear to be treatment mechanisms. © 2018 European Pain Federation - EFIC®.

Intrathecal opioids versus epidural local anesthetics for labor analgesia: a meta-analysis.

PubMed

Bucklin, Brenda A; Chestnut, David H; Hawkins, Joy L

2002-01-01

Some anesthesiologists contend that intrathecal opioid administration has advantages over conventional epidural techniques during labor. Randomized clinical trials comparing analgesia and obstetric outcome using single-injection intrathecal opioids versus epidural local anesthetics suggest that intrathecal opioids provide comparable analgesia with few serious side effects. This meta-analysis compared the analgesic efficacy, side effects, and obstetric outcome of single-injection intrathecal opioid techniques versus epidural local anesthetics in laboring women. Relevant clinical studies were identified using electronic and manual searches of the literature covering the period from 1989 to 2000. Searches used the following descriptors: intrathecal analgesia, spinal opioids, epidural analgesia, epidural local anesthetics, and analgesia for labor. Data were extracted from 7 randomized clinical trials comparing analgesic measures, incidence of motor block, pruritus, nausea, hypotension, mode of delivery, and/or Apgar scores. Combined test results indicated comparable analgesic efficacy 15 to 20 minutes after injection with single-injection intrathecal opioid administration. Intrathecal opioid injections were associated with a greater incidence of pruritus (odds ratio, 14.01; 99% confidence interval, 6.9 to 28.3), but there was no difference in the incidence of nausea or in the method of delivery. Published studies suggest that intrathecal opioids provide comparable early labor analgesia when compared with epidural local anesthetics. Intrathecal opioid administration results in a greater incidence of pruritus. The choice of technique does not appear to affect the method of delivery.

The "Performance of Rotavirus and Oral Polio Vaccines in Developing Countries" (PROVIDE) study: description of methods of an interventional study designed to explore complex biologic problems.

PubMed

Kirkpatrick, Beth D; Colgate, E Ross; Mychaleckyj, Josyf C; Haque, Rashidul; Dickson, Dorothy M; Carmolli, Marya P; Nayak, Uma; Taniuchi, Mami; Naylor, Caitlin; Qadri, Firdausi; Ma, Jennie Z; Alam, Masud; Walsh, Mary Claire; Diehl, Sean A; Petri, William A

2015-04-01

Oral vaccines appear less effective in children in the developing world. Proposed biologic reasons include concurrent enteric infections, malnutrition, breast milk interference, and environmental enteropathy (EE). Rigorous study design and careful data management are essential to begin to understand this complex problem while assuring research subject safety. Herein, we describe the methodology and lessons learned in the PROVIDE study (Dhaka, Bangladesh). A randomized clinical trial platform evaluated the efficacy of delayed-dose oral rotavirus vaccine as well as the benefit of an injectable polio vaccine replacing one dose of oral polio vaccine. This rigorous infrastructure supported the additional examination of hypotheses of vaccine underperformance. Primary and secondary efficacy and immunogenicity measures for rotavirus and polio vaccines were measured, as well as the impact of EE and additional exploratory variables. Methods for the enrollment and 2-year follow-up of a 700 child birth cohort are described, including core laboratory, safety, regulatory, and data management practices. Intense efforts to standardize clinical, laboratory, and data management procedures in a developing world setting provide clinical trials rigor to all outcomes. Although this study infrastructure requires extensive time and effort, it allows optimized safety and confidence in the validity of data gathered in complex, developing country settings. © The American Society of Tropical Medicine and Hygiene.

Reliability of diagnosis and clinical efficacy of visceral osteopathy: a systematic review.

PubMed

Guillaud, Albin; Darbois, Nelly; Monvoisin, Richard; Pinsault, Nicolas

2018-02-17

In 2010, the World Health Organization published benchmarks for training in osteopathy in which osteopathic visceral techniques are included. The purpose of this study was to identify and critically appraise the scientific literature concerning the reliability of diagnosis and the clinical efficacy of techniques used in visceral osteopathy. Databases MEDLINE, OSTMED.DR, the Cochrane Library, Osteopathic Research Web, Google Scholar, Journal of American Osteopathic Association (JAOA) website, International Journal of Osteopathic Medicine (IJOM) website, and the catalog of Académie d'ostéopathie de France website were searched through December 2017. Only inter-rater reliability studies including at least two raters or the intra-rater reliability studies including at least two assessments by the same rater were included. For efficacy studies, only randomized-controlled-trials (RCT) or crossover studies on unhealthy subjects (any condition, duration and outcome) were included. Risk of bias was determined using a modified version of the quality appraisal tool for studies of diagnostic reliability (QAREL) in reliability studies. For the efficacy studies, the Cochrane risk of bias tool was used to assess their methodological design. Two authors performed data extraction and analysis. Eight reliability studies and six efficacy studies were included. The analysis of reliability studies shows that the diagnostic techniques used in visceral osteopathy are unreliable. Regarding efficacy studies, the least biased study shows no significant difference for the main outcome. The main risks of bias found in the included studies were due to the absence of blinding of the examiners, an unsuitable statistical method or an absence of primary study outcome. The results of the systematic review lead us to conclude that well-conducted and sound evidence on the reliability and the efficacy of techniques in visceral osteopathy is absent. The review is registered PROSPERO 12th of December 2016. Registration number is CRD4201605286 .

The impact of a sense of self-efficacy on the level of stress and the ways of coping with difficult situations in Polish nursing students.

PubMed

Bodys-Cupak, Iwona; Majda, Anna; Zalewska-Puchała, Joanna; Kamińska, Alicja

2016-10-01

During their first practical classes at a clinical ward nursing students face a new environment; they take on new roles which is associated with stress and a need to handle it. The aim of this study was to evaluate the effect of a sense of self-efficacy on the level of stress and the ways of coping by Polish nursing students during the first practical classes at a clinical ward. The study included 394 undergraduate subjects studying nursing at two universities in Southern Poland. The study used the method of diagnostic questionnaire and estimation. The research tools included: an original questionnaire, Stress Scale (PSS10), Inventory to measure coping with stress (Mini Cope) and Generalized Self-efficacy Scale (GSES). Data analysis was performed using the IBM Statistical Package for Social Sciences, version 21 for Windows. The verification of differences between variables was performed using χ(2) independence test, Kruskal-Wallis test, and Spearman rank correlation coefficient. The level of significance was accepted at α=0.005. The level of stress and a sense of self-efficacy in majority of tested nursing students were high. The people with low levels of perceived stress had a significantly higher sense of self-efficacy (rhoSpearman=-0.196; p=0.0001). The people with a higher sense of self-efficacy significantly more often used active strategies in stressful situations, such as Active coping (rhoSpearman=0.284; p<0.0001), Planning (rhoSpearman=0.318, p≤0.0001), Positive revaluation (rhoSpearman=0.228, p<0.0001), Acceptance (rhoSpearman=0.188; p=0.0002), Seeking Emotional Support (rhoSpearman=0.123; p=0.0143). A sense of self-efficacy had a significant impact on the level of stress and the ways of coping with difficult situations in nursing students. Copyright © 2016 Elsevier Ltd. All rights reserved.

Audit method suited for DSS in clinical environment.

PubMed

Vicente, Javier

2015-01-01

This chapter presents a novel online method to audit predictive models using a Bayesian perspective. The auditing model has been specifically designed for Decision Support Systems (DSSs) suited for clinical or research environments. Taking as starting point the working diagnosis supplied by the clinician, this method compares and evaluates the predictive skills of those models able to answer to that diagnosis. The approach consists in calculating the posterior odds of a model through the composition of a prior odds, a static odds, and a dynamic odds. To do so, this method estimates the posterior odds from the cases that the comparing models had in common during the design stage and from the cases already viewed by the DSS after deployment in the clinical site. In addition, if an ontology of the classes is available, this method can audit models answering related questions, which offers a reinforcement to the decisions the user already took and gives orientation on further diagnostic steps.The main technical novelty of this approach lies in the design of an audit model adapted to suit the decision workflow of a clinical environment. The audit model allows deciding what is the classifier that best suits each particular case under evaluation and allows the detection of possible misbehaviours due to population differences or data shifts in the clinical site. We show the efficacy of our method for the problem of brain tumor diagnosis with Magnetic Resonance Spectroscopy (MRS).

Preclinical antivenom-efficacy testing reveals potentially disturbing deficiencies of snakebite treatment capability in East Africa

PubMed Central

Oluoch, George O.; Ainsworth, Stuart; Alsolaiss, Jaffer; Bolton, Fiona; Arias, Ana-Silvia; Gutiérrez, José-María; Rowley, Paul; Kalya, Stephen; Ozwara, Hastings; Casewell, Nicholas R.

2017-01-01

Background Antivenom is the treatment of choice for snakebite, which annually kills an estimated 32,000 people in sub-Saharan Africa and leaves approximately 100,000 survivors with permanent physical disabilities that exert a considerable socioeconomic burden. Over the past two decades, the high costs of the most polyspecifically-effective antivenoms have sequentially reduced demand, commercial manufacturing incentives and production volumes that have combined to create a continent-wide vacuum of effective snakebite therapy. This was quickly filled with new, less expensive antivenoms, many of which are of untested efficacy. Some of these successfully marketed antivenoms for Africa are inappropriately manufactured with venoms from non-African snakes and are dangerously ineffective. The uncertain efficacy of available antivenoms exacerbates the complexity of designing intervention measures to reduce the burden of snakebite in sub-Saharan Africa. The objective of this study was to preclinically determine the ability of antivenoms available in Kenya to neutralise the lethal effects of venoms from the most medically important snakes in East Africa. Methods We collected venom samples from the most medically important snakes in East Africa and determined their toxicity in a mouse model. Using a ‘gold standard’ comparison protocol, we preclinically tested the comparative venom-neutralising efficacy of four antivenoms available in Kenya with two antivenoms of clinically-proven efficacy. To explain the variant efficacies of these antivenoms we tested the IgG-venom binding characteristics of each antivenom using in vitro IgG titre, avidity and venom-protein specificity assays. We also measured the IgG concentration of each antivenom. Findings None of the six antivenoms are preclinically effective, at the doses tested, against all of the most medically important snakes of the region. The very limited snake polyspecific efficacy of two locally available antivenoms is of concern. In vitro assays of the abilities of ‘test’ antivenom IgGs to bind venom proteins were not substantially different from that of the ‘gold standard’ antivenoms. The least effective antivenoms had the lowest IgG content/vial. Conclusions Manufacture-stated preclinical efficacy statements guide decision making by physicians and antivenom purchasers in sub-Saharan Africa. This is because of the lack of both clinical data on the efficacy of most of the many antivenoms used to treat patients and independent preclinical assessment. Our preclinical efficacy assessment of antivenoms available in Kenya identifies important limitations for two of the most commonly-used antivenoms, and that no antivenom is preclinically effective against all the regionally important snakes. The potential implication to snakebite treatment is of serious concern in Kenya and elsewhere in sub-Saharan Africa, and underscores the dilemma physicians face, the need for clinical data on antivenom efficacy and the medical and societal value of establishing independent preclinical antivenom-efficacy testing facilities throughout the continent. PMID:29045429

Current Options for the Treatment of Food Allergy

PubMed Central

Lanser, Bruce J.; Wright, Benjamin L.; Orgel, Kelly A.; Vickery, Brian P.; Fleischer, David M.

2016-01-01

Food allergy is increasing in prevalence; as a result, there is intense focus on developing safe and effective therapies. Current methods of specific immunotherapy include oral, sublingual, and epicutaneous, while nonspecific methods that have been investigated include: Chinese herbal medicine, probiotics, and anti-IgE antibodies. Although some studies have demonstrated efficacy in inducing desensitization, questions regarding safety and the potential for achieving immune tolerance remain. Although some of these therapies demonstrate promise, further investigation is required before their incorporation into routine clinical practice. PMID:26456449

Application of ''Earl's Assessment "as", Assessment "for", and Assessment "of" Learning Model'' with Orthopaedic Assessment Clinical Competence

ERIC Educational Resources Information Center

Lafave, Mark R.; Katz, Larry; Vaughn, Norman

2013-01-01

Context: In order to study the efficacy of assessment methods, a theoretical framework of Earl's model of assessment was introduced. Objective: (1) Introduce the predictive learning assessment model (PLAM) as an application of Earl's model of learning; (2) test Earl's model of learning through the use of the Standardized Orthopedic Assessment Tool…

The Acute Effect of Methylphenidate in Brazilian Male Children and Adolescents with ADHD: A Randomized Clinical Trial

ERIC Educational Resources Information Center

Szobot, C. M.; Ketzer, C.; Parente, M. A.; Biederman, J.; Rohde, L. A.

2004-01-01

Objective: To evaluate the acute efficacy of methylphenidate (MPH) in Brazilian male children and adolescents with ADHD. Method: In a 4-day, double-blind, placebo-controlled, randomized, fix dose escalating, parallel-group trial, 36 ADHD children and adolescents were allocated to two groups: MPH (n = 19) and placebo (n = 17). Participants were…

Accounting for interim safety monitoring of an adverse event upon termination of a clinical trial.

PubMed

Dallas, Michael J

2008-01-01

Upon termination of a clinical trial that uses interim evaluations to determine whether the trial can be stopped, a proper statistical analysis must account for the interim evaluations. For example, in a group-sequential design where the efficacy of a treatment regimen is evaluated at interim stages, and the opportunity to stop the trial based on positive efficacy findings exists, the terminal p-value, point estimate, and confidence limits of the outcome of interest must be adjusted to eliminate bias. While it is standard practice to adjust terminal statistical analyses due to opportunities to stop for "positive" findings, adjusting due to opportunities to stop for "negative" findings is also important. Stopping rules for negative findings are particularly useful when monitoring a specific rare serious adverse event in trials designed to show safety with respect to the event. In these settings, establishing conservative stopping rules are appropriate, and therefore accounting for the interim monitoring can have a substantial effect on the final results. Here I present a method to account for interim safety monitoring and illustrate its usefulness. The method is demonstrated to have advantages over methodology that does not account for interim monitoring.

[Hematopoietic reconstitution after transplantation of uncontrolled-rate cryopreservation autologous peripheral blood hematopoietic stem cells using -80 °C mechanical freezer].

PubMed

Liu, Mo; Zhao, Yu; Sun, Jing-Fen; Zhao, Wei; Wang, Li-Li; Yu, Li

2015-02-01

This study was to identify the efficacy of -80°C cryopreservated peripheral blood hemato-poietic stem cell (PBHSC) transplantation for hematopoietic reanstitution in patients. The efficacy of 104 patients underwent autologous peripheral blood hematopoietic stem cell transplantation using uncontrolled-rate freezing and storage at -80°C was evaluated. This cryopreservation method could effectively cryopreserve peripheral blood stem cells. Out of 104 patients only 2 patients died, other patients got hematologic reconstition satisfactorily, the median engrafement times of neutrophils and platelet were 12 and 14 days respectively, the activity of cells after rehabilitation was 94%, the mean recovery rates of CD34(+) cells and mononuclear cells (MNC) were 86% and 80.3% respectively. There were no significant influences on engrafement time in sex, chemotherapy circles and radiotherapy. The engrafement of leukocytes associated with amount of CD34(+) cells. This simple uncontrolled-rate freezing PBHSC at -80°C is safe, effective and economic, and can meet clinical needs. As compared with the classical cryopreservation, there were no significant differences in hematopoietic reconstitution. Therefore, this method worth to popularize and apply in clinic.

The Effectiveness of Aromatherapy for Depressive Symptoms: A Systematic Review.

PubMed

Sánchez-Vidaña, Dalinda Isabel; Ngai, Shirley Pui-Ching; He, Wanjia; Chow, Jason Ka-Wing; Lau, Benson Wui-Man; Tsang, Hector Wing-Hong

2017-01-01

Background . Depression is one of the greatest health concerns affecting 350 million people globally. Aromatherapy is a popular CAM intervention chosen by people with depression. Due to the growing popularity of aromatherapy for alleviating depressive symptoms, in-depth evaluation of the evidence-based clinical efficacy of aromatherapy is urgently needed. Purpose . This systematic review aims to provide an analysis of the clinical evidence on the efficacy of aromatherapy for depressive symptoms on any type of patients. Methods . A systematic database search was carried out using predefined search terms in 5 databases: AMED, CINHAL, CCRCT, MEDLINE, and PsycINFO. Outcome measures included scales measuring depressive symptoms levels. Results . Twelve randomized controlled trials were included and two administration methods for the aromatherapy intervention including inhaled aromatherapy (5 studies) and massage aromatherapy (7 studies) were identified. Seven studies showed improvement in depressive symptoms. Limitations . The quality of half of the studies included is low, and the administration protocols among the studies varied considerably. Different assessment tools were also employed among the studies. Conclusions . Aromatherapy showed potential to be used as an effective therapeutic option for the relief of depressive symptoms in a wide variety of subjects. Particularly, aromatherapy massage showed to have more beneficial effects than inhalation aromatherapy.

Proliferative human cell sources applied as biocomponent in bioartificial livers: a review.

PubMed

Nibourg, Geert A A; Chamuleau, Robert A F M; van Gulik, Thomas M; Hoekstra, Ruurdtje

2012-07-01

Bioartificial livers (BALs) are urgently needed to bridge severe liver failure patients to liver transplantation or liver regeneration. When based on primary hepatocytes, their efficacy has been shown in animal experiments and their safety was confirmed in clinical trials. However, a proliferative human cell source with therapeutic functionality is needed to secure availability and move BAL application forward. This review compares the performance of BALs based on proliferative human biocomponents and primary hepatocytes. This review evaluates relevant studies identified by searching the MEDLINE database until July 2011 and some of our own unpublished data. All the discussed hepatocyte-like biocomponents show deficiencies in their hepatic functionality compared with primary hepatocytes, particularly functions occurring late in liver development. Nonetheless, the HepaRG, HepG2-GS-CYP3A4, and mesenchymal stem cells show efficacy in a statistically well-powered animal model of acute liver failure, when applied in a BAL device. Various methods to gain higher functionality of BALs, including genetic modification, the usage of combinatory cell sources, and improvement of culture methods, have scarcely been applied, but may further pave the path for BAL application. Clinical implementation of a BAL based on a human proliferative biocomponent is still several years away.

Electrolytic ablation as an adjunct to liver resection: Safety and efficacy in patients.

PubMed

Wemyss-Holden, Simon A; Berry, David P; Robertson, Gavin S M; Dennison, Ashley R; De La M Hall, Pauline; Maddern, Guy J

2002-08-01

Electrolytic ablation is a relatively new method for the local destruction of colorectal liver metastases. Experimental work in animal models has shown this method to be safe and efficacious. However, before proceeding to clinical trials it was necessary to confirm these findings in a pilot study of five patients. Five patients with colorectal liver metastases were studied prospectively. Each patient underwent a potentially curative liver resection. One of the metastases to be removed was treated using electrolysis before resection. Each patient was monitored closely during and after electrolysis to determine any morbidity associated with the treatment. Once resected, the metastases were examined histologically for completeness of ablation. All patients tolerated the electrolysis well; there were no deaths or complications related to the treatment. Histological examination of the resected metastases which had been treated electrolytically showed complete tissue destruction with no viable malignant cells remaining at the site of treatment. This pilot study of electrolytic ablation of liver metastases in five patients showed the treatment to be well tolerated and safe. Additionally, it demonstrated total destruction of the malignant tissue at the site of electrolysis. Based on these encouraging results, clinical trials can now begin.

Safety, efficacy and pharmacokinetics of rVIII-SingleChain in children with severe hemophilia A: results of a multicenter clinical trial.

PubMed

Stasyshyn, O; Djambas Khayat, C; Iosava, G; Ong, J; Abdul Karim, F; Fischer, K; Veldman, A; Blackman, N; St Ledger, K; Pabinger, I

2017-04-01

Essentials rVIII-SingleChain is a novel recombinant factor VIII with covalently bonded heavy and light chains. Efficacy, safety and pharmacokinetics were studied in pediatric patients with severe hemophilia A. Across all prophylaxis regimens, the median annualized spontaneous bleeding rate was 0.00. rVIII-SingleChain showed excellent hemostatic efficacy and a favorable safety profile. Background rVIII-SingleChain is a novel B-domain truncated recombinant factor VIII (rFVIII) comprised of covalently bonded FVIII heavy and light chains, demonstrating a high binding affinity to von Willebrand factor. Objectives This phase III study investigated the safety, efficacy and pharmacokinetics of rVIII-SingleChain in previously treated pediatric patients < 12 years of age with severe hemophilia A. Patients/Methods Patients could be assigned to prophylaxis or on-demand therapy by the investigator. For patients assigned to prophylaxis, the treatment regimen and dose were based on the bleeding phenotype. For patients receiving on-demand therapy, dosing was guided by World Federation of Hemophilia recommendations. The primary endpoint was treatment success, defined as a rating of 'excellent' or 'good' on the investigator's clinical assessment of hemostatic efficacy for all treated bleeding events. Results The study enrolled 84 patients (0 to < 6 years, n = 35; ≥ 6 to < 12 years, n = 49); 81 were assigned to prophylaxis and three to an on-demand regimen. Patients accumulated a total of 5239 exposure days (EDs), with 65 participants reaching > 50 EDs. In the 347 bleeds treated and evaluated by the investigator, hemostatic efficacy was rated as excellent or good in 96.3%. The median annualized spontaneous bleeding rate was 0.00 (Q1, Q3: 0.00, 2.20), and the median annualized bleeding rate was 3.69 (Q1, Q3: 0.00, 7.20) across all prophylaxis regimens. No participant developed an inhibitor. Conclusions rVIII-SingleChain is a novel rFVIII molecule showing excellent hemostatic efficacy and a favorable safety profile in a clinical study in children < 12 years of age with severe hemophilia A. © 2017 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

Foot orthoses and physiotherapy in the treatment of patellofemoral pain syndrome: A randomised clinical trial

PubMed Central

Vicenzino, Bill; Collins, Natalie; Crossley, Kay; Beller, Elaine; Darnell, Ross; McPoil, Thomas

2008-01-01

Background Patellofemoral pain syndrome is a highly prevalent musculoskeletal overuse condition that has a significant impact on participation in daily and physical activities. A recent systematic review highlighted the lack of high quality evidence from randomised controlled trials for the conservative management of patellofemoral pain syndrome. Although foot orthoses are a commonly used intervention for patellofemoral pain syndrome, only two pilot studies with short term follow up have been conducted into their clinical efficacy. Methods/design A randomised single-blinded clinical trial will be conducted to investigate the clinical efficacy and cost effectiveness of foot orthoses in the management of patellofemoral pain syndrome. One hundred and seventy-six participants aged 18–40 with anterior or retropatellar knee pain of non-traumatic origin and at least six weeks duration will be recruited from the greater Brisbane area in Queensland, Australia through print, radio and television advertising. Suitable participants will be randomly allocated to receive either foot orthoses, flat insoles, physiotherapy or a combined intervention of foot orthoses and physiotherapy, and will attend six visits with a physiotherapist over a 6 week period. Outcome will be measured at 6, 12 and 52 weeks using primary outcome measures of usual and worst pain visual analogue scale, patient perceived treatment effect, perceived global effect, the Functional Index Questionnaire, and the Anterior Knee Pain Scale. Secondary outcome measures will include the Lower Extremity Functional Scale, McGill Pain Questionnaire, 36-Item Short-Form Health Survey, Hospital Anxiety and Depression Scale, Patient-Specific Functional Scale, Physical Activity Level in the Previous Week, pressure pain threshold and physical measures of step and squat tests. Cost-effectiveness analysis will be based on treatment effectiveness against resource usage recorded in treatment logs and self-reported diaries. Discussion The randomised clinical trial will utilise high-quality methodologies in accordance with CONSORT guidelines, in order to contribute to the limited knowledge base regarding the clinical efficacy of foot orthoses in the management of patellofemoral pain syndrome, and provide practitioners with high-quality evidence upon which to base clinical decisions. Trial registration Australian Clinical Trials Registry ACTRN012605000463673 ClinicalTrials.gov NCT00118521 PMID:18304317

Self-efficacy, self-care behavior, anxiety, and depression in Taiwanese with type 2 diabetes: A cross-sectional survey.

PubMed

Wu, Shu-Fang Vivienne; Huang, Yi-Ching; Lee, Mei-Chen; Wang, Tsae-Jyy; Tung, Heng-Hsin; Wu, Meng-Ping

2013-06-01

The relationships between self-efficacy, self-care behavior, anxiety, and depression for Taiwanese individuals with type 2 diabetes were determined in this study. Depression and anxiety are common symptoms that can contribute toward adverse medical outcomes. A descriptive, cross-sectional, correlational design was used. The sample comprised 201 patients with type 2 diabetes from diabetes outpatient clinics at three teaching hospitals in Taiwan. The results of this study revealed that people with diabetes who had received diabetes health education, regularly made clinical visits, underwent treatment, and did not smoke demonstrated a high self-efficacy score (P < 0.05). Self-efficacy among people with diabetes positively correlated with illness duration (P < 0.05), treatment (P < 0.01), and self-care behavior (P < 0.01). Self-efficacy among people with diabetes negatively correlated with anxiety and depression (P < 0.01). Self-efficacy can be a predictor of anxiety and depression (P < 0.01). This study revealed that enhancing self-efficacy levels might reduce anxiety and depression. Self-efficacy-enhancing programs should be held regularly in clinical practices. Conducting psychological research on diabetes drives policy and healthcare system change. © 2012 Wiley Publishing Asia Pty Ltd.

[Clinical investigation on administration method of gatifloxacin based on PK/PD theory].

PubMed

Mikamo, Hiroshige; Tanaka, Kaori; Watanabe, Kunitomo; Tamaya, Teruhiko; Izumi, Koji

2006-10-01

There have not been sufficient clinical studies based on pharmacokinetics/pharmacodynamics (PK/PD) theory, on which many clinical doctors have recently focused. To consider the optimized administration method based on PK/PD theory for gatifloxacin (GFLX), which was one of the oral fluoroquinolone antibacterial, we influenzae investigated clinical efficacies and adverse events for pelvic inflammatory disease (PID) in giving GFLX daily 400 mg divided twice a day or four times a day. The number of leukocyte and the value of CRP were significantly reduced by chemotherapy in twice a day group, compared with four times a day group. We were able to measure the blood level in 4 cases. The AUC/MIC values for presumption causative bacteria (causative bacteria in both cases: Escherichia coli) in cured patients were 142.28 and 280.16, however, in therapy-failed patients, the AUC/MIC value to presumption causative bacterium were 4.10 (causative bacteria: Prevotella bivia) and 4.35 (causative bacteria: Pseudomonas aeruginosa). These results suggested the importance of the therapeutic method based on PK/PD theory.

Maleimide conjugation markedly enhances the immunogenicity of both human and murine idiotype-KLH vaccines

PubMed Central

Kafi, Kamran; Betting, David J.; Yamada, Reiko E.; Bacica, Michael; Steward, Kristopher K.; Timmerman, John M.

2009-01-01

The collection of epitopes present within the variable regions of the tumor-specific clonal immunoglobulin expressed by B cell lymphomas (idiotype, Id) can serve as a target for active immunotherapy. Traditionally, tumor-derived Id protein is chemically-conjugated to the immunogenic foreign carrier protein keyhole limpet hemocyanin (KLH) using glutaraldehyde to serve as a therapeutic vaccine. While this approach offered promising results for some patients treated in early clinical trials, glutaraldehyde Id-KLH vaccines have failed to induce immune and clinical responses in many vaccinated subjects. We recently described an alternative conjugation method employing maleimide-sulfhydryl chemistry that significantly increased the therapeutic efficacy of Id-KLH vaccines in three different murine B cell lymphoma models, with protection mediated by either CD8+ T cells or antibodies. We now define in detail the methods and parameters critical for enhancing the in vivo immunogenicity of human as well as murine Id-KLH conjugate vaccines. Optimal conditions for Id sulfhydryl pre-reduction were determined, and maleimide Id-KLH conjugates maintained stability and potency even after prolonged storage. Field flow fractionation analysis of Id-KLH particle size revealed that maleimide conjugates were far more uniform in size than glutaraldehyde conjugates. Under increasingly stringent conditions, maleimide Id-KLH vaccines maintained superior efficacy over glutaraldehyde Id-KLH in treating established, disseminated murine lymphoma. More importantly, human maleimide Id-KLH conjugates were consistently superior to glutaraldehyde Id-KLH conjugates in inducing Id-specific antibody and T cell responses. The described methods should be easily adaptable to the production of clinical grade vaccines for human trials in B cell malignancies. PMID:19046770

Estimating in vivo airway surface liquid concentration in trials of inhaled antibiotics.

PubMed

Hasan, M A; Lange, C F

2007-01-01

Antibiotic drugs exhibit concentration dependence in their efficacy. Therefore, ensuring appropriate concentration of these drugs in the relevant body fluid is important for obtaining the desired therapeutic and physiological action. Until recently there had been no suitable method available to measure or estimate concentration of drugs in the human airways resulting from inhaled aerosols or to determine the amount of inhaled antibiotics required to ensure minimum inhibitory concentration of a drug in the airway surface liquid (ASL). In this paper a numerical method is used for estimating local concentration of inhaled pharmaceutical aerosols in different generations of the human tracheobronchial airways. The method utilizes a mathematical lung deposition model to estimate amounts of aerosols depositing in different lung generations, and a recent ASL model along with deposition results to assess the concentration of deposited drugs immediately following inhalation. Examples of concentration estimates for two case studies: one for the antibiotic tobramycin against Pseudomonas aeruginosa, and another for taurolidine against Burkholderia cepacia are presented. The aerosol characteristics, breathing pattern and properties of nebulized solutions were adopted from two recent clinical studies on efficacy of these drugs in cystic fibrosis (CF) patients and from other sources in the literature. While the clinically effective tobramycin showed a concentration higher than the required in vivo concentration, that for the ineffective taurolidine was found to be below the speculated required in vivo concentration. Results of this study thus show that the mathematical ASL model combined with the lung deposition model can be an effective tool for helping decide the optimum dosage of inhaled antibiotic drugs delivered during human clinical trials.

Dynamic enhancement of drug product labels to support drug safety, efficacy, and effectiveness.

PubMed

Boyce, Richard D; Horn, John R; Hassanzadeh, Oktie; Waard, Anita de; Schneider, Jodi; Luciano, Joanne S; Rastegar-Mojarad, Majid; Liakata, Maria

2013-01-26

Out-of-date or incomplete drug product labeling information may increase the risk of otherwise preventable adverse drug events. In recognition of these concerns, the United States Federal Drug Administration (FDA) requires drug product labels to include specific information. Unfortunately, several studies have found that drug product labeling fails to keep current with the scientific literature. We present a novel approach to addressing this issue. The primary goal of this novel approach is to better meet the information needs of persons who consult the drug product label for information on a drug's efficacy, effectiveness, and safety. Using FDA product label regulations as a guide, the approach links drug claims present in drug information sources available on the Semantic Web with specific product label sections. Here we report on pilot work that establishes the baseline performance characteristics of a proof-of-concept system implementing the novel approach. Claims from three drug information sources were linked to the Clinical Studies, Drug Interactions, and Clinical Pharmacology sections of the labels for drug products that contain one of 29 psychotropic drugs. The resulting Linked Data set maps 409 efficacy/effectiveness study results, 784 drug-drug interactions, and 112 metabolic pathway assertions derived from three clinically-oriented drug information sources (ClinicalTrials.gov, the National Drug File - Reference Terminology, and the Drug Interaction Knowledge Base) to the sections of 1,102 product labels. Proof-of-concept web pages were created for all 1,102 drug product labels that demonstrate one possible approach to presenting information that dynamically enhances drug product labeling. We found that approximately one in five efficacy/effectiveness claims were relevant to the Clinical Studies section of a psychotropic drug product, with most relevant claims providing new information. We also identified several cases where all of the drug-drug interaction claims linked to the Drug Interactions section for a drug were potentially novel. The baseline performance characteristics of the proof-of-concept will enable further technical and user-centered research on robust methods for scaling the approach to the many thousands of product labels currently on the market.

A randomized trial of the efficacy and safety of sequential intravenous/oral moxifloxacin monotherapy versus intravenous piperacillin/tazobactam followed by oral amoxicillin/clavulanate for complicated skin and skin structure infections

PubMed Central

Gyssens, Inge C.; Dryden, Matthew; Kujath, Peter; Nathwani, Dilip; Schaper, Nicolaas; Hampel, Barbara; Reimnitz, Peter; Alder, Jeff; Arvis, Pierre

2011-01-01

Objectives The primary aim of the RELIEF study was to evaluate the efficacy and safety of two sequential intravenous (iv)/oral regimens: moxifloxacin iv/oral versus piperacillin/tazobactam (TZP) iv followed by oral amoxicillin/clavulanate (AMC). Patients and methods The study had a prospective, randomized, double-dummy, double-blind, multicentre design. Patients ≥18 years were prospectively stratified according to complicated skin and skin structure infection (cSSSI) subtype/diagnosis (major abscess, diabetic foot infection, wound infection or infected ischaemic ulcer), surgical intervention and severity of illness. Diagnoses and disease severity were based on predetermined criteria, documented by repeated photographs, and confirmed by an independent data review committee. Patients were randomized to receive either 400 mg of moxifloxacin iv once daily followed by 400 mg of moxifloxacin orally once daily or 4.0/0.5 g of TZP iv thrice daily followed by 875/125 mg of AMC orally twice daily for 7–21 days. The primary efficacy variable was clinical response at test of cure (TOC) for the per-protocol (PP) population. Clinical efficacy was assessed by the data review committee based on repeated photographs and case descriptions. Clinical trials registry number: NCT 00402727. Results A total of 813 patients were randomized. Clinical success rates at TOC were similar for moxifloxacin and TZP–AMC in the PP [320/361 (88.6%) versus 275/307 (89.6%), respectively; P = 0.758] and intent-to-treat (ITT) [350/426 (82.2%) versus 305/377 (80.9%), respectively; P = 0.632] populations. Thus, moxifloxacin was non-inferior to TZP–AMC. Bacteriological success rates were high in both treatment arms [moxifloxacin: 432/497 (86.9%) versus TZP–AMC: 370/429 (86.2%), microbiologically valid (MBV) population]. Moxifloxacin was non-inferior to TZP–AMC at TOC in both the MBV and the ITT populations. Both treatments were well tolerated. Conclusions Once-daily iv/oral moxifloxacin monotherapy was clinically and bacteriologically non-inferior to iv TZP thrice daily followed by oral AMC twice daily in patients with cSSSIs. PMID:21896561

Dynamic enhancement of drug product labels to support drug safety, efficacy, and effectiveness

PubMed Central

2013-01-01

Out-of-date or incomplete drug product labeling information may increase the risk of otherwise preventable adverse drug events. In recognition of these concerns, the United States Federal Drug Administration (FDA) requires drug product labels to include specific information. Unfortunately, several studies have found that drug product labeling fails to keep current with the scientific literature. We present a novel approach to addressing this issue. The primary goal of this novel approach is to better meet the information needs of persons who consult the drug product label for information on a drug’s efficacy, effectiveness, and safety. Using FDA product label regulations as a guide, the approach links drug claims present in drug information sources available on the Semantic Web with specific product label sections. Here we report on pilot work that establishes the baseline performance characteristics of a proof-of-concept system implementing the novel approach. Claims from three drug information sources were linked to the Clinical Studies, Drug Interactions, and Clinical Pharmacology sections of the labels for drug products that contain one of 29 psychotropic drugs. The resulting Linked Data set maps 409 efficacy/effectiveness study results, 784 drug-drug interactions, and 112 metabolic pathway assertions derived from three clinically-oriented drug information sources (ClinicalTrials.gov, the National Drug File – Reference Terminology, and the Drug Interaction Knowledge Base) to the sections of 1,102 product labels. Proof-of-concept web pages were created for all 1,102 drug product labels that demonstrate one possible approach to presenting information that dynamically enhances drug product labeling. We found that approximately one in five efficacy/effectiveness claims were relevant to the Clinical Studies section of a psychotropic drug product, with most relevant claims providing new information. We also identified several cases where all of the drug-drug interaction claims linked to the Drug Interactions section for a drug were potentially novel. The baseline performance characteristics of the proof-of-concept will enable further technical and user-centered research on robust methods for scaling the approach to the many thousands of product labels currently on the market. PMID:23351881

Clustering of longitudinal data by using an extended baseline: A new method for treatment efficacy clustering in longitudinal data.

PubMed

Schramm, Catherine; Vial, Céline; Bachoud-Lévi, Anne-Catherine; Katsahian, Sandrine

2018-01-01

Heterogeneity in treatment efficacy is a major concern in clinical trials. Clustering may help to identify the treatment responders and the non-responders. In the context of longitudinal cluster analyses, sample size and variability of the times of measurements are the main issues with the current methods. Here, we propose a new two-step method for the Clustering of Longitudinal data by using an Extended Baseline. The first step relies on a piecewise linear mixed model for repeated measurements with a treatment-time interaction. The second step clusters the random predictions and considers several parametric (model-based) and non-parametric (partitioning, ascendant hierarchical clustering) algorithms. A simulation study compares all options of the clustering of longitudinal data by using an extended baseline method with the latent-class mixed model. The clustering of longitudinal data by using an extended baseline method with the two model-based algorithms was the more robust model. The clustering of longitudinal data by using an extended baseline method with all the non-parametric algorithms failed when there were unequal variances of treatment effect between clusters or when the subgroups had unbalanced sample sizes. The latent-class mixed model failed when the between-patients slope variability is high. Two real data sets on neurodegenerative disease and on obesity illustrate the clustering of longitudinal data by using an extended baseline method and show how clustering may help to identify the marker(s) of the treatment response. The application of the clustering of longitudinal data by using an extended baseline method in exploratory analysis as the first stage before setting up stratified designs can provide a better estimation of treatment effect in future clinical trials.

Parameters for defining efficacy in fracture healing

PubMed Central

Shisha, Tamas

2010-01-01

Complications of the bone-healing process, especially in elderly, osteoporotic patients, are cause of important medical and economical burden. At the same time, there is no clinical study today to have shown the efficacy of a pharmacological treatment to enhance fracture repair. The author analyzes the potential criteria that could be used for the evaluation of treatment efficacy to enhance fracture healing in the frame of a clinical study. PMID:22461284

Traditional medicine in the treatment of drug addiction.

PubMed

Lu, Lin; Liu, Yanli; Zhu, Weili; Shi, Jie; Liu, Yu; Ling, Walter; Kosten, Thomas R

2009-01-01

To evaluate clinical trials and neurochemical mechanisms of the action of traditional herbal remedies and acupuncture for treating drug addiction. We used computerized literature searches in English and Chinese and examined texts written before these computerized databases existed. We used search terms of treatment and neurobiology of herbal medicines, and acupuncture for drug abuse and dependence. Acupuncture showed evidence for clinical efficacy and relevant neurobiological mechanisms in opiate withdrawal, but it showed poor efficacy for alcohol and nicotine withdrawal or relapse prevention, and no large studies supported its efficacy for cocaine in well-designed clinical trials. Clinical trials were rare for herbal remedies. Radix Puerariae showed the most promising efficacy for alcoholism by acting through daidzin, which inhibits mitocochondrial aldehyde dehydrogenase 2 and leads to disulfiram-like alcohol reactions. Peyote also has some evidence for alcoholism treatment among Native Americans. Ginseng and Kava lack efficacy data in addictions, and Kava can be hepatotoxic. Thunbergia laurifolia can protect against alcoholic liver toxicity. Withania somnifera and Salvia miltiorrhiza have no efficacy data, but can reduce morphine tolerance and alcohol intake, respectively, in animal models. Traditional herbal treatments can compliment pharmacotherapies for drug withdrawal and possibly relapse prevention with less expense and perhaps fewer side effects with notable exceptions. Both acupuncture and herbal treatments need testing as adjuncts to reduce doses and durations of standard pharmacotherapies.

Effect of clinical response to active drugs and placebo on antipsychotics and mood stabilizers relative efficacy for bipolar depression and mania: A meta-regression analysis.

PubMed

Bartoli, Francesco; Clerici, Massimo; Di Brita, Carmen; Riboldi, Ilaria; Crocamo, Cristina; Carrà, Giuseppe

2018-04-01

Randomised placebo-controlled trials investigating treatments for bipolar disorder have been hampered by wide variations of active drugs and placebo clinical response rates. It is important to estimate whether the active drug or placebo response has a greater influence in determining the relative efficacy of drugs for psychosis (antipsychotics) and relapse prevention (mood stabilisers) for bipolar depression and mania. We identified 53 randomised, placebo-controlled trials assessing antipsychotic or mood stabiliser monotherapy ('active drugs') for bipolar depression or mania. We carried out random-effects meta-regressions, estimating the influence of active drugs and placebo response rates on treatment relative efficacy. Meta-regressions showed that treatment relative efficacy for bipolar mania was influenced by the magnitude of clinical response to active drugs ( p=0.002), but not to placebo ( p=0.60). On the other hand, treatment relative efficacy for bipolar depression was influenced by response to placebo ( p=0.047), but not to active drugs ( p=0.98). Despite several limitations, our unexpected findings showed that antipsychotics / mood stabilisers relative efficacy for bipolar depression seems unrelated to active drugs response rates, depending only on clinical response to placebo. Future research should explore strategies to reduce placebo-related issues in randomised, placebo-controlled trials for bipolar depression.

Assessment of the clinical efficacy of the heart spectrum blood pressure monitor for diagnosis of atrial fibrillation: An unblinded clinical trial.

PubMed

Kao, Wei-Fong; Hou, Sen-Kuang; Huang, Chun-Yao; Chao, Chun-Chieh; Cheng, Chung-Chih; Chen, Yi-Jung

2018-01-01

Atrial fibrillation (AF) is the most common arrhythmia. The most common diagnostic method, 12-lead electrocardiogram (ECG), can record episodes of arrhythmia from which the type and severity can be determined. The Heart Spectrum Blood Pressure Monitor (P2; OSTAR Meditech Corp., New Taipei City, Taiwan) is used to measure cardiovascular pressure change with fast Fourier transform (FFT) analysis to obtain heart rate frequency variability and accurate blood pressure data. We compared the diagnostic efficacy of the Heart Spectrum Blood Pressure Monitor to a 12-lead ECG (gold standard) for patients with AF. Three measurement methods were used in this study to analyze the heart index and compare the results with simultaneous 12-lead ECG: blood pressure; mean arterial pressure, which was calculated from individual blood pressure as a constant pressure; and a constant pressure of 60 mmHg. The physician used a 12-lead ECG and the Heart Spectrum Blood Pressure Monitor simultaneously. The Heart Spectrum Blood Pressure Monitor used FFT analysis to diagnose AF, and the findings were compared to the 12-lead ECG readings. This unblinded clinical trial was conducted in the emergency department of Taipei Medical University Hospital. Twenty-nine subjects with AF and 33 without AF aged 25 to 97 y (mean, 63.5 y) were included. Subjects who were exposed to high-frequency surgical equipment during testing, those with cardiac pacemakers or implantable defibrillators, and pregnant women were excluded. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 97%, 97%, 97%, and 97%, respectively, for method 1; 90%, 100%, 100%, and 91%, respectively, for method 2; and 100%, 94%, 94%, and 100%, respectively, for method 3. The sensitivity, specificity, PPV, and NPV for both methods ranged between 90% and 100%, indicating that the Heart Spectrum Blood Pressure Monitor can be effectively applied for AF detection.

Assessment of the clinical efficacy of the heart spectrum blood pressure monitor for diagnosis of atrial fibrillation: An unblinded clinical trial

PubMed Central

Kao, Wei-Fong; Hou, Sen-Kuang; Huang, Chun-Yao; Cheng, Chung-Chih; Chen, Yi-Jung

2018-01-01

Atrial fibrillation (AF) is the most common arrhythmia. The most common diagnostic method, 12-lead electrocardiogram (ECG), can record episodes of arrhythmia from which the type and severity can be determined. The Heart Spectrum Blood Pressure Monitor (P2; OSTAR Meditech Corp., New Taipei City, Taiwan) is used to measure cardiovascular pressure change with fast Fourier transform (FFT) analysis to obtain heart rate frequency variability and accurate blood pressure data. We compared the diagnostic efficacy of the Heart Spectrum Blood Pressure Monitor to a 12-lead ECG (gold standard) for patients with AF. Three measurement methods were used in this study to analyze the heart index and compare the results with simultaneous 12-lead ECG: blood pressure; mean arterial pressure, which was calculated from individual blood pressure as a constant pressure; and a constant pressure of 60 mmHg. The physician used a 12-lead ECG and the Heart Spectrum Blood Pressure Monitor simultaneously. The Heart Spectrum Blood Pressure Monitor used FFT analysis to diagnose AF, and the findings were compared to the 12-lead ECG readings. This unblinded clinical trial was conducted in the emergency department of Taipei Medical University Hospital. Twenty-nine subjects with AF and 33 without AF aged 25 to 97 y (mean, 63.5 y) were included. Subjects who were exposed to high-frequency surgical equipment during testing, those with cardiac pacemakers or implantable defibrillators, and pregnant women were excluded. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 97%, 97%, 97%, and 97%, respectively, for method 1; 90%, 100%, 100%, and 91%, respectively, for method 2; and 100%, 94%, 94%, and 100%, respectively, for method 3. The sensitivity, specificity, PPV, and NPV for both methods ranged between 90% and 100%, indicating that the Heart Spectrum Blood Pressure Monitor can be effectively applied for AF detection. PMID:29902218

Effects of water-aging on self-healing dental composite containing microcapsules

PubMed Central

Wu, Junling; Weir, Michael D.; Melo, Mary Anne S.; Strassler, Howard E.; Xu, Hockin H. K.

2016-01-01

Objectives The objectives of this study were to develop a self-healing dental composite containing poly(urea-formaldehyde) (PUF) shells with triethylene glycol dimethacrylate (TEGDMA) and N,N-dihydroxyethyl-p-toluidine (DHEPT) as healing liquid, and to investigate the mechanical properties of the composite and its self-healing efficacy after water-aging for 6 months. Methods PUF microspheres were synthesized encapsulating a TEGDMA-DHEPT healing liquid. Composite containing 30% of a resin matrix and 70% of glass fillers by mass was incorporated with 0%, 2.5%, 5%, 7.5% and 10% of microcapsules. A flexural test was used to measure flexural strength and elastic modulus. A single edge V-notched beam method was used to measure fracture toughness (KIC) and self-healing efficacy. Specimens were water-aged at 37 °C for 1 d to 6 months and then tested for self-healing. Fractured specimens were healed while being immersed in water to examine self-healing efficacy, in comparison with that in air. Results Incorporation of up to 7.5% of microcapsules into the resin composite achieved effective self-healing, without adverse effects on the virgin mechanical properties of the composite (p > 0.1). An excellent self-healing efficacy of 64%–77% recovery was obtained (mean ± sd; n = 6). Six months of water-aging did not decrease the self-healing efficacy compared to 1 d (p > 0.1). Exposure to water did not decrease the healing efficacy, compared to that healed in air (p > 0.1). Conclusions A composite was developed with excellent self-healing efficacy even while being immersed in water. The self-healing efficacy did not decrease with increasing water-aging time for 6 months. Clinical significance The novel self-healing composite may be promising for dental applications to heal cracks, resist fracture, and increase the durability and longevity. PMID:26808158

The promise of ketamine for treatment-resistant depression: current evidence and future directions

PubMed Central

DeWilde, Kaitlin E.; Levitch, Cara F.; Murrough, James W.; Mathew, Sanjay J.; Iosifescu, Dan V.

2014-01-01

Major depressive disorder (MDD) is one of the most disabling diseases worldwide and is a significant public health threat. Current treatments for MDD primarily consist of monoamine-targeting agents and have limited efficacy. However, the glutamate neurotransmitter system has recently come into focus as a promising alternative for novel antidepressant treatments. We review the current data on the glutamate NMDA receptor antagonist ketamine, which has been shown in clinical trials to act as a rapid antidepressant in MDD. We also examine ketamine efficacy on dimensions of psychopathology, including anhedonia, cognition, and suicidality, consistent with the NIMH Research Domain Criteria (RDoC) initiative. Other aspects of ketamine reviewed in this paper include safety and efficacy, different administration methods, and the risks of misuse of ketamine outside of medical settings. Finally, we conclude with a discussion of other glutamatergic agents other than ketamine currently being tested as novel antidepressants. PMID:25649308

A review of antiviral drugs and other compounds with activity against feline herpesvirus-1

PubMed Central

Thomasy, S. M.; Maggs, D. J.

2016-01-01

Feline herpesvirus type 1 (FHV-1) is a common and important cause of ocular surface disease, dermatitis, respiratory disease, and potentially intraocular disease in cats. However, many antiviral drugs developed for the treatment of humans infected with herpesviruses have been used to treat cats infected with FHV-1. Translational use of drugs in this manner ideally requires methodical investigation of their in vitro efficacy against FHV-1 followed by pharmacokinetic and safety trials in normal cats. Subsequently, placebo-controlled efficacy studies in experimentally-inoculated animals should be performed followed, finally, by carefully designed and monitored clinical trials in client-owned animals. This review is intended to provide a concise review of the available literature regarding the efficacy of antiviral drugs and other compounds with proven or putative activity against FHV-1, as well as a discussion of their safety in cats. PMID:27091747

Randomized Placebo-Controlled Double-Blind Clinical Trial of Cannabis-Based Medicinal Product (Sativex) in Painful Diabetic Neuropathy

PubMed Central

Selvarajah, Dinesh; Gandhi, Rajiv; Emery, Celia J.; Tesfaye, Solomon

2010-01-01

OBJECTIVE To assess the efficacy of Sativex, a cannabis-based medicinal extract, as adjuvant treatment in painful diabetic peripheral neuropathy (DPN). RESEARCH DESIGN AND METHODS In this randomized controlled trial, 30 subjects with painful DPN received daily Sativex or placebo. The primary outcome measure was change in mean daily pain scores, and secondary outcome measures included quality-of-life assessments. RESULTS There was significant improvement in pain scores in both groups, but mean change between groups was not significant. There were no significant differences in secondary outcome measures. Patients with depression had significantly greater baseline pain scores that improved regardless of intervention. CONCLUSIONS This first-ever trial assessing the efficacy of cannabis has shown it to be no more efficacious than placebo in painful DPN. Depression was a major confounder and may have important implications for future trials on painful DPN. PMID:19808912

Self-efficacy is independently associated with brain volume in older women

PubMed Central

Davis, Jennifer C.; Nagamatsu, Lindsay S.; Hsu, Chun Liang; Beattie, B. Lynn; Liu-Ambrose, Teresa

2015-01-01

Background Aging is highly associated with neurodegeneration and atrophy of the brain. Evidence suggests that personality variables are risk factors for reduced brain volume. We examine whether falls-related self-efficacy is independently associated with brain volume. Method A cross-sectional analysis of whether falls-related self-efficacy is independently associated with brain volumes (total, grey, and white matter). Three multivariate regression models were constructed. Covariates included in the models were age, global cognition, systolic blood pressure, functional comorbidity index, and current physical activity level. MRI scans were acquired from 79 community-dwelling senior women aged 65 to 75 years old. Falls-related self-efficacy was assessed by the Activities Specific Balance Confidence (ABC) Scale. Results After accounting for covariates, falls-related self-efficacy was independently associated with both total brain volume and total grey matter volume. The final model for total brain volume accounted for 17% of the variance, with the ABC score accounting for 8%. For total grey matter volume, the final model accounted for 24% of the variance, with the ABC score accounting for 10%. Conclusion We provide novel evidence that falls-related self-efficacy, a modifiable risk factor for healthy aging, is positively associated with total brain volume and total grey matter volume. Trial Registration ClinicalTrials.gov Identifier: NCT00426881. PMID:22436405

Accurate quantification of 5 German cockroach (GCr) allergens in complex extracts using multiple reaction monitoring mass spectrometry (MRM MS).

PubMed

Mindaye, S T; Spiric, J; David, N A; Rabin, R L; Slater, J E

2017-12-01

German cockroach (GCr) allergen extracts are complex and heterogeneous products, and methods to better assess their potency and composition are needed for adequate studies of their safety and efficacy. The objective of this study was to develop an assay based on liquid chromatography and multiple reaction monitoring mass spectrometry (LC-MRM MS) for rapid, accurate, and reproducible quantification of 5 allergens (Bla g 1, Bla g 2, Bla g 3, Bla g 4, and Bla g 5) in crude GCr allergen extracts. We first established a comprehensive peptide library of allergens from various commercial extracts as well as recombinant allergens. Peptide mapping was performed using high-resolution MS, and the peptide library was then used to identify prototypic and quantotypic peptides to proceed with MRM method development. Assay development included a systematic optimization of digestion conditions (buffer, digestion time, and trypsin concentration), chromatographic separation, and MS parameters. Robustness and suitability were assessed following ICH (Q2 [R1]) guidelines. The method is precise (RSD < 10%), linear over a wide range (r > 0.99, 0.01-1384 fmol/μL), and sensitive (LLOD and LLOQ <1 fmol/μL). Having established the parameters for LC-MRM MS, we quantified allergens from various commercial GCr extracts and showed considerable variability that may impact clinical efficacy. Our data demonstrate that the LC-MRM MS method is valuable for absolute quantification of allergens in GCr extracts and likely has broader applicability to other complex allergen extracts. Definitive quantification provides a new standard for labelling of allergen extracts, which will inform patient care, enable personalized therapy, and enhance the efficacy of immunotherapy for environmental and food allergies. © 2017 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

Application of cetylpyridinium chloride and sodium chloride decontamination method for recovery of Mycobacterium tuberculosis from clinically suspected cases of pulmonary tuberculosis.

PubMed

Shinu, Pottathil; Singh, Varsha; Nair, Anroop; Mehrishi, Priya; Mehta, Sonia; Joshi, Ekta

2013-10-01

The study was designed to compare the efficacy of cetylpyridinium chloride (CPC) and sodium chloride (NaCl) decontamination method with N-acetyl L-Cystine (NALC) and sodium hydroxide (NaOH) decontamination (the reference method) method for the recovery of Mycobacterium tuberculosis (MTB) from clinically suspected cases of pulmonary tuberculosis. To evaluate CPC-NaCl and NALC-NaOH decontamination methods, sputum specimens (n = 796) were studied (culturing on Löwenstein-Jensen medium), and the performances were compared. The CPC-NaCl decontamination method demonstrated a sensitivity, specificity, negative predictive value, and positive predictive value of 97.99%, 87.53%, 70.19%, and 99.32%, respectively, when compared to NALC-NaOH decontamination method. In summary, CPC-NaCl decontamination method effectively detected significantly higher number of MTB cases (n = 208) than NALC-NaOH decontamination method (n = 149) particularly in sputum with scanty bacilli and smear-negative cases, indicating the potential of CPC-NaCl decontamination method to preserve paucibacillary cases more efficient than NALC-NaOH decontamination method. © 2013.

A Phase 3, Multicenter, Randomized, Double-Blind, Vehicle-Controlled Study Evaluating the Safety and Efficacy of Metronidazole Vaginal Gel 1.3% in the Treatment of Bacterial Vaginosis

PubMed Central

Schwebke, Jane R.; Marrazzo, Jeanne; Beelen, Andrew P.; Sobel, Jack D.

2015-01-01

Background Bacterial vaginosis (BV), a prevalent infection in women of reproductive age, is associated with increased risk of upper genital tract and sexually transmitted infections, and complications in pregnancy. Currently approved treatments include metronidazole, which requires once or twice daily intravaginal administration for 5 days or twice daily oral administration for 7 days. This phase 3 study determined the safety and efficacy of single-dose metronidazole vaginal gel (MVG) 1.3%. Methods In this double-blind, vehicle-controlled study, 651 women with clinical diagnosis of BV were randomized 1:1 to receive MVG 1.3% or vehicle vaginal gel. Primary efficacy measure was clinical cure (normal discharge, negative “whiff test,” and <20% clue cells) at day 21. Secondary measures included therapeutic cure (both clinical and bacteriological; day 21) and bacteriologic cure (Nugent score <4), clinical cure, and time to resolution of symptoms (day 7). Results A total of 487 participants were included in the primary analysis. Clinical and therapeutic cure rates (day 21) were higher in participants treated with MVG 1.3% compared with vehicle gel (37.2% vs. 26.6% [P = 0.010] and 16.8% vs. 7.2% [P = 0.001], respectively). Clinical and bacteriologic cure rates (day 7) were also higher in the MVG 1.3% group (46.0% vs. 20.0% [P < 0.001] and 32.7% vs. 6.3% [P < 0.001], respectively). The median time to resolution of symptoms was shorter in the MVG 1.3% (day 6) than vehicle group (not reached). No serious adverse events were reported, and incidence was similar across treatment groups. Conclusions Single-dose MVG 1.3% was safe and superior to vehicle gel in producing cure among women with BV. PMID:26222750

Pre-Exposure Prophylaxis for HIV Prevention: Safety Concerns.

PubMed

Tetteh, Raymond A; Yankey, Barbara A; Nartey, Edmund T; Lartey, Margaret; Leufkens, Hubert G M; Dodoo, Alexander N O

2017-04-01

Available evidence supports the efficacy of pre-exposure prophylaxis (PrEP) in decreasing the incidence of human immunodeficiency virus (HIV) infection among high-risk individuals, especially when used in combination with other behavioural preventive methods. Safety concerns about PrEP present challenges in the implementation and use of PrEP. The aim of this review is to discuss safety concerns observed in completed clinical trials on the use of PrEP. We performed a literature search on PrEP in PubMed, global advocacy for HIV prevention (Aids Vaccine Advocacy Coalition) database, clinical trials registry " http://www.clinicaltrials.gov " and scholar.google, using combination search terms 'pre-exposure prophylaxis', 'safety concerns in the use of pre-exposure prophylaxis', 'truvada use as PrEP', 'guidelines for PrEP use', 'HIV pre-exposure prophylaxis' and 'tenofovir' to identify clinical trials and literature on PrEP. We present findings associated with safety issues on the use of PrEP based on a review of 11 clinical trials on PrEP with results on safety and efficacy as at April 2016. We also reviewed findings from routine real-life practice reports. The pharmacological intervention for PrEP was tenofovir disoproxil fumarate/emtricitabine in a combined form as Truvada ® or tenofovir as a single entity. Both products are efficacious for PrEP and seem to have a good safety profile. Regular monitoring is recommended to prevent long-term toxic effects. The main adverse effects observed with PrEP are gastrointestinal related; basically mild to moderate nausea, vomiting and diarrhea. Other adverse drug effects worth monitoring are liver enzymes, renal function and bone mineral density. PrEP as an intervention to reduce HIV transmission appears to have a safe benefit-risk profile in clinical trials. It is recommended for widespread use but adherence monitoring and real-world safety surveillance are critical in the post-marketing phase to ensure that the benefits observed in clinical trials are maintained in real-world use.

Efficacy and toxicity differences in lung cancer populations in the era of clinical trials globalization: the 'common arm' approach.

PubMed

Mack, Philip C; Gandara, David R; Lara, Primo N

2012-12-01

Historically, notable variability has been observed in clinical trial outcomes between different regions and populations worldwide, even when employing the same cytotoxic regimen in lung cancer. These divergent results underscore the inherent challenges in interpreting trials conducted abroad and raise questions regarding the general applicability of transnational clinical trials. Various reasons have been postulated to account for these differences in efficacy and toxicity, including trial design, eligibility criteria, patient demographics and, perhaps most intriguingly, population-related pharmacogenomics. However, without methodology to control for such variables, these hypotheses remain largely untested. The authors previously developed the 'common arm' approach in order to directly compare efficacy and toxicity results of trials simultaneously performed in different countries. By standardizing clinical trial-associated variables such as treatment regimens (dose, schedule, and so on), eligibility, staging, response and toxicity criteria, this approach has the potential to determine the underlying reasons for divergences in trial outcomes across countries, and whether population-associated polymorphisms contribute to these differences. In the past decade, Japanese and US investigators have applied the common arm analytic method to trials in both extensive-stage small-cell lung cancer (SCLC) and advanced nonSCLC. In the SCLC analysis, a comparison of the cisplatin/irinotecan arms from both trials revealed significant differences in response rates and overall survival. Significant differences were also observed in the distribution of gender and performance status. The common arm analysis in nonSCLC included two trials from Japan and one from the USA, each containing a 'common' carboplatin/paclitaxel arm. Clinical results were similar in the two Japanese trials, but were significantly different from the US trial with regard to survival, neutropenia, febrile neutropenia and anemia. The underlying basis for these divergent outcomes is discussed. The common arm methodology provides a template for identifying and interpreting patient outcome differences across populations, and is an instructive lesson in the burgeoning era of clinical trials globalization.

CA6-02: Collaborative Goal Setting and HbA1c Control Among Patients With Diabetes

PubMed Central

Lafata, Jennifer Elston; Dobie, Elizabeth; Morris, Heather; Heisler, Michele; Werner, Rachel; Divine, George; Thomas, Abraham

2012-01-01

Background/Aims Helping patients set and follow up on goals may be an effective way to help patients improve their confidence (self-efficacy) and commitment to improve diabetes self- management. We evaluate associations among patient-reported use of collaborative goal setting with clinicians, patient-reported self-efficacy, and clinical control (measured by HbA1c) among patients with diabetes. Methods A cohort of insured patients aged 18+ years with diabetes who initiated oral mono-therapy between 2000–2005 was surveyed in 2008. The survey included the 3 collaborative goal-setting items from the Patient Assessment of Chronic Illness Care (PACIC), a 4-item measure of self-efficacy, measures of socio-demographics, age of diabetes onset, and height/weight. Survey data were joined with automated laboratory and encounter data for the 12 months prior to and following survey administration. A structural equation model (SEM), using path analysis and adjusting for baseline patient characteristics (including HbA1c and diabetes-related co-morbidities and complications), was fit to investigate relationships among collaborative goal setting, self-efficacy and HbA1c control. Results Completed surveys were available for 1070 patients (n=956 mail and n=114 telephone; 77% response rate). Survey respondents were on average 68 years, half were female, 60% white, 31% black, and 57% reported low self-efficacy. On average, patients reported engaging in collaborative goal setting with their clinicians ‘sometimes’ (mean = 3.1, range 1 [never]-5 [always]). At baseline, mean HbA1c was 7.2%, with 22% =8%. Results from the SEM did not support a direct relationship between the collaborative goal setting factor (Cronbach Alpha=0.83) and HbA1c control, but did support an indirect relationship (asymmetric distribution of products 95% CI = −0.02, −0.002) with increases in collaborative goal setting positively associated with a greater likelihood of average or high self-efficacy (beta, p<0.01), and average or high self-efficacy associated with lower follow-up HbA1cs level (-beta, p<0.01). These relationships persisted after controlling for baseline HbA1c and other patient characteristics. Discussion While collaborative goal setting between patients with diabetes and their clinicians is not directly associated with better clinical control, it is associated with improved self-efficacy, which in turn, is associated with improved clinical control.

Recommendations for the Design and Analysis of Treatment Trials for Alcohol Use Disorders.

PubMed

Witkiewitz, Katie; Finney, John W; Harris, Alex H S; Kivlahan, Daniel R; Kranzler, Henry R

2015-09-01

Over the past 60 years, the view that "alcoholism" is a disease for which the only acceptable goal of treatment is abstinence has given way to the recognition that alcohol use disorders (AUDs) occur on a continuum of severity, for which a variety of treatment options are appropriate. However, because the available treatments for AUDs are not effective for everyone, more research is needed to develop novel and more efficacious treatments to address the range of AUD severity in diverse populations. Here we offer recommendations for the design and analysis of alcohol treatment trials, with a specific focus on the careful conduct of randomized clinical trials of medications and nonpharmacological interventions for AUDs. This paper provides a narrative review of the quality of published clinical trials and recommendations for the optimal design and analysis of treatment trials for AUDs. Despite considerable improvements in the design of alcohol clinical trials over the past 2 decades, many studies of AUD treatments have used faulty design features and statistical methods that are known to produce biased estimates of treatment efficacy. The published statistical and methodological literatures provide clear guidance on methods to improve clinical trial design and analysis. Consistent use of state-of-the-art design features and analytic approaches will enhance the internal and external validity of treatment trials for AUDs across the spectrum of severity. The ultimate result of this attention to methodological rigor is that better treatment options will be identified for patients with an AUD. Copyright © 2015 by the Research Society on Alcoholism.

In Vivo Measurement of Drug Efficacy in Breast Cancer

DTIC Science & Technology

2016-10-01

analysis. At the clinical level, this study will result in pertinent data regarding several agents currently in clinical trials. At the basic science ...clinical level, this study will result in pertinent data regarding several agents currently in clinical trials. At the basic science level, we will...mg/kg BLZ-945 or encapsulated drug were tested in BALB/C mice expressing tumors in mammary fat pads, showing limited additional efficacy as seen

Comparison of the effectiveness of sterilizing endodontic files by 4 different methods: an in vitro study.

PubMed

Venkatasubramanian, R; Das, U M; Bhatnagar, S

2010-01-01

Sterilization is the best method to counter the threats of microorganisms. The purpose of sterilization in the field of health care is to prevent the spread of infectious diseases. In dentistry, it primarily relates to processing reusable instruments to prevent cross-infection. The aim of this study was to investigate the efficacy of 4 methods of sterilizing endodontic instruments: Autoclaving, carbon dioxide laser sterilization, chemical sterilization (with glutaraldehyde) and glass-bead sterilization. The endodontic file was sterilized by 4 different methods after contaminating it with bacillus stearothermophillus and then checked for sterility by incubating after putting it in test tubes containing thioglycollate medium. The study showed that the files sterilized by autoclave and lasers were completely sterile. Those sterilized by glass bead were 90% sterile and those with glutaraldehyde were 80% sterile. The study concluded that autoclave or laser could be used as a method of sterilization in clinical practice and in advanced clinics; laser can be used also as a chair side method of sterilization.

Excimer laser for the treatment of psoriasis: safety, efficacy, and patient acceptability

PubMed Central

Abrouk, Michael; Levin, Ethan; Brodsky, Merrick; Gandy, Jessica R; Nakamura, Mio; Zhu, Tian Hao; Farahnik, Benjamin; Koo, John; Bhutani, Tina

2016-01-01

Introduction The 308 nm excimer laser is a widely used device throughout the field of dermatology for many diseases including psoriasis. Although the laser has demonstrated clinical efficacy, there is a lack of literature outlining the safety, efficacy, and patient acceptability of the excimer laser. Methods A literature search on PubMed was used with combinations of the terms “excimer”, “excimer laser”, “308 nm”, “psoriasis”, “protocol”, “safety”, “efficacy”, acceptability”, “side effects”, and “dose”. The search results were included if they contained information pertaining to excimer laser and psoriasis treatment and description of the safety, efficacy, and patient acceptability of the treatment. Results The 308 nm excimer laser is generally safe and well tolerated with minimal side effects including erythema, blistering, and pigmentary changes. It has a range of efficacies depending on the protocol used with several different treatment protocols, including the induration protocol, the minimal erythema dose protocol, and the newer minimal blistering dose protocol. Conclusion Although the excimer laser is not a first-line treatment, it remains an excellent treatment option for psoriasis patients and has been demonstrated to be an effective treatment with little to no side effects. PMID:29387603

Calculus detection technologies: where do we stand now?

PubMed Central

Archana, V

2014-01-01

Epidemiological studies have implicated dental calculus as an ideal substrate for subgingival microbial colonization. Therefore, the main objective of periodontal therapy is to eliminate the microbial biofilm along with the calculus deposits from the root surface by root surface debridement. Over the past years, a large number of clinical and laboratory studies have been conducted to evaluate the efficacy of calculus removal by various methods. None of these conventional methods or devices was effective in completely eliminating all the calculus from the diseased root surfaces. In this context, a number of newer technologies have been developed to identify and selectively remove the dental calculus. Regarding this fact, the present article highlights a critical review of these devices based on published clinical and experimental data. PMID:25870667

Calculus detection technologies: where do we stand now?

PubMed

Archana, V

2014-01-01

Epidemiological studies have implicated dental calculus as an ideal substrate for subgingival microbial colonization. Therefore, the main objective of periodontal therapy is to eliminate the microbial biofilm along with the calculus deposits from the root surface by root surface debridement. Over the past years, a large number of clinical and laboratory studies have been conducted to evaluate the efficacy of calculus removal by various methods. None of these conventional methods or devices was effective in completely eliminating all the calculus from the diseased root surfaces. In this context, a number of newer technologies have been developed to identify and selectively remove the dental calculus. Regarding this fact, the present article highlights a critical review of these devices based on published clinical and experimental data.

Innovative use of technologies and methods to redesign care: the problem of care transitions.

PubMed

Richman, Mark; Sklaroff, Laura Myerchin; Hoang, Khathy; Wasson, Elijah; Gross-Schulman, Sandra

2014-01-01

Organizations are redesigning models of care in today's rapidly changing health care environment. Using proven innovation techniques maximizes likelihood of effective change. Our safety-net hospital aims to reduce high emergency department visit, admission, and readmission rates, key components to health care cost control. Twenty-five clinical stakeholders participated in mixed-methods innovation exercises to understand stakeholders, frame problems, and explore solutions. We identified existing barriers and means to improve post-emergency department/post-inpatient discharge care coordination/communication among patient-centered medical home care team members, including patients. Physicians and staff preferred automated e-mail notifications, including patient identifiers, medical home/primary care provider information, and relevant clinical documentation, to improve communication efficiency/efficacy.

Effects of a Brief Multimedia Psychoeducational Intervention on the Attitudes and Interest of Patients With Cancer Regarding Clinical Trial Participation: A Multicenter Randomized Controlled Trial

PubMed Central

Jacobsen, Paul B.; Wells, Kristen J.; Meade, Cathy D.; Quinn, Gwendolyn P.; Lee, Ji-Hyun; Fulp, William J.; Gray, Jhanelle E.; Baz, Rachid C.; Springett, Gregory M.; Levine, Richard M.; Markham, Merry-Jennifer; Schreiber, Fred J.; Cartwright, Thomas H.; Burke, James M.; Siegel, Robert D.; Malafa, Mokenge P.; Sullivan, Daniel

2012-01-01

Purpose The negative attitudes of patients with cancer regarding clinical trials are an important contributor to low participation rates. This study evaluated whether a brief psychoeducational intervention was effective in improving patients' attitudes as well as their knowledge, self-efficacy for decision making, receptivity to receiving more information, and general willingness to participate in clinical trials. Patients and Methods A total of 472 adults with cancer who had not been asked previously to participate in a clinical trial were randomly assigned to receive printed educational information about clinical trials or a psychoeducational intervention that provided similar information and also addressed misperceptions and concerns about clinical trials. The primary (attitudes) and secondary outcomes (knowledge, self-efficacy, receptivity, and willingness) were assessed via patient self-report before random assignment and 7 to 28 days later. Results Patients who received the psychoeducational intervention showed more positive attitudes toward clinical trials (P = .016) and greater willingness to participate (P = .011) at follow-up than patients who received printed educational information. Evidence of an indirect effect of intervention assignment on willingness to participate (estimated at 0.168; 95% CI, 0.088 to 0.248) suggested that the benefits of psychoeducation on willingness to participate were explained by the positive impact of psychoeducation on attitudes toward clinical trials. Conclusion A brief psychoeducational intervention can improve the attitudes of patients with cancer toward clinical trials and thereby increase their willingness to participate in clinical trials. Findings support conducting additional research to evaluate effects of this intervention on quality of decision making and rates of participation among patients asked to enroll onto therapeutic clinical trials. PMID:22614993

Elucidating the Aβ42 Anti-Aggregation Mechanism of Action of Tramiprosate in Alzheimer's Disease: Integrating Molecular Analytical Methods, Pharmacokinetic and Clinical Data.

PubMed

Kocis, Petr; Tolar, Martin; Yu, Jeremy; Sinko, William; Ray, Soumya; Blennow, Kaj; Fillit, Howard; Hey, John A

2017-06-01

Amyloid beta (Aβ) oligomers play a critical role in the pathogenesis of Alzheimer's disease (AD) and represent a promising target for drug development. Tramiprosate is a small-molecule Aβ anti-aggregation agent that was evaluated in phase III clinical trials for AD but did not meet the primary efficacy endpoints; however, a pre-specified subgroup analysis revealed robust, sustained, and clinically meaningful cognitive and functional effects in patients with AD homozygous for the ε4 allele of apolipoprotein E4 (APOE4/4 homozygotes), who carry an increased risk for the disease. Therefore, to build on this important efficacy attribute and to further improve its pharmaceutical properties, we have developed a prodrug of tramiprosate ALZ-801 that is in advanced stages of clinical development. To elucidate how tramiprosate works, we investigated its molecular mechanism of action (MOA) and the translation to observed clinical outcomes. The two main objectives of this research were to (1) elucidate and characterize the MOA of tramiprosate via an integrated application of three independent molecular methodologies and (2) present an integrated translational analysis that links the MOA, conformation of the target, stoichiometry, and pharmacokinetic dose exposure to the observed clinical outcome in APOE4/4 homozygote subjects. We used three molecular analytical methods-ion mobility spectrometry-mass spectrometry (IMS-MS), nuclear magnetic resonance (NMR), and molecular dynamics-to characterize the concentration-related interactions of tramiprosate versus Aβ42 monomers and the resultant conformational alterations affecting aggregation into oligomers. The molecular stoichiometry of the tramiprosate versus Aβ42 interaction was further analyzed in the context of clinical pharmacokinetic dose exposure and central nervous system Aβ42 levels (i.e., pharmacokinetic-pharmacodynamic translation in humans). We observed a multi-ligand interaction of tramiprosate with monomeric Aβ42, which differs from the traditional 1:1 binding. This resulted in the stabilization of Aβ42 monomers and inhibition of oligomer formation and elongation, as demonstrated by IMS-MS and molecular dynamics. Using NMR spectroscopy and molecular dynamics, we also showed that tramiprosate bound to Lys16, Lys28, and Asp23, the key amino acid side chains of Aβ42 that are responsible for both conformational seed formation and neuronal toxicity. The projected molar excess of tramiprosate versus Aβ42 in humans using the dose effective in patients with AD aligned with the molecular stoichiometry of the interaction, providing a clear clinical translation of the MOA. A consistent alignment of these preclinical-to-clinical elements describes a unique example of translational medicine and supports the efficacy seen in symptomatic patients with AD. This unique "enveloping mechanism" of tramiprosate also provides a potential basis for tramiprosate dose selection for patients with homozygous AD at earlier stages of disease. We have identified the molecular mechanism that may account for the observed clinical efficacy of tramiprosate in patients with APOE4/4 homozygous AD. In addition, the integrated application of the molecular methodologies (i.e., IMS-MS, NMR, and thermodynamics analysis) indicates that it is feasible to modulate and control the Aβ42 conformational dynamics landscape by a small molecule, resulting in a favorable Aβ42 conformational change that leads to a clinically relevant amyloid anti-aggregation effect and inhibition of oligomer formation. This novel enveloping MOA of tramiprosate has potential utility in the development of disease-modifying therapies for AD and other neurodegenerative diseases caused by misfolded proteins.

Evidence-based pharmacotherapy of post-traumatic stress disorder (PTSD).

PubMed

Ipser, Jonathan C; Stein, Dan J

2012-07-01

Post-traumatic stress disorder (PTSD) is a prevalent and disabling disorder. Recognition of neurobiological abnormalities associated with this condition suggests the potential efficacy of medication in its treatment. Nevertheless, questions regarding the efficacy of medications remain, despite general endorsement by clinical practice guidelines of selective serotonin reuptake inhibitors (SSRIs) as first-line agents in treating PTSD. This paper reviews evidence from randomized controlled trials (RCTs) for the efficacy of acute and long-term pharmacotherapy for PTSD, including the treatment of refractory PTSD. In addition, we conducted a systematic meta-analysis to compare the efficacy of different medications in treating PTSD. The effects of methodological study features (including year of publication, duration, number of centres) and sample characteristics (proportion of combat veterans, gender composition) were also tested. The largest body of evidence for short- and long-term efficacy of medication currently exists for SSRIs, with promising initial findings for the selective noradrenergic reuptake inhibitor venlafaxine and the atypical antipsychotic risperidone. Treatment effect was predicted by number of centres and recency of the study, with little evidence that sample characteristics predicted response. Evidence for the effectiveness of benzodiazepines is lacking, despite their continued use in clinical practice. Finally, the α1 antagonist prazosin and the atypical antipsychotics show some efficacy in treatment-resistant PTSD. Adequately powered trials that are designed in accordance with best-practice guidelines are required to provide conclusive evidence of clinically relevant differences in efficacy between agents in treating PTSD, and to help estimate clinical and methodological predictors of treatment response.

[KoMPASS--design, implementation and experiences concerning a structured communication skills training for physicians dealing with oncology].

PubMed

Vitinius, Frank; Sonntag, Bernd; Barthel, Yvette; Brennfleck, Barbara; Kuhnt, Susanne; Werner, Andreas; Schönefuß, Götz; Petermann-Meyer, Andrea; Gutberlet, Susanne; Stein, Barbara; Söllner, Wolfgang; Kruse, Johannes; Keller, Monika

2013-12-01

Goal of the KoMPASS project is to develop and test a training program that effectively improves oncologists' communication skills. The training draws with regard to concept, content and didactic methods to the specific challenges arising in interactions with cancer patients. Concept and didactical methods for an intensive training (KoMPASS Training) are being presented and complemented with experiences gathered during 39 trainings with 335 physicians, as well as findings from the training evaluation by participants. The participants' feedback after 4 months indicates successful transfer into clinical practice along with personal relief, improved self-efficacy, and communicative competencies. Even experienced practitioners ascribe high practical usefulness, and personal learning achievements to the KoMPASS training. The results of the concomitant study concerning self-efficacy, empathy, work-related stress and communicative competence will be published later. © Georg Thieme Verlag KG Stuttgart · New York.

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

A randomized, controlled phase I/II study to evaluate the safety and efficacy of MGV354 for ocular hypertension or glaucoma.

PubMed

Stacy, Rebecca; Huttner, Kenneth; Watts, Jen; Peace, James; Wirta, David; Walters, Tom; Sall, Kenneth; Seaman, John; Ni, Xiao; Prasanna, Ganesh; Mogi, Muneto; Adams, Christopher; Yan, Jing-He; Wald, Michael; He, Yunsheng; Newton, Ronald; Kolega, Randall; Grosskreutz, Cynthia

2018-05-23

To assess the clinical safety, tolerability, and efficacy of topically administered MGV354, a soluble guanylate cyclase (sGC) activator, in patients with ocular hypertension (OH) or glaucoma DESIGN: Double-masked, randomized, and vehicle-controlled study METHODS: Parts 1 and 2 evaluated safety and tolerability to identify the maximum tolerated dose (MTD) of once daily MGV354 in 32 healthy volunteers (Part 1) and 16 patients with OH or glaucoma (Part 2) at a single clinical site. Part 3 was a multi-site trial that evaluated IOP-lowering efficacy of the MTD administered nightly for one week in 50 patients with minimum IOP of 24mm Hg at 8 AM, with a main outcome measure of mean diurnal IOP at Day 8 compared to baseline (ClinicalTrials.gov NCT02743780). There was no difference in favor of MGV354 for IOP lowering; change from Baseline to Day 8 in mean diurnal IOP was -0.6 mmHg for MGV354-treated patients and -1.1 mmHg for Vehicle-treated patients in Part 3, with a confidence interval of -0.7 to 1.7. The most common adverse events reported after MGV354 administration were conjunctival and ocular hyperemia. Overall, MGV354 0.1% demonstrated no statistically significant effect compared to Vehicle in lowering IOP based upon the study's main outcome measure. MGV354 produced ocular hyperemia consistent with its pharmacology. Copyright © 2018 Elsevier Inc. All rights reserved.

Mirtazapine in the treatment of essential tremor: an open-label, observer-blind study

PubMed Central

Uccellini, Davide; Grampa, G; La Spina, I; Nasuelli, D; Neromante, I; Politini, L; Reverberi, F; Porazzi, D; Carli, V; Camardese, G

2006-01-01

Introduction Essential tremor (ET) is the most common movement disorder in the adult population. At present ET treatment shows limited efficacy, particularly in patients with severe and disabling symptoms. This study evaluates the clinical efficacy of mirtazapine in an untreated ET patient population. Materials and methods 30 ET patients (female/male = 19/11; average age = 71.4 ± 8.3 years) were examined by clinical criteria, electromyographic (EMG), and apomorphine tests to study the cortical silent period. The patients were all treated with mirtazapine 30 mg daily. Results Mirtazapine proved to be a good control agent for tremor symptomatology in 23/27 patients (85%) who completed 1 month of treatment, with a marked reduction of tremor; the benefit was maintained during the 12-month follow-up. No significant variation in EMG parameters was observed aside from two prevalent and distinct frequencies of tremors (5–6 Hz and 7–8 Hz) and a group of selected patients whose cortical silent period (SP) was markedly reduced. There were no clinical differences between the two subgroups. All apomorphine-tested patients showed an SP with no significant modifications. Conclusions Mirtazapine proved to be an efficacious drug treatment for tremor symptoms in patients suffering from ET. It had limited side effects and excellent overall tolerability, could be used as daily monotherapy, and did not interfere with any of the many other medications being taken simultaneously by the patients. PMID:19412450

Safety and efficacy of cervical laminoplasty using a piezosurgery device compared with a high-speed drill

PubMed Central

Li, Kunpeng; Zhang, Wen; Li, Bin; Xu, Hui; Li, Zhong; Luo, Dawei; Zhang, Jingtao; Ma, Jinzhu

2016-01-01

Abstract Background: Piezosurgery is a relatively new osteotomy technique using microvibrations of scalpels at ultrasonic frequencies to perform safe and effective osteotomies without damage to adjacent soft tissue, which is widely used in spinal, oral, and maxillofacial surgery. We hypothesized that such a device could also be useful in cervical laminoplasty. The purpose of this study was to compare the safety and efficacy of a piezosurgery device with those of a highspeed drill in cervical laminoplasty. Methods: A prospectively randomized clinical study was designed. Forty-two consecutive patients were enrolled in the study. All patients underwent modified expansive open-door laminoplasty and were randomly divided into 2 groups according to the instrument for transection of the lamina, using high-speed drill (drill group) or piezosurgery device (piezosurgery group). The operation time, intraoperative blood loss, and postoperative drainage were recorded. Japanese Orthopedic Association (JOA) score and visual analogue scale (VAS) as clinical assessments were quantified. Results: No significant difference was observed in the operation time between the 2 groups. In the piezosurgery group, there were less loss of the intraoperative blood and postoperative drainage compared with the drill group. However, clinical results (VAS and JOA scores) showed no significant difference between both groups during the all follow-up periods. Conclusion: The piezosurgery is a useful instrument and at least as safe and efficacious as the conventional high-speed drill in cervical laminoplasty. PMID:27631268

Evidence Gaps in the Use of Spinal Cord Stimulation for Treating Chronic Spine Conditions.

PubMed

Provenzano, David A; Amirdelfan, Kasra; Kapural, Leonardo; Sitzman, B Todd

2017-07-15

A review of literature. The aim of this study was to define and explore the current evidence gaps in the use of spinal cord stimulation (SCS) for treating chronic spine conditions. Although over the last 40 years SCS therapy has undergone significant technological advancements, evidence gaps still exist. A literature review was conducted to define current evidence gaps for the use of SCS. Areas of focus included 1) treatment of cervical spine conditions, 2) treatment of lumbar spine conditions, 3) technological advancement and device selection, 4) appropriate patient selection, 5) the ability to curb pharmacological treatment, and 6) methods to prolong efficacy over time. New SCS strategies using advanced waveforms are explored. The efficacy, safety, and cost-effectiveness of traditional SCS for chronic pain conditions are well-established. Evidence gaps do exist. Recently, advancement in waveforms and programming parameters have allowed for paresthesia-reduced/free stimulation that in specific clinical areas may improve clinical outcomes. New waveforms such as 10-kHz high-frequency have resulted in an improvement in back coverage. To date, clinical efficacy data are more prevalent for the treatment of painful conditions originating from the lumbar spine in comparison to the cervical spine. Evidence gaps still exist that require appropriate study designs with long-term follow-up to better define and improve the use of this therapy for the treatment of chronic spine pain in both the cervical and lumbar regions. N/A.

A Review of the Efficacy, Safety, and Clinical Implications of Naturally Derived Dietary Supplements for Dyslipidemia.

PubMed

Thaipitakwong, Thanchanit; Aramwit, Pornanong

2017-02-01

Dyslipidemia is recognized as a major cause of cardiovascular disease. A number of evidence-based guidelines recommend conventional synthetic drugs as standard therapy for dyslipidemia in clinical practice. However, antihyperlipidemic drugs have some serious side effects. Naturally derived dietary supplements are becoming attractive as an alternative strategy because of their high efficacy and safety, as supported by numerous data. Moreover, they could be considered an initial treatment for dyslipidemia. The aims of this literature review were to demonstrate the efficacy, safety, and clinical implications of dietary supplements for treating dyslipidemia. We reviewed the literature, including data from in vitro, in vivo, and human studies, and clinical guideline recommendations. We classified dietary supplements by their proposed mechanisms of action on lipid metabolism and also collected daily dosage recommendations, interactions with concurrent drugs and/or foods, dosage forms, and examples of commercially available products. Various types of naturally derived dietary supplements exhibit lipid-improving properties. Efficacy and safety are acceptable; however, their use in clinical practice will require further well-designed investigations and the support of scientific data.

Role of illness perception and self-efficacy in lifestyle modification among non-alcoholic fatty liver disease patients

PubMed Central

Zelber-Sagi, Shira; Bord, Shiran; Dror-Lavi, Gali; Smith, Matthew Lee; Towne Jr, Samuel D; Buch, Assaf; Webb, Muriel; Yeshua, Hanny; Nimer, Assy; Shibolet, Oren

2017-01-01

AIM To describe the relationships between non-alcoholic fatty-liver disease (NAFLD) patient’s disease consequences and treatment perceptions, self-efficacy, and healthy lifestyle maintenance. METHODS A cross-sectional study among 146 ultrasound diagnosed NAFLD patients who visited the fatty liver clinic at the Tel-Aviv Medical Center. Eighty-seven of these individuals, participated in a clinical trial of physical activity and underwent fasting blood tests, analyzed at the same lab. Exclusion criteria included positivity for serum HBsAg or anti-HCV antibodies; fatty liver suspected to be secondary to hepatotoxic drugs; excessive alcohol consumption (≥ 30 g/d in men or ≥ 20 g/d in women) and positive markers of genetic or immune-mediated liver diseases. Patients were asked to complete a self-report structured questionnaire, assembled by the Israeli Center for Disease Control. Nutrition habits were measured using six yes/no questions (0 = no, 1 = yes) adopted from the national survey questionnaire. Participants in the clinical trial completed a detailed semi-quantitative food frequency questionnaire (FFQ) reporting their habitual nutritional intake during the past year. Self-efficacy was assessed by the Self-Efficacy Scale questionnaire, emotional representation, degree of illness understanding, timeline perception, treatment perception and symptoms were measured by the Brief Illness Perception questionnaire. Illness consequences were measured by the Personal Models of Diabetes Interview questionnaire. A path analysis was performed to describe the interrelationships between the patients’ illness perceptions, and assess the extent to which the data fit a prediction of nutritional habits. RESULTS The study sample included 54.1% men, with a mean age of 47.76 ± 11.68 years (range: 20-60) and mean body mass index of 31.56 ± 4.6. The average perceived nutrition habits score was 4.73 ± 1.45 on a scale between 0-6, where 6 represents the healthiest eating habits. Most of the study participants (57.2%) did not feel they fully understood what NAFLD is. Better nutritional habits were positively predicted by the degree of illness understanding (β = 0.26; P = 0.002) and self-efficacy (β = 0.25; P = 0.003). Perceptions of more severe illness consequences were related with higher emotional representation (β = 0.55; P < 0.001), which was related with lower self-efficacy (β = -0.17; P = 0.034). The perception of treatment effectiveness was positively related with self-efficacy (β = 0.32; P < 0.001). In accordance with the correlation between self-efficacy and the perceived nutrition habits score, self-efficacy was also correlated with nutrient intake evaluated by the FFQ; negatively with saturated fat (percent of saturated fat calories from total calories) (r = -0.28, P = 0.010) and positively with fiber (r = 0.22, P = 0.047) and vitamin C intake (r = 0.34, P = 0.002). In a sub analysis of the clinical trial participants, objectively measured compliance to physical activity regimen was positively correlated with the self-efficacy level (r = 0.34, P = 0.046). CONCLUSION Self-efficacy and illness understanding are major determinants of lifestyle-modification among NAFLD patients. This information can assist clinicians in improving compliance with lifestyle changes among these patients. PMID:28348495

Testing the effectiveness of a self-efficacy based exercise intervention for inactive people with type 2 diabetes mellitus: design of a controlled clinical trial

PubMed Central

2012-01-01

Background Sufficient exercise is important for people with Type 2 Diabetes Mellitus (T2DM), as it can prevent future health problems. Despite, it is estimated that only 30-40% of people with T2DM are sufficiently active. One of the psychosocial constructs that is believed to influence physical activity behaviour, is exercise self-efficacy. The goal of this study is to evaluate a patient-tailored exercise intervention for people with T2DM that takes exercise self-efficacy into account. Methods/Design This study is conducted as a non-randomized controlled clinical trial. Patients are eligible when they are diagnosed with T2DM, exercise less than advised in the ADA guideline of 150 min/week of moderate-intensity aerobic physical activity, have an BMI >25 and are between 18 and 80 years old. Recruitment takes place at a Primary care organization of general practitioners and practice nurses in the south of the Netherlands. Participants are allocated to three groups: An advice intervention -for participants with a high exercise self-efficacy score- in which participants receive a patient-tailored exercise intervention, an intensive intervention -for participants with a low exercise self-efficacy score- in which participants receive a patient-tailored exercise intervention accomplished by a group based intervention, and a control group in which participants receive regular Dutch diabetes care. The primary outcome measure of this study is physical activity. Secondary outcome measures are health status, (symptoms of) depression, exercise self-efficacy, Body Mass Index (BMI), blood pressure and glycemic control. Discussion We aimed to design an intervention that can be implemented in Primary care, but also to design an easy accessible program. This study is innovative as it is -to our best knowledge- the first study that takes level of exercise self-efficacy of people with T2DM into account by means of giving extra support to those with the lowest exercise self-efficacy. If the program succeeds in increasing the amount of physical activity it can be implemented in regular primary care. Trial registration Dutch Trial Register NTR2734 PMID:22559322

Examining the Moderating Effect of Depressive Symptoms on the Relation Between Exercise and Self-Efficacy During the Initiation of Regular Exercise

PubMed Central

Kangas, Julie L.; Baldwin, Austin S.; Rosenfield, David; Smits, Jasper A. J.; Rethorst, Chad D.

2016-01-01

Objective People with depressive symptoms typically report lower levels of exercise self-efficacy and are more likely to discontinue regular exercise than others, but it is unclear how depressive symptoms affect people’s exercise self-efficacy. Among potential sources of self-efficacy, engaging in the relevant behavior is the strongest (Bandura, 1997). Thus, we sought to clarify how depressive symptoms affect the same-day relation between engaging in exercise and self-efficacy during the initiation of regular exercise. Methods Participants (N=116) were physically inactive adults (35% reported clinically significant depressive symptoms at baseline) who initiated regular exercise and completed daily assessments of exercise minutes and self-efficacy for four weeks. We tested whether (a) self-efficacy differed on days when exercise did and did not occur, and (b) the difference was moderated by depressive symptoms. Mixed linear models were used to examine these relations. Results An interaction between exercise occurrence and depressive symptoms (p<.001) indicated that self-efficacy was lower on days when no exercise occurred, but this difference was significantly larger for people with high depressive symptoms. People with high depressive symptoms had lower self-efficacy than those with low depressive symptoms on days when no exercise occurred (p=.03), but self-efficacy did not differ on days when exercise occurred (p=.34). Conclusions During the critical period of initiating regular exercise, daily self-efficacy for people with high depressive symptoms is more sensitive to whether they exercised than for people with low depressive symptoms. This may partially explain why people with depression tend to have difficulty maintaining regular exercise. PMID:25110850

The Relationship between Self-Efficacy and Resting Blood Pressure in Spousal Alzheimer’s Caregivers

PubMed Central

Harmell, Alexandrea L.; Mausbach, Brent T; Roepke, Susan K.; Moore, Raeanne; von Känel, Roland; Patterson, Thomas L; Dimsdale, Joel E; Mills, Paul J; Ziegler, Michael G.; Allison, Matthew A.; Ancoli-Israel, Sonia; Grant, Igor

2011-01-01

OBJECTIVE To examine whether increased self-efficacy for using problem-focused coping was significantly related to several resting blood pressure measures in spousal Alzheimer’s disease caregivers. METHODS Participants included 100 older caregivers (mean age= 73.8 ± 8.14 years) providing in home care for a spouse with Alzheimer’s disease (AD). All participants completed a 13 item short form of the coping self-efficacy scale and underwent an in-home assessment where a visiting nurse took the average of three serial blood pressure readings. Multiple regression was used to examine the relationship between self-efficacy and mean arterial pressure (MAP), systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP) after controlling for age, gender, smoking history, body mass index, the care recipient’s clinical dementia rating (CDR), diabetes, alcohol use, and the use of anti-hypertensive medications. RESULTS Overall, increased self-efficacy (as measured by the Coping Self-efficacy scale) was significantly related to lower resting MAP (β = −.26, t(90) = −2.47, p = .016) and SBP (β=−.28, t(90)= −2.74, p= .007) . Self-efficacy was marginally associated with resting DBP, but not significant (β = −.20, t(90) = −1.91, p= .06). Lastly, self-efficacy was significantly related to pulse pressure (β = −.21, t(90) = −2.31 p= .023). In addition, 1 standard deviation increase in self-efficacy was associated with a decrease of approximately 4 mmHg in SBP. CONCLUSIONS These results suggest an association between high self-efficacy on resting blood pressure. Because psychosocial interventions for Alzheimer’s caregivers have potential to increase self-efficacy, it appears possible that these interventions could have a beneficial impact on caregivers’ cardiovascular function. PMID:21489059

VALIDATION OF MICROSATELLITE MARKERS FOR USE IN GENOTYPING POLYCLONAL PLASMODIUM FALCIPARUM INFECTIONS

PubMed Central

GREENHOUSE, BRYAN; MYRICK, ALISSA; DOKOMAJILAR, CHRISTIAN; WOO, JONATHAN M.; CARLSON, ELAINE J.; ROSENTHAL, PHILIP J.; DORSEY, GRANT

2006-01-01

Genotyping methods for Plasmodium falciparum drug efficacy trials have not been standardized and may fail to accurately distinguish recrudescence from new infection, especially in high transmission areas where polyclonal infections are common. We developed a simple method for genotyping using previously identified microsatellites and capillary electrophoresis, validated this method using mixtures of laboratory clones, and applied the method to field samples. Two microsatellite markers produced accurate results for single-clone but not polyclonal samples. Four other microsatellite markers were as sensitive as, and more specific than, commonly used genotyping techniques based on merozoite surface proteins 1 and 2. When applied to samples from 15 patients in Burkina Faso with recurrent parasitemia after treatment with sulphadoxine-pyrimethamine, the addition of these four microsatellite markers to msp1 and msp2 genotyping resulted in a reclassification of outcomes that strengthened the association between dhfr 59R, an anti-folate resistance mutation, and recrudescence (P = 0.31 versus P = 0.03). Four microsatellite markers performed well on polyclonal samples and may provide a valuable addition to genotyping for clinical drug efficacy studies in high transmission areas. PMID:17123974

Efficacy and safety of fluocinolone acetonide, hydroquinone, and tretinoin cream in chinese patients with melasma: a randomized, double-blind, placebo-controlled, multicenter, parallel-group study.

PubMed

Gong, Zijian; Lai, Wei; Zhao, Guang; Wang, Xuemin; Zheng, Min; Li, Li; Yang, Qingqi; Dang, Yuping; Liu, Lunfei; Zou, Ying

2015-06-01

This study aimed to determine the efficacy and safety of fluocinolone acetonide, hydroquinone, and tretinoin (FAHT) cream for the treatment of moderate and severe facial melasma. The primary objective was assessment of clinical efficacy, instrumental measured efficacy, and integral therapeutic efficacy at the end of weeks 4 and 8. A total of 233 subjects were randomly allocated (1:1 ratio) to receive topically administered FAHT cream (n = 117) or placebo (n = 116) once nightly for 8 weeks. Observed side effects were documented throughout. In the per protocol set (PPS; those subjects who met all requirements of the protocol), the integral therapeutic efficacy rate of FAHT cream on moderate and severe melasma was 68.57% (vs. placebo, 0.94%), the clinical effective rate of FAHT cream was 74.29 % (vs. placebo, 0.94%), and the instrumental measure efficacy of FAHT cream was 71.43% (vs. placebo, 6.60%). The difference in efficacy between the two groups was statistically significant (p < 0.001). In the full analysis set (FAS; the PPS and those subjects who were lost to follow-up but received at least one study treatment), the integral therapeutic efficacy rate of FAHT cream was 64.60% (vs. placebo, 0.88%), the clinical effective rate of FAHT cream was 69.91% (vs. placebo, 0.88%), and the instrumental measure efficacy of FAHT cream was 69.03 % (vs. placebo, 7.08%). The difference in efficacy between the two groups was statistically significant (p < 0.001). Of 113 subjects in the FAHT group, 34 (30.1%) reported adverse effects. Most of the pathological adverse effects were mild and resolved with either continuous treatment or discontinuation. Of 113 subjects in the placebo group, three (2.6%) reported mild adverse effects. No severe adverse effects or other abnormal clinical results were associated with the study treatment. FAHT cream is efficacious, well tolerated, and has a high margin of safety for the treatment of moderate and severe melasma in the Chinese population.

Progression-free survival: gaining on overall survival as a gold standard and accelerating drug development.

PubMed

Lebwohl, David; Kay, Andrea; Berg, William; Baladi, Jean Francois; Zheng, Ji

2009-01-01

In clinical trials of oncology drugs, overall survival (OS) is a direct measure of clinical efficacy and is considered the gold standard primary efficacy end point. The purpose of this study was to discuss the difficulties in using OS as a primary efficacy end point in the setting of evolving cancer therapies. We suggest that progression-free survival is an appropriate efficacy end point in many types of cancer, specifically those for which OS is expected to be prolonged and for which subsequent treatments are expected to affect OS.

Computer laser system for prevention and treatment of dental diseases: new methods and results

NASA Astrophysics Data System (ADS)

Fedyai, S. G.; Prochonchukov, Alexander A.; Zhizhina, Nina A.; Metelnikov, Michael A.

1995-05-01

We report results of clinical application of the new computer-laser system. The system includes hardware and software means, which are applied for new efficient methods of prevention and treatment of main dental diseases. The hardware includes a laser physiotherapeutic device (LPD) `Optodan' and a fiberoptic laser delivery system with special endodontic rigging. The semiconductor AG-AL-AG laser diode with wavelengths in the spectral range of 850 - 950 nm (produced by Scientific-Industrial Concern `Reflector') is used as a basic unit. The LPD `Optodan' and methods of treatment are covered by Russian patent No 2014107 and certified by the Russian Ministry of Health. The automated computer system allows us to examine patients quickly and to input differential diagnosis, to determine indications (and contraindications), parameters and regimen of laser therapy, to control treatment efficacy (for carious -- through clinical indexes of enamel solubles, velocity of demineralization and other tests; for periodontal diseases trough complex of the periodontal indexes with automated registry and calculation). We present last results of application of the new technique and methods in treatment of dental diseases in Russian clinics.

The use of ketamine in ECT anaesthesia: A systematic review and critical commentary on efficacy, cognitive, safety and seizure outcomes.

PubMed

Gálvez, Verònica; McGuirk, Lucy; Loo, Colleen K

2017-09-01

This review will discuss ECT efficacy and cognitive outcomes when using ketamine as an ECT anaesthetic compared to other anaesthetics, taking into account important moderator variables that have often not been considered to date. It will also include information on safety and other ECT outcomes (seizure threshold and quality). A systematic search through MEDLINE, PubMed, PsychINFO, Cochrane Databases and reference lists from retrieved articles was performed. Search terms were: "ketamine" and "Electroconvulsive Therapy", from 1995 to September 2016. Meta-analyses, randomised controlled trials, open-label and retrospective studies published in English of depressed samples receiving ECT with ketamine anaesthesia were included (n = 24). Studies were heterogeneous in the clinical populations included and ECT treatment and anaesthetic methods. Frequently, studies did not report on ECT factors (i.e., pulse-width, treatment schedule). Findings regarding efficacy were mixed. Tolerance from repeated use may explain why several studies found that ketamine enhanced efficacy early in the ECT course but not at the end. The majority of studies did not comprehensively examine cognition and adverse effects were not systematically studied. Only a minority of the studies reported on seizure threshold and expression. The routine use of ketamine anaesthesia for ECT in clinical settings cannot yet be recommended based on published data. Larger randomised controlled trials, taking into account moderator variables, specifically reporting on ECT parameters and systematically assessing outcomes are encouraged.

Acute and sub acute toxicity and efficacy studies of Hippophae rhamnoides based herbal antioxidant supplement

PubMed Central

Ali, Rashid; Ali, Raisuddin; Jaimini, Abhinav; Nishad, Dhruv Kumar; Mittal, Gaurav; Chaurasia, Om Prakash; Kumar, Raj; Bhatnagar, Aseem; Singh, Shashi Bala

2012-01-01

Objectives: Present study was carried out to evaluate acute and subacute toxicity and efficacy of Seabuckthorn (Hippophae rhamnoides) based herbal antioxidant supplement (HAOS). Materials and Methods: In vivo toxicity studies were performed in male balb ‘C’ mice by oral administration. Acute toxicity study was done at doses ranging from 2000 to 10 000 mg/ kg while in subacute studies, HAOS was given at doses of 2000, 4000, and 8000 mg/kg body weight. Animals were observed for any toxic sign and symptoms periodically. At completion of study animals were sacrificed; their hematological, biochemical parameters were analyzed and histopathology of vital organs was done. In vivo efficacy studies in human volunteers were done and the levels of vitamin A and Vitamin C in blood samples were analyzed in comparison to a similar commercially available formulation. Results: No mortality and any clinical signs of toxicity were found in HAOS administered group of animals. There were no significant alterations in hematological and biochemical parameters. Histopathological analysis of vital organs showed normal architecture in all the HAOS administered groups. Human studies showed an increase of 32% and 172% in Vitamin A and Vitamin C levels respectively in term of bioavailability. Conclusion: The data obtained indicate no toxicity of this antioxidant supplement up to the highest dose studied. Efficacy in terms of increased bioavailability of vitamin A and C in human volunteers indicates the clinical usefulness of the supplement. PMID:23087514

Review: Current clinical applications of chimeric antigen receptor (CAR) modified T cells

PubMed Central

Geyer, Mark B.; Brentjens, Renier J.

2016-01-01

The past several years have been marked by extraordinary advances in clinical applications of immunotherapy. In particular, adoptive cellular therapy utilizing chimeric antigen receptor (CAR) modified T cells targeted to CD19 has demonstrated substantial clinical efficacy in children and adults with relapsed or refractory B cell acute lymphoblastic leukemia (B-ALL), and durable clinical benefit in a smaller subset of patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or B cell non-Hodgkin lymphoma (B-NHL). Early phase clinical trials are presently assessing CAR T cell safety and efficacy in additional malignancies. Herein, we discuss clinical results from the largest series to date investigating CD19-targeted CAR T cells in B-ALL, CLL, and B-NHL, including discussion of differences in CAR T cell design and production and treatment approach, as well as clinical efficacy, nature of severe cytokine release syndrome and neurologic toxicities, and CAR T cell expansion and persistence. We additionally review the current and forthcoming use of CAR T cells in multiple myeloma and several solid tumors, and highlight challenges and opportunities afforded by the current state of CAR T cell therapies, including strategies to overcome inhibitory aspects of the tumor microenvironment and enhance antitumor efficacy. PMID:27592405

Review: Current clinical applications of chimeric antigen receptor (CAR) modified T cells.

PubMed

Geyer, Mark B; Brentjens, Renier J

2016-11-01

The past several years have been marked by extraordinary advances in clinical applications of immunotherapy. In particular, adoptive cellular therapy utilizing chimeric antigen receptor (CAR)-modified T cells targeted to CD19 has demonstrated substantial clinical efficacy in children and adults with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) and durable clinical benefit in a smaller subset of patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or B-cell non-Hodgkin lymphoma (B-NHL). Early-phase clinical trials are currently assessing CAR T-cell safety and efficacy in additional malignancies. Here, we discuss clinical results from the largest series to date investigating CD19-targeted CAR T cells in B-ALL, CLL, and B-NHL, including discussion of differences in CAR T-cell design and production and treatment approach, as well as clinical efficacy, nature of severe cytokine release syndrome and neurologic toxicities, and CAR T-cell expansion and persistence. We additionally review the current and forthcoming use of CAR T cells in multiple myeloma and several solid tumors and highlight challenges and opportunities afforded by the current state of CAR T-cell therapies, including strategies to overcome inhibitory aspects of the tumor microenvironment and enhance antitumor efficacy. Published by Elsevier Inc.

A 13-year real-life study on efficacy, safety and biological effects of Vespula venom immunotherapy.

PubMed

Albanesi, Marcello; Nico, Andrea; Sinisi, Alessandro; Giliberti, Lucia; Rossi, Maria Pia; Rossini, Margherita; Kourtis, Georgios; Rucco, Anna Simona; Loconte, Filomena; Muolo, Loredana; Zurlo, Marco; Di Bona, Danilo; Caiaffa, Maria Filomena; Macchia, Luigi

2018-01-01

Hymenoptera venom immunotherapy (VIT) is a clinically effective treatment. However, little is known about its long-term clinical efficacy and biological effects. Several mechanisms have been proposed to account for VIT efficacy, including reduction of specific IgE and induction of allergen-specific IgG 4 , but the overall picture remains elusive. We investigated Vespula VIT clinical efficacy up to 8 years after discontinuation and the kinetics of Vespula -specific IgE and IgG 4 . Out of 686 consecutive patients we retrospectively selected and analysed a series of 23 patients with Vespula allergy that underwent a 5-year IT course, followed by a prolonged follow-up. Clinical efficacy of VIT was assessed as number and severity of reactions to Vespula re-stinging events. The presence of Vespula -specific IgE and IgG 4 was also monitored over time. During the VIT treatment, patients were protected, reporting no reactions or mild reactions in occasion of re-stinging events. This protection was entirely maintained during the follow-up, up to 8 years. Skin reactivity (reflecting mast cell-bound Vespula -specific IgE) and circulating Vespula -specific IgE levels declined substantially during VIT. Notably, this reduction was maintained over time during the follow-up. Moreover, all the patients were analysed for IgG 4 . A robust induction of Vespula -specific IgG 4 was observed during the VIT course, with a substantial decline during the follow-up. We conclude that Vespula VIT is a clinically effective treatment, which induces long-term protection after discontinuation. The reduction of specific IgE, assessed by skin tests and RAST, closely matches the VIT- induced protection, while the IgG 4 induction seems not to be associated with VIT clinical efficacy in the long term.

Current and Future Clinical Applications of High-Intensity Focused Ultrasound (HIFU) for Pancreatic Cancer.

PubMed

Jang, Hyun Joo; Lee, Jae-Young; Lee, Don-Haeng; Kim, Won-Hong; Hwang, Joo Ha

2010-09-01

High-intensity focused ultrasound (HIFU) is a novel therapeutic modality that permits noninvasive treatment of various benign and malignant solid tumors, including prostatic cancer, uterine fibroids, hepatic tumors, renal tumors, breast cancers, and pancreatic cancers. Several preclinical and clinical studies have investigated the safety and efficacy of HIFU for treating solid tumors, including pancreatic cancer. The results of nonrandomized studies of HIFU therapy in patients with pancreatic cancer have suggested that HIFU treatment can effectively alleviate cancer-related pain without any significant complications. This noninvasive method of delivering ultrasound energy into the body has recently been evolving from a method for purely thermal ablation to harnessing the mechanical effects of HIFU to induce a systemic immune response and to enhance targeted drug delivery. This review provides a brief overview of HIFU, describes current clinical applications of HIFU for pancreatic cancer, and discusses future applications and challenges.

Current and Future Clinical Applications of High-Intensity Focused Ultrasound (HIFU) for Pancreatic Cancer

PubMed Central

Jang, Hyun Joo; Lee, Jae-Young; Lee, Don-Haeng; Kim, Won-Hong

2010-01-01

High-intensity focused ultrasound (HIFU) is a novel therapeutic modality that permits noninvasive treatment of various benign and malignant solid tumors, including prostatic cancer, uterine fibroids, hepatic tumors, renal tumors, breast cancers, and pancreatic cancers. Several preclinical and clinical studies have investigated the safety and efficacy of HIFU for treating solid tumors, including pancreatic cancer. The results of nonrandomized studies of HIFU therapy in patients with pancreatic cancer have suggested that HIFU treatment can effectively alleviate cancer-related pain without any significant complications. This noninvasive method of delivering ultrasound energy into the body has recently been evolving from a method for purely thermal ablation to harnessing the mechanical effects of HIFU to induce a systemic immune response and to enhance targeted drug delivery. This review provides a brief overview of HIFU, describes current clinical applications of HIFU for pancreatic cancer, and discusses future applications and challenges. PMID:21103296

Return of the psychedelics: Psilocybin for treatment resistant depression.

PubMed

Patra, Suravi

2016-12-01

Psilocybin, the clinically most researched classic psychedelic has recently been tested for its safety and efficacy in a clinical population of treatment resistant depression. The efficacy of psilocybin in clinical depression previously demonstrated in the elecrophysiologic and neuroimaging findings as also in neuropsychological assessments is further validated by the findings of this rigorously conducted randomized trial. Mechanism of action of psilocybin and efficacy in treatment resistant depression are discussed in this paper. Ethical issues of conducting clinical trials with psychedelics are also discussed with particular emphasis on their relative safety and absence of addiction potential. Implications of these issues for conduct of larger trials for establishing risk benefit ratio in treatment resistant depression are further suggested. Copyright © 2016 Elsevier B.V. All rights reserved.

Predicting analysis time in events-driven clinical trials using accumulating time-to-event surrogate information.

PubMed

Wang, Jianming; Ke, Chunlei; Yu, Zhinuan; Fu, Lei; Dornseif, Bruce

2016-05-01

For clinical trials with time-to-event endpoints, predicting the accrual of the events of interest with precision is critical in determining the timing of interim and final analyses. For example, overall survival (OS) is often chosen as the primary efficacy endpoint in oncology studies, with planned interim and final analyses at a pre-specified number of deaths. Often, correlated surrogate information, such as time-to-progression (TTP) and progression-free survival, are also collected as secondary efficacy endpoints. It would be appealing to borrow strength from the surrogate information to improve the precision of the analysis time prediction. Currently available methods in the literature for predicting analysis timings do not consider utilizing the surrogate information. In this article, using OS and TTP as an example, a general parametric model for OS and TTP is proposed, with the assumption that disease progression could change the course of the overall survival. Progression-free survival, related both to OS and TTP, will be handled separately, as it can be derived from OS and TTP. The authors seek to develop a prediction procedure using a Bayesian method and provide detailed implementation strategies under certain assumptions. Simulations are performed to evaluate the performance of the proposed method. An application to a real study is also provided. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Pharmaco-parasitological evaluation of the ricobendazole plus levamisole nematodicidal combination in cattle.

PubMed

Canton, C; Ceballos, L; Domínguez, M P; Moreno, L; Fiel, C; Bernat, G; Farías, C; Lanusse, C; Alvarez, L

2018-02-01

The goals of the current study were to evaluate the potential pharmacokinetic (PK) interactions and the clinical efficacy occurring after the subcutaneous (s.c.) administration of ricobendazole (RBZ) and levamisole (LEV) given both separately and co-administered to calves naturally infected with susceptible gastrointestinal nematodes. The clinical efficacy was shown in two seasons, winter and spring, with predominance of different nematode populations. Groups of 15 calves were treated with RBZ alone, LEV alone and RBZ + LEV combination, and an untreated group was kept as a Control. RBZ and LEV plasma concentrations were quantified by HPLC. The clinical efficacy was determined by the faecal egg count reduction test. RBZ and LEV have similar plasma persistence, being detected in plasma over 24 hr post-treatment. No PK interactions were observed after the combined treatment, with similar PK parameters (p > .05) obtained for the single-drug and the combination-based strategy. In winter, the observed clinical efficacies were 96%, 99% and 100% for groups treated with RBZ, LEV and RBZ + LEV, respectively; however, in spring, the efficacies were 95%, 93% and 96% for the same groups. Remarkably, the combination was the only treatment that achieved 100% clinical efficacy against both Haemonchus spp and Ostertagia spp in winter; but the increased presence of Ostertagia spp. in spring (28% in untreated group) determined a tendency to reduced efficacies compared to winter time (only 10% of Ostertagia spp. in untreated group), even for the combined treatment. Overall, in a scenario where the nematode population is susceptible, the RBZ + LEV treatment may be a valid combination in cattle to delay the development of resistance, especially in winter when this combination achieved 100% of efficacy. Thus, selection of anthelmintic resistance will never occur. In fact, this is one of the greatest challenges for the whole cattle production system: to be one step ahead of anthelmintic resistance. © 2017 John Wiley & Sons Ltd.

Illustrating idiographic methods for translation research: moderation effects, natural clinical experiments, and complex treatment-by-subgroup interactions.

PubMed

Ridenour, Ty A; Wittenborn, Andrea K; Raiff, Bethany R; Benedict, Neal; Kane-Gill, Sandra

2016-03-01

A critical juncture in translation research involves the preliminary studies of intervention tools, provider training programs, policies, and other mechanisms used to leverage knowledge garnered at one translation stage into another stage. Potentially useful for such studies are rigorous techniques for conducting within-subject clinical trials, which have advanced incrementally over the last decade. However, these methods have largely not been utilized within prevention or translation contexts. The purpose of this manuscript is to demonstrate the flexibility, wide applicability, and rigor of idiographic clinical trials for preliminary testing of intervention mechanisms. Specifically demonstrated are novel uses of state-space modeling for testing intervention mechanisms of short-term outcomes, identifying heterogeneity in and moderation of within-person treatment mechanisms, a horizontal line plot to refine sampling design during the course of a clinic-based experimental study, and the need to test a treatment's efficacy as treatment is administered along with (e.g., traditional 12-month outcomes).

Model for teaching population health and community-based care across diverse clinical experiences.

PubMed

Van Dyk, Elizabeth J; Valentine-Maher, Sarah K; Tracy, Janet P

2015-02-01

The pillars constructivist model is designed to offer a unifying clinical paradigm to support consistent learning opportunities across diverse configurations of community and public health clinical sites. Thirty-six students and six faculty members participated in a mixed methods evaluation to assess the model after its inaugural semester of implementation. The evaluation methods included a rating scale that measures the model's ability to provide consistent learning opportunities at both population health and direct care sites, a case study to measure student growth within the five conceptual pillars, and a faculty focus group. Results revealed that the model served as an effective means of clinical education to support the use of multiple, small-scale public health sites. Although measurements of student growth within the pillars are inconclusive, the findings suggest efficacy. The authors recommend the continued use of the pillars constructivist model in baccalaureate programs, with further study of the author-designed evaluation tools. Copyright 2015, SLACK Incorporated.

Botulinum toxin type A products are not interchangeable: a review of the evidence

PubMed Central

Brin, Mitchell F; James, Charmaine; Maltman, John

2014-01-01

Botulinum toxin type A (BoNTA) products are injectable biologic medications derived from Clostridium botulinum bacteria. Several different BoNTA products are marketed in various countries, and they are not interchangeable. Differences between products include manufacturing processes, formulations, and the assay methods used to determine units of biological activity. These differences result in a specific set of interactions between each BoNTA product and the tissue injected. Consequently, the products show differences in their in vivo profiles, including preclinical dose response curves and clinical dosing, efficacy, duration, and safety/adverse events. Most, but not all, published studies document these differences, suggesting that individual BoNTA products act differently depending on experimental and clinical conditions, and these differences may not always be predictable. Differentiation through regulatory approvals provides a measure of confidence in safety and efficacy at the specified doses for each approved indication. Moreover, the products differ in the amount of study to which they have been subjected, as evidenced by the number of publications in the peer-reviewed literature and the quantity and quality of clinical studies. Given that BoNTAs are potent biological products that meet important clinical needs, it is critical to recognize that their dosing and product performance are not interchangeable and each product should be used according to manufacturer guidelines. PMID:25336912

Use of Benzodiazepines in Alzheimer’s Disease: A Systematic Review of Literature

PubMed Central

Defrancesco, Michaela; Marksteiner, Josef; Fleischhacker, W. Wolfgang; Blasko, Imrich

2015-01-01

Background: Benzodiazepines are frequently prescribed in patients with Alzheimer’s disease. Unfortunately, studies evaluating their benefits and risks in these patients are limited. Methods: Clinical trials focusing on the effect of benzodiazepines on cognitive functions, disease progression, behavioral symptoms, sleep disturbances, and the general frequency of benzodiazepine use were included in this review. Published articles from January 1983 to January 2015 were identified using specific search terms in MEDLINE and PubMed Library according to the recommendations of The Strengthening the Reporting of Observational Studies in Epidemiology initiative. Results: Of the 657 articles found, 18 articles met predefined selection criteria and were included in this review (8 on frequency, 5 on cognitive functions, 5 on behavioral and sleep disturbances). The frequency of benzodiazepine use ranged from 8.5% to 20%. Five studies reported accelerated cognitive deterioration in association with benzodiazepine use. Two studies reported clinical efficacy for lorazepam and alprazolam to reduce agitation in Alzheimer’s disease patients. No evidence was found for an improvement of sleep quality using benzodiazepines. Conclusion: This systematic review shows a relatively high prevalence of benzodiazepine use but limited evidence for clinical efficacy in Alzheimer’s disease patients. However, there is a paucity of methodologically high quality controlled clinical trials. Our results underscore a need for randomized controlled trials in this area. PMID:25991652

The efficacy of low-level laser treatment in reducing pain and swelling after endodontic surgery: a systematic review

NASA Astrophysics Data System (ADS)

Moshari, Amirabbas; Vatanpour, Mehdi; Zakershahrak, Mehrsa

2016-03-01

Introduction: LLLT in oral cavity believed to reduce pain after endodontic surgery and wisdom tooth removal, to accelerate wound healing and to have an anti-inflammatory and regenerative effect. The aim of this systematic review therefore was to assess the proof available for the efficacy of low-level laser treatment in reducing pain and swelling after endodontic surgery. Methods: The PubMed service of the U.S. National Library of Medicine was searched with applicable search strategies. No language restriction was applied. The last electronic search was accomplished on August 31, 2015. All randomized clinical trials on the efficiency of low-level laser treatment in reducing pain and swelling after endodontic surgery was considered for the Meta-analysis. Quality consideration of the included randomized clinical trials was appraised according to CONSORT guidelines. Results: Only two randomized clinical trials were attained. These studies clarified that laser treatment could reduce pain and swelling, but the results were not significant. Conclusions: Low-level laser therapy can be advantageous for the reduction of postoperative pain but there is no strong confirmation for its efficiency. Its clinical utility and applicability relating to endodontic surgery, Along with the optimal energy dosage and the number of laser treatments needed after surgery, still, demand further research and experiment.

Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders

PubMed Central

2014-01-01

Background Anxiety and related disorders are among the most common mental disorders, with lifetime prevalence reportedly as high as 31%. Unfortunately, anxiety disorders are under-diagnosed and under-treated. Methods These guidelines were developed by Canadian experts in anxiety and related disorders through a consensus process. Data on the epidemiology, diagnosis, and treatment (psychological and pharmacological) were obtained through MEDLINE, PsycINFO, and manual searches (1980–2012). Treatment strategies were rated on strength of evidence, and a clinical recommendation for each intervention was made, based on global impression of efficacy, effectiveness, and side effects, using a modified version of the periodic health examination guidelines. Results These guidelines are presented in 10 sections, including an introduction, principles of diagnosis and management, six sections (Sections 3 through 8) on the specific anxiety-related disorders (panic disorder, agoraphobia, specific phobia, social anxiety disorder, generalized anxiety disorder, obsessive-compulsive disorder, and posttraumatic stress disorder), and two additional sections on special populations (children/adolescents, pregnant/lactating women, and the elderly) and clinical issues in patients with comorbid conditions. Conclusions Anxiety and related disorders are very common in clinical practice, and frequently comorbid with other psychiatric and medical conditions. Optimal management requires a good understanding of the efficacy and side effect profiles of pharmacological and psychological treatments. PMID:25081580

Androgen-deprivation therapy plus chemotherapy in metastatic hormone-sensitive prostate cancer. A systematic review and meta-analysis of randomized clinical trials.

PubMed

Ramos-Esquivel, Allan; Fernández, Cristina; Zeledón, Zenén

2016-08-01

To assess the efficacy and toxicity of androgen-deprivation therapy (ADT) plus chemotherapy in patients with hormone-sensitive metastatic prostate cancer. Randomized clinical trials were identified after systematic searching of databases and conference proceedings. A random-effect model was used to determine the pooled hazard ratio (HR) for the efficacy outcomes-overall survival (OS), biochemical progression-free survival (PFS), and clinical PFS, according to the inverse-variance method. Heterogeneity was measured using the Q and I(2) statistics. A narrative review was done to explore the major adverse drug reactions reported for each trial. After systematic searching, we included 6 trials (n = 2,675) in this meta-analysis. Estramustine-based chemotherapy plus ADT was not associated with improved OS (HR = 0.64; 95% CI: 0.22-1.89; P = 0.42). In contrast, docetaxel plus ADT was associated with improved OS (HR = 0.75; 95% CI: 0.61-0.91; P = 0.004) and clinical PFS (HR = 0.64; 95% CI: 0.57-0.72; P<0.00001). There was no significant heterogeneity detected among trials. Regarding adverse drug reactions grade 3 or higher, neutropenia was the most frequent side effect reported in a range from 12% to 32%. The addition of docetaxel-based chemotherapy to ADT improves OS and clinical PFS in hormone-sensitive metastatic prostate cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Celecoxib Enhances the Efficacy of Low-Dose Antibiotic Treatment against Polymicrobial Sepsis in Mice and Clinical Isolates of ESKAPE Pathogens

PubMed Central

Annamanedi, Madhavi; Varma, Gajapati Y. N.; Anuradha, K.; Kalle, Arunasree M.

2017-01-01

Treatment of multidrug resistant bacterial infections has been a great challenge globally. Previous studies including our study have highlighted the use of celecoxib, a non-steroidal anti-inflammatory drug in combination with antibiotic has decreased the minimal inhibitory concentration to limit Staphylococcus aureus infection. However, the efficacy of this combinatorial treatment against various pathogenic bacteria is not determined. Therefore, we have evaluated the potential use of celecoxib in combination with low doses of antibiotic in limiting Gram-positive and Gram-negative bacteria in vivo in murine polymicrobial sepsis developed by cecum ligation and puncture (CLP) method and against clinically isolated human ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species). The in vivo results clearly demonstrated a significant reduction in the bacterial load in different organs and in the inflammatory markers such as COX-2 and NF-κB via activation of SIRT1 in mice treated with imipenem, a choice of antibiotic for polymicrobial sepsis treatment. Combinatorial treatment of ampicillin and celecoxib was effective on clinical isolates of ESKAPE pathogens, 45% of tested clinical isolates showed more than 50% reduction in the colony forming units when compared to ampicillin alone. In conclusion, this non-traditional treatment strategy might be effective in clinic to reduce the dose of antibiotic to treat drug-resistant bacterial infections. PMID:28533769

Celecoxib Enhances the Efficacy of Low-Dose Antibiotic Treatment against Polymicrobial Sepsis in Mice and Clinical Isolates of ESKAPE Pathogens.

PubMed

Annamanedi, Madhavi; Varma, Gajapati Y N; Anuradha, K; Kalle, Arunasree M

2017-01-01

Treatment of multidrug resistant bacterial infections has been a great challenge globally. Previous studies including our study have highlighted the use of celecoxib, a non-steroidal anti-inflammatory drug in combination with antibiotic has decreased the minimal inhibitory concentration to limit Staphylococcus aureus infection. However, the efficacy of this combinatorial treatment against various pathogenic bacteria is not determined. Therefore, we have evaluated the potential use of celecoxib in combination with low doses of antibiotic in limiting Gram-positive and Gram-negative bacteria in vivo in murine polymicrobial sepsis developed by cecum ligation and puncture (CLP) method and against clinically isolated human ESKAPE pathogens ( Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa , and Enterobacter species). The in vivo results clearly demonstrated a significant reduction in the bacterial load in different organs and in the inflammatory markers such as COX-2 and NF-κB via activation of SIRT1 in mice treated with imipenem, a choice of antibiotic for polymicrobial sepsis treatment. Combinatorial treatment of ampicillin and celecoxib was effective on clinical isolates of ESKAPE pathogens, 45% of tested clinical isolates showed more than 50% reduction in the colony forming units when compared to ampicillin alone. In conclusion, this non-traditional treatment strategy might be effective in clinic to reduce the dose of antibiotic to treat drug-resistant bacterial infections.

A Brief Course on Clinical Communication Skills: A Multi- Centered Study.

PubMed

Franco, Camila; Franco, Renato; Severo, Milton; Ferreira, Maria Amélia

2016-12-30

This paper describes and analyses the results of a multicenter course on clinical communication skills with the use of the learning in small groups, patient actors and feedback. The aim of the course was to encourage participants to develop a more effective clinical communication to recognize the different manifestations of the same disease in different patients (disease versus illness). The course was applied to third and fourth year medical students in three Brazilian universities and one university in Portugal. The evaluation was performed using scales regarding the participants' point of view, multiple choice questionnaire, a self-efficacy and attitudinal questionnaire. The study was conducted in 69 participants at the four universities. The overall evaluation of the course (from 1 - 5) was 4.70 (SD 0.494), the self-evaluation on participation was 4.07 (SD 0.671); and the evaluation about the use of simulated patients 4.51 (SD 0.501). The multiple choice questionnaire and self-efficacy scale showed significant improvement. The course methods had an excellent evaluation by students regardless of the context in which the course has been applied. Furthermore, it allowed an improvement on the knowledge and attitude of students regarding clinical communication. It was possible to develop a multi-centric learning strategy for clinical communication with a high evaluation by students who came from a Portuguese university in a cooperation project with teachers from Brazilian universities.

Efficacy of amoxycillin versus amoxycillin/clavulanate in acute exacerbations of chronic pulmonary obstructive disease in primary care

PubMed Central

Llor, Carl; Hernández, Silvia; Ribas, Anna; Álvarez, Carmen; Cots, Josep Maria; Bayona, Carolina; González, Isabel; Miravitlles, Marc

2009-01-01

Background Amoxycillin/clavulanate is considered first-line treatment for ambulatory exacerbations of COPD. However, narrow-spectrum antibiotics may be as useful for mild to moderate patients. Objective To compare the clinical efficacy of amoxycillin versus amoxicyllin/clavulanate in exacerbations of COPD in primary care. Methods A randomized, double-blind, noninferiority clinical trial was carried out in eight primary care centers in Catalonia, Spain. Spirometrically-diagnosed patients older than 40 years with COPD, without criteria of hospitalization and Anthonisen’s types I or II exacerbations were included. The main outcome was clinical cure at the end of treatment (EOT) visit on day 10. Results A total of 137 patients were enrolled in the study (68 assigned to amoxycillin and 69 to amoxycillin/clavulanate). The mean forced expiratory flow in one second was 61.6% and the mean age was 71.4 years. At EOT, 92.8% of patients in the amoxycillin/clavulanate and 90.9% in the amoxycillin group were considered clinically cured, a statistically non-significant difference. Adverse effects were observed in 11 subjects, 3 in the amoxycillin group and 8 in the amoxycillin/clavulanate group, 2 of whom required a change in treatment. Conclusions Amoxycillin was at least as effective clinically and as safe as amoxycilin/ clavulanate in the treatment of acute exacerbations of COPD in mild to moderate patients in primary care. PMID:19436696

Clinical efficacy and safety following dose tapering of ciclosporin in cats with hypersensitivity dermatitis.

PubMed

Roberts, Elizabeth S; Tapp, Tiffany; Trimmer, Ann; Roycroft, Linda; King, Stephen

2016-11-01

Objectives This study was designed to evaluate the efficacy and safety of reducing ciclosporin (CsA) dosing frequency from daily to every other day (EOD) or twice a week (TW) according to clinical response in cats with hypersensitivity dermatitis (HD) and treated with CsA. Methods One hundred and ninety-one cats with HD were given 7 mg/kg CsA daily for at least 4 weeks. Depending on clinical response, the dosing frequency was tapered from daily to EOD over the next 4 weeks and further to TW for an additional 4 weeks. Safety was evaluated through physical examinations, clinical pathology and the monitoring of adverse events (AEs). Results The majority of cats were able to have their dose of CsA tapered to either EOD (15.5%) or TW (62.9%) according to the clinical response. Observed AEs were most frequently mild and self-limiting vomiting and diarrhea. A higher percentage of AEs occurred with daily administration (73%) compared with other dosing regimens (27%). Conclusions and relevance Following 4 weeks of daily dosing at 7 mg/kg, CsA may be tapered to EOD or TW while maintaining the desired therapeutic response in cats with HD. Additionally, CsA appears to be well tolerated with fewer AEs at EOD or TW dosing. Establishing the lowest effective dosing frequency of CsA improves the drug's safety profile.

Efficacy and Clinical Outcomes of Transcatheter Arterial Embolization for Gastrointestinal Bleeding from Gastrointestinal Stromal Tumor.

PubMed

Koo, Hyun Jung; Shin, Ji Hoon; Shin, Sooyoung; Yoon, Hyun-Ki; Ko, Gi-Young; Gwon, Dong Il

2015-09-01

To evaluate the efficacy and clinical outcomes of transcatheter arterial embolization (TAE) for gastrointestinal (GI) bleeding from gastrointestinal stromal tumor (GIST). TAE was performed in 20 referred patients (male:female = 13:7; median age, 56.3 y) for GI bleeding from GISTs. The locations of GISTs were assessed using contrast-enhanced computed tomography (CT) and catheter angiography. The technical and clinical success of TAE and clinical outcomes including procedure-related complications, recurrent bleeding, 30-day and overall mortality, and cumulative survival were evaluated. The sites of GIST-related bleeding or tumor staining were the jejunum (n = 9), stomach (n = 5), ileum (n = 3), duodenum (n = 2), and jejunum and colon (n = 1). Angiography showed bleeding from GIST in 5 patients, and tumor staining was noted in only 15 patients. TAE was performed for patients with and without contrast medium extravasation on angiography. Technical and clinical success rates of TAE were 95% (19 of 20 patients) and 90% (18 of 20 patients), respectively. Recurrent bleeding was noted in 1 patient. There were no procedure-related complications. In 15 patients, surgical resection of the tumors was performed after TAE. The 30-day and overall mortality rates were 10% (2 of 20 patients) and 30% (6 of 20 patients), respectively. TAE is a safe and effective method for controlling GI bleeding from the GIST. Copyright © 2015 SIR. Published by Elsevier Inc. All rights reserved.

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.

Early Effects of Responsivity Education/Prelinguistic Milieu Teaching for Children with Developmental Delays and Their Parents

ERIC Educational Resources Information Center

Fey, Marc E.; Warren, Steven F.; Brady, Nancy; Finestack, Lizbeth H.; Bredin-Oja, Shelley L.; Fairchild, Martha; Sokol, Shari; Yoder, Paul J.

2006-01-01

Purpose: To evaluate the efficacy of a 6-month course of responsivity education/prelinguistic milieu teaching (RE/PMT) for children with developmental delay and RE/PMT's effects on parenting stress in a randomized clinical trial. Method: Fifty-one children, age 24-33 months, with no more than 10 expressive words or signs, were randomly assigned to…

Strain diversity plays no major role in the varying efficacy of rotavirus vaccines: an overview.

PubMed

Velasquez, Daniel E; Parashar, Umesh D; Jiang, Baoming

2014-12-01

While a monovalent Rotarix® [RV1] and a pentavalent RotaTeq® [RV5] have been extensively tested and found generally safe and equally efficacious in clinical trials, the question still lingers about the evolving diversity of circulating rotavirus strains over time and their relationship with protective immunity induced by rotavirus vaccines. We reviewed data from clinical trials and observational studies that assessed the efficacy or field effectiveness of rotavirus vaccines against different rotavirus strains worldwide. RV1 provided broad clinical efficacy and field effectiveness against severe diarrhea due to all major circulating strains, including the homotypic G1P[8] and the fully heterotypic G2P[4] strains. Similarly, RV5 provided broad efficacy and effectiveness against RV5 and non-RV5 strains throughout different locations. Rotavirus vaccination provides broad heterotypic protection; however continuing surveillance is needed to track the change of circulating strains and monitor the effectiveness and safety of vaccines. Published by Elsevier B.V.

Enhanced chemoprophylactic and clinical efficacy of albendazole formulated as solid dispersions in experimental cystic echinococcosis.

PubMed

Pensel, Patricia E; Castro, Silvina; Allemandi, Daniel; Bruni, Sergio Sánchez; Palma, Santiago D; Elissondo, María Celina

2014-06-16

Cystic echinococcosis is a chronic, complex, and still neglected disease. Although albendazole has demonstrated efficacy, only about one-third of patients experience complete remission or cure and 30-50% of treated patients develop some evidence of a therapeutic response. Different strategies have been developed in order to improve the albendazole water solubility and dissolution rate. The aim of the current work was to investigate the chemoprophylactic and clinical efficacy of an albendazole:poloxamer 188 solid dispersion formulation on mice infected with Echinococcus granulosus metacestodes. Albendazole formulated as solid dispersion had greater chemoprophylactic and clinical efficacy than albendazole alone. The improved in therapeutic efficacy could be a consequence of the increase in the systemic availability of albendazole sulfoxide. The work reported here demonstrates that in vivo treatment with albendazole:poloxamer 188 impairs the development of the hydatid cysts. This new pharmacotechnically based strategy could be a suitable alternative for treating cystic echinococcosis in humans. Copyright © 2014 Elsevier B.V. All rights reserved.

Microbicide clinical trial adherence: insights for introduction.

PubMed

Woodsong, Cynthia; MacQueen, Kathleen; Amico, K Rivet; Friedland, Barbara; Gafos, Mitzy; Mansoor, Leila; Tolley, Elizabether; McCormack, Sheena

2013-04-08

After two decades of microbicide clinical trials it remains uncertain if vaginally- delivered products will be clearly shown to reduce the risk of HIV infection in women and girls. Furthermore, a microbicide product with demonstrated clinical efficacy must be used correctly and consistently if it is to prevent infection. Information on adherence that can be gleaned from microbicide trials is relevant for future microbicide safety and efficacy trials, pre-licensure implementation trials, Phase IV post-marketing research, and microbicide introduction and delivery. Drawing primarily from data and experience that has emerged from the large-scale microbicide efficacy trials completed to-date, the paper identifies six broad areas of adherence lessons learned: (1) Adherence measurement in clinical trials, (2) Comprehension of use instructions/Instructions for use, (3) Unknown efficacy and its effect on adherence/Messages regarding effectiveness, (4) Partner influence on use, (5) Retention and continuation and (6) Generalizability of trial participants' adherence behavior. Each is discussed, with examples provided from microbicide trials. For each of these adherence topics, recommendations are provided for using trial findings to prepare for future microbicide safety and efficacy trials, Phase IV post-marketing research, and microbicide introduction and delivery programs.

Patterns of detection of Strongyloides stercoralis in stool specimens: implications for diagnosis and clinical trials.

PubMed Central

Dreyer, G; Fernandes-Silva, E; Alves, S; Rocha, A; Albuquerque, R; Addiss, D

1996-01-01

Reported efficacies of drugs used to treat Strongyloides stercoralis infection vary widely. Because diagnostic methods are insensitive, therapeutic trials generally require multiple negative posttreatment stool specimens as evidence of drug efficacy. However, only a single positive stool specimen is usually required for study enrollment. To determine the reproducibility of detection of S. stercoralis larvae in the stool, 108 asymptomatic infected men submitted 25 g of fresh stool once a week for eight consecutive weeks for examination by the Baermann technique. During the 8-week study, 239 (27.7%) of 864 stool specimens were positive for S. stercoralis. Rates of detection of larvae in the stool specimens ranged from eight of eight specimens in 3 (2.8%) men to none of eight specimens in 36 (33.3%) men. Of 43 men for whom S. stercoralis was detected in at least two of the first four stool specimens, only 1 (2.3%) man tested negative on all of the next four specimens. In comparison, of 29 men who had detectable larvae in only one of the first four specimens, 22 (75.9%) tested negative on all of the next four samples. Thus, if these 29 men had been enrolled in a therapeutic trial between the first and second sets of four specimens, the efficacy of a drug with no activity against this parasite would have been estimated to be 76%. These data suggest that patterns of S. stercoralis detection vary widely among infected persons and that intermittent larval shedding can lead to inflated estimates of drug efficacy. Before a patient is entered in a clinical trial of drug efficacy, four consecutive stool specimens should be examined for S. stercoralis; only persons with two or more positive specimens should be enrolled. PMID:8880521

Demonstration of the Blood-Stage Plasmodium falciparum Controlled Human Malaria Infection Model to Assess Efficacy of the P. falciparum Apical Membrane Antigen 1 Vaccine, FMP2.1/AS01

PubMed Central

Payne, Ruth O.; Milne, Kathryn H.; Elias, Sean C.; Edwards, Nick J.; Douglas, Alexander D.; Brown, Rebecca E.; Silk, Sarah E.; Biswas, Sumi; Miura, Kazutoyo; Roberts, Rachel; Rampling, Thomas W.; Venkatraman, Navin; Hodgson, Susanne H.; Labbé, Geneviève M.; Halstead, Fenella D.; Poulton, Ian D.; Nugent, Fay L.; de Graaf, Hans; Sukhtankar, Priya; Williams, Nicola C.; Ockenhouse, Christian F.; Kathcart, April K.; Qabar, Aziz N.; Waters, Norman C.; Soisson, Lorraine A.; Birkett, Ashley J.; Cooke, Graham S.; Faust, Saul N.; Woods, Colleen; Ivinson, Karen; McCarthy, James S.; Diggs, Carter L.; Vekemans, Johan; Long, Carole A.; Hill, Adrian V. S.; Lawrie, Alison M.; Dutta, Sheetij; Draper, Simon J.

2016-01-01

Background. Models of controlled human malaria infection (CHMI) initiated by mosquito bite have been widely used to assess efficacy of preerythrocytic vaccine candidates in small proof-of-concept phase 2a clinical trials. Efficacy testing of blood-stage malaria parasite vaccines, however, has generally relied on larger-scale phase 2b field trials in malaria-endemic populations. We report the use of a blood-stage P. falciparum CHMI model to assess blood-stage vaccine candidates, using their impact on the parasite multiplication rate (PMR) as the primary efficacy end point. Methods. Fifteen healthy United Kingdom adult volunteers were vaccinated with FMP2.1, a protein vaccine that is based on the 3D7 clone sequence of apical membrane antigen 1 (AMA1) and formulated in Adjuvant System 01 (AS01). Twelve vaccinees and 15 infectivity controls subsequently underwent blood-stage CHMI. Parasitemia was monitored by quantitative real-time polymerase chain reaction (PCR) analysis, and PMR was modeled from these data. Results. FMP2.1/AS01 elicited anti-AMA1 T-cell and serum antibody responses. Analysis of purified immunoglobulin G showed functional growth inhibitory activity against P. falciparum in vitro. There were no vaccine- or CHMI-related safety concerns. All volunteers developed blood-stage parasitemia, with no impact of the vaccine on PMR. Conclusions. FMP2.1/AS01 demonstrated no efficacy after blood-stage CHMI. However, the model induced highly reproducible infection in all volunteers and will accelerate proof-of-concept testing of future blood-stage vaccine candidates. Clinical Trials Registration. NCT02044198. PMID:26908756

An Objective Approach for Burkholderia pseudomallei Strain Selection as Challenge Material for Medical Countermeasures Efficacy Testing

PubMed Central

Van Zandt, Kristopher E.; Tuanyok, Apichai; Keim, Paul S.; Warren, Richard L.; Gelhaus, H. Carl

2012-01-01

Burkholderia pseudomallei is the causative agent of melioidosis, a rare disease of biodefense concern with high mortality and extreme difficulty in treatment. No human vaccines are available that protect against B. pseudomallei infection, and with the current limitations of antibiotic treatment, the development of new preventative and therapeutic interventions is crucial. Although clinical trials could be used to test the efficacy of new medical countermeasures (MCMs), the high mortality rates associated with melioidosis raises significant ethical issues concerning treating individuals with new compounds with unknown efficacies. The US Food and Drug Administration (FDA) has formulated a set of guidelines for the licensure of new MCMs to treat diseases in which it would be unethical to test the efficacy of these drugs in humans. The FDA “Animal Rule” 21 CFR 314 calls for consistent, well-characterized B. pseudomallei strains to be used as challenge material in animal models. In order to facilitate the efficacy testing of new MCMs for melioidosis using animal models, we intend to develop a well-characterized panel of strains for use. This panel will comprise of strains that were isolated from human cases, have a low passage history, are virulent in animal models, and are well-characterized phenotypically and genotypically. We have reviewed published and unpublished data on various B. pseudomallei strains to establish an objective method for selecting the strains to be included in the panel of B. pseudomallei strains with attention to five categories: animal infection models, genetic characterization, clinical and passage history, and availability of the strain to the research community. We identified 109 strains with data in at least one of the five categories, scored each strain based on the gathered data and identified six strains as candidate for a B. pseudomallei strain panel. PMID:23057010

An objective approach for Burkholderia pseudomallei strain selection as challenge material for medical countermeasures efficacy testing.

PubMed

Van Zandt, Kristopher E; Tuanyok, Apichai; Keim, Paul S; Warren, Richard L; Gelhaus, H Carl

2012-01-01

Burkholderia pseudomallei is the causative agent of melioidosis, a rare disease of biodefense concern with high mortality and extreme difficulty in treatment. No human vaccines are available that protect against B. pseudomallei infection, and with the current limitations of antibiotic treatment, the development of new preventative and therapeutic interventions is crucial. Although clinical trials could be used to test the efficacy of new medical countermeasures (MCMs), the high mortality rates associated with melioidosis raises significant ethical issues concerning treating individuals with new compounds with unknown efficacies. The US Food and Drug Administration (FDA) has formulated a set of guidelines for the licensure of new MCMs to treat diseases in which it would be unethical to test the efficacy of these drugs in humans. The FDA "Animal Rule" 21 CFR 314 calls for consistent, well-characterized B. pseudomallei strains to be used as challenge material in animal models. In order to facilitate the efficacy testing of new MCMs for melioidosis using animal models, we intend to develop a well-characterized panel of strains for use. This panel will comprise of strains that were isolated from human cases, have a low passage history, are virulent in animal models, and are well-characterized phenotypically and genotypically. We have reviewed published and unpublished data on various B. pseudomallei strains to establish an objective method for selecting the strains to be included in the panel of B. pseudomallei strains with attention to five categories: animal infection models, genetic characterization, clinical and passage history, and availability of the strain to the research community. We identified 109 strains with data in at least one of the five categories, scored each strain based on the gathered data and identified six strains as candidate for a B. pseudomallei strain panel.

Efficacy of Chinese auriculotherapy for stress in nursing staff: a randomized clinical trial

PubMed Central

Kurebayashi, Leonice Fumiko Sato; da Silva, Maria Júlia Paes

2014-01-01

Objective this randomized single blind clinical study aimed to evaluate the efficacy of auriculotherapy with and without a protocol for reducing stress levels among nursing staff. Method a total of 175 nursing professionals with medium and high scores according to Vasconcelos' Stress Symptoms List were divided into 3 groups: Control (58), Group with protocol (58), Group with no protocol (59). They were assessed at the baseline, after 12 sessions, and at the follow-up (30 days). Results in the analysis of variance, statistically significant differences between the Control and Intervention groups were found in the two evaluations (p<0.05) with greater size of effect indices (Cohen) for the No protocol group. The Yang Liver 1 and 2, Kidney, Brain Stem and Shen Men were the points most used. Conclusion individualized auriculotherapy, with no protocol, could expand the scope of the technique for stress reduction compared with auriculotherapy with a protocol. NCT: 01420835 PMID:25029046

Biosimilars in inflammatory bowel disease: A review of post-marketing experience.

PubMed

Deiana, Simona; Gabbani, Tommaso; Annese, Vito

2017-01-14

Biologic compounds are obtained from living organisms or cell cultures by means of biotechnology methods. A similar biologic drug, commonly called biosimilar, is a product copied by a native approved biologic drug whose license has expired. Biosimilar drugs usually are marketed at a lower price and provide important financial savings for public healthcare systems. Some differences between biosimilars and original biologic drugs might exist but they are acceptable if they fall within defined "boundaries of tolerance": differences in some features between the two molecules are considered important only if clinical relevant. Considering that the efficacy of the innovator biologic drug has already been established, the clinical studies required for approval of a biosimilar could be reduced compared with those required for the approval of the originator. In this review, real life data available in inflammatory bowel disease patients treated with biosimilars are reported, documenting in general satisfactory outcomes, sustained efficacy and no sign of increased immunogenicity, although, further controlled data are awaited.

Alpha lipoic acid efficacy in burning mouth syndrome. A controlled clinical trial

PubMed Central

Palacios-Sánchez, Begoña; Cerero-Lapiedra, Rocío; Llamas-Martínez, Silvia; Esparza-Gómez, Germán

2015-01-01

Background A double-blind placebo-controlled trial was conducted in order to evaluate the efficacy of alpha lipoic acid (ALA) and determine the statistical significance of the outcome variables. Burning mouth syndrome (BMS) is defined as an oral burning sensation in the absence of clinical signs which could justify the syndrome. Recent studies suggest the existence of neurological factors as a possible cause of the disease. Material and Methods 60 patients with BMS, in two groups: case group with 600 mg/day and placebo as control group; with follow up of 2 months. Results 64% of ALA patients reported some level of improvement, with a level of maintenance of 68.75% one month after treatment. 27.6% of the placebo group also demonstrated some reduction in BMS symptoms. Conclusions Long-term evolution and the intensity of symptoms are variables that reduce the probability of improvement with ALA treatment. Key words: Burning mouth syndrome, neuropathy, alpha lipoic acid. PMID:26034927

Effects of Simulation With Problem-Based Learning Program on Metacognition, Team Efficacy, and Learning Attitude in Nursing Students: Nursing Care With Increased Intracranial Pressure Patient.

PubMed

Lee, Myung-Nam; Nam, Kyung-Dong; Kim, Hyeon-Young

2017-03-01

Nursing care for patients with central nervous system problems requires advanced professional knowledge and care skills. Nursing students are more likely to have difficulty in dealing with adult patients who have severe neurological problems in clinical practice. This study investigated the effect on the metacognition, team efficacy, and learning attitude of nursing students after an integrated simulation and problem-based learning program. A real scenario of a patient with increased intracranial pressure was simulated for the students. The results showed that this method was effective in improving the metacognitive ability of the students. Furthermore, we used this comprehensive model of simulation with problem-based learning in order to assess the consequences of student satisfaction with the nursing major, interpersonal relationships, and importance of simulation-based education in relation to the effectiveness of the integrated simulation with problem-based learning. The results can be used to improve the design of clinical practicum and nursing education.

The roles of safety and compliance in determining effectiveness of topical therapy for psoriasis.

PubMed

Stein Gold, Linda; Corvari, Linda

2007-01-01

Topical therapies are the mainstays of treatment for most patients with psoriasis because they relieve symptoms and reduce the size and severity of lesions. The effectiveness of a therapeutic intervention is a function of drug efficacy (determined by randomized clinical trial results) and patient safety and compliance. Alterations in any parameter can have a substantial influence on clinical outcomes. However, topical agents can be associated with unwanted and potentially toxic side effects that make physicians reluctant to prescribe them, and patients intentionally discontinue treatment with these topical agents. To maximize effectiveness and improve patient safety, physicians may prescribe medications in combination, sequential, or rotational therapeutic regimens. This treatment strategy has the potential to improve the overall efficacy and safety of topical therapy; however, the effectiveness of this method may be compromised because the complexity of the therapeutic regimen may decrease patient compliance. Newer topical therapies that have a convenient once-daily dosing schedule are needed and will have important implications for patient compliance.

From bench to almost bedside: the long road to a licensed Ebola virus vaccine.

PubMed

Wong, Gary; Mendoza, Emelissa J; Plummer, Francis A; Gao, George F; Kobinger, Gary P; Qiu, Xiangguo

2018-02-01

The Ebola virus (EBOV) disease epidemic during 2014-16 in West Africa has accelerated the clinical development of several vaccine candidates that have demonstrated efficacy in the gold standard nonhuman primate (NHP) model, namely cynomolgus macaques. Areas covered: This review discusses the pre-clinical research and if available, clinical evaluation of the currently available EBOV vaccine candidates, while emphasizing the translatability of pre-clinical data generated in the NHP model to clinical data in humans. Expert opinion: Despite the existence of many successful EBOV vaccine candidates in the pre-clinical stages, only two platforms became the focus of Phase 2/3 efficacy trials in Liberia, Sierra Leone, and Guinea near the peak of the epidemic: the Vesicular stomatitis virus (VSV)-vectored vaccine and the chimpanzee adenovirus type 3 (ChAd3)-vectored vaccine. The results of three distinct clinical trials involving these candidates may soon pave the way for a licensed, safe and efficacious EBOV vaccine to help combat future epidemics.

From bench to almost bedside: The long road to a licensed Ebola virus vaccine

PubMed Central

Wong, Gary; Mendoza, Emelissa J.; Plummer, Francis A.; Gao, George F.; Kobinger, Gary P.; Qiu, Xiangguo

2018-01-01

Introduction The Ebola virus (EBOV) disease epidemic during 2014-16 in West Africa has accelerated the clinical development of several vaccine candidates that have demonstrated efficacy in the gold standard nonhuman primate (NHP) model, namely cynomolgus macaques. Areas covered This review discusses the pre-clinical research and if available, clinical evaluation of the currently available EBOV vaccine candidates, while emphasizing the translatability of pre-clinical data generated in the NHP model to clinical data in humans. Expert opinion Despite the existence of many successful EBOV vaccine candidates in the pre-clinical stages, only two platforms became the focus of Phase 2/3 efficacy trials in Liberia, Sierra Leone, and Guinea near the peak of the epidemic: the Vesicular stomatitis virus (VSV)-vectored vaccine and the chimpanzee adenovirus type 3 (ChAd3)-vectored vaccine. The results of three distinct clinical trials involving these candidates may soon pave the way for a licensed, safe and efficacious EBOV vaccine to help combat future epidemics. PMID:29148858

Safety and Efficacy of Granulocyte/Monocyte Apheresis in Steroid-Dependent Active Ulcerative Colitis with Insufficient Response or Intolerance to Immunosuppressants and/or Biologics [the ART Trial]: 12-week Interim Results

PubMed Central

Akbar, Ayesha; Hart, Ailsa; Subramanian, Sreedhar; Bommelaer, Gilles; Baumgart, Daniel C.; Grimaud, Jean-Charles; Cadiot, Guillaume; Makins, Richard; Hoque, Syed; Bouguen, Guillaume; Bonaz, Bruno

2016-01-01

Background and Aims: Patients with active, steroid-dependent ulcerative colitis with insufficient response or intolerance to immunosuppressants and/or biologic therapies have limited treatment options. Adacolumn, a granulocyte/monocyte adsorptive apheresis device, has shown clinical benefit in these patients. This study aimed to provide additional clinical data regarding the safety and efficacy of Adacolumn in this patient subgroup. Methods: This single-arm, open-label, multicentre trial [ART] was conducted at 18 centres across the UK, France, and Germany. Eligible patients were 18–75 years old with moderate-to-severe, steroid-dependent active ulcerative colitis with insufficient response or intolerance to immunosuppressants and/or biologics. Patients received ≥ 5 weekly apheresis sessions with Adacolumn. The primary endpoint was clinical remission rate [clinical activity index ≤ 4] at Week 12. Results: In all, 86 patients were enrolled. At Week 12, 33/84 [39.3%] of patients in the intention-to-treat population achieved clinical remission, with 47/84 [56.0%] achieving a clinical response [clinical activity index reduction of ≥ 3]. Clinical remission was achieved in 30.0% of patients with previous immunosuppressant and biologic failure; steroid-free clinical remission and response were observed in 22.6% and 35.7% of these patients, respectively. Quality of life [Short Health Scale] significantly improved at Week 12 [p < 0.0001]. The majority of adverse events were of mild/moderate intensity. Conclusions: At Week 12, Adacolumn provided significant clinical benefit in a large cohort of steroid-dependent ulcerative colitis patients with previous failure to immunosuppressant and/or biologic treatment, with a favourable safety profile. These results are consistent with previous studies and support Adacolumn use in this difficult-to-treat patient subgroup. PMID:26818659

Activation of mesocorticolimbic reward circuits for assessment of relief of ongoing pain: a potential biomarker of efficacy.

PubMed

Xie, Jennifer Y; Qu, Chaoling; Patwardhan, Amol; Ossipov, Michael H; Navratilova, Edita; Becerra, Lino; Borsook, David; Porreca, Frank

2014-08-01

Preclinical assessment of pain has increasingly explored operant methods that may allow behavioral assessment of ongoing pain. In animals with incisional injury, peripheral nerve block produces conditioned place preference (CPP) and activates the mesolimbic dopaminergic reward pathway. We hypothesized that activation of this circuit could serve as a neurochemical output measure of relief of ongoing pain. Medications commonly used clinically, including gabapentin and nonsteroidal anti-inflammatory drugs (NSAIDs), were evaluated in models of post-surgical (1 day after incision) or neuropathic (14 days after spinal nerve ligation [SNL]) pain to determine whether the clinical efficacy profile of these drugs in these pain conditions was reflected by extracellular dopamine (DA) release in the nucleus accumbens (NAc) shell. Microdialysis was performed in awake rats. Basal DA levels were not significantly different between experimental groups, and no significant treatment effects were seen in sham-operated animals. Consistent with clinical observation, spinal clonidine produced CPP and produced a dose-related increase in net NAc DA release in SNL rats. Gabapentin, commonly used to treat neuropathic pain, produced increased NAc DA in rats with SNL but not in animals with incisional, injury. In contrast, ketorolac or naproxen produced increased NAc DA in animals with incisional but not neuropathic pain. Increased extracellular NAc DA release was consistent with CPP and was observed selectively with treatments commonly used clinically for post-surgical or neuropathic pain. Evaluation of NAc DA efflux in animal pain models may represent an objective neurochemical assay that may serve as a biomarker of efficacy for novel pain-relieving mechanisms. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Lidocaine for systemic sclerosis: a double-blind randomized clinical trial

PubMed Central

2011-01-01

Background Systemic sclerosis (scleroderma; SSc) is an orphan disease with the highest case-specific mortality of any connective-tissue disease. Excessive collagen deposit in affected tissues is a key for the disease's pathogenesis and comprises most of the clinical manifestations. Lidocaine seems to be an alternative treatment for scleroderma considering that: a) the patient's having excessive collagen deposits in tissues affected by scleroderma; b) the patient's demonstrating increased activity of the enzyme prolyl hydroxylase, an essential enzyme for the biosynthesis of collagen; and c) lidocaine's reducing the activity of prolyl hydroxylase. The aim of this study was to evaluate the efficacy and safety of lidocaine in treating scleroderma. Methods A randomized double-blind clinical trial included 24 patients with scleroderma randomized to receive lidocaine or placebo intravenously in three cycles of ten days each, with a one-month interval between them. Outcomes: cutaneous (modified Rodnan skin score), oesophageal (manometry) and microvascular improvement (nailfold capillaroscopy); improvement in subjective self-assessment and in quality of life (HAQ). Results There was no statistically significant difference between the groups for any outcome after the treatment and after 6-months follow-up. Improvement in modified Rodnan skin score occurred in 66.7% and 50% of placebo and lidocaine group, respectively (p = 0.408). Both groups showed an improvement in subjective self-assessment, with no difference between them. Conclusions Despite the findings of a previous cohort study favouring the use of lidocaine, this study demonstrated that lidocaine at this dosage and means of administration showed a lack of efficacy for treating scleroderma despite the absence of significant adverse effects. However, further similar clinical trials are needed to evaluate the efficacy of lidocaine when administered in different dosages and by other means. PMID:21299861

Predictors of chemotherapy efficacy in non-small-cell lung cancer: a challenging landscape.

PubMed

Olaussen, K A; Postel-Vinay, S

2016-11-01

Conventional cytotoxic chemotherapy (CCC) is the backbone of non-small-cell lung cancer (NSCLC) treatment since decades and still represents a key element of the therapeutic armamentarium. Contrary to molecularly targeted therapies and immune therapies, for which predictive biomarkers of activity have been actively looked for and developed in parallel to the drug development process ('companion biomarkers'), no patient selection biomarker is currently available for CCC, precluding customizing treatment. We reviewed preclinical and clinical studies that assessed potential predictive biomarkers of CCC used in NSCLC (platinum, antimetabolites, topoisomerase inhibitors, and spindle poisons). Biomarker evaluation method, analytical validity, and robustness are described and challenged for each biomarker. The best-validated predictive biomarkers for efficacy are currently ERCC1, RRM1, and TS for platinum agents, gemcitabine and pemetrexed, respectively. Other potential biomarkers include hENT1 for gemcitabine, class III β-tubulin for spindle poisons, TOP2A expression and CEP17 duplication (mostly studied for predicting anthracyclines efficacy) whose applicability concerning etoposide would deserve further evaluation. However, none of these biomarkers has till now been validated prospectively in an appropriately designed and powered randomised trial, and none of them is currently ready for implementation in routine clinical practice. The search for predictive biomarkers to CCC has been proven challenging. If a plethora of biomarkers have been evaluated either in the preclinical or in the clinical setting, none of them is ready for clinical implementation yet. Considering that most mechanisms of resistance or sensitivity to CCC are multifactorial, a combinatorial approach might be relevant and further efforts are required. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Safety and efficacy of aneurysm treatment with WEB: results of the WEBCAST study.

PubMed

Pierot, Laurent; Costalat, Vincent; Moret, Jacques; Szikora, Istvan; Klisch, Joachim; Herbreteau, Denis; Holtmannspötter, Markus; Weber, Werner; Januel, Anne-Christine; Liebig, Thomas; Sychra, Vojtech; Strasilla, Christoph; Cognard, Christophe; Bonafé, Alain; Molyneux, Andrew; Byrne, James V; Spelle, Laurent

2016-05-01

OBJECT WEB is an innovative intrasaccular treatment for intracranial aneurysms. Preliminary series have shown good safety and efficacy. The WEB Clinical Assessment of Intrasaccular Aneurysm Therapy (WEBCAST) trial is a prospective European trial evaluating the safety and efficacy of WEB in wide-neck bifurcation aneurysms. METHODS Patients with wide-neck bifurcation aneurysms for which WEB treatment was indicated were included in this multicentergood clinical practices study. Clinical data including adverse events and clinical status at 1 and 6 months were collected and independently analyzed by a medical monitor. Six-month follow-up digital subtraction angiography was also performed and independently analyzed by a core laboratory. Success was defined at 6 months as complete occlusion or stable neck remnant, no worsening in angiographic appearance from postprocedure, and no retreatment performed or planned. RESULTS Ten European neurointerventional centers enrolled 51 patients with 51 aneurysms. Treatment with WEB was achieved in 48 of 51 aneurysms (94.1%). Adjunctive implants (coils/stents) were used in 4 of 48 aneurysms (8.3%). Thromboembolic events were observed in 9 of 51 patients (17.6%), resulting in a permanent deficit (modified Rankin Scale [mRS] Score 1) in 1 patient (2.0%). Intraoperative rupture was not observed. Morbidity (mRS score > 2) and mortality were 2.0% (1 of 51 patients, related to rupture status on entry to study) and 0.0% at 1 month, respectively. Success was achieved at 6 months in 85.4% of patients treated with WEB: 23 of 41 patients (56.1%) had complete occlusion, 12 of 41 (29.3%) had a neck remnant, and 6 of 41 (14.6%) had an aneurysm remnant. CONCLUSIONS The WEBCAST study showed good procedural and short-term safety of aneurysm treatment with WEB and good 6-month anatomical results.

Evaluating change in virtual reality adoption for brain injury rehabilitation following knowledge translation.

PubMed

Glegg, Stephanie M N; Holsti, Liisa; Stanton, Sue; Hanna, Steven; Velikonja, Diana; Ansley, Barbara; Sartor, Denise; Brum, Christine

2017-04-01

To evaluate the impact of knowledge translation (KT) on factors influencing virtual reality (VR) adoption and to identify support needs of therapists. Intervention will be associated with improvements in therapists' perceived ease of use and self-efficacy, and an associated increase in intentions to use VR. Single group mixed-methods pre-test-post-test evaluation of convenience sample of physical, occupational and rehabilitation therapists (n=37) from two brain injury rehabilitation centres. ADOPT-VR administered pre/post KT intervention, consisting of interactive education, clinical manual, technical and clinical support. Increases in perceived ease of use (p=0.000) and self-efficacy (p=0.001), but not behavioural intention to use VR (p=0.158) were found following KT, along with decreases in the frequency of perceived barriers. Post-test changes in the frequency and nature of perceived facilitators and barriers were evident, with increased emphasis on peer influence, organisational-level supports and client factors. Additional support needs were related to clinical reasoning, treatment programme development, technology selection and troubleshooting. KT strategies hold potential for targeting therapists' perceptions of low self-efficacy and ease of use of this technology. Changes in perceived barriers, facilitators and support needs at post-test demonstrated support for repeated evaluation and multi-phased training initiatives to address therapists' needs over time. Implications for Rehabilitation Therapists' learning and support needs in integrating virtual reality extend beyond technical proficiency to include clinical decision-making and application competencies spanning the entire rehabilitation process. Phased, multi-faceted strategies may be valuable in addressing therapists' changing needs as they progress from novice to experienced virtual reality users. The ADOPT-VR is a sensitive measure to re-evaluate the personal, social, environmental, technology-specific and system-level factors influencing virtual reality adoption over time.