Science.gov

Sample records for clinical trials as topic

  1. Clinical Trials.Gov: A Topical Analyses.

    PubMed

    Anand, Vibha; Cahan, Amos; Ghosh, Soumya

    2017-01-01

    ClinicalTrials.gov was established as a web-based registry for clinical trials of human participants in 2000. Mandatory registration started in 2008. Given more than a decade of registered trials, it's important to understand the "topic" areas and their evolution over time from this resource. This information may help in identifying current knowledge gaps. We use dynamic topic model (DTM) methods to discover topics and their evolution over last 17 years. Our model suggests that there are disease or organ specific trials such as 'Cardiovascular disorders', Heart & Brain conditions', or 'Breast & Prostate cancer' as well as trials registered for general health. General health trials are less likely to be FDA regulated, but both health and pain management, as well as surgical, heart, and brain trials have upward trend in recent years while advanced cancer trials have downward trended. Our model derives unique insights from metadata associated with each topic area.

  2. Lavender-thymol as a new topical aromatherapy preparation for episiotomy: A randomised clinical trial.

    PubMed

    Marzouk, T; Barakat, R; Ragab, A; Badria, F; Badawy, A

    2015-01-01

    The objective of this study was to evaluate the effectiveness of topical lavender-thymol in promoting episiotomy healing. This placebo-controlled, single-blinded, randomised clinical trial involved 60 primiparous women. REEDA score was used to evaluate the outcome of the trial. On the 7th post-partum day, women in Placebo-treated group had worse Redness, Edema, Ecchymosis, Discharge and Approximation (REEDA) score of 3.93 ± 3.65 compared with those in Lavender-thymol-treated group (2.03 ± 1.7) with significant difference (P = 0.013). Visual analogue Scale (VAS) score for pain at episiotomy in Lavender-thymol-treated group was 3.5 ± 1.9, whereas in Placebo-treated group it was 2.1 ± 2.2 (p = 0.011) for dyschezia, 3.8 ± 1.7 and 2.8 ± 1.6 in Placebo- and Lavender-thymol-treated women, respectively (p = 0.023). At 7th post-partum week, dyspareunia was more severe in Placebo-treated group compared with that in Lavender-thymol-treated group (5.3 ± 2.7 vs 2.7 ± 1.5 and p < 0.001). Topical aromatherapy using lavender-thymol was highly effective, suitable and safe for episiotomy wound care with little or no expected side effects compared with that using placebo.

  3. 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

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

    PubMed

    Adalatkhah, Hassan; Sadeghi-Bazargani, Homayoun

    2015-01-01

    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. To investigate efficacy of 1% flutamide cream versus 4% hydroquinone cream on melasma. 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. 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. 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.

  5. Strategies of persuasion in offers to participate in cancer clinical trials I: Topic placement and topic framing.

    PubMed

    Barton, Ellen; Eggly, Susan; Winckles, Andrew; Albrecht, Terrance L

    2014-01-01

    Clinical trials are the gold standard in medical research evaluating new treatments in cancer care; however, in the United States, too few patients enroll in trials, especially patients from minority groups. Offering patients the option of a clinical trial is an ethically-charged communicative event for oncologists. One particularly vexed ethical issue is the use of persuasion in trial offers. Based on a corpus of 22 oncology encounters with Caucasian-American (n = 11) and African-American (n = 11) patients, this discourse analysis describes oncologists' use of two persuasive strategies related to the linguistic structure of trial offers: topic placement and topic framing. Findings are presented in total and by patient race, and discussed in terms of whether these strategies may constitute ethical or unethical persuasion, particularly with respect to the ethical issue of undue influence and the social issue of underrepresentation of minorities in cancer clinical trials.

  6. Randomized clinical trial of topical tranexamic acid after reduction mammoplasty

    PubMed Central

    Ausen, K; Fossmark, R; Spigset, O; Pleym, H

    2015-01-01

    Background The antifibrinolytic drug tranexamic acid is currently being rediscovered for both trauma and major surgery. Intravenous administration reduces the need for blood transfusion and blood loss by about one-third, but routine administration in surgery is not yet advocated owing to concerns regarding thromboembolic events. The aim of this study was to investigate whether topical application of tranexamic acid to a wound surface reduces postoperative bleeding. Methods This was a randomized double-blind placebo-controlled trial on 30 consecutive women undergoing bilateral reduction mammoplasty. On one side the wound surfaces were moistened with 25 mg/ml tranexamic acid before closure, and placebo (saline) was used on the other side. Drain fluid production was measured for 24 h after surgery, and pain was measured after 3 and 24 h. Postoperative complications including infection, seroma, rebleeding and suture reactions were recorded. Results Topical application of tranexamic acid to the wound surface after reduction mammoplasty reduced drain fluid production by 39 per cent (median 12·5 (range 0–44) versus 20·5 (0–100) ml; P = 0·038). Adverse effects were not observed. There were no significant differences in postoperative pain scores or complications. Conclusion Topical application of dilute tranexamic acid reduced bleeding in this model. The study adds to the evidence that this simple procedure may reduce wound bleeding after surgery. Registration number: NCT01964781 (http://www.clinicaltrials.gov). PMID:26349843

  7. Quality Randomized Clinical Trials of Topical Diabetic Foot Ulcer Healing Agents

    PubMed Central

    Bolton, Laura L.

    2016-01-01

    Significance: Diabetic foot ulcers (DFU) significantly add to global economic, social, and clinical burdens. Healing a DFU fast and well limits complications that can lead to lower extremity amputation, morbidity, and mortality. Recent Advances: Many promising topical DFU healing agents have been studied in randomized clinical trials (RCT), but only one, becaplermin, has been cleared for this use by the United States Food and Drug Administration (FDA). Critical Issues: This critical review of DFU topical healing RCTs summarizes issues identified in their design and conduct, highlighting ways to improve study quality so researchers can increase the likelihood of RCT success in propelling effective topical DFU healing agents toward clinical use. Key issues include (1) inadequate sample size, (2) risk of bias, (3) irrelevant or unreported inclusion criteria, (4) substandard outcome measures, (5) unmatched group characteristics that predict nonhealing at baseline, (6) unequal or uncontrolled concurrent interventions or standard of care, (7) heterogeneous subject or DFU samples (8) unblinded allocation, treatment, or outcome measures, or (9) inadequate follow-up for clinical relevance. These can add bias or unexplained variability to RCT outcomes, limiting clinical or statistical significance and accuracy of results. Future Directions: This critical review summarizes ways to overcome these deficiencies to optimize DFU clinical trial design and conduct. It provides a blueprint for future excellence in RCTs testing safety and efficacy of topical DFU healing agents and smoothing the path to their clinical use. PMID:26989579

  8. Topical interleukin 1 receptor antagonist for treatment of dry eye disease: a randomized clinical trial.

    PubMed

    Amparo, Francisco; Dastjerdi, Mohammad H; Okanobo, Andre; Ferrari, Giulio; Smaga, Leila; Hamrah, Pedram; Jurkunas, Ula; Schaumberg, Debra A; Dana, Reza

    2013-06-01

    The immunopathogenic mechanisms of dry eye disease (DED), one of the most common ophthalmic conditions, is incompletely understood. Data from this prospective, double-masked, randomized trial demonstrate that targeting interleukin 1 (IL-1) by topical application of an IL-1 antagonist is efficacious in significantly reducing DED-related patient symptoms and corneal epitheliopathy. To evaluate the safety and efficacy of treatment with the topical IL-1 receptor antagonist anakinra (Kineret; Amgen Inc) in patients having DED associated with meibomian gland dysfunction. Prospective phase 1/2, randomized, double-masked, vehicle-controlled clinical trial. Seventy-five patients with refractory DED. Participants were randomized to receive treatment with topical anakinra, 2.5% (n = 30), anakinra, 5% (n = 15), or vehicle (1% carboxymethylcellulose) (n = 30) 3 times daily for 12 weeks. Primary outcomes were corneal fluorescein staining (CFS), complete bilateral CFS clearance, dry eye-related symptoms as measured by the Ocular Surface Disease Index, tear film breakup time, and meibomian gland secretion quality. Topical anakinra was well tolerated compared with vehicle, with no reports of serious adverse reactions attributable to the therapy. After 12 weeks of therapy, participants treated with anakinra, 2.5%, achieved a 46% reduction in their mean CFS score (P = .12 compared with vehicle and P < .001 compared with baseline); participants treated with anakinra, 5%, achieved a 17% reduction in their mean CFS score (P = .88 compared with vehicle and P = .33 compared with baseline); and patients treated with vehicle achieved a 19% reduction in their mean CFS score (P = .11). Complete bilateral CFS clearance was noted in 8 of 28 patients (29%) treated with anakinra, 2.5%, vs in 2 of 29 patients (7%) treated with vehicle (P = .03). By week 12, treatment with anakinra, 2.5%, and treatment with anakinra, 5%, led to significant reductions in symptoms of 30% and 35%, respectively (P

  9. Randomized clinical trial comparing 5% and 1% topical minoxidil for the treatment of androgenetic alopecia in Japanese men.

    PubMed

    Tsuboi, Ryoji; Arano, Osamu; Nishikawa, Tooru; Yamada, Hidekazu; Katsuoka, Kensei

    2009-08-01

    Minoxidil is efficacious in inducing hair growth in patients with androgenetic alopecia by inducing hair follicles to undergo transition from the early to late anagen phase. Although the efficacy of 1% topical minoxidil has been confirmed in Japan, no controlled study of 5% topical minoxidil has been conducted using male Japanese subjects. The objective of this trial was to verify the superiority in clinical efficacy of 5% topical minoxidil to 1% topical minoxidil in a double-blind controlled study with male, Japanese androgenetic alopecia patients as the subjects. The trial included 300 Japanese male patients aged 20 years or older with androgenetic alopecia who were administered either 5% topical minoxidil (n = 150) or 1% topical minoxidil (n = 150) for 24 weeks. The mean change from the baseline in non-vellus hair/cm(2), the primary efficacy variable, was 26.4 (n = 142) in the 5% topical minoxidil group and 21.2 (n = 144) in the 1% topical minoxidil group at 16 weeks, the main time point for the evaluation. The difference between the groups was significant (P = 0.020). The incidence of adverse events was 8.7% (13/150) in the 5% group and 5.3% (8/150) in the 1% group, with no significant difference between the groups (chi(2)-test: P = 0.258). Our findings confirmed the superiority of 5% topical minoxidil to 1% topical minoxidil in treating Japanese men with androgenetic alopecia.

  10. Controlled clinical trial of oral and topical diethylcarbamazine in treatment of onchocerciasis.

    PubMed

    Taylor, H R; Greene, B M; Langham, M E

    1980-05-03

    In a double-blind controlled clinical trial comparing the safety and efficacy of oral diethylcarbamazine citrate (DEC) with topical DEC for the treatment of onchocerciasis twenty men with moderate skin-snip microfilarial counts received daily therapy for 1 week, then weekly therapy for the rest of 6 months. The number of microfilariae per skin snip dropped quickly to 2% of initial levels and remained at low levels in those receiving oral DEC, and to 20% of initial levels in patients treated with DEC lotion. Side-effects in both groups included lymphadenopathy, fever, pruritus, rash, proteinuria, and chorioretinitis; they were commoner with topical DEC.

  11. Systematic review and meta‐analysis of randomised clinical trials on topical treatments for vernal keratoconjunctivitis

    PubMed Central

    Mantelli, F; Santos, M S; Petitti, T; Sgrulletta, R; Cortes, M; Lambiase, A; Bonini, S

    2007-01-01

    Aims The aim of this study was to assess the efficacy of currently available topical drugs for vernal keratoconjunctivitis (VKC) through a meta‐analysis of randomised clinical trials (RCTs). Methods Twenty‐seven RCTs (n = 2184 eyes) that had evaluated the efficacy of topical drugs for the treatment of VKC were selected according to the set criteria; 10 of these trials were suitable for statistical analysis and were enrolled in the meta‐analysis. Articles published up to December 2005 were identified from the following data sources: Medline, Embase, Lilacs, the Cochrane Controlled Trials Register, and references from relevant articles. Articles in any language published with an English abstract, were screened, and those selected for inclusion were written in English, French, German, Italian, Portuguese or Spanish. The quality of the trials was assessed by the Delphi list. Statistical analysis was performed using STATA® software. Results A significant improvement in all signs and symptoms, except photophobia, was observed after topical treatment for active VKC, independent of the type of treatment. Comparison of the efficacy of different drugs was not possible due to a lack of standardised criteria among studies. Conclusion The currently available topical drugs are effective in treating acute phases of VKC. However, there is a lack of evidence to support the recommendation of one specific type of medication for treating this disorder. There is a need for standard criteria to assess diagnosis and therapy based on severity. There is also a need for RCTs assessing long‐term effects of single drugs to control the disease and to prevent complications. PMID:17588996

  12. Effect of Topical Fluorouracil Cream on Photodamage: Secondary Analysis of a Randomized Clinical Trial.

    PubMed

    Korgavkar, Kaveri; Lee, Kachiu C; Weinstock, Martin A

    2017-09-06

    Photoaging, which is premature skin aging caused by long-term UV exposure, is of aesthetic concern to many patients. To investigate the effect of topical fluorouracil, 5%, cream on photoaging using validated photonumeric scales. The Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial was a randomized clinical trial of 932 US veterans with a recent history of 2 or more keratinocyte carcinomas performed from September 30, 2011, through June 30, 2014, to assess the chemopreventive effects of a standard course of topical fluorouracil. Photographs were taken at baseline and at numerous time points for up to 4 years. In our secondary analysis, 2 independent dermatologists graded these photographs using 4 validated photonumeric scales. A total of 3042 photographs from 281 participants randomized to apply topical fluorouracil or placebo were evaluated at baseline, 6 months, 12 months, and 18 months using 4 photonumeric scales (Griffiths scale, Allergan forehead lines scale, melomental folds scale, and crow's feet scale). Data analysis was performed from November 1, 2016, to January 1, 2017. Participants were randomized to apply topical fluorouracil, 5%, cream or a vehicle control cream to the face and ears twice daily for 2 to 4 weeks for a total of 28 to 56 doses. Effect of a standard course of fluorouracil on the extent of photodamage as measured using 4 photonumeric scales. The study population was predominantly male (274 [97.5%]) and white (281 [100%]), with a mean (SD) age of 71.5 (0.57) years. No statistically significant changes were found in photodamage between baseline and 6 months (Griffiths scale: χ2 = 0.01, P = .93; Allergan forehead lines scale: χ2 = 0.18, P = .67; melomental fold scale: χ2 = 0.03, P = .87; crow's feet scale: χ2 = 2.41, P = .12), 12 months (Griffiths scale: χ2 = 1.39, P = .24; Allergan forehead lines scale: χ2 = 0.64, P = .43; melomental fold scale: χ2 = 0.12, P = .73

  13. Successful treatment of mild to moderate acne vulgaris with Dr Michaels® (also branded as Zitinex®) topical products family: a clinical trial.

    PubMed

    Wollina, U; Tirant, M; Bayer, P; Coburn, M; Anderson, P; Donnelly, B; Kennedy, T; Gaibor, J; Arora, M; Clews, L; Walmsley, S; Hercogovấ, J; Fioranelli, M; Gianfaldoni, S; Chokoeva, A A; Tchernev, G; Novotny, F; Roccia, M G; Maximov, G K; França, K; Lotti, T

    2016-01-01

    Acne vulgaris is an epidemic inflammatory skin disease of multi-factorial origin, frequently seen in adolescents and often persisting or occurring through to adulthood. Acne vulgaris is a nearly universal skin disease afflicting 79-95% of the adolescent population in westernized societies and is a significant cause of psychological morbidity in affected patients. Despite the various treatment options available for acne, there is still a need for a safe and effective option. The aim of the study was to investigate the efficacy and tolerability of Dr Michaels® (Zitinex®) product family in the treatment of papulo-pustular acne. 25 patients (17 female/8 male), aged 15-22, with a mild to moderate papulo-pustular acne, localized on the face and on the trunk, were included in this study. None of the patients had used any other kind of treatment in the 3 months prior to commencing this study. All of the patients were treated with Dr Michaels® (Zitinex®) facial exfoliating cleanser, activator formula, a cream, PSC 200 and PSC 900 oral supplements. Application time of Dr Michaels® (Zitinex®) products was 12 weeks. The treatment was been evaluated clinically at 0, 4, 8 and 12 weeks. All of the patients showed an improvement in all parameters of their acne (comedones, papules, pustules, hyperpigmentation and scars). The acne lesions and erythema had mostly resolved. The hyperpigmentation and pitted scarring had significantly reduced also, with the skin appearing smoother. The treatment was well tolerated and no side effects have been described. Our study demonstrates that the Dr Michaels® (Zitinex®) facial exfoliating cleanser, activator formula, cream and oral supplements PSC 200 and PSC 900 are an effective therapeutic option for the treatment of moderately severe acne vulgaris. Moreover, it highlights the safety profile of the Dr Michaels® (Zitinex®) product family in a case of acne compared to traditional first-line treatments.

  14. A Topical Gel From Flax Seed Oil Compared With Hand Splint in Carpal Tunnel Syndrome: A Randomized Clinical Trial.

    PubMed

    Setayesh, Mohammad; Sadeghifar, Amir Reza; Nakhaee, Nozar; Kamalinejad, Mohammad; Rezaeizadeh, Hossein

    2016-12-01

    This study compared the therapeutic effect of flax seed oil topical gel and hand splint in the treatment of carpal tunnel syndrome. This study was a randomized clinical trial. Forty-nine patients, 96 hands, with mild to moderate idiopathic carpal tunnel syndrome were divided into 2 groups randomly. One group was treated by topical gel and the other group by hand splint. Intensity of symptoms and function before and after intervention was measured via Boston Carpal Tunnel Questionnaire. After intervention, the ANCOVA showed a significant difference between the symptom and function scores of the 2 groups. In both cases, recovery was higher in the gel group (P < .001). The topical use of flax seed oil gel is more effective in the improvement of symptoms and function of patients with mild to moderate carpal tunnel syndrome as compared with hand splint, and it can be introduced as an effective treatment. © The Author(s) 2016.

  15. Topical Allium ampeloprasum subsp Iranicum (Leek) extract cream in patients with symptomatic hemorrhoids: a pilot randomized and controlled clinical trial.

    PubMed

    Mosavat, Seyed Hamdollah; Ghahramani, Leila; Sobhani, Zahra; Haghighi, Ehsan Rahmanian; Heydari, Mojtaba

    2015-04-01

    Allium ampeloprasum subsp iranicum (Leek) has been traditionally used in antihemorrhoidal topical herbal formulations. This study aimed to evaluate its safety and efficacy in a pilot randomized controlled clinical trial. Twenty patients with symptomatic hemorrhoids were randomly allocated to receive the topical leek extract cream or standard antihemorrhoid cream for 3 weeks. The patients were evaluated before and after the intervention in terms of pain, defecation discomfort, bleeding severity, anal itching severity, and reported adverse events. A significant decrease was observed in the grade of bleeding severity and defecation discomfort in both the leek and antihemorrhoid cream groups after the intervention, while no significant change was observed in pain scores. There was no significant difference between the leek and antihemorrhoid cream groups with regard to mean changes in outcome measures. This pilot study showed that the topical use of leek cream can be as effective as a standard antihemorrhoid cream. © The Author(s) 2015.

  16. Topical tranexamic acid as a novel treatment for bleeding peptic ulcer: A randomised controlled trial

    PubMed Central

    Rafeey, Mandana; Shoaran, Maryam; Ghergherechi, Robabeh

    2016-01-01

    Background: Peptic ulcers are among the most common causes of upper gastrointestinal (GI) bleeding in children. The standard care for GI bleeding is endoscopy for diagnostic and therapeutic purposes. We aimed to assess the effect of topical tranexamic acid (TXA) via endoscopic procedures in children with GI bleeding caused by bleeding ulcers. Procedure: In this randomised controlled trial, 120 children were evaluated by diagnostic procedures for GI bleeding, of which 63 (30 girls, 33 boys) aged 1-month to 15 years were recruited. The patients were randomly divided into case and control groups. In the case group, TXA was administered directly under endoscopic therapy. In the control group, epinephrine (1/10,000) was submucosally injected to the four quadrants of ulcer margins as the routine endoscopic therapy. In both groups, the patients received supportive medical therapy with intravenous fluids and proton pump inhibitor drugs. Results: The mean ± standard deviation age of the children was 5 ± 2.03 years. Rebleeding occurred in 15 (11.4%) and 21 (9.8%) patients in the case and control groups, respectively (P = 0.50). The frequency of blood transfusion episodes (P = 0.06) and duration of hospital stay (P = 0.07) were not statistically different between the groups. Conclusion: Using topical TXA via endoscopic procedures may be effective in cases of GI bleedings caused by active bleeding ulcers. In order to establish this therapeutic effect, a large number of clinical studies are needed. PMID:27251517

  17. Efficacy of topical atorvastatin for the treatment of pressure ulcers: a randomized clinical trial.

    PubMed

    Farsaei, Shadi; Khalili, Hossein; Farboud, Effat Sadat; Karimzadeh, Iman; Beigmohammadi, Mohammad Taghi

    2014-01-01

    To evaluate the effects of topical atorvastatin on the healing process of pressure ulcers in critically ill patients. Randomized, double-blind, placebo-controlled clinical trial. Medical-surgical intensive care unit of a university-affiliated teaching hospital in Tehran, Iran. One hundred four patients with stage I or II pressure ulcers, graded according to the 2-digit Stirling Pressure Sore Severity Scale. Patients were randomized to receive topical atorvastatin 1% ointment (51 patients [atorvastatin group]) or placebo ointment (53 patients [control group]) applied once/day to pressure ulcers for 14 days in addition to standard care for pressure ulcers. The efficacy of each treatment was assessed on days 7 and 14. Efficacy was determined based on the degree of healing of the existing pressure ulcer by using the 2-digit Stirling scale. The baseline stage of the pressure ulcers did not differ significantly between the control and atorvastatin groups. However, the mean ± SD stage of pressure ulcers significantly decreased in the atorvastatin group compared with the control group on day 7 (0.97 ± 0.76 vs 1.74 ± 0.75, p<0.01) and day 14 (0.42 ± 0.67 vs 1.71 ± 0.78, p<0.01) of treatment. In addition, the mean ± SD surface areas of ulcers in the atorvastatin group were significantly declined compared with the control group after 7 days (5.55 ± 4.55 vs 9.41 ± 5.03 cm², p<0.01) and 14 days (3.72 ± 4.45 vs 10.41 ± 6.41 cm², p<0.01) of treatment. Topical application of atorvastatin ointment 1% for 14 days in addition to standard care significantly accelerated the healing of stage I or II pressure ulcers in critically ill patients. © 2013 Pharmacotherapy Publications, Inc.

  18. Clinical effectiveness of dermal substitution in burns by topical negative pressure: a multicenter randomized controlled trial.

    PubMed

    Bloemen, Monica C T; van der Wal, Martijn B A; Verhaegen, Pauline D H M; Nieuwenhuis, Marianne K; van Baar, Margriet E; van Zuijlen, Paul P M; Middelkoop, Esther

    2012-01-01

    Previous research has shown clinical effectiveness of dermal substitution; however, in burn wounds, only limited effect has been shown. A problem in burn wounds is the reduced take of the autograft, when the substitute and graft are applied in one procedure. Recently, application of topical negative pressure (TNP) was shown to improve graft take. The aim of this study was to investigate if application of a dermal substitute in combination with TNP improves scar quality after burns. In a four-armed multicenter randomized controlled trial, a split-skin graft with or without a dermal substitute and with or without TNP was compared in patients with deep dermal or full-thickness burns requiring skin transplantation. Graft take and rate of wound epithelialization were evaluated. Three and 12 months postoperatively, scar parameters were measured. The results of 86 patients showed that graft take and epithelialization did not reveal significant differences. Significantly fewer wounds in the TNP group showed postoperative contamination, compared to other groups. Highest elasticity was measured in scars treated with the substitute and TNP, which was significantly better compared to scars treated with the substitute alone. Concluding, this randomized controlled trial shows the effectiveness of dermal substitution combined with TNP in burns, based on extensive wound and scar measurements. © 2012 by the Wound Healing Society.

  19. Effect of Topical Furosemide on Rhinosinusal Polyposis Relapse After Endoscopic Sinus Surgery: A Randomized Clinical Trial.

    PubMed

    Hashemian, Farnaz; Ghorbanian, Mohammad Ali; Hashemian, Farshad; Mortazavi, Seyed Alireza; Sheikhi, Mojgan; Jahanshahi, Javaneh; Poorolajal, Jalal

    2016-11-01

    Evidence from previous studies suggests that furosemide may be effective in reducing the recurrence of polyps after sinus surgery. However, the evidence is limited and insufficient, and further investigations are required. To assess the effect of topical furosemide on recurrence rate of rhinosinusal polyposis after endoscopic sinus surgery. Triple-blind randomized clinical trial of patients aged 18 to 60 years with chronic rhinosinusitis associated with polyposis who did not respond to medical treatment and were candidates for endoscopic sinus surgery at Besat Hospital, Hamadan University of Medical Sciences, from April 2014 to June 2015. Patients were randomly assigned to receive postoperative nasal spray, 2 puffs twice a day for 2 months, either 300 µg of furosemide per day or placebo. Six months after surgery, the patients were examined for nasal and paranasal sinus polyposis using Meltzer endoscopic grading, computed tomographic (CT) scan of paranasal sinuses (PNS) scoring, Sino-Nasal Outcome Test (SNOT-22) scoring, and visual analog scale (VAS). Of 110 patients enrolled, 84 patients remained for analysis (53 men and 31 women; mean age in the furosemide group, 37.02 years, range, 18-58 years; mean age in the placebo group, 36.30 years, range, 18-60 years). Six months after the intervention, the grade of polyposis decreased in both groups, but this reduction was substantial in the furosemide group vs the placebo group. The severity of polyposis was significantly lower in the furosemide group vs the placebo group based on SNOT-22 scoring (difference, 8.05; 95% CI, 3.24-12.85) and VAS (difference, 0.81; 95% CI, 0.22-1.39) but not significantly different based on CT scan of PNS scoring (difference, 2.52; 95% CI, -0.35 to 5.39). The incidence of adverse effects (nasal irritation, headache, and constipation) were not significantly different between the 2 groups. These findings indicate that topical furosemide is a safe drug, with no important adverse effects, that

  20. Randomized clinical trial of topical betaxolol for persistent macular edema after vitrectomy and epiretinal membrane removal.

    PubMed

    Kobayashi, Hiroshi; Kobayashi, Kaori; Okinami, Satoshi

    2003-08-01

    To report the efficacy and safety of topical betaxolol for treatment of persistent macular edema. Randomized clinical trial. Thirty-seven eyes (37 patients) with best-corrected visual acuity between 20/200 and 20/50 and macular edema that remained for 3 months after vitrectomy and removal of epiretinal membrane were prospectively, randomly assigned to receive betaxolol or placebo. Nineteen eyes of 19 patients received betaxolol twice daily, and 18 eyes of 18 patients received placebo as a randomized comparison group. The patients were followed up for 6 months. This study evaluated the effect of betaxolol on best-corrected visual acuity and area of macular edema, which was digitally measured on serial fluorescein angiogram. Calculations of mean best-corrected visual acuity were based on logarithm of the minimal angle of resolution (logMAR). To assess changes in area of edema, the initial (pretreatment) size of the edema was set to 100%, and all posttreatment measurements were normalized relative to the initial size. Mean best-corrected visual acuity at baseline was 0.216 (20 of 92.6) and 0.244 (20 of 82.0) in the treatment and control group, respectively. Mean area of macular edema was 2.271 +/- 1.629 mm(2) and 2.273 +/- 1.209 mm(2) in the treatment and control group; there was no significant difference. The visual acuity at 6 months after the start of the follow-up was 0.471 (20 of 42.5) in the treatment group and 0.236 (20 of 84.7) in the control group. Mean changes in logMAR of visual acuity for 3- and 6-month follow-up were -0.282 +/- 0.191 and -0.337 +/- 0.197 in the treatment group, and -0.016 +/- 0.186 and +0.015 +/- 0.267 in the control group; a significant difference was found (P <.0001; P <.0001). Areas of macular edema at 6 months after the start of the follow-up were 1.492 +/- 1.357 mm(2) in the treatment group and 2.125 +/- 1.434 mm(2)in the control group. Mean change in area of the edema for 6 months were 76.5% +/- 24.1% and 63.4% +/- 28.3% in the

  1. Oral and Topical Antibiotics for Clinically Infected Eczema in Children: A Pragmatic Randomized Controlled Trial in Ambulatory Care

    PubMed Central

    Francis, Nick A.; Ridd, Matthew J.; Thomas-Jones, Emma; Butler, Christopher C.; Hood, Kerenza; Shepherd, Victoria; Marwick, Charis A.; Huang, Chao; Longo, Mirella; Wootton, Mandy; Sullivan, Frank

    2017-01-01

    PURPOSE Eczema may flare because of bacterial infection, but evidence supporting antibiotic treatment is of low quality. We aimed to determine the effect of oral and topical antibiotics in addition to topical emollient and corticosteroids in children with clinically infected eczema. METHODS We employed a 3-arm, blinded, randomized controlled trial in UK ambulatory care. Children with clinical, non-severely infected eczema were randomized to receive oral and topical placebos (control), oral antibiotic (flucloxacillin) and topical placebo, or topical antibiotic (fusidic acid) and oral placebo, for 1 week. We compared Patient Oriented Eczema Measure (POEM) scores at 2 weeks using analysis of covariance (ANCOVA). RESULTS We randomized 113 children (40 to control, 36 to oral antibiotic, and 37 to topical antibiotic). Mean (SD) baseline Patient Oriented Eczema Measure scores were 13.4 (5.1) for the control group, 14.6 (5.3) for the oral antibiotic group, and 16.9 (5.5) for the topical antibiotic group. At baseline, 104 children (93%) had 1 or more of the following findings: weeping, crusting, pustules, or painful skin. Mean (SD) POEM scores at 2 weeks were 6.2 (6.0) for control, 8.3 (7.3) for the oral antibiotic group, and 9.3 (6.2) for the topical antibiotic group. Controlling for baseline POEM score, neither oral nor topical antibiotics produced a significant difference in mean (95% CI) POEM scores (1.5 [−1.4 to 4.4] and 1.5 [−1.6 to 4.5] respectively). There were no significant differences in adverse effects and no serious adverse events. CONCLUSIONS We found rapid resolution in response to topical steroid and emollient treatment and ruled out a clinically meaningful benefit from the addition of either oral or topical antibiotics. Children seen in ambulatory care with mild clinically infected eczema do not need treatment with antibiotics. PMID:28289111

  2. Topical Imiquimod Plus Nab-paclitaxel for Breast Cancer Cutaneous Metastases: A Phase 2 Clinical Trial.

    PubMed

    Salazar, Lupe G; Lu, Hailing; Reichow, Jessica L; Childs, Jennifer S; Coveler, Andrew L; Higgins, Doreen M; Waisman, James; Allison, Kimberly H; Dang, Yushe; Disis, Mary L

    2017-07-01

    Salvage chemotherapy for recurrent chest wall lesions in breast cancer results in response rates of 20% to 30%. Preclinical studies showed significant disease regression could be induced in murine chest wall mammary cancers with a topical toll-like receptor (TLR)-7 agonist, imiquimod. To evaluate the safety and objective response rate (ORR) of imiquimod in combination with systemic albumin bound paclitaxel in treatment-refractory breast cancer of the chest wall. A single arm phase 2 clinical trial of 15 patients with breast cancer previously treated in an academic medical center setting between 2009 and 2012 for chest wall disease that had recurred. Imiquimod cream, 5%, was applied topically to a designated target lesion once per day for 4 consecutive days on days 1 through 4, 8 through 11, 15 through 18, and 22 through 25 of a 28-day cycle, for 12 weeks. Albumin bound paclitaxel, 100 mg/m2, was given intravenously on days 1, 8, and 15, and repeated every 28 days over the 12-week period. The primary endpoint was safety and ORR. Secondary endpoints included the generation of tumor-infiltrating lymphocytes and modulation of immune cell populations. The median age at baseline of the 15 study participants was 54 years (range, 46-92 years). Fourteen patients were evaluable. Combination therapy was associated with low-grade toxic effects. Of 358 adverse events 330 (92%) were grades 1 and 2. Five (36%) patients achieved a compete response and another 5 (36%) were partial responders for an overall response rate of 72% (10 of 14). The response duration was limited. Pretreatment levels of programmed death-1 (PD-1)+ peripheral blood T cells (PD-1+ cluster of differentiation [CD]4+; 95% CI, 2.68-6.63; P < .001 and PD-1+CD8+; 95% CI, 1.13-8.35; P = .01) and monocytic myeloid derived suppressor cells (mMDSC) (95% CI, 3.62-12.74; P = .001) greater than controls predicted suboptimal clinical response. Chemoimmunomodulation with a TLR-7 agonist and albumin bound

  3. Mechanism for prevention of infection in preterm neonates by topical emollients: a randomized, controlled clinical trial.

    PubMed

    Darmstadt, Gary L; Ahmed, Saifuddin; Ahmed, A S M Nawshad Uddin; Saha, Samir K

    2014-11-01

    Topical applications of emollients such as sunflower seed oil and Aquaphor have been shown to reduce the incidence of bloodstream infections and mortality of preterm infants in resource-poor settings. The causal mechanism for prevention of infection through cutaneous portals of entry is not well understood. We examined the relationship between skin condition score as a measure of skin barrier integrity and risk for bloodstream infection, and the effect of emollients on that relationship. Data for this study come from a randomized controlled trial of the impact of topical emollient therapy on nosocomial infections in 491 preterm infants <33 weeks gestational age at Dhaka Shishu Hospital, Bangladesh. Latent growth trajectory model with random-coefficient and multivariable logistic regression were utilized. Rate of deterioration of skin condition was significantly lower (P < 0.05) in both emollient arms compared with the untreated control group. Adjusted odds ratio of skin score for infection was 1.32 (95% confidence interval: 1.06-1.65). Emollients reduced the incidence of infection only when the skin had no signs of deterioration [Aquaphor incidence rate ratio: 0.43 (95% confidence interval: 0.19-0.97) and sunflower seed oil incidence rate ratio: 0.46 (95% confidence interval: 0.21-0.99)]. Skin condition deteriorated progressively after birth and compromised skin condition increased the risk of infection. Emollients preserved skin integrity and thus prevented infection in preterm neonates. To optimize benefits of emollients for the prevention of bloodstream infection, use of emollients should begin immediately after birth when the skin is still intact.

  4. The efficacy of topical prophylactic antiglaucoma therapy in primary closed angle glaucoma in dogs: a multicenter clinical trial.

    PubMed

    Miller, P E; Schmidt, G M; Vainisi, S J; Swanson, J F; Herrmann, M K

    2000-01-01

    The ability of either 0.5% betaxolol (1 drop topically, bid; n=31) or a combination of 0.25% demecarium bromide and a topical corticosteroid (gentamicin/betamethasone) (DB/GB; 1 drop of each topically, sid; n=55) to prevent glaucoma in the fellow eye of dogs with unilateral, primary closed angle glaucoma (PCAG) was investigated in a multicenter, open-label, clinical trial. Untreated control dogs (n=20) developed glaucoma significantly sooner (median, eight mos; p less than 0.001) than dogs treated either with DB/GB (median, 31 mos) or betaxolol (median, 30.7 mos). Although DB/GB and betaxolol equally delayed or prevented the onset of glaucoma in the second eye, a less frequent dosing schedule for DB/GB suggests demecarium bromide in combination with a topical corticosteroid may be preferable to betaxolol in preventing PCAG in dogs.

  5. Clinical Trial: Marine Lipid Suppositories as Laxatives

    PubMed Central

    Ormarsson, Orri Thor; Geirsson, Thormodur; Bjornsson, Einar Stefan; Jonsson, Tomas; Moller, Pall; Loftsson, Thorsteinn; Stefansson, Einar

    2012-01-01

    Cod-liver oil and other marine products containing polyunsaturated fatty acids have anti-inflammatory, anti-bacterial and anti-viral effects and may be useful in the treatment of various inflammatory and infectious diseases. We developed suppositories and ointment with 30% free fatty acid (FFA) extract from omega-3 fish oil. Our purpose was to evaluate the safety of marine lipid suppositories and ointment in healthy volunteers and to explore the laxative effect of the suppositories. Thirty healthy volunteers were randomized either to a study group administrating 30% FFA suppositories and applying 30% FFA ointment to the perianal region twice per day for two weeks, or to a control group using placebo suppositories and ointment in a double blinded manner. Results: No serious toxic effects or irritation were observed. In the study group 93% felt the urge to defecate after administration of the suppositories as compared to 37% in the control group (P = 0.001). Subsequently 90% in the study group defecated, compared to 33% in the control group (P = 0.001). Conclusion: The marine lipid suppositories and ointment were well tolerated with no significant toxic side effects observed during the study period. The suppositories have a distinct laxative effect and we aim to explore this effect in further clinical trials. PMID:23118720

  6. Topical terbinafine in the treatment of cutaneous leishmaniasis: triple blind randomized clinical trial.

    PubMed

    Farajzadeh, Saeedeh; Heshmatkhah, Amireh; Vares, Behrooz; Mohebbi, Elham; Mohebbi, Azadeh; Aflatoonian, Mahin; Eybpoosh, Sana; Sharifi, Iraj; Aflatoonian, Mohammad Reza; Shamsi Meymandi, Simin; Fekri, Ali Reza; Mostafavi, Mahshid

    2016-12-01

    Leishmaniasis is a spectrum of disease condition with considerable health impacts, caused by different species of Leishmania. This disease is currently endemic in 98 countries and territories in the world. There are many treatment modalities for cutaneous leishmaniasis. The use of topical terbinafine in the treatment of cutaneous leishmaniasis has recently been considered. Eighty-eight participants more than two years old with proven acute CL by a positive direct smear were randomly allocated to one of the two study arms: first group received meglumine antimoniate (Glucantime) 20 mg/kg/day intramuscular injection (IM) plus a placebo ointment (Mahan Vaseline) for 20 days. The second group received meglumine antimoniate (Glucantime) 20 mg/kg/day IM plus topical terbinafine, for 20 days and were monitored closely by dermatologist during the course of the study. Crude regression analysis showed that there was no significant difference between placebo and intervention group regarding partial or complete treatment (partial treatment: HRcrude = 1.1, CI 95 % = 0.7-1.7; complete treatment: HRcrude = 1.1, CI 95 % = 0.8-1.7). Although, there was no statistically significant different between the two treatment groups, but clinically it seems that the treatment rate in those who receive glucantime plus terbinafine was more effective than the other group. However this rate depended on the type of lesions. As data indicated ulcerated nodules, papules and plaque in experimental group have been completely improved two times faster than placebo group. Ulcerated nodules, nodules and plaque were partially improved faster in those used tebinafine than placebo ointment.

  7. Randomized clinical trial of topical mupirocin versus oral erythromycin for impetigo.

    PubMed Central

    Goldfarb, J; Crenshaw, D; O'Horo, J; Lemon, E; Blumer, J L

    1988-01-01

    The safety and efficacy of a new topical antiinfective agent, mupirocin, was compared with that of oral erythromycin ethylsuccinate in the treatment of impetigo in children. Sixty-two children aged 5 months to 13 years with impetigo were assigned to be treated with either mupirocin in three daily applications or erythromycin ethylsuccinate (40 mg/kg of body weight per day divided into four doses) according to a randomized treatment schedule. On the initial visit, exudate or cleansed infected sites or both were cultured and therapy was begun. All patients were treated for 8 days. Patients were seen again on days 4 to 5 of therapy, at the end of therapy, and 7 days after the end of therapy. Sites of infection were comparable between the groups, as were bacteriologic responses. At the first visit, 24 of 30 children in the mupirocin group and 14 of 32 children in the erythromycin group were cured or had at least a 75% reduction in size of the lesions. At the end of the study, all 29 of the children in the mupirocin group who came to follow-up, compared with 27 of 29 in the erythromycin group, were cured. Side effects were few. Five children in the erythromycin group developed mild diarrhea. Thus, mupirocin appears to be safe and effective in treating impetigo in children. Our data show a trend toward more rapid clinical response with mupirocin than with erythromycin. PMID:3149884

  8. Original article title: "Comparison of therapeutic efficacy of topical corticosteroid and oral zinc sulfate-topical corticosteroid combination in the treatment of vitiligo patients: a clinical trial"

    PubMed Central

    2011-01-01

    Background Vitiligo is the most prevalent pigmentary disorder which occurs worldwide, with an incidence rate between 0.1-4 percent. It is anticipated that the discovery of biological pathways of vitiligo pathogenesis will provide novel therapeutic and prophylactic targets for future approaches to the treatment and prevention of vitiligo. The purposes of this study were evaluating the efficacy of supplemental zinc on the treatment of vitiligo. Methods This randomized clinical trial was conducted for a period of one year. Thirty five patients among 86 participants were eligible to entrance to the study. The patients in two equal randomized groups took topical corticosteroid and combination of oral zinc sulfate-topical corticosteroid. Results The mean of responses in the corticosteroid group and the zinc sulfate-corticosteroid combination group were 21.43% and 24.7%, respectively. Conclusion Although, the response to corticosteroid plus zinc sulfate was more than corticosteroid, there was no statistically significant difference between them. It appeared that more robust long-term randomized controlled trials on more patients, maybe with higher doses of zinc sulfate, are needed to fully establish the efficacy of oral zinc in management of vitiligo. Trial Registration chiCTRTRC10000930 PMID:21453467

  9. Clinical Trials

    MedlinePlus

    ... Sponsors Why Are They Important How Do They Work Who Can Participate What To Expect During Benefits and Risks How They Protect Participants Finding Clinical Trials Links Children & Clinical Studies NHLBI Trials Clinical Trial Websites What Are Clinical ...

  10. Topical tazarotene cream (0.1%) in the treatment of facial acne: an open clinical trial.

    PubMed

    Zakaria, A S M; Paul, H K; Rahman, M A; Islam, M T; Choudhury, A M

    2010-08-01

    Tazarotene is a new 3rd generation topical acetylenic retinoid. It normalizes keratinocyte differentiation, reduces keratinocyte proliferation and decreases expression of inflammatory markers. Tazarotene was approved by U.S.F.D.A. in 1997 for acne vulgaris. To evaluate the efficacy and safety of topical tazarotene 0.1% cream in the treatment of facial acne. 67 patients with facial acne in the age range of 13-30 years were enrolled in the study. Purposive sampling was done. Patients were treated with topical Tazarotene cream (0.1%) and were instructed to apply the medication as a thin film over the affected area in the evening once daily for 12 weeks. Follow-up was done at 2nd, 4th week, 8th week and at 12th week. Of the 67 patients, 53% got remission, 9% had good response, 34% had poor response and there was no response in 4% of the patients by 12 weeks of treatment. Among the patients, 9 (13.43%) developed mild side effects. Topical tazarotene cream (0.1%) is a effective and safe treatment option for acne vulgaris affecting face. It is mostly effective in grade-1 and grade-2 acne.

  11. A randomized clinical trial of 5% topical minoxidil versus 2% topical minoxidil and placebo in the treatment of androgenetic alopecia in men.

    PubMed

    Olsen, Elise A; Dunlap, Frank E; Funicella, Toni; Koperski, Judith A; Swinehart, James M; Tschen, Eduardo H; Trancik, Ronald J

    2002-09-01

    Topical minoxidil solution 2% stimulates new hair growth and helps stop the loss of hair in individuals with androgenetic alopecia (AGA). Results can be variable, and historical experience suggests that higher concentrations of topical minoxidil may enhance efficacy. The purpose of this 48-week, double-blind, placebo-controlled, randomized, multicenter trial was to compare 5% topical minoxidil with 2% topical minoxidil and placebo in the treatment of men with AGA. A total of 393 men (18-49 years old) with AGA applied 5% topical minoxidil solution (n = 157), 2% topical minoxidil solution (n = 158), or placebo (vehicle for 5% solution; n = 78) twice daily. Efficacy was evaluated by scalp target area hair counts and patient and investigator assessments of change in scalp coverage and benefit of treatment. After 48 weeks of therapy, 5% topical minoxidil was significantly superior to 2% topical minoxidil and placebo in terms of change from baseline in nonvellus hair count, patient rating of scalp coverage and treatment benefit, and investigator rating of scalp coverage. Hair count data indicate that response to treatment occurred earlier with 5% compared with 2% topical minoxidil. Additionally, data from a patient questionnaire on quality of life, global benefit, hair growth, and hair styling demonstrated that 5% topical minoxidil helped improve patients' psychosocial perceptions of hair loss. An increased occurrence of pruritus and local irritation was observed with 5% topical minoxidil compared with 2% topical minoxidil. In men with AGA, 5% topical minoxidil was clearly superior to 2% topical minoxidil and placebo in increasing hair regrowth, and the magnitude of its effect was marked (45% more hair regrowth than 2% topical minoxidil at week 48). Men who used 5% topical minoxidil also had an earlier response to treatment than those who used 2% topical minoxidil. Psychosocial perceptions of hair loss in men with AGA were also improved. Topical minoxidil (5% and 2%) was

  12. Topical cidofovir to treat high-grade anal intraepithelial neoplasia in HIV-infected patients: a pilot clinical trial.

    PubMed

    Sendagorta, Elena; Bernardino, Jose I; Álvarez-Gallego, Mario; Feíto, Marta; Feltes, Rosa; Beato, Maria J; Pérez-Molina, Jose A; Yllescas, Maria; Díaz-Almirón, Mariana; Arribas, Jose R; González-García, Juan; Herranz, Pedro

    2016-01-02

    To evaluate the efficacy of 1% topical cidofovir cream for the treatment of anal high-grade squamous intraepithelial lesions (HSILs) in HIV-infected individuals. Single-arm, open-label, pilot clinical trial. The study medication was applied intraanally three times per week for 4 weeks. Lesions were assessed with high-resolution anoscopy and biopsy at weeks 12 and 24. The primary endpoint was complete remission (CR) at week 12, defined as clinical and histological remission. We also evaluated partial remission defined as regression to low-grade squamous intraepithelial lesion. We included 17 HIV-infected patients with intraanal HSIL. Median (interquartile range) age was 36 years (28-41), median (interquartile range) CD4 cell count was 545 cells/μl (358-630), and viral load was less than 50  copies/ml in 93.7%. Two patients were lost to follow-up, one of them did not apply treatment. At 12 weeks, in the intention-to-treat population, 10 out of 16 patients [62.5%; 95% confidence interval (CI), 38.2-85.7%] had achieved CR. At 24 weeks, seven of the 10 patients (70%; 95% CI, 47-93%) remained in CR, but two out of 10 patients (20%; 95% CI, 0-40%) presented HSIL. One patient did not attend the visit at 24 weeks. Three patients with persistent HSIL at 12 weeks improved at 24 weeks (partial response in one and CR in two). The mean number of human papillomavirus genotypes decreased from 5.2 to 2.7 at 12 weeks (P = 0.002). Local adverse effects were frequent (81%), although there were no discontinuations because of adverse events. One percent topical cidofovir could be an appropriate alternative therapy in HIV-infected patients with anal HSIL. gov unique identifier: NCT01946009.

  13. Topical interferon alpha-2B topic as the first therapeutic option in a clinical case of conjunctival intraepithelial neoplasia.

    PubMed

    Pagán Carrasco, S; Arranz Maestro, D

    2017-09-01

    Conjunctival intraepithelial neoplasia is a pre-malignant lesion of the ocular surface. It can be treated with topical interferon alpha-2b (INF α-2b) as first choice. A 71-year-old man referred for corneal-conjunctival, gelatinous lesion in the left eye (LE) with an area of almost 270°. The clinical diagnosis was compatible with a corneal-conjunctival intraepithelial neoplasia. Topical treatment was started with INF α-2b at a dose of one million international units (IU)/ml, 4 times/day for 4 months, with remission being achieved. The isolated use of topical INF α-2b is an effective treatment as a first option in the case of corneal-conjunctival intraepithelial neoplasia, positioning itself as a form of effective and safe treatment compared to other therapeutic options. Surgical excision and use of other chemotherapy agents could lead to severe limbic deficits and other side effects. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  14. The Effect of Topical Rosa damascena (Rose) Oil on Pregnancy-Related Low Back Pain: A Randomized Controlled Clinical Trial.

    PubMed

    Shirazi, Mahbobeh; Mohebitabar, Safieh; Bioos, Sodabeh; Yekaninejad, Mir Saeed; Rahimi, Roja; Shahpiri, Zahra; Malekshahi, Farhad; Nejatbakhsh, Fatemeh

    2017-01-01

    The study aimed to assess the efficacy of topical rose oil in women with pregnancy-related low back pain. A randomized controlled clinical trial was conducted on 120 women with pregnancy-related low back pain. Patients were allocated to 3 parallel groups to receive topical rose oil (in the carrier of almond oil), placebo (carrier oil), or no intervention. All groups were followed for 4 weeks. All participants were evaluated by Visual Analog Scale and the Roland-Morris Disability Questionnaires to assess the pain intensity and its impact on daily activities before and after the intervention. Significant decrease in pain intensity compared to carrier oil or no intervention was observed. The rose oil also improves the functional ability of these patients in contrast with no intervention, while its effect on function is not significant compared to carrier oil. Rose oil reduced pregnancy-related low back pain intensity without any significant adverse effect.

  15. Randomised, double-blind, placebo-controlled clinical trial of a new topical glyceryl trinitrate patch for chronic lateral epicondylosis.

    PubMed

    Paoloni, J A; Murrell, G A C; Burch, R M; Ang, R Y

    2009-04-01

    This study aimed to determine whether a new glyceryl trinitrate patch preparation is effective in treating chronic lateral epicondylosis. Randomised double-blind controlled clinical trial. Private practice 154 adult patients with chronic lateral epicondylosis were recruited, with 136 patients completing the trial. 8 weeks of glyceryl trinitrate patch application (dosages of 72 mg/24 h, 1.44 mg/24 h, and 3.6 mg/24 h), or placebo patch application. Subjective global assessment of change in elbow symptoms, patient-rated tennis elbow evaluation, visual analogue pain at rest, visual analogue pain with activity, visual analogue pain intensity, grip strength, and strength testing using the Orthopaedic Research Institute-Tennis Elbow Testing System. At 8 weeks there was a significant decrease in elbow pain with activity in the glyceryl trinitrate 0.72 mg/24 h group compared with placebo (p = 0.04). There were no other significant differences. Continuous 1.25 mg/24 h topical glyceryl trinitrate treatment, when combined with daily exercise rehabilitation, has previously demonstrated efficacy in treating chronic lateral epicondylosis. There was significantly decreased elbow pain with activity at 8 weeks in the glyceryl trinitrate 0.72 mg/24 h group (p = 0.04). This short-term dose-ranging study did not demonstrate a treatment effect of a new topical glyceryl trinitrate patch in dosages of 1.44 mg/24 h or 3.6 mg/24 h, which conflicts with previous studies on topical glyceryl trinitrate treatment. NCT00447928.

  16. Assessing the effectiveness of topical betamethasone to treat chronic chilblains: a randomised clinical trial in primary care.

    PubMed

    Souwer, Ibo H; Bor, Jacobus Hj; Smits, Paul; Lagro-Janssen, Antoine Lm

    2017-03-01

    GPs prescribe topical corticosteroids to patients with chronic chilblains despite poor evidence for their effectiveness. The authors of the current study therefore decided to assess the effectiveness of topical steroids in a primary care setting. To assess the effectiveness of topical application of betamethasone valerate 0.1% cream in patients with chronic chilblains. A placebo-controlled, double-blind, crossover, randomised clinical trial in a Dutch primary care setting. The study population consisted of 34 participants suffering from chronic chilblains. Intervention was topical application of betamethasone valerate 0.1% cream twice a day for 6 weeks compared with placebo. Primary outcome was the visual analogue scale on complaints (VOC). Secondary outcome was the visual analogue scale on disability (VOD). Both were assessed with a diary of daily scores on a 100 mm visual analogue scale. The authors took ambient temperatures into account, checked for a carry-over effect, performed additional analysis, and monitored adverse effects. On the primary outcome mean VOC, there was a difference of 0.56 mm (95% confidence interval [CI] = -2.88 to 3.99 mm) in favour of placebo (P = 0.744). On the secondary outcome mean VOD, there was a difference of 0.88 mm (95% CI = -2.22 to 3.98 mm) in favour of placebo (P = 0.567). This study found no carry-over effect and no adverse effects. In this study, topical betamethasone was not superior to placebo in the treatment of chronic chilblains. Topical betamethasone should not be used for chronic chilblains without new evidence. © British Journal of General Practice 2017.

  17. SMi's Conducting Clinical Trials in Europe.

    PubMed

    Jago, Charlotte

    2009-12-01

    The Conducting Clinical Trials in Europe meeting, held in London, included topics covering new developments in the field of clinical trials and recommendations on how to best conduct a trial. This conference report highlights selected presentations on the state of affairs of trials in Europe, conducting trials in emerging markets, strategies for improving trials, trial design options, peri-approval and pediatric trials, and the role of key players, such as physicians. Company perspectives from Pfizer Inc and Nycomed are also included.

  18. Topical Application of Honey on Surgical Wounds: A Randomized Clinical Trial.

    PubMed

    Goharshenasan, Peiman; Amini, Shahideh; Atria, Ali; Abtahi, Hamidreza; Khorasani, Ghasemali

    2016-01-01

    The antimicrobial and anti-inflammatory activity of honey and its ability to accelerate wound healing make it an attractive option in surgical wound care. We performed a randomized clinical trial to compare the efficacy of honey dressing with conventional dressing regarding the aesthetic outcome. Bilateral symmetric incisions in randomly selected plastic surgical patients were randomly covered postoperatively with conventional dressing and honey dressing for five days. The aesthetic outcome of the two sides was rated on a Visual Analog Scale by the surgeon and the patient and compared at month three and six after surgery. Seventy two symmetrical incisions in 52 patients were evaluated during the study. The mean width of the scar after the third and the sixth month was 3.64 +/- 0.83 mm and 3.49 +/- 0.87 mm on the side that received honey dressing and 5.43 +/- 0.05 mm and 5.30+/- 1.35 mm in the control group. Wilcoxon signed-rank test showed significant difference between honey and conventional dressing outcomes at third and sixth month (p < 0.001). The healing process of the surgical wound and its final aesthetic result could be improved by using honey dressing. © 2016 S. Karger GmbH, Freiburg.

  19. Comparison of topical hemostatic agents in elective hepatic resection: a clinical prospective randomized trial.

    PubMed

    Kohno, H; Nagasue, N; Chang, Y C; Taniura, H; Yamanoi, A; Nakamura, T

    1992-01-01

    To compare the difference in efficacy of microcrystalline collagen powder (CL) and fibrin glue (FG) in elective hepatic resection, 62 patients (female 14, male 48) with ages ranging from 51 to 75 years were randomly allocated to receive either CL or FG as a topical agent during hepatectomy. There were no significant differences between the patients treated with CL (n = 31) and those treated with FG (n = 31) regarding sex, age, liver function, coagulation function, platelet counts, type of liver resection, and operative duration. A dry cut surface of the liver was obtained during surgery in 27 (87%) patients and 25 (81%) patients treated with CL and FG, respectively. Both CL and FG showed similar hemostatic effects. The CL and FG groups were not different in terms of postoperative rebleeding, bile leakage, or morbidity and mortality rates (6% vs. 6%, 6% vs. 6%, 45% vs. 39%, and 13% vs. 10%, respectively). Of the 52 patients with a dry cut surface of the liver during surgery, 3 patients in the CL group encountered rebleeding (n = 1) or bile leakage (n = 2) from the cut surface postoperatively, while no such complications were noted in the FG group. The results seem to favor FG for reliability in the postoperative period. The application of CL or FG may be better performed with consideration of the characteristics of each agent.

  20. A Clinical Trial Comparing the Safety and Efficacy of Topical Tacrolimus versus Methylprednisolone in Ocular Graft-Versus-Host Disease

    PubMed Central

    Abud, Tulio B; Amparo, Francisco; Saboo, Ujwala S; Di Zazzo, Antonio; Dohlman, Thomas H; Ciolino, Joseph B; Hamrah, Pedram; Dana, Reza

    2016-01-01

    Purpose To evaluate the safety and efficacy of topical tacrolimus 0.05% vs. topical methylprednisolone 0.5% in patients with ocular graft-versus-host disease (GVHD). Design Phase I/II, prospective, randomized, double-masked clinical trial. Subjects Eighty eyes from 40 patients diagnosed with chronic ocular GVHD were enrolled. Methods Forty patients with ocular GVHD were randomized; 24 patients were treated with topical tacrolimus 0.05% and 16 patients with topical methylprednisolone 0.5% twice a day for 10 weeks, in addition to continuing their baseline treatment regimen. Main Outcome Measures Safety was evaluated based on occurrence of adverse events. Tolerability was assessed based on subjects’ reports of discomfort after drop instillation. Intraocular pressure (IOP) was monitored. The main efficacy endpoints were: corneal fluorescein staining (CFS), tear break-up time (TBUT), Schirmer test, and expression of the ocular surface inflammatory markers human leukocyte antigen-DR (HLA-DR) and intercellular adhesion molecule-1 (ICAM-1). Symptoms were evaluated using the Ocular Surface Disease Index (OSDI). Results After 10 weeks of treatment, no major adverse events occurred in either treatment group, and there was no significant difference in the composite tolerability scores between the two groups (P=0.06). However, burning sensation was more pronounced with tacrolimus (P=0.002). Topical tacrolimus was more effective than methylprednisolone in reducing the CFS score at week 10 (55% vs. 23% reduction, respectively; P=0.01), and achieved significant improvement in TBUT when compared to baseline (P<0.001). OSDI score reduction achieved statistical significance with tacrolimus (27% reduction; P=0.02) but was marginal with methylprednisolone (32% reduction; P=0.06). ICAM-1 expression by ocular surface epithelium decreased significantly in both groups (tacrolimus P=0.003; methylprednisolone P=0.008), while HLA-DR expression significantly decreased only in the tacrolimus

  1. A Clinical Trial Comparing the Safety and Efficacy of Topical Tacrolimus versus Methylprednisolone in Ocular Graft-versus-Host Disease.

    PubMed

    Abud, Tulio B; Amparo, Francisco; Saboo, Ujwala S; Di Zazzo, Antonio; Dohlman, Thomas H; Ciolino, Joseph B; Hamrah, Pedram; Dana, Reza

    2016-07-01

    To evaluate the safety and efficacy of topical tacrolimus 0.05% versus topical methylprednisolone 0.5% in patients with ocular graft-versus-host disease (GVHD). Phase 1/2 prospective, randomized, double-masked clinical trial. Eighty eyes of 40 patients diagnosed with chronic ocular GVHD were enrolled. Forty patients with ocular GVHD were randomized; 24 patients were treated with topical tacrolimus 0.05% and 16 patients were treated with topical methylprednisolone 0.5% twice daily for 10 weeks, in addition to continuing their baseline treatment regimen. Safety was evaluated based on occurrence of adverse events. Tolerability was assessed based on subject reports of discomfort after drop instillation. Intraocular pressure (IOP) was monitored. The main efficacy end points were corneal fluorescein staining (CFS), tear film break-up time (TBUT), Schirmer test results, and expression of the ocular surface inflammatory markers human leukocyte antigen-DR (HLA-DR) and intercellular adhesion molecule-1 (ICAM-1). Symptoms were evaluated using the Ocular Surface Disease Index (OSDI). After 10 weeks of treatment, no major adverse events occurred in either treatment group, and there was no significant difference in the composite tolerability scores between the 2 groups (P = 0.06). However, burning sensation was more pronounced with tacrolimus (P = 0.002). Topical tacrolimus was more effective than methylprednisolone in reducing the CFS score at week 10 (55% vs. 23% reduction, respectively; P = 0.01) and achieved significant improvement in TBUT when compared with baseline (P < 0.001). Reduction in OSDI score achieved statistical significance with tacrolimus (27% reduction; P = 0.02), but was marginal with methylprednisolone (32% reduction; P = 0.06). Expression of ICAM-1 by ocular surface epithelium decreased significantly in both groups (tacrolimus, P = 0.003; methylprednisolone, P = 0.008), whereas HLA-DR expression decreased significantly only in the tacrolimus group

  2. Evaluating clinical trial design: systematic review of randomized vehicle-controlled trials for determining efficacy of benzoyl peroxide topical therapy for acne.

    PubMed

    Lamel, Sonia A; Sivamani, Raja K; Rahvar, Maral; Maibach, Howard I

    2015-11-01

    Determined efficacies of benzoyl peroxide may be affected by study design, implementation, and vehicle effects. We sought to elucidate areas that may allow improvement in determining accurate treatment efficacies by determining rates of active treatment and vehicle responders in randomized controlled trials assessing the efficacy of topical benzoyl peroxide to treat acne. We conducted a systematic review of randomized vehicle-controlled trials evaluating the efficacy of topical benzoyl peroxide for the treatment of acne. We compared response rates of vehicle treatment arms versus those in benzoyl peroxide arms. Twelve trials met inclusion criteria with 2818 patients receiving benzoyl peroxide monotherapy treatment and 2004 receiving vehicle treatment. The average percent reduction in total number of acne lesions was 44.3 (SD = 9.2) and 27.8 (SD = 21.0) for the active and vehicle treatment groups, respectively. The average reduction in non-inflammatory lesions was 41.5 % (SD = 9.4) in the active treatment group and 27.0 % (SD = 20.9) in the vehicle group. The average percent decrease in inflammatory lesions was 52.1 (SD = 10.4) in the benzoyl peroxide group and 34.7 (SD = 22.7) in the vehicle group. The average percentage of participants achieving success per designated study outcomes was 28.6 (SD = 17.3) and 15.2 (SD = 9.5) in the active treatment and vehicle groups, respectively. Patient responses in randomized controlled trials evaluating topical acne therapies may be affected by clinical trial design, implementation, the biologic effects of vehicles, and natural disease progression. "No treatment" groups may facilitate determination of accurate treatment efficacies.

  3. Topical Insulin Accelerates Wound Healing in Diabetes by Enhancing the AKT and ERK Pathways: A Double-Blind Placebo-Controlled Clinical Trial

    PubMed Central

    Lima, Maria H. M.; Caricilli, Andréa M.; de Abreu, Lélia L.; Araújo, Eliana P.; Pelegrinelli, Fabiana F.; Thirone, Ana C. P.; Tsukumo, Daniela M.; Pessoa, Ana Flávia M.; dos Santos, Marinilce F.; de Moraes, Maria A.; Carvalheira, José B. C.; Velloso, Lício A.; Saad, Mario J. A.

    2012-01-01

    Background Wound healing is impaired in diabetes mellitus, but the mechanisms involved in this process are virtually unknown. Proteins belonging to the insulin signaling pathway respond to insulin in the skin of rats. Objective The purpose of this study was to investigate the regulation of the insulin signaling pathway in wound healing and skin repair of normal and diabetic rats, and, in parallel, the effect of a topical insulin cream on wound healing and on the activation of this pathway. Research Design and Methods We investigated insulin signaling by immunoblotting during wound healing of control and diabetic animals with or without topical insulin. Diabetic patients with ulcers were randomized to receive topical insulin or placebo in a prospective, double-blind and placebo-controlled, randomized clinical trial (NCT 01295177) of wound healing. Results and Conclusions Expression of IR, IRS-1, IRS-2, SHC, ERK, and AKT are increased in the tissue of healing wounds compared to intact skin, suggesting that the insulin signaling pathway may have an important role in this process. These pathways were attenuated in the wounded skin of diabetic rats, in parallel with an increase in the time of complete wound healing. Upon topical application of insulin cream, the wound healing time of diabetic animals was normalized, followed by a reversal of defective insulin signal transduction. In addition, the treatment also increased expression of other proteins, such as eNOS (also in bone marrow), VEGF, and SDF-1α in wounded skin. In diabetic patients, topical insulin cream markedly improved wound healing, representing an attractive and cost-free method for treating this devastating complication of diabetes. Trial Registration ClinicalTrials.gov NCT01295177 PMID:22662132

  4. Efficacy and tolerance of the topical application of potassium hydroxide (10% and 15%) in the treatment of molluscum contagiosum: Randomized clinical trial: Research protocol

    PubMed Central

    2011-01-01

    Background Molluscum contagiosum is a non-severe pediatric viral infection. Because it is highly contagious and current treatments have negative aesthetic and psychological effects, we want to test an alternative treatment in the primary care setting, consisting of two different concentrations of potassium hydroxide solution. Methods/design The study design is a double-blind, randomized clinical trial, using three types of topical treatment. The treatment consist of daily applications of potassium hydroxide (KOH) in aqueous solution at 10% and 15% concentration, and a placebo administered in the control group. Four follow-up visits (at 15, 30, 45 and 60 days) are planned to evaluate treatment effectiveness and patient tolerance. The main outcome measure of the trial will be the healing rate, defined as lesion disappearance in the affected zones after the topic application of the experimental treatment. Secondary measures will be the principal characteristics and evolution of the affected zone (surface area, number of lesions, size and density of lesions), treatment tolerance (hyperpigmentation, itching, burning, pain), recurrence rate and the natural evolution of lesions in the control group. Discussion KOH can potentially be an effective and safe treatment for MC in primary care, and can also reduce referrals to dermatologists and hospital pediatric departments. In addition, KOH may be a valid and less expensive alternative to current invasive treatments (surgical excision). Trial Registration ClinicalTrials.gov: NCT01348386 PMID:22011376

  5. Long-term Efficacy of Topical Fluorouracil Cream, 5%, for Treating Actinic Keratosis: A Randomized Clinical Trial.

    PubMed

    Pomerantz, Hyemin; Hogan, Daniel; Eilers, David; Swetter, Susan M; Chen, Suephy C; Jacob, Sharon E; Warshaw, Erin M; Stricklin, George; Dellavalle, Robert P; Sidhu-Malik, Navjeet; Konnikov, Nellie; Werth, Victoria P; Keri, Jonette; Lew, Robert; Weinstock, Martin A

    2015-09-01

    Topical fluorouracil was demonstrated to be effective in reducing the number of actinic keratoses (AKs) for up to 6 months, but no randomized trials studied its long-term efficacy. To evaluate the long-term efficacy of a single course of fluorouracil cream, 5%, for AK treatment. The Veterans Affairs Keratinocyte Carcinoma Chemoprevention (VAKCC) trial was a randomized, double-blinded, placebo-controlled trial with patients from dermatology clinics at 12 VA medical centers recruited from 2009 to 2011 and followed up until 2013. Our study population comprised 932 veterans with 2 or more keratinocyte carcinomas in the 5 years prior to enrollment. The mean follow-up duration was 2.6 years in both treatment and control groups. Participants applied either topical fluorouracil cream, 5% (n = 468), or vehicle control cream (n = 464) to the face and ears twice daily for up to 4 weeks. This study reports on AK counts and treatments, which were secondary outcomes of the VAKCC trial. Actinic keratoses on the face and ears were counted by study dermatologists at enrollment and at study visits every 6 months. The number of spot treatments for AKs on the face and ears at semiannual study visits and in between study visits was recorded. The number of AKs on the face and ears per participant was not different between the fluorouracil and control groups at randomization (11.1 vs 10.6, P > .10). After randomization, the fluorouracil group had fewer AKs compared with the control group at 6 months (3.0 vs 8.1, P < .001) and for the overall study duration (P < .001). The fluorouracil group also had higher complete AK clearance rates (38% vs 17% at 6 months) and fewer spot treatments at 6-month intervals, at study visits, and in between study visits during the trial (P < .01 for all). The fluorouracil group took longer to require the first spot AK treatment (6.2 months) compared with the control group (6.0 months) (hazard ratio, 0.69; 95% CI, 0.60-0.79). The

  6. Clinical Trials

    MedlinePlus

    Clinical trials are research studies that test how well new medical approaches work in people. Each study answers scientific ... screen for, diagnose, or treat a disease. Clinical trials may also compare a new treatment to a ...

  7. Comparative Efficacy of Topical Curcumin and Triamcinolone for Oral Lichen Planus: A Randomized, Controlled Clinical Trial

    PubMed Central

    Kia, Seid Javad; Shirazian, Shiva; Mansourian, Arash; Khodadadi Fard, Leila; Ashnagar, Sajjad

    2015-01-01

    Objectives: Lichen planus (LP) is a chronic inflammatory mucocutaneous disease. Its treatment is often symptomatic and includes topical and systemic corticosteroids. Although corticosteroid therapy is usually successful, it has side effects and thus, an alternative treatment is favorable. The aim of this study was to compare the efficacy of topical curcumin and triamcinolone for treatment of oral lichen planus (OLP). Materials and Methods: In this study, 50 patients (36 women and 14 men) in the age range of 38 to 73 years with OLP were randomly divided into two groups. Each group received 0.1% triamcinolone or 5% curcumin oral paste three times a day for four weeks. Assessment of the appearance score and severity of pain was done at baseline and at the end of two and four weeks and recorded in the patients’ questionnaires. The data were analyzed by SPSS 17 software, using the Mann-Whitney and Spearman's tests. Results: With respect to pain reduction, nine patients (36%) in the curcumin group and eight patients (32%) in the triamcinolone group showed complete remission. With respect to the appearance score, one patient (4%) in each group showed complete remission. No statistically significant difference was noted between the two groups. Conclusion: Application of curcumin is suggested for treatment of OLP because of its desirable anti-inflammatory effects and insignificant side effects. PMID:27507989

  8. Efficacy of Topical Alpha Ointment (Containing Natural Henna) Compared to Topical Hydrocortisone (1%) in the Healing of Radiation-Induced Dermatitis in Patients with Breast Cancer: A Randomized Controlled Clinical Trial

    PubMed Central

    Ansari, Mansour; Dehsara, Farzin; Mosalaei, Ahmad; Omidvari, Shapour; Ahmadloo, Niloofar; Mohammadianpanah, Mohammad

    2013-01-01

    Background: This two-arm, randomized clinical study aimed to compare efficacy between topical Alpha ointment and topical hydrocortisone cream (1%) in the healing of radiation-induced dermatitis in breast cancer patients. Methods: The inclusion criteria comprised newly pathologically proven, locally advanced breast cancer (treated with modified radical mastectomy followed by sequential adjuvant treatments, including chest wall radiotherapy [45-50.4 Gy]) and grade 2 and/or 3 chest wall dermatitis. The exclusion criteria were comprised of any underlying disease or medications interfering with the wound healing process, previous history of chest wall radiotherapy, and concurrent use of chemotherapy. Sixty eligible patients were randomly assigned to use either topical Alpha ointment (study arm, n=30) or topical hydrocortisone cream (1%) (control arm, n=30) immediately after receiving a total dose of 45-50 Gy chest wall radiotherapy. Results: The mean radiation dose was 49.1 Gy in the control arm and 48.8 Gy in the study arm. The mean dermatitis area was 13.54 cm2 in the control arm and 17.02 cm2 in the study arm. Topical Alpha ointment was more effective on the healing of radiation-induced dermatitis than was topical hydrocortisone cream (1%) (P=0.001). This effect was significant in the second week (P=0.007). In addition, Alpha ointment decreased the patients’ complaints such as pain (P<0.001), pruritus (P=0.009), and discharge (P=0.010) effectively and meaningfully. Conclusion: Topical Alpha ointment was more effective on the healing of radiation-induced dermatitis than was topical hydrocortisone cream (1%) in our patients with breast cancer. Trial Registration Numbers: IRCT201206099979N1, ACTRN12612000837820 PMID:24293782

  9. Involving clinical experts in prioritising topics for health technology assessment: a randomised controlled trial.

    PubMed

    Cook, Andrew; Streit, Elke; Davage, Gill

    2017-08-21

    The objective of this study was to explore whether reducing the material supplied to external experts during peer review and decreasing the burden of response would maintain review quality into prioritising research questions for a major research funder. Clinical experts who agreed to review documents outlining research for potential commissioning were screened for eligibility and randomised in a factorial design to two types of review materials (long document versus short document) and response modes (structured review form versus free text email response). Previous and current members of the funder's programme groups were excluded. Response quality was assessed by use of a four-point scoring tool and analysed by intention to treat. 554 consecutive experts were screened for eligibility and 460 were randomised (232 and 228 to long document or short document, respectively; 230 each to structured response or free text). 356 participants provided reviews, 90 did not respond and 14 were excluded after randomisation as not eligible.The pooled mean quality score was 2.4 (SD=0.95). The short document scored 0.037 (Cohen's d=0.039) extra quality points over the long document arm, and the structured response scored 0.335 (Cohen's d=0.353) over free text. The allocation did not appear to have any effect on the experts' willingness to engage with the task. Neither providing a short or a long document outlining suggested research was shown to be superior. However, providing a structured form to guide the expert response provided more useful information than allowing free text. The funder should continue to use a structured form to gather responses. It would be acceptable to provide shorter documents to reviewers, if there were reasons to do so. ANZCTR12614000167662. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  10. Evaluation of the efficacy of a topical sialogogue spray containing malic acid 1% in elderly people with xerostomia: a double-blind, randomized clinical trial.

    PubMed

    Gómez-Moreno, Gerardo; Cabrera-Ayala, Maribel; Aguilar-Salvatierra, Antonio; Guardia, Javier; Ramírez-Fernández, María Piedad; González-Jaranay, Maximino; Calvo-Guirado, José Luis

    2014-12-01

    The aim of this study was to evaluate the clinical efficacy of a topical sialogogue spray containing 1% malic acid for elderly people affected by xerostomia. This research took the form of a double-blind, randomized clinical trial. Forty-one individuals (mean age: 78.7 years) with xerostomia were divided into two groups: for the first 'intervention group' (21 subjects) a topical sialogogue spray (1% malic acid) was applied, while for the second 'control group' (20 subjects), a placebo spray was applied; for both groups, the sprays were applied on demand during 2 weeks. The Xerostomia Inventory (XI) was used to evaluate xerostomia levels before and after product/placebo application. Unstimulated and stimulated salivary flows rates, before and after spray application, were measured. XI scores decreased significantly (clinically meaningful) from 36.4 ± 7.3 points to 29.1 ± 7.1 (p < 0.05) with an XI difference of 7.2 ± 6.1, after the combination among 1% malic acid with xylitol and fluoride application. After 2 weeks of 1% malic acid application, unstimulated and stimulated salivary flows rates increased significantly (p < 0.05). A topical sialogogue spray containing 1% malic acid improved xerostomia in an elderly population and increased unstimulated and stimulated salivary flows rates. © 2013 The Gerodontology Society and John Wiley & Sons A/S.

  11. The Effect of Topical Use of Petroselinum Crispum (Parsley) Versus That of Hydroquinone Cream on Reduction of Epidermal Melasma: A Randomized Clinical Trial.

    PubMed

    Khosravan, Shahla; Alami, Ali; Mohammadzadeh-Moghadam, Hossein; Ramezani, Vahide

    Melasma disfigures the skin and thus influences people's self-image and self-concept. Therefore, melasma influences emotional and psychosocial health in addition to physical health. This clinical trial was performed to assess the effect of the topical use of Petroselinum crispum (parsley) on reduction of the severity of epidermal melasma.

  12. The clinical trials supporting benzyl alcohol lotion 5% (Ulesfia): a safe and effective topical treatment for head lice (pediculosis humanus capitis).

    PubMed

    Meinking, Terri L; Villar, Maria E; Vicaria, Maureen; Eyerdam, Debbie H; Paquet, Diane; Mertz-Rivera, Kamara; Rivera, Hector F; Hiriart, Javier; Reyna, Susan

    2010-01-01

    Benzyl alcohol lotion 5% (BAL 5%) is a non-neurotoxic topical head lice treatment that is safe and effective in children as young as 6 months of age. The safety and efficacy of this pediculicide has been studied in 695 (confirm number) subjects in all phases of clinical development. Scanning electron micrographs (SEM) demonstrated that the active agent appears to stun the breathing spiracles open, enabling the vehicle to penetrate the respiratory mechanism (spiracles), therefore asphyxiating the lice. Initial phase II trials compared this novel product to RID using identical volumes of treatment (4 oz/application) and yielding, almost, identical efficacy. This outcome pointed to the significant importance of completely saturating the hair with the product in order to achieve maximum treatment success. A second phase II trial, which allowed the use of sufficient product to saturate the hair, resulted in 100% efficacy after both 10 and 30 minute treatments. A third phase II trial verified an effective dose. Phase III trials compared BAL 5% to vehicle placebo for two 10-minute applications. It proved to be safe and effective (p < 0.001) for treatment of head lice and is the first FDA-approved non-neurotoxic lice treatment, now available in the United States as Ulesfia lotion.

  13. Topical Treatment With an Agent Disruptive to P. acnes Biofilm Provides Positive Therapeutic Response: Results of a Randomized Clinical Trial.

    PubMed

    Bernhardt, Michael J; Myntti, Matthew F

    2016-06-01

    The traditional disease model of acne has been one of follicular plugging due to 'sticky epithelial cells' associated with increased sebum production with deep follicular anaerobic conditions favoring P. acnes- generated inflammation. P. acnes biofilms have been found more frequently in patients with acne than controls. Biofilms are genetically coded to create adhesion to the pilosebaceous unit followed by production of a mucopolysaccharide coating capable of binding to lipid surfaces. Traditional therapies for acne have involved mixtures of oral and topical antibiotics admixed with topical keratolytics and retinoids, which are aimed at traditional bacterial reduction as well as downregulating the inflammatory cascade. These approaches are limited by side effect and compliance/tolerability issues. As the P. acnes biofilm may, in fact, be the instigator of this process, we studied the use of a topical agent designed to reduce the P. acnes biofilm to see if reducing the biofilm would be therapeutically efficacious. We present data of a proprietary topical non-prescription agent with a novel pharmaco mechanism designed to attack the biofilm produced by P. acnes. Our data shows a decrease of inflammatory lesions by 44% and non-inflammatory lesions by 32% after 12 weeks and also provided for a meaningful improvement in the quality of life of the patients in the study. These improvements were achieved with a product that was not associated with burning, chafing, irritation, or erythema, which can be seen with topical treatments. It is apparent from this study that by addressing the biofilm which protects the P. acnes bacteria through the use of the Acne Gel, the incidence of acne symptoms can be greatly reduced, while having no negative impacts on the patients' skin (ClinicalTrials.gov registry number NCT02404285).

    J Drugs Dermatol. 2016;15(6):677-683.

  14. Topical Fluorometholone Protects the Ocular Surface of Dry Eye Patients from Desiccating Stress: A Randomized Controlled Clinical Trial.

    PubMed

    Pinto-Fraga, José; López-Miguel, Alberto; González-García, María J; Fernández, Itziar; López-de-la-Rosa, Alberto; Enríquez-de-Salamanca, Amalia; Stern, Michael E; Calonge, Margarita

    2016-01-01

    To assess the efficacy of topical 0.1% fluorometholone in dry eye disease (DED) patients for ameliorating the worsening of the ocular surface when exposed to adverse environments. Single-center, double-masked, randomized, vehicle-controlled clinical trial. Forty-one patients showing moderate to severe DED. Patients randomly received 1 drop 4 times daily of either topical 0.1% fluorometholone (FML group) or topical polyvinyl alcohol (PA group) for 22 days. Corneal and conjunctival staining, conjunctival hyperemia, tear film breakup time (TBUT), tear osmolarity, and the Symptom Assessment in Dry Eye (SANDE) questionnaire scores were determined at baseline. Variables were reassessed on day 21 before and after undergoing a 2-hour controlled adverse environment exposure and again on day 22. Percentage of patients showing an increase 1 point or more in corneal staining and a reduction of 2 points or more (0-10 scale) in SANDE score, after the controlled adverse environment exposure and 24 hours later. After 21 days of treatment, the FML group showed greater improvements in corneal and conjunctival staining, hyperemia, and TBUT than the PA group (P≤0.03). After the adverse exposure, the percentage of patients having a 1-grade or more increase in corneal staining was significantly (P = 0.03) higher in the PA group (63.1% vs. 23.8%, respectively). Additionally, the FML group showed no significant changes in corneal staining (mean, 0.86; 95% confidence interval [CI], 0.47-1.25; vs. mean, 1.05; 95% CI, 0.59-1.51, for visit 2 and 3, respectively), conjunctival staining (mean, 0.95; 95% CI, 0.54-1.37 vs. mean, 1.19; 95% CI, 0.75-1.63), and hyperemia (mean, 0.71; 95% CI, 0.41-1.02 vs. 1.14; 95% CI, 0.71-1.58) after the exposure, whereas for the PA group, there was significant worsening (P≤0.009) in these variables (corneal staining: mean, 1.95; 95% CI, 1.57-2.33 vs. mean, 2.58; 95% CI, 2.17-2.98; conjunctival staining: mean, 1.68; 95% CI, 1.29-2.08 vs. mean, 2.47; 95% CI

  15. Topical Penile Microbicide Use by Men to Prevent Recurrent Bacterial Vaginosis in Sex Partners: A Randomized Clinical Trial

    PubMed Central

    Bukusi, Elizabeth; Thomas, Katherine K.; Nguti, Rosemary; Cohen, Craig R.; Weiss, Noel; Coombs, Robert W.; Holmes, King K.

    2012-01-01

    Background Bacterial vaginosis (BV) recurs frequently after metronidazole treatment. This randomized, single-blinded clinical trial (RCT) evaluated the efficacy of topical application of 62% ethyl alcohol in emollient gel (gel) to the penis by male partners of women diagnosed with BV for preventing post-treatment BV recurrence. Methods Among 587 Kenyan women presenting with vulvovaginal symptoms, 236 had BV (vaginal Gram stain Nugent score ≥ 7), of whom 223 (94.3%) agreed, along with their partners, to be randomized: 115 to the intervention and 108 to the control arm. In the intervention arm, male partners agreed to apply gel each morning, and before and after sexual intercourse. All couples received counseling, condoms, and syndromic treatment of STI symptoms. Follow-up visits were scheduled 1 week, 1 month, and 2 months post-enrollment, with vaginal Gram stains at every visit and culture for H2O2-producing lactobacilli at the 2 month visit. The primary outcome was time to diagnosis of BV during follow-up. Results In the primary intent-to-treat analysis, diagnosis of BV was significantly more frequent in the intervention arm (Hazard ratio 1.44, 95% CI 1.01-2.04). After adjustment for baseline covariates, the hazard ratio was 1.39 (95% CI 0.98-1.99). At the 2 month visit, prevalences of any vaginal lactobacilli or of H2O2-producing lactobacilli did not differ appreciably in the two study arms (p=0.81, and 0.32 respectively). Conclusion Daily use of the 62% ethyl alcohol gel by men before and after sex significantly increased persistence or early recurrence of BV in their partners through two months after metronidazole treatment. However, no difference was observed in prevalences of vaginal lactobacilli within this same period. PMID:22256334

  16. Analgesic Effect of Topical Sodium Diclofenac before Retinal Photocoagulation for Diabetic Retinopathy: A Randomized Double-masked Placebo-controlled Intraindividual Crossover Clinical Trial

    PubMed Central

    Entezari, Morteza; Shahbazi, Mohammad Mehdi; Semnani, Yosef; Nikkhah, Homayoun; Yaseri, Mehdi

    2017-01-01

    Purpose To evaluate the analgesic effect of topical sodium diclofenac 0.1% before retinal laser photocoagulation for diabetic retinopathy. Methods Diabetic patients who were candidates for peripheral laser photocoagulation were included in a randomized, placebo-controlled, intraindividual, two-period, and crossover clinical trial. At the first session and based on randomization, one eye received topical sodium diclofenac 0.1% and the other eye received an artificial tear drop (as placebo) three times before laser treatment. At the second session, eyes were given the alternate drug. Patients scored their pain using visual analogue scale (max, 10 cm) at both sessions. Patients and the surgeon were blinded to the drops given. Difference of pain level was the main outcome measure. Results A total of 200 eyes of 100 patients were enrolled. Both treatments were matched regarding the applied laser. Pain sensation based on visual analogue scale was 5.6 ± 3.0 in the treated group and 5.5 ± 3.0 in the control group. The calculated treatment effect was 0.15 (95% confidence interval, −0.27 to 0.58; p = 0.486). The estimated period effect was 0.24 (p = 0.530) and the carryover effect was not significant (p = 0.283). Conclusions Pretreatment with topical sodium diclofenac 0.1% does not have any analgesic effect during peripheral retinal laser photocoagulation in diabetic patients. PMID:28367037

  17. Analgesic Effect of Topical Sodium Diclofenac before Retinal Photocoagulation for Diabetic Retinopathy: A Randomized Double-masked Placebo-controlled Intraindividual Crossover Clinical Trial.

    PubMed

    Ramezani, Alireza; Entezari, Morteza; Shahbazi, Mohammad Mehdi; Semnani, Yosef; Nikkhah, Homayoun; Yaseri, Mehdi

    2017-04-01

    To evaluate the analgesic effect of topical sodium diclofenac 0.1% before retinal laser photocoagulation for diabetic retinopathy. Diabetic patients who were candidates for peripheral laser photocoagulation were included in a randomized, placebo-controlled, intraindividual, two-period, and crossover clinical trial. At the first session and based on randomization, one eye received topical sodium diclofenac 0.1% and the other eye received an artificial tear drop (as placebo) three times before laser treatment. At the second session, eyes were given the alternate drug. Patients scored their pain using visual analogue scale (max, 10 cm) at both sessions. Patients and the surgeon were blinded to the drops given. Difference of pain level was the main outcome measure. A total of 200 eyes of 100 patients were enrolled. Both treatments were matched regarding the applied laser. Pain sensation based on visual analogue scale was 5.6 ± 3.0 in the treated group and 5.5 ± 3.0 in the control group. The calculated treatment effect was 0.15 (95% confidence interval, -0.27 to 0.58; p = 0.486). The estimated period effect was 0.24 (p = 0.530) and the carryover effect was not significant (p = 0.283). Pretreatment with topical sodium diclofenac 0.1% does not have any analgesic effect during peripheral retinal laser photocoagulation in diabetic patients.

  18. Effect of Topical Application of Nigella Sativa Oil and Oral Acetaminophen on Pain in Elderly with Knee Osteoarthritis: A Crossover Clinical Trial

    PubMed Central

    Kooshki, Akram; Forouzan, Reza; Rakhshani, Mohammad Hassan; Mohammadi, Maryam

    2016-01-01

    Background Limited evidence supports Nigella sativa’s role as an effective complementary and alternative medicine and the anti-inflammatory effects of Nigella sativa on patients with allergic rhinitis. Objective The aim of this study was to investigate the effect of topical application of Nigella sativa oil and oral acetaminophen on pain in the elderly with knee osteoarthritis residing in a parents’ home in Sabzevar. Methods This study is done as a crossover clinical trial. After obtaining written consent of elderly patients with osteoarthritis of the knee, they were randomly divided into two groups. In step 1, in group 1, 1 cc of Nigella sativa oil was applied on the knee joint every 8 hours for 3 weeks; for the second group, every 8 hours for 3 weeks, patients were given 1 tablet of 325 mg acetaminophen. After a period of 1 month without medication to wash out each group, in step 2, each treatment group received the drug interaction in the same way as above. Pain was determined using a visual scale (VAS) before and after the first and second stages. Treatment response was defined as a decrease in pain scores over 1.5. Data analysis was performed with an R software mixed model. Results This study was done on 40 elderly patients: 18 (45%) men and 22 (55%) women. Their mean year and weight were 75.66±8.9 years and 69.67±14.33 kg, respectively. Study results showed that topical application of Nigella sativa oil and oral acetaminophen reduced pain in elderly with knee osteoarthritis; after using Nigella sativa oil, the reduction of pain was higher (p=0.01). Conclusion The results of this study showed that topical application of Nigella sativa oil was effective in reducing pain in patients with knee osteoarthritis; therefore, it is recommended as a safe supplement for these elderly. Trial registration The trial was registered at TCTR (http://www.clinicaltrials.in.th/) with the ID: TCTR20160125003. Funding This study was approved and supported by the Sabzevar

  19. Human Pulp Response to Direct Pulp Capping and Miniature Pulpotomy with MTA after Application of Topical Dexamethasone: A Randomized Clinical Trial

    PubMed Central

    Mousavi, Seyed Amir; Ghoddusi, Jamileh; Mohtasham, Nooshin; Shahnaseri, Shirin; Paymanpour, Payam; Kinoshita, Jun-Ichiro

    2016-01-01

    Introduction: The aim of this randomized clinical trial was to compare the histologic pulp tissue response to one-step direct pulp capping (DPC) and miniature pulpotomy (MP) with mineral trioxide aggregate (MTA) after application of dexamethasone in healthy human premolars. Methods and Materials: Forty intact premolars from 10 orthodontic patients, were randomly chosen for DPC (n=20) or MP (n=20). In 10 teeth from each group, after exposure of the buccal pulp horn, topical dexamethasone was applied over the pulp. In all teeth the exposed/miniaturely resected pulp tissue was covered with MTA and cavities were restored with glass ionomer. Teeth vitality was evaluated during the next 7, 21, 42, and 60 days. Signs and/or symptoms of irreversible pulpitis or pulp necrosis were considered as failure. According to the orthodontic schedule, after 60 days the teeth were extracted and submitted for histological examination. The Kruskal-Wallis and Fisher’s exact tests were used for statistical analysis of the data (P=0.05). Results: Although dexamethasone specimens showed less inflammation, calcified bridge, pulpal blood vasculature, collagen fibers and granulation tissue formation were not significantly different between the groups (P>0.05). Conclusion: Topical dexamethasone did not hindered pulp healing but reduced the amount of underlying pulpal tissue inflammation after DPC and MP in healthy human premolars. PMID:27141213

  20. A topical microemulsion for the prevention of allergic rhinitis symptoms: results of a randomized, controlled, double-blind, parallel group, multicentre, multinational clinical trial (Nares study)

    PubMed Central

    2013-01-01

    Background Since barrier protection measures to avoid contact with allergens are being increasingly developed, we assessed the clinical efficacy and tolerability of a topical nasal microemulsion made of glycerol esters in patients with allergic rhinitis. Methods Randomized, controlled, double-blind, parallel group, multicentre, multinational clinical trial in which adult patients with allergic rhinitis or rhinoconjunctivitis due to sensitization to birch, grass or olive tree pollens received treatment with topical microemulsion or placebo during the pollen seasons. Efficacy variables included scores in the mini-RQLQ questionnaire, number and severity of nasal, ocular and lung signs and symptoms, need for symptomatic medications and patients’ satisfaction with treatment. Adverse events were also recorded. Results Demographic characteristics were homogeneous between groups and mini-RQLQ scores did not differ significantly at baseline (visit 1). From symptoms recorded in the diary cards, the ME group showed statistically significant better scores for nasal congestion (0.72 vs. 1.01; p = 0.017) and mean total nasal symptoms (0.7 vs. 0.9; p = 0.045). At visit 2 (pollen season), lower values were observed in the mini-RQLQ in the ME group, although there were no statistically significant differences between groups in both full analysis set (FAS) and patients completing treatment (PPS) populations. The results obtained in the nasal symptoms domain of the mini-RQLQ at visit 2 showed the highest difference (−0.43; 95% CI: -0.88 to 0.02) for the ME group in the FAS population. The topical microemulsion was safe and well tolerated and no major discomforts were observed. Satisfaction rating with the treatment was similar between the groups. Conclusions The topical application of the microemulsion is a feasible and safe therapy in the prevention of allergic symptoms, particularly nasal congestion. Trial registration ClinicalTrials.gov Identifier: NCT01478425 PMID

  1. Topical Citrullus colocynthis (bitter apple) extract oil in painful diabetic neuropathy: A double-blind randomized placebo-controlled clinical trial.

    PubMed

    Heydari, Mojtaba; Homayouni, Kaynoosh; Hashempur, Mohammad Hashem; Shams, Mesbah

    2016-03-01

    The aim of the present study was to examine the safety and efficacy of a topical formulation of Citrullus colocynthis in patients with painful diabetic polyneuropathy (PDPN). The study was designed as a two-arm double-blind randomized placebo-controlled clinical trial using a parallel design. Sixty patients with PDPN were randomly allocated to receive either a topical formulation of C. colocynthis or placebo (1:1 allocation ratio) for 3 months. Patients were evaluated before and after the intervention using the neuropathic pain scale, electrodiagnostic findings, World Health Organization Biomedical Research and Education Foundation (BREF) quality of life (WHOQOL-BREF) scores, and reported adverse events. There was a significantly greater decrease in mean pain score after 3 months in the C. colocynthis (-3.89; 95% confidence interval [CI] -3.19, -4.60) than placebo (-2.28; 95% CI -1.66, -2.90) group (P < 0.001). Mean changes in nerve conduction velocity of the tibial nerve, distal latency of the superficial peroneal nerve and sural nerve, and sensory amplitude of the sural nerve were significantly higher in the intervention than placebo group (P < 0.001) in favour of the intervention. In the different domains of WHOQOL-BREF, there was a significant improvement only for the mean score in the physical domain. Application of a topical formulation of C. colocynthis fruit extract can decrease pain in patients with PDPN. It also may have some uncertain effects on nerve function and the physical domain of quality of life, which require further investigation in studies with larger sample sizes and of longer duration. © 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  2. Topical antioxidants in radiodermatitis: a clinical review.

    PubMed

    Kodiyan, Joyson; Amber, Kyle T

    2015-09-01

    Radiation-induced skin toxicity is the most prevalent side effect of radiation therapy. Not only does it have a significant effect on patients' quality of life, but it also results in poor follow-up and early termination of radiotherapy treatment. Several skin care practices and topical applications have been studied in the field of radiodermatitis, including skin washing, topical steroids, and mechanical skin barriers. Aside from these methods, many patients turn to complementary and alternative medicine for the prevention and treatment of radiodermatitis. Many of these alternative therapies are topically applied antioxidants. While the rationale behind the use of antioxidants in treating radiodermatitis is strong, clinical studies have been far less consistent. Even in large scale randomised controlled trials, findings have been limited by the inconsistent use of topical vehicles and placebos. In this article, the authors review the role of topical antioxidants to better help the practitioner navigate through different available skin directed antioxidants.

  3. Effect of Topical Application of Nigella Sativa Oil and Oral Acetaminophen on Pain in Elderly with Knee Osteoarthritis: A Crossover Clinical Trial.

    PubMed

    Kooshki, Akram; Forouzan, Reza; Rakhshani, Mohammad Hassan; Mohammadi, Maryam

    2016-11-01

    Limited evidence supports Nigella sativa's role as an effective complementary and alternative medicine and the anti-inflammatory effects of Nigella sativa on patients with allergic rhinitis. The aim of this study was to investigate the effect of topical application of Nigella sativa oil and oral acetaminophen on pain in the elderly with knee osteoarthritis residing in a parents' home in Sabzevar. This study is done as a crossover clinical trial. After obtaining written consent of elderly patients with osteoarthritis of the knee, they were randomly divided into two groups. In step 1, in group 1, 1 cc of Nigella sativa oil was applied on the knee joint every 8 hours for 3 weeks; for the second group, every 8 hours for 3 weeks, patients were given 1 tablet of 325 mg acetaminophen. After a period of 1 month without medication to wash out each group, in step 2, each treatment group received the drug interaction in the same way as above. Pain was determined using a visual scale (VAS) before and after the first and second stages. Treatment response was defined as a decrease in pain scores over 1.5. Data analysis was performed with an R software mixed model. This study was done on 40 elderly patients: 18 (45%) men and 22 (55%) women. Their mean year and weight were 75.66±8.9 years and 69.67±14.33 kg, respectively. Study results showed that topical application of Nigella sativa oil and oral acetaminophen reduced pain in elderly with knee osteoarthritis; after using Nigella sativa oil, the reduction of pain was higher (p=0.01). The results of this study showed that topical application of Nigella sativa oil was effective in reducing pain in patients with knee osteoarthritis; therefore, it is recommended as a safe supplement for these elderly. The trial was registered at TCTR (http://www.clinicaltrials.in.th/) with the ID: TCTR20160125003. This study was approved and supported by the Sabzevar University of Medical Sciences.

  4. Animal research as a basis for clinical trials.

    PubMed

    Faggion, Clovis M

    2015-04-01

    Animal experiments are critical for the development of new human therapeutics because they provide mechanistic information, as well as important information on efficacy and safety. Some evidence suggests that authors of animal research in dentistry do not observe important methodological issues when planning animal experiments, for example sample-size calculation. Low-quality animal research directly interferes with development of the research process in which multiple levels of research are interconnected. For example, high-quality animal experiments generate sound information for the further planning and development of randomized controlled trials in humans. These randomized controlled trials are the main source for the development of systematic reviews and meta-analyses, which will generate the best evidence for the development of clinical guidelines. Therefore, adequate planning of animal research is a sine qua non condition for increasing efficacy and efficiency in research. Ethical concerns arise when animal research is not performed with high standards. This Focus article presents the latest information on the standards of animal research in dentistry, more precisely in the field of implant dentistry. Issues on precision and risk of bias are discussed, and strategies to reduce risk of bias in animal research are reported. © 2015 Eur J Oral Sci.

  5. Topical Rapamycin as a Treatment for Fibrofolliculomas in Birt-Hogg-Dubé Syndrome: A Double-Blind Placebo-Controlled Randomized Split-Face Trial

    PubMed Central

    Martens, Herm; Oduber, Charlene E. U.; Henquet, Charles J. M.; Starink, Theo M.; Prins, Martin H.; Menko, Fred H.; Nelemans, Patty J.; van Steensel, Maurice A. M.

    2014-01-01

    Background Birt-Hogg-Dubé syndrome (BHD) is a rare autosomal dominant disorder characterised by the occurrence of benign, mostly facial, skin tumours called fibrofolliculomas, multiple lung cysts, spontaneous pneumothorax and an increased renal cancer risk. Current treatments for fibrofolliculomas have high rates of recurrence and carry a risk of complications. It would be desirable to have a treatment that could prevent fibrofolliculomas from growing. Animal models of BHD have previously shown deregulation of mammalian target of rapamycin (mTOR). Topical use of the mTOR inhibitor rapamycin is an effective treatment for the skin tumours (angiofibromas) in tuberous sclerosis complex, which is also characterised by mTOR deregulation. In this study we aimed to determine if topical rapamycin is also an effective treatment for fibrofolliculomas in BHD. Methods We performed a double blinded, randomised, facial left-right controlled trial of topical rapamycin 0.1% versus placebo in 19 BHD patients. Trial duration was 6 months. The primary outcome was cosmetic improvement as measured by doctors and patients. Changes in fibrofolliculoma number and size were also measured, as was occurrence of side effects. Results No change in cosmetic status of fibrofolliculomas was reported in the majority of cases for the rapamycin treated (79% by doctors, 53% by patients) as well as the placebo treated facial sides (both 74%). No significant differences between rapamycin and placebo treated facial halves were observed (p = 1.000 for doctors opinion, p = 0.344 for patients opinion). No significant difference in fibrofolliculoma number or change in size of the fibrofolliculomas was seen after 6 months. Side effects occurred more often after rapamycin treatment (68% of patients) than after placebo (58% of patients; p = 0.625). A burning sensation, erythema, itching and dryness were most frequently reported. Conclusions This study provides no evidence that treatment of

  6. Xylitol pediatric topical oral syrup to prevent dental caries: a double blind, randomized clinical trial of efficacy

    PubMed Central

    Milgrom, Peter; Ly, Kiet A.; Tut, Ohnmar K.; Mancl, Lloyd; Roberts, Marilyn C.; Briand, Kennar; Gancio, Mary Jane

    2009-01-01

    Objective To evaluate the effectiveness of a xylitol pediatric topical oral syrup to reduce the incidence of dental caries of very young children. Design Randomized, double-blinded, controlled trial. Setting Communities in the Republic of the Marshall Islands. Participants 108 children aged 9 to 15 months were screened and 100 were enrolled. Intervention Children were randomized and parents administered topical oral xylitol syrup two times (Xyl-2X, two xylitol 4.00 g/dose + one sorbitol dose) or three times (Xyl-3X, three xylitol 2.67 g/dose) per day (total 8 g) or control (one xylitol 2.67 g/dose + two sorbitol dose). Outcome Measures The outcome end-point of the study was the number of decayed primary teeth. Results Ninety-four of 100 children (mean±SD age, 15.0±2.7 months at randomization) with at least one follow-up exam were included in the intent-to-treat analysis. The mean±SD follow-up period was 10.5±2.2 months. Nearly 52% of children in the control condition had tooth decay compared to 40.6% among Xyl-3X and 24.2% among Xyl-2X conditions. The mean±SD number of decayed teeth was 1.9±2.4 for control, 1.0±1.4 for Xyl-3X, and 0.6±1.1 for Xyl-2X condition. Compared to controls, there was significantly fewer decayed teeth in the Xyl-2X (relative risk [RR], 0.30; 95% confidence interval [CI] 0.13, 0.66; P=.003) and Xyl-3X (RR, 0.50; 95% CI 0.26, 0.96; P=0.037) conditions. There was no statistical difference between the two xylitol treatment conditions (P=0.22). Conclusion Oral xylitol syrup administered topically two or three times each day at a total dose of 8 g was effective in preventing Early Childhood Caries. PMID:19581542

  7. Topical steroid application versus circumcision in pediatric patients with phimosis: a prospective randomized placebo controlled clinical trial.

    PubMed

    Esposito, Ciro; Centonze, Antonella; Alicchio, Francesca; Savanelli, Antonio; Settimi, Alessandro

    2008-04-01

    Topical steroids have been advocated as an effective alternative treatment to circumcision in boys with phimosis. We evaluated the effectiveness of topical steroid therapy compared to a placebo neutral cream in 240 patients with phimosis. A prospective study was carried out over a 24-months period, on an out-patient basis on two groups of patients with phimosis. One-hundred twenty patients applied a steroid cream twice a day for 4 weeks, and another group of 120 pts used a placebo cream twice a day for 4 weeks. Patients were assigned to either group by a computer-generated random choice. All patients in our series completed the two treatment periods without interruption. At a median follow-up of 20 months (6-30 months) therapeutic success was obtained in 43.75% (99/240) of cases, independently of the protocol. In particular, therapeutic success was obtained in 65.8% (79/120) of cases in the steroids group and in 16.6% (20/120) of cases in the placebo group, the difference being statistically significant (P < 0.0001, Mann-Withney test). Our study shows that topical steroids represent a good alternative to surgery in case of phimosis. Steroid therapy using monometasone furoate 0.1% in our series gave better results that placebo with an overall efficacy of 65.8%. In patients where a phimotic ring persist after steroid therapy, circumcision is mandatory.

  8. Effect of Topically-Applied Hyaluronic-Acid on Pain and Palatal Epithelial Wound Healing: An Examiner-Blind, Randomized, Controlled Clinical Trial.

    PubMed

    Yıldırım, Selin; Özener, Hafize Öztürk; Doğan, Başak; Kuru, Bahar

    2017-09-15

    This study aimed to evaluate the effects of two different concentrations of topical hyaluronic-acid on post-operative patient discomfort and wound healing of palatal donor sites following free gingival graft (FGG) surgery. Thirty-six patients requiring FGG were randomly assigned into three groups in an examiner-blind, randomized-controlled clinical trial. After harvesting palatal grafts, 0.2% and 0.8% hyaluronic-acid gels were used in the test-1 and -2 groups, respectively. Gels were applied on donor sites and protected with periodontal dressing in the test groups whereas the wound was covered only with periodontal dressing in the control group. On days 3-7-14 and 21, pain and burning sensation were recorded by using visual analog scale (VAS) as well as other parameters such as complete epithelization (CE) and color match on days 3-7-14-21-42. Test groups experienced less pain than the control group on days 3 and 7 (P<0.001 and P<0.001, respectively). The mean VAS score for burning sensation was higher in the control group on day 3 compared to the test-1 and -2 groups (P=0.033 and P=0.020, respectively). CE in all patients was achieved on day 21 in both test groups while it was achieved on day 42 in the control group. The test groups showed higher color match scores than the control group on days 21 (P<0.001 and P<0.001, respectively) and 42 (P=0.004 and P=0.002, respectively). Topical application of hyaluronic-acid exhibits positive impact on post-operative pain, burning sensation and accelerates palatal wound healing in terms of epithelization and color match.

  9. Effect of Topical Anesthesia with Lidocaine-prilocaine (EMLA) Cream and Local Pressure on Pain during Infiltration Injection for Maxillary Canines: A Randomized Double-blind clinical trial.

    PubMed

    Milani, Amin S; Zand, Vahid; Abdollahi, Amir A; Froughreyhani, Mohammad; Zakeri-Milani, Parvin; Jafarabadi, Mohammad A

    2016-07-01

    This study compared the effect of local pressure and topical lidocaine-prilocaine (EMLA) cream on pain during infiltration injection for maxillary canine teeth. A total of 140 volunteer students participated in this split-mouth design randomized clinical trial. The subjects were randomly divided into four groups (n = 35). Before administration of anesthesia, in each group, one side was randomly selected as the experimental and the opposite side as the control. In group 1, finger pressure was applied on the alveolar mucosa on the experimental side and on the tooth crown on the control side. In group 2, 5% EMLA cream and placebo; in group 3, finger pressure and 5% EMLA cream; and in group 4, 5% EMLA cream and 20% benzocaine gel were applied. In all the groups, a buccal infiltration procedure was carried out. Pain during injection was recorded with visual analog scale (VAS). Wilcoxon and McNemar tests were used for statistical analysis of the results. Statistical significance was set at p < 0.05. The results showed that EMLA reduced the injection pain significantly more than benzocaine (p = 0.02). Also, injection pain was significantly lower with the use of EMLA in comparison to placebo (p = 0.00). Application of local pressure reduced the injection pain, but the difference from the control side was not significant (p = 0.05). Furthermore, the difference between application of local pressure and EMLA was not statistically significant (p = 0.08). Topical anesthesia of 5% EMLA was more effective than 20% benzocaine in reducing pain severity during infiltration injection. However, it was not significantly different in comparison to the application of local pressure.

  10. Efficacy and safety of permethrin 5% topical gel vs. placebo for rosacea: a double-blind randomized controlled clinical trial.

    PubMed

    Raoufinejad, K; Mansouri, P; Rajabi, M; Naraghi, Z; Jebraeili, R

    2016-12-01

    Rosacea is a chronic, multifactorial, dermatological condition. Increased density of Demodex folliculorum mites in the skin of rosacea patients suggests a possible role for these mites in the pathophysiology of rosacea. To evaluate the effects of permethrin 5% topical gel vs. placebo on Demodex density (Dd) and clinical presentations of rosacea patients, and also to further refine the quantitative assessment of Dd in the non-invasive standard skin surface biopsy (SSSB). Twenty patients with bilateral papulopustular rosacea and ≥5 mites/cm(2) were enrolled in the study. Participants and physicians were blinded to the group assignments. Each patient applied permethrin on one side and placebo on the other side of the face twice daily for 12 weeks. SSSB and photography and Rosacea Clinical Scorecard of the National Rosacea Society were used to assess the patients at the baseline, 2nd, 5th, 8th, and 12th weeks for both sides of the face. Causality and severity of adverse drug reactions (ADRs) were assessed by WHO Scale and Hartwig Scale, respectively. Dd was not significantly different between the two groups at the baseline. In both groups, Dd significantly decreased after 12 weeks compared to the baseline. At the end of the 12th week, the Dd in the permethrin group was significantly lower than the placebo group. Severity of the clinical presentations decreased in both groups at the end of week 12 in comparison to the baseline, particularly in the permethrin group. ADRs were all mild and in most cases unlikely related to permethrin. Permethrin 5% gel can significantly reduce the Dd and severity of presentations in rosacea patients and can be a safe and effective option in the management of this chronic disorder. This new SSSB technique offers an easy, quick, inexpensive, and non-invasive sampling method proper for quantitative assessment of Dd. © 2016 European Academy of Dermatology and Venereology.

  11. Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP panel: clinical trial design

    PubMed Central

    Lammertse, D; Tuszynski, MH; Steeves, JD; Curt, A; Fawcett, JW; Rask, C; Ditunno, JF; Fehlings, MG; Guest, JD; Ellaway, PH; Kleitman, N; Blight, AR; Dobkin, BH; Grossman, R; Katoh, H; Privat, A; Kalichman, M

    2014-01-01

    The International Campaign for Cures of Spinal Cord Injury Paralysis established a panel tasked with reviewing the methodology for clinical trials for spinal cord injury (SCI), and making recommendations on the conduct of future trials. This is the fourth of four papers. Here, we examine the phases of a clinical trial program, the elements, types, and protocols for valid clinical trial design. The most rigorous and valid SCI clinical trial would be a prospective double-blind randomized control trial utilizing appropriate placebo control subjects. However, in specific situations, it is recognized that other trial procedures may have to be considered. We review the strengths and limitations of the various types of clinical trials with specific reference to SCI. It is imperative that the design and conduct of SCI clinical trials should meet appropriate standards of scientific inquiry to insure that meaningful conclusions about efficacy and safety can be achieved and that the interests of trial subjects are protected. We propose these clinical trials guidelines for use by the SCI clinical research community. PMID:17179970

  12. A randomised placebo-controlled trial of oral and topical antibiotics for children with clinically infected eczema in the community: the ChildRen with Eczema, Antibiotic Management (CREAM) study.

    PubMed Central

    Francis, Nick A; Ridd, Matthew J; Thomas-Jones, Emma; Shepherd, Victoria; Butler, Christopher C; Hood, Kerenza; Huang, Chao; Addison, Katy; Longo, Mirella; Marwick, Charis; Wootton, Mandy; Howe, Robin; Roberts, Amanda; Haq, Mohammed Inaam-Ul; Madhok, Vishnu; Sullivan, Frank

    2016-01-01

    consistent with the finding of no or limited difference and a trend towards worse outcomes in the intervention groups. Sensitivity analyses, including adjusting for compliance and imputation for missing data, were consistent with the main findings. CONCLUSIONS Our data suggest that oral and topical antibiotics have no effect, or a harmful effect, on subjective eczema severity in children with clinically infected eczema in the community. The CIs around our estimates exclude a meaningful beneficial effect (published minimal clinically important difference for POEM is 3.4). Although most patients in this trial had features suggestive of infection and S. aureus on their skin, participants primarily had mild-moderate eczema and those with signs of more severe infection were often excluded. Clinicians should consider avoiding oral and topical antibiotic use in children with suspected infected eczema in the community who do not have signs of 'severe infection'. Further research should seek to understand how best to encourage the use of topical steroids and limit use of antibiotics in those with eczema flares without signs of severe infection, as well as developing tools to better phenotype eczema flares, in order to better define a population that may benefit from antibiotic treatment. TRIAL REGISTRATION European Union Drug Regulating Authorities Clinical Trials (EudraCT) number 2011-003591-37 and Current Controlled Trials ISRCTN96705420. FUNDING The National Institute for Health Research Health Technology Assessment programme. PMID:26938214

  13. Partial lateral internal sphincterotomy versus combined botulinum toxin A injection and topical diltiazem in the treatment of chronic anal fissure: a randomized clinical trial.

    PubMed

    Gandomkar, Hossein; Zeinoddini, Atefeh; Heidari, Reza; Amoli, Hadi Ahmadi

    2015-02-01

    The aim of this study is to evaluate the effectiveness and complications associated with combined topical diltiazem cream and botulinum toxin A injection versus partial lateral internal sphincterotomy in chronic anal fissure. This study is a parallel, randomized controlled trial (using the block randomization method). This study was performed at a university hospital in Iran. Ninety-nine patients who had chronic anal fissures were included. A total of 99 patients were randomly assigned to 2 groups; the first group received combined topical diltiazem ointment (for 6 weeks) and botulinum toxin A injection (once) (n = 49), and the second group received partial lateral internal sphincterotomy (n = 50). All the patients were followed up for 1 year. The primary outcomes measured were the healing of the anal fissure and the development of incontinence as the major adverse event during the 1-year follow-up period. The overall healing rate was 65% and 94% in the botulinum toxin A-diltiazem and partial lateral internal sphincterotomy groups (p < 0.001). The patients in the partial lateral internal sphincterotomy group experienced significantly higher incontinence scores (p = 0.04) according to the Cleveland Clinic Florida-Fecal Incontinence scoring system. In patients who had chronic anal fissure for ≤12 months, no statistical difference was observed in the healing rate between the botulinum toxin A-diltiazem and partial lateral internal sphincterotomy groups (100% vs 100%). However, in the patients with longer chronic fissures, the healing rate was significantly higher in the partial lateral internal sphincterotomy group (86% [18/21] vs 23% [5/21], p < 0.001). The 1-year follow-up period, subjective definitions of itching, and lack of anorectal manometry examinations and data regarding the effect of each treatment on anal sphincter pressure at rest and contraction are the key limitations of this study. Combined botulinum toxin A injection with a topical application of

  14. Topical Silymarin Administration for Prevention of Capecitabine-Induced Hand-Foot Syndrome: A Randomized, Double-Blinded, Placebo-Controlled Clinical Trial.

    PubMed

    Elyasi, Sepideh; Shojaee, Farzaneh Sadat Rezazadeh; Allahyari, Abolghasem; Karimi, Gholamreza

    2017-09-01

    Hand-foot syndrome (HFS) is a frequent dose-limiting adverse reaction of capecitabine in patient with gastrointestinal cancers. Silymarin is a polyphenolic flavonoid extracted from the Silybum marianum that exhibits strong antioxidant and antiinflammatory activities. In this study, we evaluated silymarin efficacy in prevention of capecitabine-induced HFS in patients with gastrointestinal cancers, as the first human study. During this pilot, randomized, double-blinded, placebo-controlled clinical trial, the effect of silymarin gel 1%, which is applied on the palms and soles twice daily starting at the first day of chemotherapy for 9 weeks, on HFS occurrence was assessed. Forty patients fulfilled the inclusion criteria assigned to the silymarin or placebo group. World Health Organization HFS grading scale scores were recorded at baseline and every 3 weeks during these 9 weeks. The median WHO HFS scores were significantly lower in silymarin group at the end of the 9(th) week (p < 0.05). The scores increased significantly in both placebo and silymarin groups during chemotherapy, but there was a delay for HFS development and progression in silymarin group. Prophylactic administration of silymarin topical formulation could significantly reduce the severity of capecitabine-induced HFS and delays its occurrence in patients with gastrointestinal cancer after 9 weeks of application. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  15. TU-G-BRB-01: Topic Introduction: Do We Need Clinical Trials in Particle Therapy and How Can Medical Physics Support Them?

    SciTech Connect

    Schulte, R.

    2015-06-15

    Proton therapy, in particular, and ion therapy, just beginning, are becoming an increasing focus of attention in clinical radiation oncology and medical physics. Both modalities have been criticized of lacking convincing evidence from randomized trials proving their efficacy, justifying the higher costs involved in these therapies. This session will provide an overview of the current status of clinical trials in proton therapy, including recent developments in ion therapy. As alluded to in the introductory talk by Dr. Schulte, opinions are diverging widely as to the usefulness and need for clinical trials in particle therapy and the challenge of equipoise. The lectures will highlight some of the challenges that surround clinical trials in particle therapy. One, presented by Dr. Choy from UT Southwestern, is that new technology and even different types of particles such as helium and carbon ions are introduced into this environment, increasing the phase space of clinical variables. The other is the issue of medical physics quality assurance with physical phantoms, presented by Mrs. Taylor from IROC Houston, which is more challenging because 3D and 4D image guidance and active delivery techniques are in relatively early stages of development. The role of digital phantoms in developing clinical treatment planning protocols and as a QA tool will also be highlighted by Dr. Lee from NCI. The symposium will be rounded off by a panel discussion among the Symposium speakers, arguing pro or con the need and readiness for clinical trials in proton and ion therapy. Learning Objectives: To get an update on the current status of clinical trials allowing or mandating proton therapy. Learn about the status of planned clinical trials in the U.S. and worldwide involving ion therapy. Discuss the challenges in the design and QA of clinical trials in particle therapy. Learn about existing and future physical and computational anthropomorphic phantoms for charged particle clinical trial

  16. Phase I Clinical Trial of O6-Benzylguanine and Topical Carmustine in the Treatment of Cutaneous T-Cell Lymphoma, Mycosis Fungoides Type

    PubMed Central

    Apisarnthanarax, Narin; Wood, Gary S.; Stevens, Seth R.; Carlson, Sean; Chan, Derek V.; Liu, Lili; Szabo, Sarolta K.; Fu, Pingfu; Gilliam, Anita C.; Gerson, Stanton L.; Remick, Scot C.; Cooper, Kevin D.

    2012-01-01

    Objectives To evaluate the toxic effects and maximum tolerated dose of topical carmustine [1,3-bis (2-chloroethyl)-1-nitrosourea] following intravenous O6-benzylguanine in the treatment of cutaneous T-cell lymphoma (CTCL), and to determine pharmacodynamics of O6-alkylguanine DNA alkyltransferase activity in treated CTCL lesions. Design Open-label, dose-escalation, phase I trial. Setting Dermatology outpatient clinic and clinical research unit at a university teaching hospital. Patients A total of 21 adult patients (11 male, 10 female) with early-stage (IA-IIA) refractory CTCL, mycosis fungoides type, treated with topical carmustine following intravenous O6-benzylguanine. Intervention Treatment once every 2 weeks with 120 mg/m2 intravenous O6-benzylguanine followed 1 hour later by whole-body, low-dose topical carmustine starting at 10 mg, with 10-mg incremental dose-escalation in 3 patient cohorts. Cutaneous T-cell lymphoma lesional skin biopsy specimens were taken at baseline and 6 hours, 24 hours, and 1 week after the first O6-benzylguanine infusion for analysis of O6-alkylguanine-DNA alkyltransferase activity. Main Outcome Measures Clinical response measured by physical examination and severity-weighted assessment tool measurements, safety data acquired by review of adverse events at study visits, and O6-alkylguanine-DNA alkyltransferase activity in treated lesion skin biopsy specimens. Results A minimal toxic effect was observed through the 40-mg carmustine dose level with 76% of adverse events being grade 1 based on the National Cancer Institute Common Terminology Criteria for Adverse Events. Mean baseline O6-alkylguanine-DNA alkyl-transferase activity in CTCL lesions was 3 times greater than in normal controls and was diminished by a median of 100% at 6 and 24 hours following O6-benzyl-guanine with recovery at 1 week. Clinical disease reduction correlated positively with O6-alkylguanine-DNA alkyltransferase activity at 168 hours (P= .02) and inversely with

  17. A randomised placebo-controlled trial of oral and topical antibiotics for children with clinically infected eczema in the community: the ChildRen with Eczema, Antibiotic Management (CREAM) study.

    PubMed

    Francis, Nick A; Ridd, Matthew J; Thomas-Jones, Emma; Shepherd, Victoria; Butler, Christopher C; Hood, Kerenza; Huang, Chao; Addison, Katy; Longo, Mirella; Marwick, Charis; Wootton, Mandy; Howe, Robin; Roberts, Amanda; Haq, Mohammed Inaam-ul; Madhok, Vishnu; Sullivan, Frank

    2016-03-01

    intervention groups. Sensitivity analyses, including adjusting for compliance and imputation for missing data, were consistent with the main findings. Our data suggest that oral and topical antibiotics have no effect, or a harmful effect, on subjective eczema severity in children with clinically infected eczema in the community. The CIs around our estimates exclude a meaningful beneficial effect (published minimal clinically important difference for POEM is 3.4). Although most patients in this trial had features suggestive of infection and S. aureus on their skin, participants primarily had mild-moderate eczema and those with signs of more severe infection were often excluded. Clinicians should consider avoiding oral and topical antibiotic use in children with suspected infected eczema in the community who do not have signs of 'severe infection'. Further research should seek to understand how best to encourage the use of topical steroids and limit use of antibiotics in those with eczema flares without signs of severe infection, as well as developing tools to better phenotype eczema flares, in order to better define a population that may benefit from antibiotic treatment. European Union Drug Regulating Authorities Clinical Trials (EudraCT) number 2011-003591-37 and Current Controlled Trials ISRCTN96705420. The National Institute for Health Research Health Technology Assessment programme.

  18. ClinicalTrials.gov as a data source for semi-automated point-of-care trial eligibility screening.

    PubMed

    Pfiffner, Pascal B; Oh, JiWon; Miller, Timothy A; Mandl, Kenneth D

    2014-01-01

    Implementing semi-automated processes to efficiently match patients to clinical trials at the point of care requires both detailed patient data and authoritative information about open studies. To evaluate the utility of the ClinicalTrials.gov registry as a data source for semi-automated trial eligibility screening. Eligibility criteria and metadata for 437 trials open for recruitment in four different clinical domains were identified in ClinicalTrials.gov. Trials were evaluated for up to date recruitment status and eligibility criteria were evaluated for obstacles to automated interpretation. Finally, phone or email outreach to coordinators at a subset of the trials was made to assess the accuracy of contact details and recruitment status. 24% (104 of 437) of trials declaring on open recruitment status list a study completion date in the past, indicating out of date records. Substantial barriers to automated eligibility interpretation in free form text are present in 81% to up to 94% of all trials. We were unable to contact coordinators at 31% (45 of 146) of the trials in the subset, either by phone or by email. Only 53% (74 of 146) would confirm that they were still recruiting patients. Because ClinicalTrials.gov has entries on most US and many international trials, the registry could be repurposed as a comprehensive trial matching data source. Semi-automated point of care recruitment would be facilitated by matching the registry's eligibility criteria against clinical data from electronic health records. But the current entries fall short. Ultimately, improved techniques in natural language processing will facilitate semi-automated complex matching. As immediate next steps, we recommend augmenting ClinicalTrials.gov data entry forms to capture key eligibility criteria in a simple, structured format.

  19. Using Vascular Quality Initiative as a Platform for Organizing Multicenter, Prospective, Randomized Clinical Trials: OVERPAR Trial

    PubMed Central

    Eslami, Mohammad H.; Doros, Gheorghe; Goodney, Philip P.; Elderup-Jorgenson, Jens; Cronenwett, Jack L.; Malikova, Marina; Farber, Alik

    2014-01-01

    Background We describe the organization of a prospective, randomized, multicenter trial comparing the effectiveness of open popliteal artery aneurysm repair (OPAR) and endovascular popliteal artery aneurysm repair (EPAR) of asymptomatic popliteal artery aneurysms (PAAs) as an example for how to use the Vascular Quality Initiative (VQI) framework. Given that many centers participate in the VQI, this model can be used to perform multicenters’ prospective trials on very modest budget. Methods VQI prospectively collects data on many vascular procedures. These data include many important perioperative, intraoperative, and postoperative details regarding both patients and their procedures. We describe a study where minimal changes to the collected data by participating centers can provide level-1 evidence regarding a significant clinical question. Data will be collected using modified VQI forms within the existing VQI data reporting structure. We plan to enroll 148 patients with asymptomatic PAAs into the open and endovascular surgery cohorts. Patients from participating VQI centers will be randomized 1:1 to either OPAR or EPAR and will be followed for an average of 2.5 years. Our primary hypothesis is that major adverse limb event–free survival is lower in the EPAR cohort and that EPAR is associated with more secondary interventions, improved quality of life, and decreased length of stay. The budget for this trial is fixed at $10,000/year for the course of the study, and the trial is judged to be feasible because of the functionality of the VQI platform. Conclusions Using the existing VQI infrastructure, Open versus Endovascular Repair of Popliteal Artery Aneurysm will provide level 1 data for PAA treatment on a modest budget. The proposed trial has an adequately powered comparative design that will use objective performance goals to describe limb-related morbidity and procedural reintervention rates. PMID:25311746

  20. Early termination of cardiovascular trials as a consequence of poor accrual: analysis of ClinicalTrials.gov 2006–2015

    PubMed Central

    Baldi, Ileana; Lanera, Corrado; Berchialla, Paola; Gregori, Dario

    2017-01-01

    Objectives To present a snapshot of experimental cardiovascular research with a focus on geographical and temporal patterns of early termination due to poor accrual. Setting The Aggregate Analysis of ClinicalTrials.gov (AACT) database, reflecting ClinicalTrials.gov as of 27 March 2016. Design The AACT database was searched for all cardiovascular clinical trials that started from January 2006 up to December 2015. Results Thirteen thousand and seven hundred twenty-nine cardiovascular trials were identified. Of these, 8900 (65%) were classified as closed studies. Globally, 11% of closed trials were terminated. This proportion varied from 9.6% to 14% for trials recruiting from Europe and Americas, respectively, with a slightly decreasing trend (p=0.02) over the study period. The most common reason for trials failing to complete was poor accrual (41%). Intercontinental trials exhibited lower figures of poor accrual as the reason for their early stopping, as compared with trials recruiting in a single continent (28% vs 44%, p=0.002). Conclusions Poor accrual significantly challenges the successful completion of cardiovascular clinical trials. Findings are suggestive of a positive effect of globalisation of cardiovascular clinical research on the achievement of enrolment goals within a reasonable time frame. PMID:28619765

  1. Early termination of cardiovascular trials as a consequence of poor accrual: analysis of ClinicalTrials.gov 2006-2015.

    PubMed

    Baldi, Ileana; Lanera, Corrado; Berchialla, Paola; Gregori, Dario

    2017-06-15

    To present a snapshot of experimental cardiovascular research with a focus on geographical and temporal patterns of early termination due to poor accrual. The Aggregate Analysis of ClinicalTrials.gov (AACT) database, reflecting ClinicalTrials.gov as of 27 March 2016. The AACT database was searched for all cardiovascular clinical trials that started from January 2006 up to December 2015. Thirteen thousand and seven hundred twenty-nine cardiovascular trials were identified. Of these, 8900 (65%) were classified as closed studies. Globally, 11% of closed trials were terminated. This proportion varied from 9.6% to 14% for trials recruiting from Europe and Americas, respectively, with a slightly decreasing trend (p=0.02) over the study period. The most common reason for trials failing to complete was poor accrual (41%). Intercontinental trials exhibited lower figures of poor accrual as the reason for their early stopping, as compared with trials recruiting in a single continent (28% vs 44%, p=0.002). Poor accrual significantly challenges the successful completion of cardiovascular clinical trials. Findings are suggestive of a positive effect of globalisation of cardiovascular clinical research on the achievement of enrolment goals within a reasonable time frame. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  2. Topical nitric oxide application in the treatment of chronic extensor tendinosis at the elbow: a randomized, double-blinded, placebo-controlled clinical trial.

    PubMed

    Paoloni, Justin A; Appleyard, Richard C; Nelson, Janis; Murrell, George A C

    2003-01-01

    Extensor tendinosis ("tennis elbow") is a degenerative overuse tendinopathy of the wrist extensors at their attachment to the lateral humeral epicondyle. No treatment has been universally successful. Topical application of nitric oxide has been used effectively to treat fractures and cutaneous wounds in animal models, presumably by stimulation of collagen synthesis in fibroblasts. To determine whether topical nitric oxide can improve outcome of patients with extensor tendinosis. Prospective, randomized, double-blinded clinical trial. Eighty-six patients with extensor tendinosis were randomized into two equal groups; both were instructed to perform a standard tendon rehabilitation program. One group received an active glyceryl trinitrate transdermal patch, and the other group received a placebo patch. Patients in the glyceryl trinitrate group had significantly reduced elbow pain with activity at 2 weeks, reduced epicondylar tenderness at 6 and 12 weeks, and an increase in wrist extensor mean peak force and total work at 24 weeks. At 6 months, 81% of treated patients were asymptomatic during activities of daily living, compared with 60% of patients who had tendon rehabilitation alone. Application of topical nitric oxide improved early pain with activity, late functional measures, and outcomes of patients with extensor tendinosis.

  3. Topical tranexamic acid as an adjuvant treatment in melasma: Side-by-side comparison clinical study.

    PubMed

    Chung, Jong Yoon; Lee, Jong Hee; Lee, Joo Heung

    2016-08-01

    Tranexamic acid (TNA) is a novel therapeutic agent for hyperpigmented skin disorders. The efficacy and safety of topical TNA in patients with melasma has not been heretofore studied. The main objective of this study is to evaluate the efficacy and safety of topical TNA combined with intense pulsed light (IPL) treatment in Asians with melasma. A randomized, split-face (internally controlled) study was conducted in 15 women who received four monthly sessions of IPL to both sides of the face. Topical TNA or vehicle was applied to a randomly assigned side during and after IPL treatment. Patients were followed up for 12 weeks after completing the IPL treatments. Baseline and follow-up melanin index (MI; measured by Mexameter®, Courage and Khazaka, Cologne, Germany) and modified melasma area and severity index (mMASI) scores were determined. Thirteen subjects completed the study without serious adverse events. MI and mMASI decreased significantly from baseline to 12 weeks after the last IPL treatment on the topical TNA side but not on the vehicle side. The efficacy of topical TNA in preventing rebound pigmentation after IPL treatment was also statistically significant. Topical TNA can be considered an effective and safe adjuvant to conventional treatment for melasma.

  4. Randomized double-blind clinical trial comparing clobetasol and dexamethasone for the topical treatment of symptomatic oral chronic graft-versus-host disease.

    PubMed

    Noce, Cesar W; Gomes, Alessandra; Shcaira, Vanessa; Corrêa, Maria Elvira P; Moreira, Maria Cláudia R; Silva Júnior, Arley; Gonçalves, Lúcio Souza; Garnica, Marcia; Maiolino, Angelo; Torres, Sandra R

    2014-08-01

    Patients who undergo allogeneic stem cell transplantation frequently develop an immunologic disease caused by the reactivation of the graft to the host tissues. This disease is called graft-versus-host disease (GVHD) and it is usually a systemic disorder. In a large proportion of cases, oral disorders that are related to a chronic phase of GVHD (cGVHD) occur, and their treatment involves the use of topical immunosuppressive drugs. Several medications have been studied for this purpose, but only a small number of clinical trials have been published. The present study is a randomized, double-blind clinical trial that compares topical clobetasol and dexamethasone for the treatment of symptomatic oral cGVHD. Patients were randomly assigned to treatment with clobetasol propionate .05% or dexamethasone .1 mg/mL for 28 days. In both arms, nystatin 100,000 IU/mL was administered with the corticosteroid. Oral lesions were evaluated by the modified oral mucositis rating scale (mOMRS) and symptoms were registered using a visual analogue scale. Thirty-five patients were recruited, and 32 patients were randomized into the study groups: 18 patients (56.3%) to the dexamethasone group and 14 patients (43.8%) to the clobetasol group. The use of clobetasol resulted in a significant reduction in mOMRS total score (P = .04) and in the score for ulcers (P = .03). In both groups, there was significant symptomatic improvement but the response was significantly greater in the clobetasol group (P = .02). In conclusion, clobetasol was significantly more effective than dexamethasone for the amelioration of symptoms and clinical aspects of oral lesions in cGVHD.

  5. Design of clinical trials.

    PubMed

    Rollo, David; Machado, Sanjay; Ceschin, Mauro

    2010-09-01

    Clinical trial design for nuclear medicine diagnostic imaging radiopharmaceuticals must include a design for preclinical safety studies. These studies should establish that the investigational product (IP) does not have a toxic effect. As a further requirement, radiopharmaceutical clinical trials include a human study (phase 1) that provides biodistribution, pharmacokinetics, and radiation dosimetry information. These studies demonstrate to the Food and Drug Administration that the IP either meets or exceeds the toxicology and radiation exposure safety limits. Satisfying this requirement can result in the Food and Drug Administration approving the performance of late-phase (phase 2/3) clinical trials that are designed to validate the clinical efficacy of the diagnostic imaging agent in patients who have a confirmed diagnosis for the intended application. Emphasis is placed on the most typical trial design for diagnostic imaging agents that use a comparator to demonstrate that the new IP is similar in efficacy to an established standard comparator. Such trials are called equivalence, or noninferiority, trials that attempt to show that the new IP is not less effective than the comparator by more than a statistically defined amount. Importantly, the trial design must not inappropriately favor one diagnostic imaging agent over the other. Bias is avoided by the use of a core laboratory with expert physicians who are not involved in the trial for interpreting and objectively scoring the image sets obtained at the clinical trial sites. Clinical trial design must also follow Good Clinical Practice (GCP) guidelines. GCP stipulates the clinical trial process, including protocol and Case Report Form design, analyses planning, as well as analyzing and preparing interim and final clinical trial/study reports.

  6. Pharmacogenomic biomarkers as inclusion criteria in clinical trials of oncology-targeted drugs: a mapping of ClinicalTrials.gov.

    PubMed

    Vivot, Alexandre; Li, Jacques; Zeitoun, Jean-David; Mourah, Samia; Crequit, Perrine; Ravaud, Philippe; Porcher, Raphaël

    2016-08-01

    The aim of this study was to describe pharmacogenomics-based inclusion criteria (enrichment) and the main characteristics of clinical trials involving oncology-targeted therapies. Clinical trials of oncology-targeted therapies approved after 2005 with pharmacogenomic testing required or recommended in their label were retrieved from a mapping of the ClinicalTrials.gov database. We examined information for 12 drugs and 858 trials. Overall, 434 trials (51%) were enriched on the biomarker first mentioned in the label and 145 (17%) were enriched on another biomarker, whereas 270 trials (31%) included all patients. The median proportion of trials corresponding to both the drug's indication and drug's target was 35%. Of the 361 trials that tested drugs in another disease than the first one in the label, 219 (61%) were without enrichment and 87 (24%) were actually enriched but on another biomarker than the first one in the label. Several drugs have been tested in trials enriched on many different biomarkers. Nonetheless, most targeted therapies have been developed only using biomarker-positive patients; therefore, exclusion of biomarker-negative patients from treatment relies on only preclinical data and on biological understanding of the disease and target.Genet Med 18 8, 796-805.

  7. Comparative efficacy of topical application of tacrolimus and clotrimazole in the treatment of pityriasis versicolor: A single blind, randomised clinical trial.

    PubMed

    Sepaskhah, Mozhdeh; Sadat, Maryam Sadat; Pakshir, Keyvan; Bagheri, Zahra

    2017-05-01

    Pityriasis versicolor (PV) is a common superficial fungal disease. Possibility of emergence of resistant strains to azoles, and difficulty in differentiation of hypopigmented PV and early vitiligo, encouraged us to evaluate the efficacy of topical tacrolimus (a calcineurin inhibitor agent with proven in vitro anti-Malassezia effect) for PV treatment generally and its effect on PV-induced hypopigmentation specifically. To evaluate the efficacy of topical tacrolimus on pityriasis versicolor. Fifty PV patients were randomly allocated into two equal groups applying either topical clotrimazol or tacrolimus twice daily for 3 weeks. They were evaluated at the beginning of study, in the third and fifth weeks clinically and mycologically (direct smear). Although both treatments resulted in global, clinical, and mycological cure of PV, there was no significant difference regarding the mentioned aspects of cure between tacrolimus and clotrimazole treated patients. (P-value: .63, .45, and .26, respectively) Tacrolimus had no significant effect on hypopigmentation in the fifth week follow-up. (P-value: .62). In spite of the lack of efficacy of tacrolimus on PV-induced hypopigmentation, the therapeutic effect on PV introduces tacrolimus as a therapeutic option for PV, especially when early vitiligo is among the differential diagnoses without concerning the aggravating effect of topical corticosteroids on PV. © 2017 Blackwell Verlag GmbH.

  8. Novel, single-dose, topical treatment of tinea pedis using terbinafine: results of a dose-finding clinical trial.

    PubMed

    de Chauvin, Martine Feuilhade; Viguié-Vallanet, Claude; Kienzler, Jean-Luc; Larnier, Catherine

    2008-01-01

    Tinea pedis is the most common dermatophytosis requiring topical antifungals for at least 1-4 weeks. To determine the effectiveness of a novel topical single dose formulation of terbinafine (film forming solution-FFS) in the treatment of tinea pedis, 344 outpatients from 43 dermatological centres in France and Bulgaria suffering from tinea pedis with possible extension to soles confirmed by mycological examination (direct and culture) were evaluated for efficacy of terbinafine 1%, 5%, 10% FFS in a randomised double blind vehicle controlled parallel group dose finding study. Evaluations were carried out at baseline, 1 and 6 weeks after a single application of FFS. Effective treatment rate based on negative mycology (direct and culture) and minimal signs and symptoms (two or less with only mild recorded) was measured at week 6. Effective treatment rates at week 6 with terbinafine 1%, 5% and 10% FFS were 66%, 70%, 61% compared with 18% with placebo. All three active preparations were shown to be significantly superior to placebo (P < 0.001). Terbinafine 1% and 5% FFS were shown to be non-inferior to terbinafine 10% FFS. Terbinafine 1% FFS is an effective, safe dose for the treatment of tinea pedis. This novel product represents a significant advance with the enhanced compliance and convenience that it offers.

  9. Meta-analysis of randomized and quasi-randomized clinical trials of topical antibiotics after primary closure for the prevention of surgical-site infection.

    PubMed

    Heal, C F; Banks, J L; Lepper, P; Kontopantelis, E; van Driel, M L

    2017-08-01

    Surgical-site infections (SSIs) increase patient morbidity and costs. The aim was to identify and synthesize all RCTs evaluating the effect of topical antibiotics on SSI in wounds healing by primary intention. The search included Ovid MEDLINE, Ovid Embase, the Cochrane Wounds Specialized Register, Central Register of Controlled Trials and EBSCO CINAHL from inception to May 2016. There was no restriction of language, date or setting. Two authors independently selected studies, extracted data and assessed risk of bias. When sufficient numbers of comparable trials were available, data were pooled in meta-analysis. Fourteen RCTs with 6466 participants met the inclusion criteria. Pooling of eight trials (5427 participants) showed that topical antibiotics probably reduced the risk of SSI compared with no topical antibiotic (risk ratio (RR) 0·61, 95 per cent c.i. 0·42 to 0·87; moderate-quality evidence), equating to 20 fewer SSIs per 1000 patients treated. Pooling of three trials (3012 participants) for risk of allergic contact dermatitis found no clear difference between antibiotics and no antibiotic (RR 3·94, 0·46 to 34·00; very low-quality evidence). Pooling of five trials (1299 participants) indicated that topical antibiotics probably reduce the risk of SSI compared with topical antiseptics (RR 0·49, 0·30 to 0·80; moderate-quality evidence); 43 fewer SSIs per 1000 patients treated. Pooling of two trials (541 participants) showed no clear difference in the risk of allergic contact dermatitis with antibiotics or antiseptic agents (RR 0·97, 0·52 to 1·82; very low-quality evidence). Topical antibiotics probably prevent SSI compared with no topical antibiotic or antiseptic. No conclusion can be drawn regarding whether they cause allergic contact dermatitis. © 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.

  10. Time as a Key Topic in Health Professionals’ Perceptions of Clinical Handovers

    PubMed Central

    Watson, Bernadette M.; Jones, Liz; Cretchley, Julia

    2014-01-01

    Clinical handovers are an essential part of the daily care and treatment of hospital patients. We invoked a language and social psychology lens to investigate how different health professional groups discussed the communication problems and strengths they experienced in handovers. We conducted in-depth interviews with three different health professional groups within a large metropolitan hospital. We used Leximancer text analytics software as a tool to analyze the data. Results showed that time was of concern to all groups in both similar and diverse ways. All professionals discussed time management, time pressures, and the difficulties of coordinating different handovers. Each professional group had its own unique perceptions and priorities about handovers. Our findings indicated that health professionals understood what was required for handover improvement but did not have the extra capacity to alter their current environment. Hospital management, with clinicians, need to implement handover schedule processes that prioritize interprofessional representation. PMID:28462291

  11. A double-blind controlled clinical trial assessing the effect of topical gels on striae distensae (stretch marks): a non-invasive imaging, morphological and immunohistochemical study.

    PubMed

    Ud-Din, Sara; McAnelly, Sarah-Louise; Bowring, Alison; Whiteside, Sigrid; Morris, Julie; Chaudhry, Iskander; Bayat, Ardeshir

    2013-09-01

    Striae distensae (SD) are cutaneous lesions often presenting post-pregnancy with atrophy and flattening of the epidermis. SD is poorly understood and treatment remains ill-defined. Our aim was to assess the effect of topical application of silicone gel compared with placebo on SD using non-invasive devices and by immunohistochemical analysis of sequential tissue biopsies in a double-blind controlled trial. Twenty volunteers massaged silicone and placebo gels into separate sides of the abdomen, daily for 6 weeks. Objective non-invasive imaging plus subjective self-assessment of SD were performed on days 0, 21, 42, 90, in addition to tissue biopsies on days 0 and 42. Non-invasive imaging demonstrated an increase in melanin and a decrease in haemoglobin, collagen and pliability over the 6-week period on both sides. Additionally, collagen levels in SD were significantly higher (p value = 0.001) and melanin levels lower (p value = 0.048) with silicone gel compared with placebo. Histological analysis revealed epidermal flattening with a reduction of rete ridges in SD on both sides. Vascular count significantly decreased with placebo gel (p = 0.002). Corroborating the clinical results, melanin levels increased, whilst collagen type 1 and elastin decreased on both sides. Non-invasive techniques showed that the application of silicone gel increased collagen levels and reduced pigmentation compared with placebo. However, both clinical and histological data revealed that melanin increased whilst collagen, elastin and pliability decreased over the 6-week period with both gels. Furthermore, vascularity significantly decreased with placebo gel. These findings provide preliminary evidence of the utility of topical gels in the clinical management of SD.

  12. Topical fluorometholone treatment for ocular dryness in patients with Sjögren syndrome: a randomized clinical trial in China.

    PubMed

    Lin, Tong; Gong, Lan

    2015-02-01

    The purpose of the study was to evaluate the efficacy of an ophthalmic solution containing 0.1% fluorometholone (FML) and 0.1% sodium hyaluronate (HA) for the treatment of ocular dryness in Sjögren syndrome (SS) patients.Forty SS patients were randomly assigned to the FML or cyclosporin A (CsA) treatment groups. The FML group was treated with 0.1% FML and 0.1% HA, and the CsA group was treated with 0.5% CsA and 0.1% HA. Primary outcomes were corneal fluorescein staining (CFS), the Ocular Surface Disease Index (OSDI) score, conjunctival goblet cell density, and the severity of conjunctival congestion. Patients were also evaluated based on tear film breakup time (TFBUT) and the Schirmer test. After 8 weeks of treatment, the mean CFS scores were significantly lower in both the groups, compared with the baseline values, and the CFS score of the FML group at week 2 was significantly lower than that of the CsA group (P = 0.042). The OSDI scores improved significantly in both the groups throughout the study, and the OSDI score in the FML group at week 4 was significantly lower than that of the CsA group (P = 0.042). After 8 weeks of therapy, the conjunctival goblet cell density was significantly higher in both the groups (P < 0.001 for both) compared with the baseline values. Conjunctival congestion was reduced in both the groups throughout the study, and the severity in the FML group was significantly less at week 4 compared with that in the CsA group (P = 0.035). The TFBUT in the FML group at week 8 was significantly longer than in the CsA group (P = 0.04). Treatment using topical 0.1% FML provided faster improvement in the symptoms of ocular dryness in SS patients compared with topical 0.5% CsA.

  13. Clinical Trials

    MedlinePlus

    ... existing treatments. Some may study new forms of psychotherapy (talk therapy). Others may study a combination of ... period. In trials that test new forms of psychotherapy, one group may be randomly assigned to a ...

  14. A randomized controlled clinical trial of topical insulin-like growth factor-1 therapy for sudden deafness refractory to systemic corticosteroid treatment.

    PubMed

    Nakagawa, Takayuki; Kumakawa, Kozo; Usami, Shin-ichi; Hato, Naohito; Tabuchi, Keiji; Takahashi, Mariko; Fujiwara, Keizo; Sasaki, Akira; Komune, Shizuo; Sakamoto, Tatsunori; Hiraumi, Harukazu; Yamamoto, Norio; Tanaka, Shiro; Tada, Harue; Yamamoto, Michio; Yonezawa, Atsushi; Ito-Ihara, Toshiko; Ikeda, Takafumi; Shimizu, Akira; Tabata, Yasuhiko; Ito, Juichi

    2014-11-19

    To date, no therapeutic option has been established for sudden deafness refractory to systemic corticosteroids. This study aimed to examine the efficacy and safety of topical insulin-like growth factor-1 (IGF-1) therapy in comparison to intratympanic corticosteroid therapy. We randomly assigned patients with sudden deafness refractory to systemic corticosteroids to receive either gelatin hydrogels impregnated with IGF-1 in the middle ear (62 patients) or four intratympanic injections with dexamethasone (Dex; 58 patients). The primary outcome was the proportion of patients showing hearing improvement (10 decibels or greater in pure-tone average hearing thresholds) 8 weeks after treatment. The secondary outcomes included the change in pure-tone average hearing thresholds over time and the incidence of adverse events. In the IGF-1 group, 66.7% (95% confidence interval [CI], 52.9-78.6%) of the patients showed hearing improvement compared to 53.6% (95% CI, 39.7-67.0%) of the patients in the Dex group (P = 0.109). The difference in changes in pure-tone average hearing thresholds over time between the two treatments was statistically significant (P = 0.003). No serious adverse events were observed in either treatment group. Tympanic membrane perforation did not persist in any patient in the IGF-1 group, but did persist in 15.5% (95% CI, 7.3-27.4%) of the patients in the Dex group (P = 0.001). The positive effect of topical IGF-1 application on hearing levels and its favorable safety profile suggest utility for topical IGF-1 therapy in patients with sudden deafness. UMIN Clinical Trials Registry Number UMIN000004366, October 30th, 2010.

  15. Exploratory Clinical Trial to Evaluate the Efficacy of a Topical Traditional Chinese Herbal Medicine in Psoriasis Vulgaris

    PubMed Central

    Yan, Yuhe; Liu, Wali; Andres, Philippe; Pernin, Colette; Chantalat, Laurent; Briantais, Philippe; Lin, Albert; Feng, Lilian

    2015-01-01

    Objective. To evaluate the efficacy and safety of herbal ointment, Shi Du Ruan Gao, in patients with plaque-type psoriasis. Design. Single-center, randomized, investigator-blinded, parallel group, placebo-controlled study. Participants. One hundred outpatients with mild to moderate chronic plaque-type psoriasis were enrolled. Intervention. The patients applied either Shi Du Ruan Gao ointment or vehicle ointment topically to for 8 weeks. Main Outcome Measures. The outcomes were assessed using the following criteria: Total Severity Score (TSS, sum of erythema, scaling, and plaque elevation/induration, on a 0 to 4 scale), Investigator Global Assessment (IGA) evaluated on a 0 (Clear) to 4 (s to very severe) scale, and Global Subjects' Assessment of treatment response on a 7-point scale from −1 (worse) to 5 (Cleared). Results. Significant reductions in the Total Severity Score (P < 0.001) (mean score: 2.7 after Shi Du Ruan Gao treatment versus 5.1 in control subjects). Both Investigator Global Assessment (IGA) and Global Subjects' Assessment of treatment are better in the Shi Du Ruan Gao group than the control group (P < 0.001). Conclusion. Shi Du Ruan Gao ointment was a safe, and effective therapy for plaque-type psoriasis. PMID:25834623

  16. Topical peptides as cosmeceuticals.

    PubMed

    Pai, Varadraj Vasant; Bhandari, Prasana; Shukla, Pankaj

    2017-01-01

    Peptides are known to have diverse biological roles, most prominently as signaling/regulatory molecules in a broad variety of physiological processes including defense, immunity, stress, growth, homeostasis and reproduction. These aspects have been used in the field of dermatology and cosmetology to produce short, stable and synthetic peptides for extracellular matrix synthesis, pigmentation, innate immunity and inflammation. The evolution of peptides over the century, which started with the discovery of penicillin, has now extended to their usage as cosmeceuticals in recent years. Cosmeceutical peptides may act as signal modulators of the extracellular matrix component, as structural peptides, carrier peptides and neurotransmitter function modulators. Transdermal delivery of peptides can be made more effective by penetration enhancers, chemical modification or encapsulation of peptides. The advantages of using peptides as cosmeceuticals include their involvement in many physiological functions of the skin, their selectivity, their lack of immunogenicity and absence of premarket regulatory requirements for their use. However, there are disadvantages: clinical evidence for efficacy is often weak, absorption may be poor due to low lipophilicity, high molecular weight and binding to other ingredients, and prices can be quite high.

  17. Clinical trials of homoeopathy.

    PubMed Central

    Kleijnen, J; Knipschild, P; ter Riet, G

    1991-01-01

    OBJECTIVE--To establish whether there is evidence of the efficacy of homoeopathy from controlled trials in humans. DESIGN--Criteria based meta-analysis. Assessment of the methodological quality of 107 controlled trials in 96 published reports found after an extensive search. Trials were scored using a list of predefined criteria of good methodology, and the outcome of the trials was interpreted in relation to their quality. SETTING--Controlled trials published world wide. MAIN OUTCOME MEASURES--Results of the trials with the best methodological quality. Trials of classical homoeopathy and several modern varieties were considered separately. RESULTS--In 14 trials some form of classical homoeopathy was tested and in 58 trials the same single homoeopathic treatment was given to patients with comparable conventional diagnosis. Combinations of several homoeopathic treatments were tested in 26 trials; isopathy was tested in nine trials. Most trials seemed to be of very low quality, but there were many exceptions. The results showed a positive trend regardless of the quality of the trial or the variety of homeopathy used. Overall, of the 105 trials with interpretable results, 81 trials indicated positive results whereas in 24 trials no positive effects of homoeopathy were found. The results of the review may be complicated by publication bias, especially in such a controversial subject as homoeopathy. CONCLUSIONS--At the moment the evidence of clinical trials is positive but not sufficient to draw definitive conclusions because most trials are of low methodological quality and because of the unknown role of publication bias. This indicates that there is a legitimate case for further evaluation of homoeopathy, but only by means of well performed trials. PMID:1825800

  18. A randomized clinical trial on arresting dentine caries in preschool children by topical fluorides--18 month results.

    PubMed

    Duangthip, D; Chu, C H; Lo, E C M

    2016-01-01

    This study aimed to compare the effectiveness of three topical fluoride application protocols in arresting dentine caries in primary teeth of preschool children in a fluoridated area. Children aged 3-4 years who had at least one active dentine caries lesion were randomly allocated into three intervention groups: Group 1-application of 30% silver diammine fluoride (SDF) solution every 12 months; Group 2-three applications of 30% SDF solution at weekly interval at baseline; and Group 3-three applications of 5% sodium fluoride (NaF) varnish at weekly interval at baseline. A masked examiner carried out follow-up examinations every 6 months to assess whether the treated lesions had become arrested. A total of 304 children with 1670 tooth surfaces with dentine caries received treatment at baseline. After 18 months, 275 children (91%) remained in the study. The caries arrest rates at tooth surface level were 40%, 35% and 27% for Groups 1, 2 and 3, respectively (p<0.001). Result of the multi-level survival analysis showed that the two SDF application protocols could shorten the time to arrest of dentine caries compared with the NaF application protocol. Presence of plaque on lesion surface, tooth type and tooth surface all had significant effects on caries arrest rates. Annual or three consecutive weekly applications of SDF solution is more effective in arresting dentine caries in primary teeth than three consecutive weekly applications of NaF varnish. In a water fluoridated area, application of SDF solution, either three weekly applications at baseline or annually, can arrest active dentine caries lesions in primary teeth faster than three weekly applications of NaF varnish at baseline. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Clinical Trials Infrastructure as a Quality Improvement Intervention in Low- and Middle-Income Countries.

    PubMed

    Denburg, Avram; Rodriguez-Galindo, Carlos; Joffe, Steven

    2016-06-01

    Mounting evidence suggests that participation in clinical trials confers neither advantage nor disadvantage on those enrolled. Narrow focus on the question of a "trial effect," however, distracts from a broader mechanism by which patients may benefit from ongoing clinical research. We hypothesize that the existence of clinical trials infrastructure-the organizational culture, systems, and expertise that develop as a product of sustained participation in cooperative clinical trials research-may function as a quality improvement lever, improving the quality of care and outcomes of all patients within an institution or region independent of their individual participation in trials. We further contend that this "infrastructure effect" can yield particular benefits for patients in low- and middle-income countries (LMICs). The hypothesis of an infrastructure effect as a quality improvement intervention, if correct, justifies enhanced research capacity in LMIC as a pillar of health system development.

  20. Clinical Trials

    MedlinePlus

    ... your information private 5. What happens when the study ends The Possible Risks and Benefits The trial may provide treatments or screenings, but there is no promise that your health will get better. The medicine, test, or treatment may not work for you. 6. The benefits of the treatments ...

  1. Using mathematical modeling as a resource in clinical trials.

    PubMed

    Afenya, Evans K

    2005-07-01

    In light of recent clinical developments, the importance of mathematical modeling in cancer prevention and treatment is discussed. An exist- ing model of cancer chemotherapy is reintroduced and placed within current investigative frameworks regarding approaches to treatment optimization. Areas of commonality between the model predictions and the clinical findings are investigated as a way of further validating the model predictions and also establishing mathematical foundations for the clinical studies. The model predictions are used to propose additional ways that treatment optimization could enhance the clinical processes. Arising out of these, an expanded model of cancer is proposed and a treatment model is subsequently obtained. These models predict that malignant cells in the marrow and peripheral blood exhibit the tendency to evolve toward population levels that enable them to replace normal cells in these compartments in the untreated case. In the case of dose-dense treatment along with recombinant hematopoietic growth factors, the models predict a situation in which normal and abnormal cells in the marrow and peripheral blood are obliterated by drug action, while the normal cells regain their growth capabilities through growth-factor stimulation.

  2. [Analysis on the requirements for clinical trial protocol writing of external treatment of TCM such as tuina].

    PubMed

    Gao, Shuang; Wang, Jingui; Wang, Hui

    2015-06-01

    According to Standard Protocol Items: Recommendations for Interventional Trials, Consolidated Standard of Reporting Trials 2010 Statement (CONSORT), CONSORT Extension for Non-Pharmacologic Treatment Interventions (CONSORT for NPT) and Good Clinical Practice, the detailed requirements for protocol writing, reporting, and practicing of clinical trial were classified and summarized in this article. By combining the practical situation of clinical trial of external treatment of TCM such as tuina, the requirernents for clinical trial protocol writing of external treatment of TCM were analyzed and acquired which could improve the quality of clinical trial protocol of external treatment of TCM, thus to provide references for standardized execution of TMC clinical trial and reports of research results.

  3. Clinical trials face heightened scrutiny as science and commerce appear to merge.

    PubMed

    Lorman, Alvin J

    2001-01-01

    Clinical trials involving human subjects face increased scrutiny and regulation by the federal government that may lead to costly changes to the process. Prompted by a highly publicized death in a gene therapy trial, federal regulators are examining almost all aspects of clinical trial conduct, from how patients are recruited and how they give informed consent, to the relationship between the researchers and the company sponsoring the research. In addition to the heightened regulation, the government has announced that it will seek the power to impose civil money penalties on researchers who do not observe applicable patient protection regulations. In an effort to include more senior citizens in clinical trials, the government for the first time will cover certain costs of Medicare beneficiaries who participate in clinical trials. The risk of increased government involvement includes criminal prosecution of physicians for failing to follow the rules, as an innovative case in California demonstrates.

  4. Topical corticosteroid has no influence on inflammation or efficacy after ingenol mebutate treatment of grade I to III actinic keratoses (AK): A randomized clinical trial.

    PubMed

    Erlendsson, Andrés Már; Karmisholt, Katrine Elisabeth; Haak, Christina Skovbølling; Stender, Ida-Marie; Haedersdal, Merete

    2016-04-01

    Ingenol mebutate (IngMeb) is approved for treatment of actinic keratoses (AK) and may cause unpredictable local skin responses (LSR). We sought to investigate whether IngMeb-induced LSR, pain, and pruritus could be alleviated with a topical glucocorticoid and, further, to assess efficacy, cosmetic outcome, and patient satisfaction in patients with severe photodamage. In this blinded, randomized controlled clinical trial, patients with multiple AK and field cancerization of the face or scalp were treated in 2 areas with IngMeb (0.015%) daily for 3 days. After finalized IngMeb treatment, 1 area was randomized to receive topical clobetasol propionate (0.05%) twice daily for 4 days. Assessments included LSR (0-24; days 1, 4, 8, 15, 57), pain (0-10) and pruritus (0-3; days 1-15), AK clearance (days 15, 57), and cosmetic outcome (0-3; day 57). Clobetasol propionate application had no influence on LSR (P = .939), pain (P = .500), pruritus (P = .312), or AK cure rate (P = .991). Overall, IngMeb cleared 86% of all AK lesions, exerting a therapeutic effect on all AK severity grades; cure rates were 88%, 70%, and 60% for grade I, II, and III AK, respectively. Skin texture improved significantly in remedied areas (2.0 vs 1.0; P < .001); no hypopigmentation, hyperpigmentation, or scarring were observed. These results do not provide safety and efficacy beyond 2 months of follow-up. Application of clobetasol propionate does not alleviate IngMeb-induced LSR after 3 days of IngMeb treatment. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  5. Clinical Trials - Multiple Languages

    MedlinePlus

    ... Tiếng Việt) Arabic (العربية) Expand Section Clinical Trials - English Clinical Trials - العربية (Arabic) PDF American Cancer Society ... Traditional (Cantonese dialect) (繁體中文) Expand Section Clinical Trials - English Clinical Trials - 繁體中文 (Chinese, Traditional (Cantonese dialect)) PDF ...

  6. Oral teriflunomide for patients with a first clinical episode suggestive of multiple sclerosis (TOPIC): a randomised, double-blind, placebo-controlled, phase 3 trial.

    PubMed

    Miller, Aaron E; Wolinsky, Jerry S; Kappos, Ludwig; Comi, Giancarlo; Freedman, Mark S; Olsson, Tomas P; Bauer, Deborah; Benamor, Myriam; Truffinet, Philippe; O'Connor, Paul W

    2014-10-01

    Teriflunomide is a once-daily oral immunomodulator approved for the treatment of relapsing-remitting multiple sclerosis. We aimed to assess the efficacy and safety of teriflunomide in patients with a first clinical episode suggestive of multiple sclerosis. In this randomised, double-blind, placebo-controlled, parallel-group study, we enrolled patients aged 18-55 years with clinically isolated syndrome (defined as a neurological event consistent with demyelination, starting within 90 days of randomisation, and two or more T2-weighted MRI lesions ≥3 mm in diameter) from 112 centres (mostly hospitals) in 20 countries. Participants were randomly assigned (1:1:1) in a double-blind manner (by an interactive voice response system) to once-daily oral teriflunomide 14 mg, teriflunomide 7 mg, or placebo, for up to 108 weeks. Patients, staff administering the interventions, and outcome assessors were masked to treatment assignment. The primary endpoint was time to relapse (a new neurological abnormality separated by ≥30 days from a preceding clinical event, present for ≥24 h in the absence of fever or known infection), which defined conversion to clinically definite multiple sclerosis. The key secondary endpoint was time to relapse or new gadolinium-enhancing or T2 lesions on MRI, whichever occurred first. The primary outcome was analysed for the modified intention-to-treat population; safety analyses included all randomised patients who were exposed to the study drug, as treated. This trial is registered with ClinicalTrials.gov, number NCT00622700. Between Feb 13, 2008, and Aug 22, 2012, 618 patients were enrolled and randomly assigned to teriflunomide 14 mg (n=216), teriflunomide 7 mg (n=205), or placebo (n=197). Two patients in each of the teriflunomide groups did not receive the study drug, so the modified intention-to-treat population comprised 214 patients in the teriflunomide 14 mg group, 203 in the teriflunomide 7 mg group, and 197 in the placebo group. Compared

  7. Randomized, controlled clinical trial of safety and plasma concentrations of diclofenac in healthy neonatal foals after repeated topical application of 1% diclofenac sodium cream.

    PubMed

    Barnett, Susan E; Sellon, Debra C; Hines, Melissa T; Seino, Kathy K; Knych, Heather K

    2017-04-01

    OBJECTIVE To determine the plasma pharmacokinetics and safety of 1% diclofenac sodium cream applied topically to neonatal foals every 12 hours for 7 days. ANIMALS Twelve 2- to 14-day old healthy Arabian and Arabian-pony cross neonatal foals. PROCEDURES A 1.27-cm strip of cream containing 7.3 mg of diclofenac sodium (n = 6 foals) or an equivalent amount of placebo cream (6 foals) was applied topically to a 5-cm square of shaved skin over the anterolateral aspect of the left tarsometatarsal region every 12 hours for 7 days. Physical examination, CBC, serum biochemistry, urinalysis, gastric endoscopy, and ultrasonographic examination of the kidneys and right dorsal colon were performed before and after cream application. Venous blood samples were collected at predefined intervals following application of the diclofenac cream, and plasma diclofenac concentrations were determined by liquid chromatography-mass spectrometry. RESULTS No foal developed any adverse effects attributed to diclofenac application, and no significant differences in values of evaluated variables were identified between treatment groups. Plasma diclofenac concentrations peaked rapidly following application of the diclofenac cream, reaching a maximum of < 1 ng/mL within 2 hours, and declined rapidly after application ceased. CONCLUSIONS AND CLINICAL RELEVANCE Topical application of the 1% diclofenac sodium cream to foals as described appeared safe, and low plasma concentrations of diclofenac suggested minimal systemic absorption. Practitioners may consider use of this medication to treat focal areas of pain and inflammation in neonatal foals.

  8. Effect of Topical Application of the Cream Containing Magnesium 2% on Treatment of Diaper Dermatitis and Diaper Rash in Children A Clinical Trial Study.

    PubMed

    Nourbakhsh, Seyyed Mohammad-Kazem; Rouhi-Boroujeni, Hojjatollah; Kheiri, Maryam; Mobasheri, Mahmoud; Shirani, Majid; Ahrani, Saeedeh; Karami, Javad; Hafshejani, Zahra Keivani

    2016-01-01

    Diaper dermatitis is referred to the inflammation in outer layers of the skin in the perineal area, lower abdomen, and inner thighs. The lesions are maculopapular and usually itchy, which could cause bacterial or candida infection, and predispose the infants to penis or vaginal and urinary infection and lead to discomfort, irritability, and restlessness. The drugs which have been so far administered for this disease (topical steroids) cause special complications for the sensitive skin in this area. Magnesium (Mg) is known for its anti-inflammatory and wound-healing properties. The aim of the present study was to study the effect of the cream containing Mg 2% on treatment of diaper dermatitis and diaper rash in children. In this clinical trial study, 64 children aged less than two years old with diaper dermatitis referring Paediatric Ward of Hajar Hospital were randomly assigned to two groups of 32. Group one was treated with the combined cream Mg 2% and Calendula and group two with Calendula cream alone. The duration of recovery was compared between the two groups. The duration of recovery was significantly lower in the intervention group than the control group (p-value<0.001), but there was no significant difference in the lesions size and diapers' number between the two groups. Based on the finding of this study, Mg is effective on treatment of diaper dermatitis and could be used for treating diaper dermatitis and other types of dermatitis.

  9. Effect of Topical Application of the Cream Containing Magnesium 2% on Treatment of Diaper Dermatitis and Diaper Rash in Children A Clinical Trial Study

    PubMed Central

    Nourbakhsh, Seyyed Mohammad-Kazem; Rouhi-Boroujeni, Hojjatollah; Kheiri, Maryam; Mobasheri, Mahmoud; Shirani, Majid; Ahrani, Saeedeh; Karami, Javad

    2016-01-01

    Introduction Diaper dermatitis is referred to the inflammation in outer layers of the skin in the perineal area, lower abdomen, and inner thighs. The lesions are maculopapular and usually itchy, which could cause bacterial or candida infection, and predispose the infants to penis or vaginal and urinary infection and lead to discomfort, irritability, and restlessness. The drugs which have been so far administered for this disease (topical steroids) cause special complications for the sensitive skin in this area. Magnesium (Mg) is known for its anti-inflammatory and wound-healing properties. Aim The aim of the present study was to study the effect of the cream containing Mg 2% on treatment of diaper dermatitis and diaper rash in children. Materials and Methods In this clinical trial study, 64 children aged less than two years old with diaper dermatitis referring Paediatric Ward of Hajar Hospital were randomly assigned to two groups of 32. Group one was treated with the combined cream Mg 2% and Calendula and group two with Calendula cream alone. The duration of recovery was compared between the two groups. Results The duration of recovery was significantly lower in the intervention group than the control group (p-value<0.001), but there was no significant difference in the lesions size and diapers’ number between the two groups. Conclusion Based on the finding of this study, Mg is effective on treatment of diaper dermatitis and could be used for treating diaper dermatitis and other types of dermatitis. PMID:26894161

  10. OARSI Clinical Trials Recommendations: Design and conduct of clinical trials of rehabilitation interventions for osteoarthritis.

    PubMed

    Fitzgerald, G K; Hinman, R S; Zeni, J; Risberg, M A; Snyder-Mackler, L; Bennell, K L

    2015-05-01

    A Task Force of the Osteoarthritis Research Society International (OARSI) has previously published a set of guidelines for the conduct of clinical trials in osteoarthritis (OA) of the hip and knee. Limited material available on clinical trials of rehabilitation in people with OA has prompted OARSI to establish a separate Task Force to elaborate guidelines encompassing special issues relating to rehabilitation of OA. The Task Force identified three main categories of rehabilitation clinical trials. The categories included non-operative rehabilitation trials, post-operative rehabilitation trials, and trials examining the effectiveness of devices (e.g., assistive devices, bracing, physical agents, electrical stimulation, etc.) that are used in rehabilitation of people with OA. In addition, the Task Force identified two main categories of outcomes in rehabilitation clinical trials, which include outcomes related to symptoms and function, and outcomes related to disease modification. The guidelines for rehabilitation clinical trials provided in this report encompass these main categories. The report provides guidelines for conducting and reporting on randomized clinical trials. The topics include considerations for entering patients into trials, issues related to conducting trials, considerations for selecting outcome measures, and recommendations for statistical analyses and reporting of results. The focus of the report is on rehabilitation trials for hip, knee and hand OA, however, we believe the content is broad enough that it could be applied to rehabilitation trials for other regions as well.

  11. ClinicalTrials.gov

    MedlinePlus

    ... Content ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of ... This Site ClinicalTrials.gov Background About the Results Database History, Policies, and Laws Media/Press Resources Linking ...

  12. How Do Clinical Trials Work?

    MedlinePlus

    ... Work Who Can Participate What To Expect During Benefits and Risks How They Protect Participants Finding Clinical Trials Links Children & Clinical Studies NHLBI Trials Clinical Trial Websites How Do Clinical Trials Work? If you take part in a clinical trial, ...

  13. Challenging Issues in Clinical Trial Design: Part 4 of a 4-Part Series on Statistics for Clinical Trials.

    PubMed

    Pocock, Stuart J; Clayton, Tim C; Stone, Gregg W

    2015-12-29

    As a sequel to last week's paper on the fundamentals of clinical trial design, this paper tackles related controversial issues: noninferiority trials, the value of factorial designs, the importance and challenges of strategy trials, Data Monitoring Committees (including when to stop a trial early), and the role of adaptive designs. All topics are illustrated by relevant examples from cardiology trials. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  14. Conducting multiple-site clinical trials in medical rehabilitation research.

    PubMed

    Fuhrer, Marcus J

    2005-11-01

    This article examines the distinctive opportunities and challenges of multiple-site clinical trials, as distinguished from trials conducted by a single program. Among the topics discussed are: the role of clinical trials generally in medical rehabilitation research; definitions of "clinical trials" and "multiple site"; the distinction between exploratory and capstone trials; the potential advantages and disadvantages of multiple-site trials; planning issues in terms of sampling designs, the choice of outcome measures, approaches to dealing with intervention fidelity, organizational structures, authorship, and the conduct of collateral studies; and implementation issues in terms of pilot-testing procedures, handling emerging issues, and optimizing communication.

  15. Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP Panel: clinical trial inclusion/exclusion criteria and ethics.

    PubMed

    Tuszynski, M H; Steeves, J D; Fawcett, J W; Lammertse, D; Kalichman, M; Rask, C; Curt, A; Ditunno, J F; Fehlings, M G; Guest, J D; Ellaway, P H; Kleitman, N; Bartlett, P F; Blight, A R; Dietz, V; Dobkin, B H; Grossman, R; Privat, A

    2007-03-01

    The International Campaign for Cures of Spinal Cord Injury Paralysis established a panel tasked with reviewing the methodology for clinical trials for spinal cord injury (SCI), and making recommendations on the conduct of future trials. This is the third of four papers. It examines inclusion and exclusion criteria that can influence the design and analysis of clinical trials in SCI, together with confounding variables and ethical considerations. Inclusion and exclusion criteria for clinical trials should consider several factors. Among these are (1) the enrollment of subjects at appropriate stages after SCI, where there is supporting data from animal models or previous human studies; (2) the severity, level, type, or size of the cord injury, which can influence spontaneous recovery rate and likelihood that an experimental treatment will clinically benefit the subject; and (3) the confounding effects of various independent variables such as pre-existing or concomitant medical conditions, other medications, surgical interventions, and rehabilitation regimens. An issue of substantial importance in the design of clinical trials for SCI is the inclusion of blinded assessments and sham surgery controls: every effort should be made to address these major issues prospectively and carefully, if clear and objective information is to be gained from a clinical trial. The highest ethical standards must be respected in the performance of clinical trials, including the adequacy and clarity of informed consent.

  16. Efficacy of cryotherapy plus topical Juniperus excelsa M. Bieb cream versus cryotherapy plus placebo in the treatment of Old World cutaneous leishmaniasis: A triple-blind randomized controlled clinical trial.

    PubMed

    Parvizi, Mohammad Mahdi; Handjani, Farhad; Moein, Mahmoodreza; Hatam, Gholamreza; Nimrouzi, Majid; Hassanzadeh, Jafar; Hamidizadeh, Nasrin; Khorrami, Hamid Reza; Zarshenas, Mohammad Mehdi

    2017-10-05

    Cutaneous leishmaniasis is one of the highly prevalent endemic diseases in the Middle East and North Africa. Many treatment modalities have been recommended for this condition but success rates remain limited. Herbal remedies have also been used for treatment but evidence-based clinical trials with these products are sparse. In-vitro and in-vivo studies have shown the anti-leishmanial and curative effects of extract of fruits and leaves of Juniperus excelsa (J. excelsa). The aim of this study was to determine the efficacy of topical J. excelsa M. Bieb extract as an adjuvant to cryotherapy for the treatment of human CL. This study was designed as a two-arm triple-blind randomized placebo-controlled clinical trial using a parallel design. Seventy-two patients with clinical diagnosis of CL confirmed by leishmania smears were allocated to receive either a topical formulation of leaf of J. excelsa extract (group A) or placebo (group B) for 3 months. Both groups received cryotherapy as baseline standard treatment. Patients were evaluated before and weekly after the intervention was initiated until complete cure. Overall, 82% of patients in group A, experienced complete cure and 9% of them had partial cure. On the other hand, 34% in group B reported complete cure, while 14% of them had partial cure at the end of treatment protocol with a significant difference between the two groups (P< 0.001). The mean duration to healing of the lesions in patients who received J. excelsa extract was statistically significantly shorter than the placebo group (p = 0.04). No significant side effect was seen in the J. excelsa extract group except for mild to moderate local irritation after a few weeks in a few numbers of patients. The results of this study showed that topical J. excelsa extract can be used as an adjuvant treatment modality in addition to cryotherapy for accelerating the time to cure in addition to increasing the complete cure rate in CL. ClinicalTrials.gov IRCT2015082523753

  17. [Role of the state as regulatory authority of clinical trials in Peru].

    PubMed

    Fuentes, Duilio; Minaya, Gabriela; Ayala-Quintanilla, Beatriz

    2012-01-01

    This article sheds the light on historical review of the clinical trials regulatory process to the publication of the Clinical Trials Regulation in Peru, by Supreme Decree 017-2006-SA. In this context, that Regulation was amended within one year, with many critics including from the Ombudsman. It also considers the achievements as a regulatory authority that has strengthened its steering and its main objective of protecting the rights, safety and welfare of human subjects in clinical trials. Those achievements are: the internal register of clinical trials, strengthening inspections on all stakeholders that take part in research, the Notification System of Serious Adverse Events (REAS-NET), the publication of the Guideline: "Ethical, Legal and methodology in clinical trials for use of the Ethical Review Board" which won an international award; the 1st prize in the category of fizcalization and accomplishment of the law by the Good Practice of Public Management: "Protecting the rights of human subjects in experimental studies", the publication of the new Manual of Procedures for Clinical Trials and the implementation Plan of the National Bioethics Network in Peru.

  18. Communication about Children's Clinical Trials as Observed and Experienced: Qualitative Study of Parents and Practitioners

    PubMed Central

    Shilling, Valerie; Williamson, Paula R.; Hickey, Helen; Sowden, Emma; Beresford, Michael W.; Smyth, Rosalind L.; Young, Bridget

    2011-01-01

    Background Recruiting children to clinical trials is perceived to be challenging. To identify ways to optimise recruitment and its conduct, we compared how parents and practitioners described their experiences of recruitment to clinical trials. Methods and Findings This qualitative study ran alongside four children's clinical trials in 11 UK research sites. It compared analyses of semi-structured interviews with analyses of audio-recordings of practitioner-family dialogue during trial recruitment discussions. Parents from 59 families were interviewed; 41 had participated in audio-recorded recruitment discussions. 31 practitioners were interviewed. Parents said little in the recruitment discussions contributing a median 16% of the total dialogue and asking a median of one question. Despite this, parents reported a positive experience of the trial approach describing a sense of comfort and safety. Even if they declined or if the discussion took place at a difficult time, parents understood the need to approach them and spoke of the value of research. Some parents viewed participation as an ‘exciting’ opportunity. By contrast, practitioners often worried that approaching families about research burdened families. Some practitioners implied that recruiting to clinical trials was something which they found aversive. Many were also concerned about the amount of information they had to provide and believed this overwhelmed families. Whilst some practitioners thought the trial information leaflets were of little use to families, parents reported that they used and valued the leaflets. However, both parties agreed that the leaflets were too long and wanted them to be more reader-friendly. Conclusions Parents were more positive about being approached to enter their child into a clinical trial than practitioners anticipated. The concerns of some practitioners, that parents would be overburdened, were unfounded. Educating practitioners about how families perceive clinical

  19. Clinical trial of intramuscular injection as contraceptive compound.

    PubMed

    Lay, C L

    1970-01-01

    99 women of proven fertility received 778 intramuscular contraceptive injections. An injectable compound containing 150 mg dihy droxyprogesterone acetophenide and 10 mg of estradiol enanthate (Deladroxate) in castor oil was prepared in a 1-cc disposable syringe. The injections were administered intramuscularly in the upper outer glut eal region on Day 8 of each menstrual cycle. The study was initiated in September 1965 and was completed by February 1969, with all data being recorded on a computer for future analysis. No pregnancies occurred. No serious side effects were noted. There were improvements in cases of dysmenorrhea and premenstrual tension. Minor complaints were not a problem in the use of the contraceptive except for intermenstrual spotting, which prompted 8 patients to discontinue the method. It is concluded that the long-acting intramuscular injection of estrogen-progesterone given once a month is effective and useful in difficult contraceptive patients in a public health clinic.

  20. Comparing clinical effects of photodynamic therapy as a novel method with topical corticosteroid for treatment of Oral Lichen Planus.

    PubMed

    Bakhtiari, Sedigheh; Mojahedi, Seyyed Masoud; Azari-Marhabi, Saranaz; Namdari, Mahshid; Rankohi, Zahra Elmi

    2017-06-29

    Oral lichen planus is an autoimmune disorder with several challenges in treatment. Photodynamic therapy has been proposed as a new treatment option for the disease. The present study compared the clinical effects of the photodynamic therapy and dexamethasone mouthwash in the treatment of oral lichen planus lesions. In this randomized clinical trial, 30 patients with oral lichen planus were included.15 patients were treated with 5% methylene blue mediated photodynamic therapy using Fotosan device for 30seconds (630nm wavelength and 7.2-14.4J/CM2 dose) for 4 sessions in the days 1,4,7,14. In another group, the treatment was done on 15 patients by 0.5mg tab dexamethasone solution in 5cc water, rinsed 4 times in a day within two weeks. The sign score, symptoms scores (pain), clinical severity and treatment efficacy were measured at the days 15,30,60,90 after beginning of the treatment. The results were subjected to Mann-whitney U test in both groups. No significant difference existed between two modalities regarding the treatment efficacy index, sign score, symptom score and clinical severity on the 15, 30, 60 and 90 post-treatment days. Decreases in patient's symptoms were statistically significant in both groups. Photodynamic therapy was as effective as the dexamethasone mouth wash in the treatment of oral lichen planus It could be used as a safe modality in the treatment of oral lichen planus lesions without identified side effects. Copyright © 2017. Published by Elsevier B.V.

  1. Evaluation of gender as a clinically relevant outcome variable in the treatment of onychomycosis with efinaconazole topical solution 10.

    PubMed

    Rosen, Ted

    2015-09-01

    Although there are limited data available on gender as an outcome variable in the treatment of onychomycosis, differences in disease prevalence and impact in males versus females have been observed. This article provides a gender subgroup analysis based on results from recent studies evaluating the efficacy, safety, and tolerability of efinaconazole topical solution 10% in the treatment of onychomycosis. Data were collected from two 52-week, prospective, multicenter, randomized, double-blind studies of patients 
(age range, 18-70 years) randomized to receive either efinaconazole topical solution 10% or vehicle for treatment of onychomycosis. Results from this analysis indicated that once-daily application of efinaconazole topical solution 10% may provide a useful topical option for treatment of mild to moderate toenail onychomycosis, especially in female patients.

  2. Clinical Trials in Noninfectious Uveitis

    PubMed Central

    Kim, Jane S.; Knickelbein, Jared E.; Nussenblatt, Robert B.; Sen, H. Nida

    2015-01-01

    The treatment of noninfectious uveitis continues to remain a challenge for many ophthalmologists. Historically, clinical trials in uveitis have been sparse, and thus, most treatment decisions have largely been based on clinical experience and consensus guidelines. The current treatment paradigm favors initiation then tapering of corticosteroids with addition of steroid-sparing immunosuppressive agents for persistence or recurrence of disease. Unfortunately, in spite of a multitude of highly unfavorable systemic effects, corticosteroids are still regarded as the mainstay of treatment for many patients with chronic and refractory noninfectious uveitis. However, with the success of other conventional and biologic immunomodulatory agents in treating systemic inflammatory and autoimmune conditions, interest in targeted treatment strategies for uveitis has been renewed. Multiple clinical trials on steroid-sparing immunosuppressive agents, biologic agents, intraocular corticosteroid implants, and topical ophthalmic solutions have already been completed, and many more are ongoing. This review discusses the results and implications of these clinical trials investigating both alternative and novel treatment options for noninfectious uveitis. PMID:26035763

  3. Clinical Evaluation of self and professionally applied desensitizing agents in relieving dentin hypersensitivity after a single topical application: A Randomized Controlled Trial

    PubMed Central

    Khatri, Sachin G.; Acharya, Shashidhar

    2014-01-01

    Objectives: The objective of this study is to evaluate the efficacy of self and professionally applied desensitizing agents in relieving dentinal hypersensitivity after single direct topical application. Study Design: This was a randomized controlled trial conducted among 57 patients. 8% Arginine paste was self-applied by the subject and Gluma desensitizer was applied by investigator. Numeric rating scale was used to measure hypersensitivity after tactile stimulus, Schiff scale was used for cold and air blast stimuli respectively. Scores were recorded at baseline, immediately, 15 and 30 days after the application. Friedman, Wilcoxon test as post hoc was used to analyze within group differences, between group differences analyzed using Mann Whitney U test (P<0.05 considered significant). Results: 8% Arginine paste elicited significantly higher reductions in sensitivity (P<0.05) than that of Gluma group at all follow ups. There was a significant decrease in hypersensitivity for both the groups from baseline till final follow-up (P<0.05) for all three stimuli. 8% Arginine paste was found to be more effective than Gluma desensitizer in providing immediate relief from dentine hypersensitivity and also sustained the effect significantly for a period of 30 days. Conclusions: Self applied 8% Arginine paste is effective than professionally applied Gluma desensitizer in relieving dentinal hypersensitivity immediately and over a period of one month. Key words:Dentine hypersensitivity, arginine, gluma, desensitizing agents. PMID:25593653

  4. Research Areas - Clinical Trials

    Cancer.gov

    Information about NCI programs and initiatives that sponsor, conduct, develop, or support clinical trials, including NCI’s Clinical Trial Network (NCTN) and NCI Community Oncology Research Program (NCORP) initiatives.

  5. Randomized controlled pilot trial of nifedipine as oral therapy vs. topical application in the treatment of fissure-in-ano.

    PubMed

    Agrawal, Vivek; Kaushal, Gourav; Gupta, Rachna

    2013-11-01

    Fissure-in-ano is a common condition that leads to pain and affects quality of life. Sphincterotomy remains the gold standard, but it may lead to troublesome incontinence in some patients. To overcome this problem, numerous pharmacologic therapies have been tested with varying outcomes. The investigators compared the effect of the addition of oral and topical nifedipine to conservative measures in the treatment of patients with fissure-in-ano. Ninety patients with fissure-in-ano, randomized into 3 groups of 30 each, were included in the study. Group I received conventional treatment, group II received oral nifedipine and conventional treatment, and group III received topical nifedipine along with conventional treatment. Patients were followed for 8 weeks for pain relief (assessed using a visual analogue scale) and healing to evaluate the effect of treatment. Pain relief was significantly better in the group III at 3 weeks and 2 months compared with group I (P < .05). Groups II and III were comparable in terms of pain relief. Healing rates were significantly better in group II (P = .03) and group III (P = .00) compared with group I, but groups II and III were found to be comparable. Adverse effects were most commonly reported by group II patients, but these were not significantly higher than in other 2 groups. We recommend the addition of either oral or topical nifedipine to conservative measures to significantly improve pain relief and healing rates in patients with fissure-in-ano. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Clinical efficacy and IL-17 targeting mechanism of Indigo naturalis as a topical agent in moderate psoriasis.

    PubMed

    Cheng, Hui-Man; Wu, Yang-Chang; Wang, Qingmin; Song, Michael; Wu, Jackson; Chen, Dion; Li, Katherine; Wadman, Eric; Kao, Shung-Te; Li, Tsai-Chung; Leon, Francisco; Hayden, Karen; Brodmerkel, Carrie; Chris Huang, C

    2017-09-02

    Indigo naturalis is a Traditional Chinese Medicine (TCM) ingredient long-recognized as a therapy for several inflammatory conditions, including psoriasis. However, its mechanism is unknown due to lack of knowledge about the responsible chemical entity. We took a different approach to this challenge by investigating the molecular profile of Indigo naturalis treatment and impacted pathways. A randomized, double-blind, placebo-controlled clinical study was conducted using Indigo naturalis as topical monotherapy to treat moderate plaque psoriasis in a Chinese cohort (n = 24). Patients were treated with Indigo naturalis ointment (n = 16) or matched placebo (n = 8) twice daily for 8 weeks, with 1 week of follow-up. At week 8, significant improvements in Psoriasis Area and Severity Index (PASI) scores from baseline were observed in Indigo naturalis-treated patients (56.3% had 75% improvement [PASI 75] response) compared with placebo (0.0%). A gene expression signature of moderate psoriasis was established from baseline skin biopsies, which included the up-regulation of the interleukin (IL)-17 pathway as a key component; Indigo naturalis treatment resulted in most of these signature genes returning toward normal, including down-regulation of the IL-17 pathway. Using an in vitro keratinocyte assay, an IL-17-inhibitory effect was observed for tryptanthrin, a component of Indigo naturalis. This study demonstrated the clinical efficacy of Indigo naturalis in moderate psoriasis, and exemplified a novel experimental medicine approach to understand TCM targeting mechanisms. NCT01901705 .

  7. Hyperthermia-related clinical trials on cancer treatment within the ClinicalTrials.gov registry.

    PubMed

    Cihoric, Nikola; Tsikkinis, Alexandros; van Rhoon, Gerard; Crezee, Hans; Aebersold, Daniel M; Bodis, Stephan; Beck, Marcus; Nadobny, Jacek; Budach, Volker; Wust, Peter; Ghadjar, Pirus

    2015-01-01

    Hyperthermia has been shown to improve the effectiveness of chemotherapy and radiotherapy in the treatment of cancer. This paper summarises all recent clinical trials registered in the ClinicalTrials.gov registry. The records of 175,538 clinical trials registered at ClinicalTrials.gov were downloaded on 29 September 2014 and a database was established. We searched this database for hyperthermia or equivalent words. A total of 109 trials were identified in which hyperthermia was part of the treatment regimen. Of these, 49 trials (45%) had hyperthermic intraperitoneal chemotherapy after cytoreductive surgery (HIPEC) as the primary intervention, and 14 other trials (13%) were also testing some form of intraperitoneal hyperthermic chemoperfusion. Seven trials (6%) were testing perfusion attempts to other locations (thoracic/pleural n = 4, limb n = 2, hepatic n = 1). Sixteen trials (15%) were testing regional hyperthermia, 13 trials (12%) whole body hyperthermia, seven trials (6%) superficial hyperthermia and two trials (2%) interstitial hyperthermia. One remaining trial tested laser hyperthermia. In contrast to the general opinion, this analysis shows continuous interest and ongoing clinical research in the field of hyperthermia. Interestingly, the majority of trials focused on some form of intraperitoneal hyperthermic chemoperfusion. Despite the high number of active clinical studies, HIPEC is a topic with limited attention at the annual meetings of the European Society for Hyperthermic Oncology and the Society of Thermal Medicine. The registration of on-going clinical trials is of paramount importance for the achievement of a comprehensive overview of available clinical research activities involving hyperthermia.

  8. Progression-Free Survival as a Surrogate for Overall Survival in Clinical Trials of Targeted Therapy in Advanced Solid Tumors.

    PubMed

    Michiels, Stefan; Saad, Everardo D; Buyse, Marc

    2017-03-23

    Over the past 15 years, targeted therapy has revolutionized the systemic treatment of cancer. In parallel, there has been a growing debate on the choice of end points in clinical trials in oncology. This debate basically hinges on the choice between overall survival (OS) and progression-free survival (PFS). PFS is advantageous because it is measured earlier than OS, requires a smaller sample size than OS to achieve the desired power, and is not influenced by cross-over. On the other hand, PFS is prone to measurement error and bias, and may not capture the entire treatment effect on the outcomes of most interest to patients with an incurable disease: a prolonged survival and improved quality of life. Therefore, how can we choose between two imperfect end points? The answer to this question would certainly be made easier if PFS could be demonstrated to be a valid surrogate for OS. The validation of a surrogate end point is best made using individual-patient data (IPD) from randomized trials, which allows for standardized assessments of the patient-level and the trial-level correlations between surrogate and final end points. Proper IPD meta-analytical evaluations for targeted agents have still been rare, and to our knowledge only three studies on this topic are currently available in the metastatic setting: one in breast cancer, one in colorectal cancer and one in lung cancer. Although these three studies suffer from limitations inherent to the availability of IPD and the design of the original clinical trials, they have not been able to validate PFS as surrogate for OS, because only modest correlations were found between these two end points, both at the patient and at the trial level. Even if properly conducted surrogate-endpoint evaluations have thus far been unsuccessful, these evaluations are a step in the right direction and can be expected to be applied on a much larger scale in the era of data sharing of clinical trials.

  9. The Effect of Sodium Hypochlorite and Chlorhexidine as Irrigant Solutions for Root Canal Disinfection: A Systematic Review of Clinical Trials.

    PubMed

    Gonçalves, Lucio Souza; Rodrigues, Renata Costa Val; Andrade Junior, Carlos Vieira; Soares, Renata G; Vettore, Mario Vianna

    2016-04-01

    This systematic review aimed to compare the effectiveness of sodium hypochlorite and chlorhexidine for root canal disinfection during root canal therapy. A literature search for clinical trials was made on the PubMed (MEDLINE), Web of Knowledge, SCOPUS, and Science Direct databases and in the reference lists of the identified articles up to January 2015. Quality assessment of the selected studies was performed according to the Consolidated Standards of Reporting Trials statement. One clinical trial and 4 randomized clinical trials were selected from the 172 articles initially identified. There was heterogeneity in the laboratory methods used to assess the root canal disinfection as well as in the concentrations of the irrigants used. Therefore, meta-analysis was not performed. Two studies reported effective and similar reductions in bacterial levels for both irrigants. Sodium hypochlorite was more effective than chlorhexidine in reducing microorganisms in 1 study, and another reported opposite findings. Both root irrigants were ineffective in eliminating endotoxins from necrotic pulp root canals in 1 study. Trial design and information regarding randomization procedures were not clearly described in the clinical trials. No study compared laboratory results with clinical outcomes. The available evidence on this topic is scarce, and the findings of studies were not consistent. Additional randomized clinical trials using clinical outcomes to compare the use of sodium hypochlorite and chlorhexidine during root canal therapy are needed. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  10. The topical treatment of anthroponotic cutaneous leishmaniasis with the tincture of thioxolone plus benzoxonium chloride (Thio-Ben) along with cryotherapy: a single-blind randomized clinical trial.

    PubMed

    Daie Parizi, Mohammad Hossein; Karvar, Mehran; Sharifi, Iraj; Bahrampour, Abbas; Heshmat Khah, Amireh; Rahnama, Zahra; Baziar, Zahra; Amiri, Rezvan

    2015-01-01

    A simple efficacious topical treatment for cutaneous leishmaniasis (CL) is still an unresolved challenge. This study aimed to evaluate the efficacy of the topical use of thioxolone plus benzoxonium chloride (Thio-Ben) tincture in combination with cryotherapy in comparison with intralesional meglumine antimoniate (Glucantime) along with cryotherapy in treating anthroponotic CL (ACL). The study was conducted in Leishmaniasis Center in Dadbin Health Care Clinic, Kerman, Iran. Sixty-four CL lesions were randomly assigned to receive Thio-Ben plus cryotherapy (TC) (n = 32) or Glucantime plus cryotherapy (GC) (n = 32). Thio-Ben was used topically every other day and Glucantime was used intralesionally once a week for a maximum of 3 months. In both study groups, cryotherapy was administered using liquid nitrogen once every 2 weeks. Of 64 recruited lesions, 47 lesions completed the study protocol. Twenty lesions (91%) in TC group and 23 lesions (92%) in GC group showed complete cure. TC group showed faster clinical response. Pain, hypersensitivity reaction, dizziness, and nausea were only seen in GC group. This study showed that the topical use of Thio-Ben combined with cryotherapy has a good efficacy in treating ACL with the benefit that Thio-Ben has more patient compliance and less side effects than intralesional Glucantime.

  11. Topical Hyaluronic acid vs. Standard of Care for the Prevention of Radiation Dermatitis after Adjuvant Radiotherapy for Breast Cancer: Single-Blind Randomized Phase III Clinical Trial

    PubMed Central

    Pinnix, Chelsea; Perkins, George H.; Strom, Eric A.; Tereffe, Welela; Woodward, Wendy; Oh, Julia L.; Arriaga, Lisa; Munsell, Mark F.; Kelly, Patrick; Hoffman, Karen E.; Smith, Benjamin D.; Buchholz, Thomas A.; Yu, T. Kuan

    2014-01-01

    Purpose To determine the efficacy of an emulsion containing hyaluronic acid to reduce the development of ≥ grade 2 radiation dermatitis after adjuvant breast radiation (RT) compared with best supportive care. Materials and Methods Women with breast cancer who had undergone lumpectomy and were to receive whole-breast RT to 50 Gy with a 10- to 16-Gy surgical bed boost were enrolled in a prospective randomized trial to compare the effectiveness of a hyaluronic acid-based gel (RadiaPlex) and a petrolatum-based gel (Aquaphor) for preventing the development of dermatitis. Each patient was randomly assigned to use hyaluronic acid gel, on the medial half or the lateral half of the irradiated breast, and the control gel to the other half. Dermatitis was graded weekly according to the Common Terminology Criteria v3.0 by the treating physician, who was blinded as to which gel was used on which area of the breast. The primary endpoint was development of ≥grade 2 dermatitis. Results The study closed early based on a recommendation from the Data and Safety Monitoring Board after 74 of the planned 92 patients were enrolled. Breast skin treated with the hyaluronic acid gel developed significantly higher rate of ≥grade 2 dermatitis than did skin treated with petrolatum gel (61.5% [40/65] vs. 47.7% [31/65], P = 0.027). Only one patient developed grade 3 dermatitis using either gel. A higher proportion of patients had worse dermatitis in the breast segment treated with hyaluronic acid gel than petrolatum gel at the end of RT (42% vs. 14%, P = 0.003). Conclusion We found no benefit from use of a topical hyaluronic acid-based gel for reducing the development of grade ≥2 dermatitis after adjuvant RT for breast cancer. Additional studies are needed to determine the efficacy of hyaluronic acid-based gel in controlling radiation dermatitis symptoms after they develop. PMID:22172912

  12. Directed shift of vaginal flora after topical application of sucrose gel in a phase III clinical trial: a novel treatment for bacterial vaginosis.

    PubMed

    Zeng, Zhong-ming; Liao, Qin-pin; Yao, Chen; Geng, Li; Feng, Li-hua; Shi, Hui-rong; Xin, Xiao-yan; Li, Ping; Wang, Hui-lan; Pang, Yi-cun; Liu, Shu-wen; Jiang, Shi-bo

    2010-08-05

    Bacterial vaginosis (BV) is one of the most common infectious diseases among sexually active women and is associated with the increased acquisition of a variety of sexually transmitted diseases. This study aimed to compare the efficacy of a non-antibiotic sucrose gel against an antibiotic metronidazole gel for the treatment of BV. A randomized, double-blinded, multi-center, parallel-group, placebo-controlled phase III clinical trial was conducted at eight hospitals in China. A total of 560 subjects with clinically diagnosed BV were randomly assigned into three groups for vaginally receiving sucrose, metronidazole, and placebo gels, respectively, twice daily for five consecutive days. The efficacy of therapeutic cure, defined as an achievement of both microbiologic cure (a Nugent score of 3 or less) and clinical cure (a resolution of the clinical findings from the baseline visit), was evaluated at the 1st and 2nd test-of-cure (TOC) visits at 7-10 and 21-35 days after the start of treatment, respectively. Therapeutic cure rates for sucrose, metronidazole, and placebo gel groups were 83.13%, 71.30% and 0.92%, at the 1st TOC, and 61.04%, 66.67% and 7.34%, at the 2nd TOC, respectively. While there was no significant difference between the sucrose and metronidazole gel groups at the 2nd TOC (P = 0.305), and sucrose gel was more effective than metronidazole gel at the 1st TOC (P = 0.009). These findings suggest that sucrose gel restores normal vaginal flora more rapidly than metronidazole gel and can be used as a novel treatment for BV.

  13. ASCPRO Recommendations for the Assessment of Fatigue as an Outcome in Clinical Trials

    PubMed Central

    Barsevick, Andrea M.; Cleeland, Charles S.; Manning, Donald C.; O'Mara, Ann M.; Reeve, Bryce B.; Scott, Jane A.; Sloan, Jeff A.

    2010-01-01

    Context Development of pharmacologic and behavioral interventions for cancer-related fatigue (CRF) requires adequate measures of this symptom. A guidance document from the Food and Drug Administration offers criteria for the formulation and evaluation of patient-reported outcome measures used in clinical trials to support drug or device labeling claims. Methods An independent working group, ASCPRO (Assessing Symptoms of Cancer Using Patient-Reported Outcomes), has begun developing recommendations for the measurement of symptoms in oncology clinical trials. The recommendations of the Fatigue Task Force for measurement of CRF are presented here. Results There was consensus that CRF could be measured effectively in clinical trials as the sensation of fatigue or tiredness, impact of fatigue/tiredness on usual functioning or as both sensation and impact. The ASCPRO Fatigue Task Force constructed a definition and conceptual model to guide measurement of CRF. ASCPRO recommendations do not endorse a specific fatigue measure but clarify how to evaluate and implement fatigue assessments in clinical studies. The selection of a CRF measure should be tailored to the goals of the research. Measurement issues related to various research environments were also discussed. Conclusion There exist in the literature good measures of CRF for clinical trials with strong evidence of clarity and comprehensibility to patients, content and construct validity, reliability, sensitivity to change in conditions in which one would expect them to change (assay sensitivity), and sufficient evidence to establish guides for interpreting changes in scores. Direction for future research is discussed. PMID:20538190

  14. Adaptive clinical trial design.

    PubMed

    Chow, Shein-Chung

    2014-01-01

    In recent years, the use of adaptive design methods in clinical trials based on accumulated data at interim has received much attention because of its flexibility and efficiency in pharmaceutical/clinical development. In practice, adaptive design may provide the investigators a second chance to modify or redesign the trial while the study is still ongoing. However, it is a concern that a shift in target patient population may occur after significant adaptations are made. In addition, the overall type I error rate may not be preserved. Moreover, the results may not be reliable and hence are difficult to interpret. As indicated by the US Food and Drug Administration draft guidance on adaptive design clinical trials, the adaptive design has to be a prospectively planned opportunity and should be based on information collected within the study, with or without formal statistical hypothesis testing. This article reviews the relative advantages, limitations, and feasibility of commonly considered adaptive designs in clinical trials. Statistical concerns when implementing adaptive designs are also discussed.

  15. Gastric Water Emptying under Fed State Clinical Trial Conditions Is as Fast as under Fasted Conditions.

    PubMed

    Grimm, Michael; Scholz, Elisabeth; Koziolek, Mirko; Kühn, Jens-Peter; Weitschies, Werner

    2017-10-05

    The Magenstrasse (stomach road) describes the fast emptying of ingested liquids from the postprandial stomach. The occurrence of the Magenstrasse has great importance for drugs administered together with food as it represents a shortcut through the fed stomach and allows rapid onset of plasma levels. In this study, we investigated the effect of different meals and their texture and fat content on the occurrence of the Magenstrasse. Since the administration of water is common 60 min after drug intake in clinical trials, we also investigated the effect of time point of water administration on the Magenstrasse by a second water administration. The texture of solid meals and a higher amount of solid food components turned out to favor the presence of the Magenstrasse. On the other hand, the effect of fat content of the meals was negligible. Additionally, the gastric emptying of water was comparable between the first and the second (60 min later) fluid administration, which could lead to an entrainment of drug substance. So far, the Magenstrasse is proven for water; an investigation of other liquid vehicles might be interesting for further mechanistic understanding and utilization. It turned out that the phenomenon of the Magenstrasse can also occur at later time points in clinical studies and may have great impact on the pharmacokinetic profiles obtained in these studies.

  16. Managing clinical trials

    PubMed Central

    2010-01-01

    Managing clinical trials, of whatever size and complexity, requires efficient trial management. Trials fail because tried and tested systems handed down through apprenticeships have not been documented, evaluated or published to guide new trialists starting out in this important field. For the past three decades, trialists have invented and reinvented the trial management wheel. We suggest that to improve the successful, timely delivery of important clinical trials for patient benefit, it is time to produce standard trial management guidelines and develop robust methods of evaluation. PMID:20626885

  17. 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

  18. [Critical reading of clinical trials].

    PubMed

    Aptel, F; Cucherat, M; Blumen-Ohana, E; Denis, P

    2011-12-01

    Clinical trials are playing an increasingly crucial role in modern evidence based medicine, allowing for rigorous scientific evaluation of treatment strategies and validation of patient care. The results of clinical trials often form the rational basis from which physicians draw information used to adapt their therapeutic practices. Critical reading and analysis of trials involves the assessment of whether the available data provide enough credible evidence that the treatment will result in a clinically significant and relevant improvement. Evaluating the quality of a clinical trial is a process that draws upon sometimes complex methodological and statistical concepts, with which the reader should nonetheless be familiar in order to come to impartial conclusions regarding the raw data presented in the clinical trials. The goal of the current article is to review the methodological and statistical concepts required for the design and interpretation of clinical trials, so as to allow for a critical analysis of publications or presentations of clinical trials. The first section describes the major methodological principles of clinical trial design required for a rigorous evaluation of the treatment benefit, as well as the various pitfalls or biases that could lead to erroneous conclusions. The second section briefly describes the main statistical tests used in clinical trials, as well as certain situations that may increase the risk of false positive findings (type 1 error), such as multiple, subgroup, intermediate and non-inferiority analysis. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  19. INFANT LUNG FUNCTION TESTS AS ENDPOINTS IN THE ISIS MULTICENTER CLINICAL TRIAL IN CYSTIC FIBROSIS

    PubMed Central

    Davis, Stephanie D.; Ratjen, Felix; Brumback, Lyndia C.; Johnson, Robin C.; Filbrun, Amy G.; Kerby, Gwendolyn S.; Panitch, Howard B.; Donaldson, Scott H.; Rosenfeld, Margaret

    2015-01-01

    Background The Infant Study of Inhaled Saline (ISIS) in CF was the first multicenter clinical trial to utilize infant pulmonary function tests (iPFTs) as an endpoint. Methods Secondary analysis of ISIS data was conducted in order to assess feasibility of iPFT measures and their associations with respiratory symptoms. Standard deviations were calculated to aid in power calculations for future clinical trials. Results 73 participants enrolled, 70 returned for the final visit; 62 (89%) and 45 (64%) had acceptable paired functional residual volume (FRC) and raised volume measurements, respectively. Mean baseline FEV0.5, FEF75 and FRC z-scores were 0.3 (SD: 1.2), −0.2 (SD: 2.0) and 1.8 (SD: 2.0). Conclusions iPFTs are not appropriate primary endpoints for multicenter clinical trials due to challenges of obtaining acceptable data and near-normal average raised volume measurements. Raised volume measures have potential to serve as secondary endpoints in future clinical CF trials. PMID:26547590

  20. Infant lung function tests as endpoints in the ISIS multicenter clinical trial in cystic fibrosis.

    PubMed

    Davis, Stephanie D; Ratjen, Felix; Brumback, Lyndia C; Johnson, Robin C; Filbrun, Amy G; Kerby, Gwendolyn S; Panitch, Howard B; Donaldson, Scott H; Rosenfeld, Margaret

    2016-05-01

    The Infant Study of Inhaled Saline (ISIS) in CF was the first multicenter clinical trial to utilize infant pulmonary function tests (iPFTs) as an endpoint. Secondary analysis of ISIS data was conducted in order to assess feasibility of iPFT measures and their associations with respiratory symptoms. Standard deviations were calculated to aid in power calculations for future clinical trials. Seventy-three participants enrolled, 70 returned for the final visit; 62 (89%) and 45 (64%) had acceptable paired functional residual capacity (FRC) and raised volume measurements, respectively. Mean baseline FEV0.5, FEF75 and FRC z-scores were 0.3 (SD: 1.2), -0.2 (SD: 2.0), and 1.8 (SD: 2.0). iPFTs are not appropriate primary endpoints for multicenter clinical trials due to challenges of obtaining acceptable data and near-normal average raised volume measurements. Raised volume measures have potential to serve as secondary endpoints in future clinical CF trials. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  1. Birth Control in Clinical Trials

    PubMed Central

    Stewart, J.; Beyer, B. K.; Chadwick, K.; De Schaepdrijver, L.; Desai, M.; Enright, B.; Foster, W.; Hui, J. Y.; Moffat, G. J.; Tornesi, B.; Van Malderen, K.; Wiesner, L.; Chen, C. L.

    2015-01-01

    The Health and Environmental Sciences Institute (HESI) Developmental and Reproductive Toxicology Technical Committee sponsored a pharmaceutical industry survey on current industry practices for contraception use during clinical trials. The objectives of the survey were to improve our understanding of the current industry practices for contraception requirements in clinical trials, the governance processes set up to promote consistency and/or compliance with contraception requirements, and the effectiveness of current contraception practices in preventing pregnancies during clinical trials. Opportunities for improvements in current practices were also considered. The survey results from 12 pharmaceutical companies identified significant variability among companies with regard to contraception practices and governance during clinical trials. This variability was due primarily to differences in definitions, areas of scientific uncertainty or misunderstanding, and differences in company approaches to enrollment in clinical trials. The survey also revealed that few companies collected data in a manner that would allow a retrospective understanding of the reasons for failure of birth control during clinical trials. In this article, suggestions are made for topics where regulatory guidance or scientific publications could facilitate best practice. These include provisions for a pragmatic definition of women of childbearing potential, guidance on how animal data can influence the requirements for male and female birth control, evidence-based guidance on birth control and pregnancy testing regimes suitable for low- and high-risk situations, plus practical methods to ascertain the risk of drug-drug interactions with hormonal contraceptives. PMID:27042398

  2. Comparing community and specialty provider-based recruitment in a randomized clinical trial: clinical trial in fecal incontinence

    USDA-ARS?s Scientific Manuscript database

    Recruitment of participants to clinical trials remains a significant challenge, especially for research addressing topics of a sensitive nature such as fecal incontinence (FI). The Fiber Study, a randomized controlled trial on symptom management for FI, successfully enrolled 189 community-living adu...

  3. Incorporating Topic Assignment Constraint and Topic Correlation Limitation into Clinical Goal Discovering for Clinical Pathway Mining

    PubMed Central

    Xu, Xiao; Wei, Zhijie

    2017-01-01

    Clinical pathways are widely used around the world for providing quality medical treatment and controlling healthcare cost. However, the expert-designed clinical pathways can hardly deal with the variances among hospitals and patients. It calls for more dynamic and adaptive process, which is derived from various clinical data. Topic-based clinical pathway mining is an effective approach to discover a concise process model. Through this approach, the latent topics found by latent Dirichlet allocation (LDA) represent the clinical goals. And process mining methods are used to extract the temporal relations between these topics. However, the topic quality is usually not desirable due to the low performance of the LDA in clinical data. In this paper, we incorporate topic assignment constraint and topic correlation limitation into the LDA to enhance the ability of discovering high-quality topics. Two real-world datasets are used to evaluate the proposed method. The results show that the topics discovered by our method are with higher coherence, informativeness, and coverage than the original LDA. These quality topics are suitable to represent the clinical goals. Also, we illustrate that our method is effective in generating a comprehensive topic-based clinical pathway model.

  4. Comparison of Topical Nifedipine With Oral Nifedipine for Treatment of Anal Fissure: A Randomized Controlled Trial

    PubMed Central

    Golfam, Farzaneh; Golfam, Parisa; Golfam, Babak; Pahlevani, Puyan

    2014-01-01

    Background: Medical sphincterotomy has gained popularity as a treatment for anal fissure. Calcium channel blockers in topical forms could also be appropriate with low adverse effects. Objectives: This was a prospective randomized controlled trial to compare topical and oral nifedipine in the treatment of chronic anal fissure. Patients and Methods: A prospective randomized controlled trial was conducted at two centers of Shahed University. One hundred and thirty patients with chronic anal fissure aged 18 to 60 years managed in our clinics were included in this study. The patients were randomly divided into two groups. Sixty-five patients received topical nifedipine (TN) and the same number received oral nifedipine (ON). Results: Ulcer healing occurred in 43 (73.33%) of topical nifedipine group compared to 29 (49.5%) patients in oral nifedipine, which was significantly different (P < 0.05). Side effects such as headache and flushing in oral nifedipine group were more prevalent than topical nifedipine, which was statistically different. Recurrence rates were the same after six months of follow-up. Conclusions: Although oral nifedipine can reduce symptom and signs of anal fissure, topical nifedipine has a superior role for anal fissure treatment with higher healing rate and lower side effects. PMID:25389477

  5. Effectiveness of Topical Nigella sativa Seed Oil in the Treatment of Cyclic Mastalgia: A Randomized, Triple-Blind, Active, and Placebo-Controlled Clinical Trial.

    PubMed

    Huseini, Hasan Fallah; Kianbakht, Saeed; Mirshamsi, Mohammad Hossein; Zarch, Ali Babaei

    2016-03-01

    Cyclic mastalgia is common in women and has no optimal therapy. Analgesic effects of Nigella sativa have been reported. Thus, the effect of a standardized N. sativa seed oil (600 mg applied to the site of pain bis in die for 2 months) on the 10-centimeter visual analog scale scores of pain severity in 52 women with cyclic mastalgia was compared to that of topical diclofenac (20 mg bis in die) (n = 51) and placebo (n = 53). There was no significant difference between the 1- and 2-month pain scores in the active treatment groups (p > 0.05). The pain scores of the active treatment groups did not differ significantly at 1 and 2 months (p > 0.05). The endpoint pain scores of the active treatment groups decreased significantly compared with the baseline (both p < 0.001). The pain scores of the active treatment groups at 1 and 2 months were significantly smaller than those of the placebo group (both p < 0.001). The pain scores of the placebo group at 1 and 2 months were not significantly different from the baseline (p > 0.05). No adverse effect was observed. In conclusion, topical N. sativa seed oil is safe, more effective than placebo, and has clinical effectiveness comparable to topical diclofenac in the treatment of cyclic mastalgia.

  6. Clinical and cytological effects of pimecrolimus cream 1% after resolution of active atopic dermatitis lesions by topical corticosteroids: a randomized controlled trial.

    PubMed

    Bangert, Christine; Strober, Bruce E; Cork, Michael; Ortonne, Jean-Paul; Luger, Thomas; Bieber, Thomas; Ferguson, Adam; Ecker, Rupert C; Kopp, Tamara; Weise-Riccardi, Sophia; Guettner, Achim; Stingl, Georg

    2011-02-01

    Topical pimecrolimus may maintain remissions of atopic dermatitis (AD) by inhibiting subclinical inflammation. To evaluate clinical and cytological effects of pimecrolimus in topical corticosteroid-treated and resolved AD lesions. Patients (n=67) with resolved AD lesions were randomized to 3-week double-blind treatment with either pimecrolimus cream 1% or vehicle cream. Outcome measures were reduction in Eczema Area and Severity Index (EASI) and number of leukocytes in skin biopsies in all randomized patients who were evaluable at the end of study. The proportion of patients with a localized EASI<2 at the end of study was higher with pimecrolimus cream 1% than with vehicle cream (73.5 vs. 39.4%, respectively). There was a significant decrease in the number of infiltrating CD45+ cells in pimecrolimus cream 1% compared with placebo cream (-88.2 vs. 43.2 cells/mm(2), respectively, p=0.047) and a slight but nonsignificant reduction in the number of dermal dendritic cells, Langerhans cells, T cells and macrophages with pimecrolimus versus vehicle cream. This was an exploratory study. Topical pimecrolimus was effective at maintaining betamethasone-17α-valerate-induced AD remission by inhibiting recurrences of the inflammatory infiltrate in the skin. Copyright © 2010 S. Karger AG, Basel.

  7. Topical Hyaluronic Acid vs. Standard of Care for the Prevention of Radiation Dermatitis After Adjuvant Radiotherapy for Breast Cancer: Single-Blind Randomized Phase III Clinical Trial

    SciTech Connect

    Pinnix, Chelsea; Perkins, George H.; Strom, Eric A.; Tereffe, Welela; Woodward, Wendy; Oh, Julia L.; Arriaga, Lisa; Munsell, Mark F.; Kelly, Patrick; Hoffman, Karen E.; Smith, Benjamin D.; Buchholz, Thomas A.; Yu, T. Kuan

    2012-07-15

    Purpose: To determine the efficacy of an emulsion containing hyaluronic acid to reduce the development of {>=}Grade 2 radiation dermatitis after adjuvant breast radiation compared with best supportive care. Methods and Materials: Women with breast cancer who had undergone lumpectomy and were to receive whole-breast radiotherapy to 50 Gy with a 10- to 16-Gy surgical bed boost were enrolled in a prospective randomized trial to compare the effectiveness of a hyaluronic acid-based gel (RadiaPlex) and a petrolatum-based gel (Aquaphor) for preventing the development of dermatitis. Each patient was randomly assigned to use hyaluronic acid gel on the medial half or the lateral half of the irradiated breast and to use the control gel on the other half. Dermatitis was graded weekly according to the Common Terminology Criteria v3.0 by the treating physician, who was blinded as to which gel was used on which area of the breast. The primary endpoint was development of {>=}Grade 2 dermatitis. Results: The study closed early on the basis of a recommendation from the Data and Safety Monitoring Board after 74 of the planned 92 patients were enrolled. Breast skin treated with the hyaluronic acid gel developed a significantly higher rate of {>=}Grade 2 dermatitis than did skin treated with petrolatum gel: 61.5% (40/65) vs. 47.7% (31/65) (p = 0.027). Only 1ne patient developed Grade 3 dermatitis using either gel. A higher proportion of patients had worse dermatitis in the breast segment treated with hyaluronic acid gel than in that treated with petrolatum gel at the end of radiotherapy (42% vs. 14%, p = 0.003). Conclusion: We found no benefit from the use of a topical hyaluronic acid-based gel for reducing the development of {>=}Grade 2 dermatitis after adjuvant radiotherapy for breast cancer. Additional studies are needed to determine the efficacy of hyaluronic acid-based gel in controlling radiation dermatitis symptoms after they develop.

  8. Topical hyaluronic acid vs. standard of care for the prevention of radiation dermatitis after adjuvant radiotherapy for breast cancer: single-blind randomized phase III clinical trial.

    PubMed

    Pinnix, Chelsea; Perkins, George H; Strom, Eric A; Tereffe, Welela; Woodward, Wendy; Oh, Julia L; Arriaga, Lisa; Munsell, Mark F; Kelly, Patrick; Hoffman, Karen E; Smith, Benjamin D; Buchholz, Thomas A; Yu, T Kuan

    2012-07-15

    To determine the efficacy of an emulsion containing hyaluronic acid to reduce the development of ≥ Grade 2 radiation dermatitis after adjuvant breast radiation compared with best supportive care. Women with breast cancer who had undergone lumpectomy and were to receive whole-breast radiotherapy to 50 Gy with a 10- to 16-Gy surgical bed boost were enrolled in a prospective randomized trial to compare the effectiveness of a hyaluronic acid-based gel (RadiaPlex) and a petrolatum-based gel (Aquaphor) for preventing the development of dermatitis. Each patient was randomly assigned to use hyaluronic acid gel on the medial half or the lateral half of the irradiated breast and to use the control gel on the other half. Dermatitis was graded weekly according to the Common Terminology Criteria v3.0 by the treating physician, who was blinded as to which gel was used on which area of the breast. The primary endpoint was development of ≥ Grade 2 dermatitis. The study closed early on the basis of a recommendation from the Data and Safety Monitoring Board after 74 of the planned 92 patients were enrolled. Breast skin treated with the hyaluronic acid gel developed a significantly higher rate of ≥ Grade 2 dermatitis than did skin treated with petrolatum gel: 61.5% (40/65) vs. 47.7% (31/65) (p = 0.027). Only one patient developed Grade 3 dermatitis using either gel. A higher proportion of patients had worse dermatitis in the breast segment treated with hyaluronic acid gel than in that treated with petrolatum gel at the end of radiotherapy (42% vs. 14%, p = 0.003). We found no benefit from the use of a topical hyaluronic acid-based gel for reducing the development of ≥ Grade 2 dermatitis after adjuvant radiotherapy for breast cancer. Additional studies are needed to determine the efficacy of hyaluronic acid-based gel in controlling radiation dermatitis symptoms after they develop. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Physicians’ Religious Topic Avoidance during Clinical Interactions

    PubMed Central

    Villagran, Melinda M.; MacArthur, Brenda L.; Lee, Lauren E.; Ledford, Christy J. W.; Canzona, Mollie R.

    2017-01-01

    Religious and spiritual (R/S) conversations at the end-of-life function to help patients and their families find comfort in difficult circumstances. Physicians who feel uncertain about how to discuss topics related to religious beliefs may seek to avoid R/S conversations with their patients. This study utilized a two-group objective structured clinical examination with a standardized patient to explore differences in physicians’ use of R/S topic avoidance tactics during a clinical interaction. Results indicated that physicians used more topic avoidance tactics in response to patients’ R/S inquiries than patients’ R/S disclosures; however, the use of topic avoidance tactics did not eliminate the need to engage in patient-initiated R/S interactions. PMID:28481290

  10. [CLINICAL TRIAL DESIGN].

    PubMed

    Morita, Satoshi

    2016-01-01

    Clinical trials/research are conducted to examine the clinical questions of practicing physicians. It is important to design trials appropriately in advance, taking their feasibility into account. A randomized, controlled trial is the ultimate design for treatment comparisons at the final confirmatory stage. However, randomized trials do not necessarily provide all answers to clinical questions. This article summarizes fundamental points of clinical trial design and the important role of randomization and contrasts superiority and noninferiority trials. In addition, it focuses on propensity score matching, a useful method to compare two treatment arms, especially in the context where randomization is infeasible. The propensity score-matching method is increasingly used in surgical clinical research.

  11. The efficacy of topical royal jelly on healing of diabetic foot ulcers: a double-blind placebo-controlled clinical trial.

    PubMed

    Siavash, Mansour; Shokri, Saeideh; Haghighi, Sepehr; Shahtalebi, Mohammad Ali; Farajzadehgan, Ziba

    2015-04-01

    Foot ulcers are major sources of morbidity in individuals with diabetes mellitus. As royal jelly (RJ, a worker honey bee product) contains enzymatic, antibacterial and vasodilative properties, it can potentially help in healing of diabetic foot ulcers (DFUs). This study aimed to evaluate the efficacy of topical RJ on healing of DFUs. Diabetic patients with foot ulcers who were referred to us at Khorshid Hospital, Isfahan, Iran, were managed by offloading, infection control, vascular improvement and debridement (if required). Then, all ulcers were randomly selected to receive either 5% sterile topical RJ or placebo on their total surface area. Patients were followed for 3 months or until complete healing. Twenty-five patients (6 females and 19 males) and a total of 64 ulcers were included and randomly allocated to case or control group (32 per group). Four ulcers were excluded and 60 ulcers included in the final analysis. Healing parameters including depth, length and width reduction rate, duration of complete healing and incidence of complete healing did not show any significant difference (P = 0·69, 0·95, 0·7, 0·74 and 0·6, respectively) between groups. We did not observe any side effect of topical RJ application. This study could not confirm any significant superiority of 5% topical RJ over placebo for the treatment of DFUs.

  12. Justification for conducting neurological clinical trials as part of patient care within private practice.

    PubMed

    Beran, R G; Stepanova, D; Beran, M E

    2016-05-01

    The aim of this review was to assess the benefits and drawbacks of conducting neurological clinical trials and research in private practice for the patients, clinician, Practice Manager, sponsors/Clinical Research Organisations (CROs) and Clinical Trial Coordinator (CTC) to determine if this is justified for all involved. A combination of literature reviews, original research articles and books were selected from 2005 to 2015. Provided that the practice has sufficient number of active trials to prevent financial loss, support staff, adequate facilities and equipment and time, the benefits outweigh the drawbacks. Clinical trials provide patients with more thorough monitoring, re-imbursement of trial-related expenses and the opportunity to try an innovative treatment at no charge when other options have failed. For the clinician, clinical trials provide more information to ensure better care for their patients and improved treatment methods, technical experience and global recognition. Trials collect detailed and up-to-date information on the benefits and risks of drugs, improving society's confidence in clinical research and pharmaceuticals, allow trial sponsors to explore new scientific questions and accelerate innovation. For the CTC, industry-sponsored clinical trials allow potential entry for a career in clinical research giving CTCs the opportunity to become Clinical Research Associates (CRAs), Study Start-Up Managers or Drug Safety Associates. © 2016 John Wiley & Sons Ltd.

  13. Clinical trial structures

    PubMed Central

    Evans, Scott R.

    2011-01-01

    Most errors in clinical trials are a result of poor planning. Fancy statistical methods cannot rescue design flaws. Thus careful planning with clear foresight is crucial. The selection of a clinical trial design structure requires logic and creativity. Common structural designs are discussed. PMID:21423788

  14. [Acupuncture clinical trials published in high impact factor journals].

    PubMed

    Hu, Min; Liu, Jian-Ping; Wu, Xiao-Ke

    2014-12-01

    Acupuncture clinical trials are designed to provide reliable evidence of clinical efficacy, and SCI papers is one of the high-quality clinical efficacy of acupuncture research. To analyze these papers published in high impact factor journals on acupuncture clinical trials, we can study clinical trials from design to implementation, the efficacy of prevention and cure, combined with international standard practices to evaluate the effectiveness and safety of acupuncture. That is the core of acupuncture clinical trials, as well as a prerequisite for outstanding academic output. A scientific and complete acupuncture clinical trial should be topically novel, designed innovative, logically clear, linguistically refining, and the most important point lies in a great discovery and solving the pragmatic problem. All of these are critical points of papers to be published in high impact factor journal, and directly affect international evaluation and promotion of acupuncture.

  15. Randomized, split-body, single-blinded clinical trial of topical broccoli sprout extract: Assessing the feasibility of its use in keratin-based disorders.

    PubMed

    Kerns, Michelle L; Guss, Lark; Fahey, Jed; Cohen, Bernard; Hakim, Jill M C; Sung, Sarah; Lu, Rosemary G; Coulombe, Pierre A

    2017-03-01

    Epidermolysis bullosa simplex is a skin-blistering disorder caused by mutations in keratin (K)14 or K5. Treatment with nuclear factor (erythroid-derived 2)-like 2 inducer sulforaphane ameliorated skin blistering in Krt14-null mice, correlating with induction of K17. To be therapeutically useful for epidermolysis bullosa simplex, topical broccoli sprout extract (BSE), enriched for sulforaphane, would ideally induce the expression of homologous keratins (eg, K6, K17, K16) in the basal layer of human epidermis without impacting expression of defective keratins (K5/K14). The purpose of this 1-week, randomized, split-body, single-blinded, placebo-controlled trial was to assess the impact of BSE on keratin expression. Five subjects (34-71 years old) applied BSE (500 nmol of sulforaphane/mL) or vehicle alone to the inner aspect of the arm daily. Expression of keratin, nuclear factor (erythroid-derived 2)-like 2, and other markers was assessed using reverse transcription-polymerase chain reaction and indirect immunofluorescence. One subject (age 71 years) was excluded a posteriori because of poor tissue quality. Topical BSE activated nuclear factor (erythroid-derived 2)-like 2 and up-regulated K17 in the epidermis of all subjects, had variable effects on K16 and K6 expression, and did not alter expression of K14 or K5. Small sample size is a limitation. BSE represents an attractive therapeutic candidate for K14-associated epidermolysis bullosa simplex. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  16. Randomized, placebo-controlled, double-blind clinical trial to evaluate the efficacy of polyhexanide for topical decolonization of MRSA carriers.

    PubMed

    Landelle, C; von Dach, E; Haustein, T; Agostinho, A; Renzi, G; Renzoni, A; Pittet, D; Schrenzel, J; François, P; Harbarth, S

    2016-02-01

    The objective of this study was to evaluate the efficacy of polyhexanide (Prontoderm(®)) in eliminating MRSA carriage. In a 1900 bed teaching hospital, MRSA-colonized patients were randomized into a double-blind, placebo-controlled superiority trial between January 2011 and July 2014. Patients were treated with either polyhexanide or placebo applied to the anterior nares (thrice daily) and skin (once daily) for 10 days. The primary outcome was MRSA decolonization at day 28 (D28) after the end of treatment assessed by ITT responder and PP analyses (microbiological follow-up ± 7 days and topical treatment ≥ 5 days). Secondary outcomes included safety, emergence of resistance and MRSA genotype changes. Registered trial number ISRCTN02288276. Of 2590 patients screened, 146 (polyhexanide group, 71; placebo group, 75) were included. ITT analysis showed that 24/71 (33.8%) patients in the polyhexanide group versus 22/75 (29.3%) in the placebo group were MRSA-free at D28 (risk difference, 4.5%; 95% CI, -10.6% to 19.5%; P = 0.56). PP analysis confirmed the results with 19/53 (35.8%) decolonized polyhexanide-treated patients versus 17/56 (30.4%) in the placebo arm (risk difference, 5.5%; 95% CI, -12.2% to 23%; P = 0.54). Nine serious adverse events occurred in the polyhexanide group versus 12 in the placebo group; none was attributable to study medication. Emergence of polyhexanide resistance or cross-resistance between polyhexanide and chlorhexidine was not observed. No case of exogenous recolonization by a genotypically different MRSA strain was documented. This study suggests that under real-life conditions, a single polyhexanide decolonization course is not effective in eradicating MRSA carriage. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  17. Suspected acute exacerbation of idiopathic pulmonary fibrosis as an outcome measure in clinical trials

    PubMed Central

    2013-01-01

    Background Acute exacerbation of idiopathic pulmonary fibrosis has become an important outcome measure in clinical trials. This study aimed to explore the concept of suspected acute exacerbation as an outcome measure. Methods Three investigators retrospectively reviewed subjects enrolled in the Sildenafil Trial of Exercise Performance in IPF who experienced a respiratory serious adverse event during the course of the study. Events were classified as definite acute exacerbation, suspected acute exacerbation, or other, according to established criteria. Results Thirty-five events were identified. Four were classified as definite acute exacerbation, fourteen as suspected acute exacerbation, and seventeen as other. Definite and suspected acute exacerbations were clinically indistinguishable. Both were most common in the winter and spring months and were associated with a high risk of disease progression and short-term mortality. Conclusions In this study one half of respiratory serious adverse events were attributed to definite or suspected acute exacerbations. Suspected acute exacerbations are clinically indistinguishable from definite acute exacerbations and represent clinically meaningful events. Clinical trialists should consider capturing both definite and suspected acute exacerbations as outcome measures. PMID:23848435

  18. Efficacy and Tolerability of a Combined Moxifloxacin/Dexamethasone Formulation for Topical Prophylaxis in Phacoemulsification: An Open-Label Single-Arm Clinical Trial

    PubMed Central

    Espiritu, Cesar Ramon G.; Sy, Mary Ellen A.; Tayengco, Tommee Lynne G.

    2011-01-01

    Background. The use of a fixed-combination antibiotic corticosteroid for infection prophylaxis in Asian patients undergoing phacoemulsification has not been reported. Methods. A 15-day, open-label, single-arm trial of 64 patients for phacoemulsification with intraocular lens (IOL) implantation is described. Patients applied moxifloxacin 0.5%/dexamethasone 0.1% (Vigadexa) eye drops four times daily before and until 15 days after surgery. Anterior chamber (AC) reaction, visual acuity, ocular pain and signs, and intraocular pressure (IOP) were assessed at baseline and on postoperative days 1, 3, 8, and 15. Results. At day 15, 55 (91.7%) patients scored 0 (<5 cells) in AC reaction. No surgery-related infection occurred. Mean best-corrected visual acuity improved 0.5 logMAR from baseline to 0.0 logMAR (P < .0001). Mean IOP remained at 12-13 mm Hg over the 15-day treatment. Only 2 patients (3.1%) reported minimum ocular pain. Two (3.1%) patients were shifted to prednisolone acetate for severe inflammation. At the end of the study period, 8.3% were given fluorometholone for 1 week for AC reaction grade >0. No drug-related adverse event was reported. Conclusion. Following phacoemulsification and IOL implantation, the topical combination moxifloxacin 0.5%/dexamethasone 0.1% was effective in preventing infection and controlling inflammation and was well tolerated. PMID:21772987

  19. Editorial--Avoiding Unethical Helicobacter pylori Clinical Trials: Susceptibility-Based Studies and Probiotics as Adjuvants.

    PubMed

    Graham, David Y

    2015-10-01

    As a general rule, any clinical study where the result is already known or when the investigator(s) compares an assigned treatment against another assigned treatment known to be ineffective in the study population (e.g., in a population with known clarithromycin resistance) is unethical. As susceptibility-based therapy will always be superior to empiric therapy in any population with a prevalence of antimicrobial resistance >0%, any trial that randomizes susceptibility-based therapy with empiric therapy would be unethical. The journal Helicobacter welcomes susceptibility or culture-guided studies, studies of new therapies, and studies of adjuvants and probiotics. However, the journal will not accept for review any study we judge to be lacking clinical equipoise or which assign subjects to a treatment known to be ineffective, such as a susceptibility-based clinical trial with an empiric therapy comparator. To assist authors, we provide examples and suggestions regarding trial design for comparative studies, for susceptibility-based studies, and for studies testing adjuvants or probiotics.

  20. Topical therapy for osteoarthritis: clinical and pharmacologic perspectives.

    PubMed

    Altman, Roy; Barkin, Robert L

    2009-03-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) have shown efficacy in patients with osteoarthritis (OA) pain but are also associated with a dose-dependent risk of gastrointestinal, cardiovascular, hematologic, hepatic, and renal adverse events (AEs). Topical NSAIDs were developed to provide analgesia similar to their oral counterparts with less systemic exposure and fewer serious AEs. Topical NSAIDs have long been available in Europe for the management of OA, and guidelines of the European League Against Rheumatism and the Osteoarthritis Research Society International specify that topical NSAIDs are preferred over oral NSAIDs for patients with knee or hand OA of mild-to-moderate severity, few affected joints, and/or a history of sensitivity to oral NSAIDs. In contrast, the guidelines of the American Pain Society and American College of Rheumatology have in the past recommended topical methyl salicylate and topical capsaicin, but not topical NSAIDs. This reflects the fact that the American guidelines were written several years before the first topical NSAID was approved for use in the United States. Neither salicylates nor capsaicin have shown significant efficacy in the treatment of OA. In October 2007, diclofenac sodium 1% gel (Voltaren Gel) became the first topical NSAID for OA therapy approved in the United States following a long history of use internationally. Topical diclofenac sodium 1% gel delivers effective diclofenac concentrations in the affected joint with limited systemic exposure. Clinical trial data suggest that diclofenac sodium 1% gel provides clinically meaningful analgesia in OA patients with a low incidence of systemic AEs. This review discusses the pharmacology, clinical efficacy, and safety profiles of diclofenac sodium 1% gel, salicylates, and capsaicin for the management of hand and knee OA.

  1. Silicones as nonocclusive topical agents.

    PubMed

    De Paepe, K; Sieg, A; Le Meur, M; Rogiers, V

    2014-01-01

    Silicone excipients are commonly used ingredients because of their emollient and skin-conditioning effects, and their ability to form uniform, water-resistant, yet permeable films. Based on comparisons with organic materials and conflicting knowledge from silicones used in scar treatment, the misconception still exists that silicone topical excipients are occlusive substances that may block the passive loss of water through the upper skin layers. Therefore, 3 types of common silicone excipients and 3 water-in-(oil-plus-silicone) or W/(O + Si) creams, containing 10% (w/w) of the respective silicones, were investigated as a function of time and compared to petrolatum. Transepidermal water loss (TEWL) and skin hydration measurements were carried out after a single topical application on forearm skin of 26 healthy young female volunteers. Both petrolatum and silicones significantly decreased TEWL 15 min after application, but the measurements for the silicones were not significantly different from the untreated control values. The tested silicones did not moisturize the skin. Petrolatum formed an occlusive layer, creating an increase in skin hydration for more than 4 h. The results measured for the W/(O + Si) creams indicated that they moisturized the skin, without any effect on TEWL. A clear difference was shown between the skin occlusive properties of petrolatum and the water vapor permeability of the common silicone excipient materials. © 2014 S. Karger AG, Basel.

  2. Patient education level as a predictor of survival in lung cancer clinical trials.

    PubMed

    Herndon, James E; Kornblith, Alice B; Holland, Jimmie C; Paskett, Electra D

    2008-09-01

    To investigate the effect of socioeconomic status, as measured by education, on the survival of 1,577 lung cancer patients treated on 11 studies conducted by the Cancer and Leukemia Group B. Sociodemographic data, including education, was reported by the patient at the time of clinical trial accrual. Cox proportional hazards model stratified by treatment arm/study was used to examine the effect of education on survival after adjustment for known prognostic factors. The patient population included 1,177 patients diagnosed with non-small-cell lung cancer (NSCLC; stage III or IV) and 400 patients diagnosed with small-cell lung cancer (SCLC; extensive or limited). Patients with less than an eighth grade education (13% of patients) were significantly more likely to be male, nonwhite, and older; have a performance status (PS) of 1 or 2; and have chest pain. Significant predictors of poor survival in the final model included male sex, PS of 1 or 2, dyspnea, weight loss, liver or bone metastases, unmarried, presence of adrenal metastases and high alkaline phosphatase levels among patients with NSCLC, and high WBC levels among patients with advanced disease. Education was not predictive of survival. The physical condition of patients with low education who enroll onto clinical trials is worse than patients with higher education. Once enrolled onto a clinical trial, education does not affect the survival of patients with SCLC or stage III or IV NSCLC. The standardization of treatment and follow-up within a clinical trial, regardless of education, is one possible explanation for this lack of effect.

  3. Do current clinical trials meet society's needs?: a critical review of recent evidence.

    PubMed

    Pocock, Stuart J; Gersh, Bernard J

    2014-10-14

    This paper describes some important controversies regarding the current state of clinical trials research in cardiology. Topics covered include the inadequacy of trial research on medical devices, problems with industry-sponsored trials, the lack of head-to-head trials of new effective treatments, the need for wiser handling of drug safety issues, the credibility (or lack thereof) of trial reports in medical journals, problems with globalization of trials, the role of personalized (stratified) medicine in trials, the need for new trials of old drugs, the need for trials of treatment withdrawal, the importance of pragmatic trials of treatment strategies, and the limitations of observational comparative effectiveness studies. All issues are illustrated by recent topical trials in cardiology. Overall, we explore the extent to which clinical trials, as currently practiced, are successful in meeting society's expectations.

  4. Topical tea tree oil effective in canine localised pruritic dermatitis--a multi-centre randomised double-blind controlled clinical trial in the veterinary practice.

    PubMed

    Reichling, J; Fitzi, J; Hellmann, K; Wegener, T; Bucher, S; Saller, R

    2004-10-01

    Tea tree oil, a volatile oil, is well known for its broad antibacterial and antifungal activity. A standardised and stabilised 10% tea tree oil cream was tested against a commercial skin care cream (control cream) in the management of canine localised acute and chronic dermatitis. Fifty-seven dogs with clinical manifestations of mostly pruritic skin lesions or alterations, skin fold pyodermas and other forms of dermatitis, corroborated by predominantly positive fungal and bacterial skin isolates, were enrolled by seven practising veterinarians and randomly allocated to two study groups (28:29) and were treated twice daily with a blinded topical preparation. After 10 days of treatment, success rates of 71% for the tea tree oil cream and 41% for the control cream (over-all efficacy documented by the veterinary investigator) differed significantly (p = 0.04), favouring tea tree oil cream treatment. Accordingly on day 10, the tea tree oil cream caused significantly faster relief than the control cream (p = 0.04) for two common clinical dermatitis signs, pruritus (occurring in 84 % of dogs) and alopecia. Only one adverse event was reported in the tea tree oil group (suspected not to be causally related to the study drug) and none in the control cream group. The tested herbal cream appears to be a fast-acting safe alternative to conventional therapy for symptomatic treatment of canine localised dermatitis with pruritus.

  5. Effect of minoxidil topical foam on frontotemporal and vertex androgenetic alopecia in men: a 104-week open-label clinical trial.

    PubMed

    Kanti, V; Hillmann, K; Kottner, J; Stroux, A; Canfield, D; Blume-Peytavi, U

    2016-07-01

    Topical minoxidil formulations have been shown to be effective in treating androgenetic alopecia (AGA) for 12 months. Efficacy and safety in both frontotemporal and vertex regions over longer application periods have not been studied so far. To evaluate the effect of 5% minoxidil topical foam (5% MTF) in the frontotemporal and vertex areas in patients with moderate AGA over 104 weeks. An 80-week, open-label extension phase was performed, following a 24-week randomized, double-blind, placebo-controlled study in men with AGA grade IIIvertex to VI. Group 1 (n = 22) received ongoing 5% MTF for 104 weeks, Group 2 (n = 23) received placebo topical foam (plaTF) until week 24, followed by 5% MTF until week 104 during the extension phase. Frontotemporal and vertex target area non-vellus hair counts (f-TAHC, v-TAHC) and cumulative hair width (f-TAHW, v-TAHW) were assessed at baseline and at weeks 24, 52, 76 and 104. In Group 1, f-TAHW and f-TAHC showed a statistically significant increase from baseline to week 52 and week 76, respectively, returning to values comparable to baseline at week 104. No significant differences were found between baseline and week 104 in v-TAHC in Group 1 as well as f-TAHC, v-TAHC, f-TAHW and v-TAHW values in Group 2. 5% MTF is effective in stabilizing hair density, hair width and scalp coverage in both frontotemporal and vertex areas over an application period of 104 weeks, while showing a good safety and tolerability profile with a low rate of irritant contact dermatitis. © 2015 European Academy of Dermatology and Venereology.

  6. Topical insulin-like growth factor 1 treatment using gelatin hydrogels for glucocorticoid-resistant sudden sensorineural hearing loss: a prospective clinical trial.

    PubMed

    Nakagawa, Takayuki; Sakamoto, Tatsunori; Hiraumi, Harukazu; Kikkawa, Yayoi S; Yamamoto, Norio; Hamaguchi, Kiyomi; Ono, Kazuya; Yamamoto, Masaya; Tabata, Yasuhiko; Teramukai, Satoshi; Tanaka, Shiro; Tada, Harue; Onodera, Rie; Yonezawa, Atsushi; Inui, Ken-ichi; Ito, Juichi

    2010-11-25

    Sudden sensorineural hearing loss (SSHL) is a common condition in which patients lose the hearing in one ear within 3 days. Systemic glucocorticoid treatments have been used as standard therapy for SSHL; however, about 20% of patients do not respond. We tested the safety and efficacy of topical insulin-like growth factor 1 (IGF1) application using gelatin hydrogels as a treatment for SSHL. Patients with SSHL that showed no recovery to systemic glucocorticoid administration were recruited. We applied gelatin hydrogels, impregnated with recombinant human IGF1, into the middle ear. The primary outcome measure was the proportion of patients showing hearing improvement 12 weeks after the test treatment. The secondary outcome measures were the proportion of patients showing improvement at 24 weeks and the incidence of adverse events. The null hypothesis was that 33% of patients would show hearing improvement, as was reported for a historical control after hyperbaric oxygen therapy. In total, 25 patients received the test treatment at a median of 23 days (range 15-32) after the onset of SSHL, between 2007 and 2009. At 12 weeks after the test treatment, 48% (95% CI 28% to 69%; P = 0.086) of patients showed hearing improvement, and the proportion increased to 56% (95% CI 35% to 76%; P = 0.015) at 24 weeks. No serious adverse events were observed. Topical IGF1 application using gelatin hydrogels is well tolerated and may be efficacious for hearing recovery in patients with SSHL that is resistant to systemic glucocorticoids.

  7. Assessing the readability of ClinicalTrials.gov

    PubMed Central

    Wu, Danny TY; Hanauer, David A; Mei, Qiaozhu; Clark, Patricia M; An, Lawrence C; Proulx, Joshua; Zeng, Qing T; Vydiswaran, VG Vinod; Collins-Thompson, Kevyn

    2016-01-01

    Objective ClinicalTrials.gov serves critical functions of disseminating trial information to the public and helping the trials recruit participants. This study assessed the readability of trial descriptions at ClinicalTrials.gov using multiple quantitative measures. Materials and Methods The analysis included all 165 988 trials registered at ClinicalTrials.gov as of April 30, 2014. To obtain benchmarks, the authors also analyzed 2 other medical corpora: (1) all 955 Health Topics articles from MedlinePlus and (2) a random sample of 100 000 clinician notes retrieved from an electronic health records system intended for conveying internal communication among medical professionals. The authors characterized each of the corpora using 4 surface metrics, and then applied 5 different scoring algorithms to assess their readability. The authors hypothesized that clinician notes would be most difficult to read, followed by trial descriptions and MedlinePlus Health Topics articles. Results Trial descriptions have the longest average sentence length (26.1 words) across all corpora; 65% of their words used are not covered by a basic medical English dictionary. In comparison, average sentence length of MedlinePlus Health Topics articles is 61% shorter, vocabulary size is 95% smaller, and dictionary coverage is 46% higher. All 5 scoring algorithms consistently rated CliniclTrials.gov trial descriptions the most difficult corpus to read, even harder than clinician notes. On average, it requires 18 years of education to properly understand these trial descriptions according to the results generated by the readability assessment algorithms. Discussion and Conclusion Trial descriptions at CliniclTrials.gov are extremely difficult to read. Significant work is warranted to improve their readability in order to achieve CliniclTrials.gov’s goal of facilitating information dissemination and subject recruitment. PMID:26269536

  8. Assessing the readability of ClinicalTrials.gov.

    PubMed

    Wu, Danny T Y; Hanauer, David A; Mei, Qiaozhu; Clark, Patricia M; An, Lawrence C; Proulx, Joshua; Zeng, Qing T; Vydiswaran, V G Vinod; Collins-Thompson, Kevyn; Zheng, Kai

    2016-03-01

    ClinicalTrials.gov serves critical functions of disseminating trial information to the public and helping the trials recruit participants. This study assessed the readability of trial descriptions at ClinicalTrials.gov using multiple quantitative measures. The analysis included all 165,988 trials registered at ClinicalTrials.gov as of April 30, 2014. To obtain benchmarks, the authors also analyzed 2 other medical corpora: (1) all 955 Health Topics articles from MedlinePlus and (2) a random sample of 100,000 clinician notes retrieved from an electronic health records system intended for conveying internal communication among medical professionals. The authors characterized each of the corpora using 4 surface metrics, and then applied 5 different scoring algorithms to assess their readability. The authors hypothesized that clinician notes would be most difficult to read, followed by trial descriptions and MedlinePlus Health Topics articles. Trial descriptions have the longest average sentence length (26.1 words) across all corpora; 65% of their words used are not covered by a basic medical English dictionary. In comparison, average sentence length of MedlinePlus Health Topics articles is 61% shorter, vocabulary size is 95% smaller, and dictionary coverage is 46% higher. All 5 scoring algorithms consistently rated CliniclTrials.gov trial descriptions the most difficult corpus to read, even harder than clinician notes. On average, it requires 18 years of education to properly understand these trial descriptions according to the results generated by the readability assessment algorithms. Trial descriptions at CliniclTrials.gov are extremely difficult to read. Significant work is warranted to improve their readability in order to achieve CliniclTrials.gov's goal of facilitating information dissemination and subject recruitment. Published by Oxford University Press on behalf of the American Medical Informatics Association 2015. This work is written by US Government

  9. Evidence and Clinical Trials.

    NASA Astrophysics Data System (ADS)

    Goodman, Steven N.

    1989-11-01

    This dissertation explores the use of a mathematical measure of statistical evidence, the log likelihood ratio, in clinical trials. The methods and thinking behind the use of an evidential measure are contrasted with traditional methods of analyzing data, which depend primarily on a p-value as an estimate of the statistical strength of an observed data pattern. It is contended that neither the behavioral dictates of Neyman-Pearson hypothesis testing methods, nor the coherency dictates of Bayesian methods are realistic models on which to base inference. The use of the likelihood alone is applied to four aspects of trial design or conduct: the calculation of sample size, the monitoring of data, testing for the equivalence of two treatments, and meta-analysis--the combining of results from different trials. Finally, a more general model of statistical inference, using belief functions, is used to see if it is possible to separate the assessment of evidence from our background knowledge. It is shown that traditional and Bayesian methods can be modeled as two ends of a continuum of structured background knowledge, methods which summarize evidence at the point of maximum likelihood assuming no structure, and Bayesian methods assuming complete knowledge. Both schools are seen to be missing a concept of ignorance- -uncommitted belief. This concept provides the key to understanding the problem of sampling to a foregone conclusion and the role of frequency properties in statistical inference. The conclusion is that statistical evidence cannot be defined independently of background knowledge, and that frequency properties of an estimator are an indirect measure of uncommitted belief. Several likelihood summaries need to be used in clinical trials, with the quantitative disparity between summaries being an indirect measure of our ignorance. This conclusion is linked with parallel ideas in the philosophy of science and cognitive psychology.

  10. Seeking harmony: estimands and sensitivity analyses for confirmatory clinical trials.

    PubMed

    Mehrotra, Devan V; Hemmings, Robert J; Russek-Cohen, Estelle

    2016-08-01

    In October 2014, the Steering Committee of the International Conference on Harmonization endorsed the formation of an expert working group to develop an addendum to the International Conference on Harmonization E9 guideline ("Statistical Principles for Clinical Trials"). The addendum will focus on two topics involving randomized confirmatory clinical trials: estimands and sensitivity analyses. Both topics are motivated, in part, by the need to improve the precision with which scientific questions of interest are formulated and addressed by clinical trialists and regulators, specifically in the context of post-randomization events such as use of rescue medication or missing data resulting from dropouts. Given the importance of these topics for the statistical and medical community, we articulate the reasons for the planned addendum. The resulting "ICH E9/R1" guideline will include a framework for improved trial planning, conduct, analysis, and interpretation; a draft is expected to be ready for public comment in the second half of 2016.

  11. Hepatitis C: Clinical Trials

    MedlinePlus

    ... Financial Report (AFR) Budget Submission Recovery Act Resources Business Congressional Affairs Jobs Benefits Booklet Data & Statistics National ... Participation in any clinical trial is voluntary and choosing not to participate will not affect your VA ...

  12. Honey as a topical treatment for wounds.

    PubMed

    Jull, Andrew B; Cullum, Nicky; Dumville, Jo C; Westby, Maggie J; Deshpande, Sohan; Walker, Natalie

    2015-03-06

    Honey is a viscous, supersaturated sugar solution derived from nectar gathered and modified by the honeybee, Apis mellifera. Honey has been used since ancient times as a remedy in wound care. Evidence from animal studies and some trials has suggested that honey may accelerate wound healing. The objective of this review was to assess the effects of honey compared with alternative wound dressings and topical treatments on the of healing of acute (e.g. burns, lacerations) and/or chronic (e.g. venous ulcers) wounds. For this update of the review we searched the Cochrane Wounds Group Specialised Register (searched 15 October 2014); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 9); Ovid MEDLINE (1946 to October Week 1 2014); Ovid MEDLINE (In-Process & Other Non-Indexed Citations 13 October 2014); Ovid EMBASE (1974 to 13 October 2014); and EBSCO CINAHL (1982 to 15 October 2014). Randomised and quasi-randomised trials that evaluated honey as a treatment for any sort of acute or chronic wound were sought. There was no restriction in terms of source, date of publication or language. Wound healing was the primary endpoint. Data from eligible trials were extracted and summarised by one review author, using a data extraction sheet, and independently verified by a second review author. All data have been subsequently checked by two more authors. We identified 26 eligible trials (total of 3011 participants). Three trials evaluated the effects of honey in minor acute wounds, 11 trials evaluated honey in burns, 10 trials recruited people with different chronic wounds including two in people with venous leg ulcers, two trials in people with diabetic foot ulcers and single trials in infected post-operative wounds, pressure injuries, cutaneous Leishmaniasis and Fournier's gangrene. Two trials recruited a mixed population of people with acute and chronic wounds. The quality of the evidence varied between different comparisons and

  13. Gateways to clinical trials.

    PubMed

    Moral, M A; Tomillero, A

    2008-03-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 131-I-Chlorotoxin, 423557; Abatacept, Ad.Egr.TNF.11D, Adalimumab, AE-941, Ambrisentan, AMR-001, Anacetrapib, Anakinra, Aripiprazole, Atazanavir sulfate; BAY-639044, Bazedoxifene acetate, Belimumab, Bevacizumab, Bortezomib, Botulinum toxin type B, Brivaracetam, Bucindolol hydrochloride; Carfilzomib, Carisbamate, CCX-282, CD20Bi, Ceftobiprole, Certolizumab pegol, CF-101, Cinacalcet hydrochloride, Cypher; Darifenacin hydrobromide, Degarelix acetate, Denosumab, Desvenlafaxine succinate, Dexlansoprazole, Dexverapamil, Drotrecogin alfa (activated), Duloxetine hydrochloride, Dutasteride; Efalizumab, EPs-7630, Escitalopram oxalate, Etoricoxib; Fluticasone furoate, Fondaparinux sodium, Fospropofol disodium; Hexadecyloxypropyl-cidofovir, HIV gp120/NefTat/AS02A, HPV-6/11/16/18; INCB-18424, Incyclinide, Inhalable human insulin, Insulin detemir; KNS-760704, KW-0761; Lacosamide, Lenalidomide, Levetiracetam, Licofelone, Lidocaine/prilocaine; mAb 216, MEDI-528, Men ACWY, Meningococcal C-CRM197 vaccine, Methylnaltrexone bromide; Nemifitide ditriflutate, Nicotine conjugate vaccine, Nilotinib hydrochloride monohydrate; Octaparin; Parathyroid hormone (human recombinant), Pegaptanib octasodium, Pitrakinra, Prasterone, Pregabalin; Ranelic acid distrontium salt, Rasagiline mesilate, Retigabine, Rimonabant, RTS,S/AS02D; Sarcosine, Sitaxentan sodium, Solifenacin succinate, Sunitinib malate; Taranabant, Taxus, Teduglutide, Teriparatide, Ticagrelor, Travoprost, TRU-015; USlipristal acetate, Urocortin 2; Vardenafil hydrochloride hydrate; YM-155, Yttrium 90 (90Y) ibritumomab tiuxetan; Zanolimumab, Zoledronic acid monohydrate, Zotarolimus

  14. Investigation of the clinical efficacy of 0.2% topical stannous fluoride for the treatment of canine superficial pyoderma: a prospective, randomized, double-blinded, placebo-controlled trial.

    PubMed

    Seltzer, Judith D; Flynn-Lurie, Alison K; Marsella, Rosanna; Brennan, Meghan M

    2010-06-01

    Stannous fluoride (SF) is an antibacterial compound that has been successfully used to treat gingivitis in people and dogs, and cutaneous bacterial infections in horses. The purpose of this prospective, double-blinded, placebo-controlled clinical trial was to investigate the efficacy of 0.2% SF spray (BacDerm; Emerald 3 Enterprises Inc., Camdenton, MO, USA) for the treatment of canine superficial pyoderma. Twenty-six privately owned dogs with bacterial skin infections diagnosed on clinical signs, cytology and aerobic culture were enrolled. Dogs were randomly assigned to vehicle only or active ingredient treatment groups. The product was applied topically to affected areas once daily for 28 days, with assessments at days 0, 14, 28 and 42. Clinical and cytological evaluations were performed by the same investigators at each visit. Owners scored the improvement of hair coat, odour, pruritus and overall improvement at each recheck. Linear mixed models showed significant effects of treatment (P < 0.0001) and time (P = 0.0037) for investigator's scores, and a significant time effect for owners' haircoat (P = 0.0077) and odour (P = 0.0170) improvement scores. Dogs in both placebo and SF groups showed some improvement over time, and the investigator's scores on days 0 and 28 were not significantly different between groups for both (t-test P > 0.05). Spearman's rho correlation coefficients revealed a significant negative correlation between investigator's scores and all categories of owners' assessment scores in dogs of both groups. Although some dogs improved on SF, this study does not support the use of 0.2% SF as sole therapy for canine superficial pyoderma.

  15. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2007-12-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Intergrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 249553, 2-Methoxyestradiol; Abatacept, Adalimumab, Adefovir dipivoxil, Agalsidase beta, Albinterferon alfa-2b, Aliskiren fumarate, Alovudine, Amdoxovir, Amlodipine besylate/atorvastatin calcium, Amrubicin hydrochloride, Anakinra, AQ-13, Aripiprazole, AS-1404, Asoprisnil, Atacicept, Atrasentan; Belimumab, Bevacizumab, Bortezomib, Bosentan, Botulinum toxin type B, Brivaracetam; Catumaxomab, Cediranib, Cetuximab, cG250, Ciclesonide, Cinacalcet hydrochloride, Curcumin, Cypher; Darbepoetin alfa, Denosumab, Dihydrexidine; Eicosapentaenoic acid/docosahexaenoic acid, Entecavir, Erlotinib hydrochloride, Escitalopram oxalate, Etoricoxib, Everolimus, Ezetimibe; Febuxostat, Fenspiride hydrochloride, Fondaparinux sodium; Gefitinib, Ghrelin (human), GSK-1562902A; HSV-tk/GCV; Iclaprim, Imatinib mesylate, Imexon, Indacaterol, Insulinotropin, ISIS-112989; L-Alanosine, Lapatinib ditosylate, Laropiprant; Methoxy polyethylene glycol-epoetin-beta, Mipomersen sodium, Motexafin gadolinium; Natalizumab, Nimotuzumab; OSC, Ozarelix; PACAP-38, Paclitaxel nanoparticles, Parathyroid Hormone-Related Protein-(1-36), Pasireotide, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Pertuzumab, Picoplatin, Pimecrolimus, Pitavastatin calcium, Plitidepsin; Ranelic acid distrontium salt, Ranolazine, Recombinant human relaxin H2, Regadenoson, RFB4(dsFv)-PE38, RO-3300074, Rosuvastatin calcium; SIR-Spheres, Solifenacin succinate, Sorafenib, Sunitinib malate; Tadalafil, Talabostat, Taribavirin hydrochloride, Taxus, Temsirolimus, Teriparatide, Tiotropium bromide, Tipifarnib, Tirapazamine, Tocilizumab; UCN-01, Ularitide

  16. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X

    2008-01-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prouse Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 101M, 3F8; Abatacept, ABT-263, Adalimumab, AG-7352, Agatolimod sodium, Alfimeprase, Aliskiren fumarate, Alvimopan hydrate, Aminolevulinic acid hexyl ester, Ammonium tetrathiomolybdate, Anakinra, Aripiprazole, AS-1404, AT-9283, Atomoxetine hydrochloride, AVE-1642, AVE-9633, Axitinib, AZD-0530; Becocalcidiol, Belotecan hydrochloride, Bevacizumab, BG-9928, BIBF-1120, BMS-275183, Bortezomib, Bosentan; Catumaxomab, Cetuximab, CHR-2797, Ciclesonide, Clevidipine, Cypher, Cytarabine/daunorubicin; Darifenacin hydrobromide, Darunavir, Denosumab, Desvenlafaxine succinate, Disufenton sodium, Duloxetine hydrochloride, Dutasteride; Eculizumab, Efalizumab, Eicosapentaenoic acid/docosahexaenoic acid, Eplerenone, Epratuzumab, Erlotinib hydrochloride, Escitalopram oxalate, Ethynylcytidine, Etravirine, Everolimus, Ezetimibe; Fulvestrant; Garenoxacin mesilate, Gefitinib, Gestodene; HI-164, Hydralazine hydrochloride/isosorbide dinitrate; Icatibant acetate, ICX-RHY, Idraparinux sodium, Indacaterol, Ispronicline, Ivabradine hydrochloride, Ixabepilone; KB-2115, KW-2449; L-791515, Lapatinib ditosylate, LGD-4665, Licofelone, Liposomal doxorubicin, Lisdexamfetamine mesilate, Lumiracoxib; Methoxy polyethylene glycol-epoetin-beta, Miglustat, Mipomersen sodium, Mitumprotimut-T, MK-0822A, MK-0974; Nelarabine; Obatoclax mesylate, Olmesartan medoxomil, Olmesartan medoxomil/hydrochlorothiazide; Paliperidone, Palonosetron hydrochloride, Panitumumab, Pegfilgrastim, Peginterferon alfa-2a, Pemetrexed disodium, Perospirone hydrochloride, Pertuzumab, Pimecrolimus, Pitrakinra, Pixantrone maleate, Posaconazole, Pregabalin; Quercetin; RALGA, Raltegravir

  17. Social media in clinical trials.

    PubMed

    Thompson, Michael A

    2014-01-01

    Social media has potential in clinical trials for pointing out trial issues, addressing barriers, educating, and engaging multiple groups involved in cancer clinical research. Social media is being used in clinical trials to highlight issues such as poor accrual and barriers; educate potential participants and physicians about clinical trial options; and is a potential indirect or direct method to improve accrual. We are moving from a passive "push" of information to patients to a "pull" of patients requesting information. Patients and advocates are often driving an otherwise reluctant health care system into communication. Online patient communities are creating new information repositories. Potential clinical trial participants are using the Twittersphere and other sources to learn about potential clinical trial options. We are seeing more organized patient-centric and patient-engaged forums with the potential to crowd source to improve clinical trial accrual and design. This is an evolving process that will meet many individual, institutional, and regulatory obstacles as we move forward in a changed research landscape.

  18. A Study of Practical Parameters and Their Relative Importance as Perceived by Various Stakeholders in Clinical Trials

    PubMed Central

    Pant, R; Joshi, Y

    2011-01-01

    A contract research organization (CRO) is a company which conducts a Good Clinical Practice (GCP) in clinical trial. There are literally hundreds of CROs worldwide employing a workforce of nearly 100,000 professionals. The project proposes the study of practical parameters and their relative importance as perceived by the various stakeholders in clinical trials. The survey was conducted in Bangalore and New Delhi. Primary market data was obtained by primary market research which included 80 clinical trial stakeholders by having a preliminary communication with them, followed by administering a questionnaire along with prior permission. There were 15 Sponsors/ CROs, 27 Investigators /Monitors and 38 Ethics committee members involved in the study. It was shown from the study that a clinical investigator involved in a clinical trial is responsible for ensuring that an investigation is conducted according to the signed investigator statement, the investigational plan, and applicable regulations; for protecting the rights, safety, and welfare of the subjects under the investigator’s care; and for the control of drugs under investigation. It was also shown from the study that the sponsors of a clinical trial carry the ultimate responsibility for the initiation, management and financing of the clinical trial. The study has identified a specific training need at the level of the individual stakeholder to perform a particular job function and to identify the actual practical parameters in the Indian context important for the conduction of clinical trials (GCP) with respect to the different stakeholders, to determine the relative importance of these parameters as perceived by various stakeholders involved in clinical trials, and to identify the relative contributions of different stakeholders to the success/ satisfactory conduct of a clinical trial. PMID:21607056

  19. A study of practical parameters and their relative importance as perceived by various stakeholders in clinical trials.

    PubMed

    Pant, R; Joshi, Y

    2011-01-01

    A contract research organization (CRO) is a company which conducts a Good Clinical Practice (GCP) in clinical trial. There are literally hundreds of CROs worldwide employing a workforce of nearly 100,000 professionals. The project proposes the study of practical parameters and their relative importance as perceived by the various stakeholders in clinical trials. The survey was conducted in Bangalore and New Delhi. Primary market data was obtained by primary market research which included 80 clinical trial stakeholders by having a preliminary communication with them, followed by administering a questionnaire along with prior permission. There were 15 Sponsors/ CROs, 27 Investigators /Monitors and 38 Ethics committee members involved in the study. It was shown from the study that a clinical investigator involved in a clinical trial is responsible for ensuring that an investigation is conducted according to the signed investigator statement, the investigational plan, and applicable regulations; for protecting the rights, safety, and welfare of the subjects under the investigator's care; and for the control of drugs under investigation. It was also shown from the study that the sponsors of a clinical trial carry the ultimate responsibility for the initiation, management and financing of the clinical trial. The study has identified a specific training need at the level of the individual stakeholder to perform a particular job function and to identify the actual practical parameters in the Indian context important for the conduction of clinical trials (GCP) with respect to the different stakeholders, to determine the relative importance of these parameters as perceived by various stakeholders involved in clinical trials, and to identify the relative contributions of different stakeholders to the success/ satisfactory conduct of a clinical trial.

  20. Photosensitizer fluorescence and singlet oxygen luminescence as dosimetric predictors of topical 5-aminolevulinic acid photodynamic therapy induced clinical erythema

    PubMed Central

    Mallidi, Srivalleesha; Anbil, Sriram; Lee, Seonkyung; Manstein, Dieter; Elrington, Stefan; Kositratna, Garuna; Schoenfeld, David; Pogue, Brian; Davis, Steven J.; Hasan, Tayyaba

    2014-01-01

    Abstract. The need for patient-specific photodynamic therapy (PDT) in dermatologic and oncologic applications has triggered several studies that explore the utility of surrogate parameters as predictive reporters of treatment outcome. Although photosensitizer (PS) fluorescence, a widely used parameter, can be viewed as emission from several fluorescent states of the PS (e.g., minimally aggregated and monomeric), we suggest that singlet oxygen luminescence (SOL) indicates only the active PS component responsible for the PDT. Here, the ability of discrete PS fluorescence-based metrics (absolute and percent PS photobleaching and PS re-accumulation post-PDT) to predict the clinical phototoxic response (erythema) resulting from 5-aminolevulinic acid PDT was compared with discrete SOL (DSOL)-based metrics (DSOL counts pre-PDT and change in DSOL counts pre/post-PDT) in healthy human skin. Receiver operating characteristic curve (ROC) analyses demonstrated that absolute fluorescence photobleaching metric (AFPM) exhibited the highest area under the curve (AUC) of all tested parameters, including DSOL based metrics. The combination of dose-metrics did not yield better AUC than AFPM alone. Although sophisticated real-time SOL measurements may improve the clinical utility of SOL-based dosimetry, discrete PS fluorescence-based metrics are easy to implement, and our results suggest that AFPM may sufficiently predict the PDT outcomes and identify treatment nonresponders with high specificity in clinical contexts. PMID:24503639

  1. Photosensitizer fluorescence and singlet oxygen luminescence as dosimetric predictors of topical 5-aminolevulinic acid photodynamic therapy induced clinical erythema.

    PubMed

    Mallidi, Srivalleesha; Anbil, Sriram; Lee, Seonkyung; Manstein, Dieter; Elrington, Stefan; Kositratna, Garuna; Schoenfeld, David; Pogue, Brian; Davis, Steven J; Hasan, Tayyaba

    2014-02-01

    The need for patient-specific photodynamic therapy (PDT) in dermatologic and oncologic applications has triggered several studies that explore the utility of surrogate parameters as predictive reporters of treatment outcome. Although photosensitizer (PS) fluorescence, a widely used parameter, can be viewed as emission from several fluorescent states of the PS (e.g., minimally aggregated and monomeric), we suggest that singlet oxygen luminescence (SOL) indicates only the active PS component responsible for the PDT. Here, the ability of discrete PS fluorescence-based metrics (absolute and percent PS photobleaching and PS re-accumulation post-PDT) to predict the clinical phototoxic response (erythema) resulting from 5-aminolevulinic acid PDT was compared with discrete SOL (DSOL)-based metrics (DSOL counts pre-PDT and change in DSOL counts pre/post-PDT) in healthy human skin. Receiver operating characteristic curve (ROC) analyses demonstrated that absolute fluorescence photobleaching metric (AFPM) exhibited the highest area under the curve (AUC) of all tested parameters, including DSOL based metrics. The combination of dose-metrics did not yield better AUC than AFPM alone. Although sophisticated real-time SOL measurements may improve the clinical utility of SOL-based dosimetry, discrete PS fluorescence-based metrics are easy to implement, and our results suggest that AFPM may sufficiently predict the PDT outcomes and identify treatment nonresponders with high specificity in clinical contexts.

  2. Designing clinical trials for amblyopia

    PubMed Central

    Holmes, Jonathan M.

    2015-01-01

    Randomized clinical trial (RCT) study design leads to one of the highest levels of evidence, and is a preferred study design over cohort studies, because randomization reduces bias and maximizes the chance that even unknown confounding factors will be balanced between treatment groups. Recent randomized clinical trials and observational studies in amblyopia can be taken together to formulate an evidence-based approach to amblyopia treatment, which is presented in this review. When designing future clinical studies of amblyopia treatment, issues such as regression to the mean, sample size and trial duration must be considered, since each may impact study results and conclusions. PMID:25752747

  3. Designing clinical trials for amblyopia.

    PubMed

    Holmes, Jonathan M

    2015-09-01

    Randomized clinical trial (RCT) study design leads to one of the highest levels of evidence, and is a preferred study design over cohort studies, because randomization reduces bias and maximizes the chance that even unknown confounding factors will be balanced between treatment groups. Recent randomized clinical trials and observational studies in amblyopia can be taken together to formulate an evidence-based approach to amblyopia treatment, which is presented in this review. When designing future clinical studies of amblyopia treatment, issues such as regression to the mean, sample size and trial duration must be considered, since each may impact study results and conclusions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Data fraud in clinical trials

    PubMed Central

    George, Stephen L; Buyse, Marc

    2015-01-01

    Highly publicized cases of fabrication or falsification of data in clinical trials have occurred in recent years and it is likely that there are additional undetected or unreported cases. We review the available evidence on the incidence of data fraud in clinical trials, describe several prominent cases, present information on motivation and contributing factors and discuss cost-effective ways of early detection of data fraud as part of routine central statistical monitoring of data quality. Adoption of these clinical trial monitoring procedures can identify potential data fraud not detected by conventional on-site monitoring and can improve overall data quality. PMID:25729561

  5. Efficacy of egg yolk and nitroglycerin ointment as treatments for acute anal fissures: A randomized clinical trial study

    PubMed Central

    Salari, Masoumeh; Salari, Roshanak; Dadgarmoghadam, Maliheh; Khadem-Rezaiyan, Majid; Hosseini, Mousalreza

    2016-01-01

    Background Acute anal fissure as a common disease in society has several etiologies and manifestations such as severe anal pain and bleeding. Nitroglycerin ointment 0.2% is the most common topical treatment used. The most common side effect of nitroglycerin is headache, which is annoying for patients and often leads to discontinuation of the drug. Objective Comparison of egg yolk as a natural substance with analgesic and anti-inflammatory properties and minimal side effects with nitroglycerin ointment in the treatment of acute anal fissure. Methods This randomized clinical trial was carried out during a 10-day period in the Gastroenterology clinic of Ghaem Hospital, Mashhad, Iran (year 2015). 126 patients who filled the inclusion criteria were enrolled. The patients were randomly divided into two groups. Nitroglycerin ointment (0.2%) was applied by patients in the first group, twice daily for 10 days. For the second group, one egg yolk once a day was administered rectally up to 10 days. The pain and bleeding severity were recorded every two days up to 10 days after finishing the treatment course, based on visual scale Results The results showed that egg yolk caused a significant reduction in pain and bleeding compared with nitroglycerin (p<0.05). At the beginning of the study, the difference in pain intensity between the two groups was not statistically significant (p-value = 0.25). However, it became significant in the following days. Changes in the frequency of rectorrhagia were also significant in both groups, showing a major decrease in the number of rectorrhagia cases (p<0.001). Conclusion Egg yolk is more efficient than nitroglycerin in the treatment of acute anal fissure. In addition, lack of any side effects results in the completion of the treatment course by the patients. Trial Registration The trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the Irct ID: IRCT2015050718915N3. Funding This work was supported by a

  6. [Globalization of clinical trials].

    PubMed

    Akaza, Hideyuki; Fukuoka, Masahiro; Ohtsu, Atsushi; Usami, Michiyuki; Ikeda, Tadashi; Aiba, Keisuke; Isonishi, Seiji; Ohashi, Yasuo; Saijo, Nagahiro; Sone, Saburo; Tsukagoshi, Shigeru; Tsuruo, Takashi; Kato, Masuhiro; Mikami, Osamu; Dong, Rui-Ping; von Euler, Mikael; Blackledge, George; Stribling, Don

    2003-04-01

    Based on reviews of the Japanese clinical trial situation in lung cancer, gastric cancer, prostate cancer and breast cancer, it was clear that much progress has been made in short time. There are considerable differences between Japan and the West and also differences between clinical areas in Japan. For regulatory purposes bridging studies have become increasingly important. Use of identical protocols are required for effective bridging. Participations in global phase III trials is the best way of achieving registration in Japan. For successful global trials in Japan it is important to include Japanese investigators in the preparation of the protocol and to recognise the challenges facing such a project. Clinical practice in diagnosis and treatment have many differences, thus it is recommended to have clear and detailed information in the protocol. Hard end points like survival are important since they are not biased by cultural differences. There are clear difficulties with HE or QOL outcomes. The emergence of focus on evidence based medicine is also happening in Japan and will help to harmonize documentation across the world. For large adjuvant or prevention cancer global trials are essential. To facilitate global studies further development of infrastructure is necessary in Japan. Use of electronic data capture web based communication etc. will help overcome communication difficulties. Other improvements that will make Japanese participation in global trials easier and better include establishment of clinical trial centre at each hospital, introduction of trial coordinators or study nurses and an improved collaboration with company staff. A critical issue that also need addressing is agreement of centre target recruitment. We need to introduce a new flexible system in Japan if participation in global trial is to be optimised. If we can address these issues Japanese investigators and collaborative groups should be able to initiate and lead global trials in the

  7. Multicenter Evaluation of Infant Lung Function Tests as Cystic Fibrosis Clinical Trial Endpoints

    PubMed Central

    Davis, Stephanie D.; Rosenfeld, Margaret; Kerby, Gwendolyn S.; Brumback, Lyndia; Kloster, Margaret H.; Acton, James D.; Colin, Andrew A.; Conrad, Carol K.; Hart, Meeghan A.; Hiatt, Peter W.; Mogayzel, Peter J.; Johnson, Robin C.; Wilcox, Stephanie L.; Castile, Robert G.

    2010-01-01

    Rationale: The conducting of clinical trials in infants with cystic fibrosis (CF) has been hindered by lack of sensitive outcome measures. Objectives: To evaluate safety, feasibility, and ability to detect abnormalities in lung function of serial pulmonary function tests (PFTs) in infants with CF. Methods: Multicenter observational study using a commercial device, rigorous training, ongoing quality control, and over-reading of data by an independent panel. Raised volume rapid thoracoabdominal compression technique and plethysmography were performed at enrollment and at 6 and 12 months, with an additional 1-month reproducibility visit. Measurements and Main Results: A total of 342 procedures were performed in 100 infants with CF at 10 centers. FRC measurements were acceptable at a higher proportion of study visits (89%) than raised volume (72%) or fractional lung volume (68%) measurements. Average Z scores for many parameters differed significantly from historical control values. Mean (95% confidence interval) Z scores were: −0.52 (−0.78 to −0.25) for forced expiratory flow at 75% (FEF75) for FVC; 1.92 (1.39–2.45) for FRC; 1.22 (0.68–1.76) for residual volume; 0.87 (0.60–1.13) for FRC/total lung capacity; and 0.66 (0.27–1.06) for residual volume/total lung capacity. For future multicenter clinical trials using infant PFTs as primary endpoints, minimum detectable treatment effects are presented for several sample sizes. Conclusions: In this 10-center study, key PFT measures were significantly different in infants with CF than in historical control subjects. However, infant PFTs do not yet appear ready as primary efficacy endpoints for multicenter clinical trials, particularly at inexperienced sites, based on acceptability rates, variability, and potentially large sample sizes required to detect reasonable treatment effects. PMID:20622043

  8. Quality Assurance for Clinical Trials

    PubMed Central

    Ibbott, Geoffrey S.; Haworth, Annette; Followill, David S.

    2013-01-01

    Cooperative groups, of which the Radiation Therapy Oncology Group is one example, conduct national clinical trials that often involve the use of radiation therapy. In preparation for such a trial, the cooperative group prepares a protocol to define the goals of the trial, the rationale for its design, and the details of the treatment procedure to be followed. The Radiological Physics Center (RPC) is one of several quality assurance (QA) offices that is charged with assuring that participating institutions deliver doses that are clinically consistent and comparable. The RPC does this by conducting a variety of independent audits and credentialing processes. The RPC has compiled data showing that credentialing can help institutions comply with the requirements of a cooperative group clinical protocol. Phantom irradiations have been demonstrated to exercise an institution’s procedures for planning and delivering advanced external beam techniques (1–3). Similarly, RPC data indicate that a rapid review of patient treatment records or planning procedures can improve compliance with clinical trials (4). The experiences of the RPC are presented as examples of the contributions that a national clinical trials QA center can make to cooperative group trials. These experiences illustrate the critical need for comprehensive QA to assure that clinical trials are successful and cost-effective. The RPC is supported by grants CA 10953 and CA 81647 from the National Cancer Institute, NIH, DHHS. PMID:24392352

  9. [Evaluation of clinical trials].

    PubMed

    Ural, Dilek

    2010-03-01

    Women are under-represented in landmark clinical trials that form the basis of evidence based management of cardiovascular diseases. Differences among male and female patients emerged in effectiveness and safety of therapeutics in some diseases. Especially in dyslipidemia, ischemic heart diseases and heart failure, trials in which women are better represented and guidelines that evaluate findings in women more detailed are needed. This article evaluates differences among men and women in some landmark trials that are used among main references in management guidelines.

  10. Clinical trials of interventional oncology.

    PubMed

    Arai, Yasuaki

    2012-08-01

    Interventional oncology has great potential to be a good treatment modality in the field of oncology, because its procedures are minimally invasive and fairly quick. However, except for a few procedures such as percutaneous radiofrequency ablation and trans-catheter arterial chemo-embolization that have been recognized as standard treatments for hepatocellular carcinoma, most procedures have not been established as the standard treatment modality due to the limited number of clinical trials with compelling evidence. There are several common problems when performing clinical trials of interventional oncology. The first is that the outcomes of clinical trials are greatly influenced by the level of technical skill of the physicians. The second is that equipment and devices vary widely in countries and regions, and they also influence the outcomes. The third is that the methodology of clinical trials for techniques such as interventional oncology has not yet been established. The fourth is the difficulty of setting appropriate endpoints; quality of life is suitable for evaluating interventional oncology in palliative care, but it is not easy to set as the endpoint. The fifth is the difficulty of employing a blinded design, because the procedure cannot be performed without the physician's awareness. Despite such difficult situations, many multi-institutional clinical trials of interventional oncology have been carried out in Japan, with some challenging results. Establishing evidence is critical to making interventional oncology the standard treatment. Interventional radiologists should know the importance of clinical trials, and should move ahead in this direction in a step-by-step manner.

  11. Ocular surface evaluation in patients treated with a fixed combination of prostaglandin analogues with 0.5% timolol maleate topical monotherapy: a randomized clinical trial

    PubMed Central

    Russ, Heloisa Helena; Nogueira-Filho, Pedro Antônio; de Nadai Barros, Jeison; de Faria, Nubia Vanessa Lima; Montiani-Ferreira, Fabiano; Gomes, José Álvaro Pereira; Mello, Paulo Augusto Arruda

    2013-01-01

    OBJECTIVES: To compare ocular surface changes induced via glaucoma treatment in patients using fixed combinations of prostaglandin analogues (travoprost, latanoprost and bimatoprost) with 0.5% timolol maleate METHODS: A prospective, multicenter, randomized, parallel group, single-blind clinical trial was performed in 33 patients with ocular hypertension or open angle glaucoma who had not been previously treated. The ocular surface was evaluated prior to and three months after treatment, with a daily drop instillation of one of the three medications. The main outcome measurements included the tear film break-up time, Schirmer's test, Lissamine green staining, the Ocular Surface Disease Index questionnaire, impression cytology using HE and PAS and immunocytochemistry for interleukin-6 and HLA-DR. Ensaiosclinicos.gov.br: UTN - U1111-1129-2872 RESULTS: All of the drugs induced a significant reduction in intraocular pressure. Decreases in the Schirmer's test results were observed with all of the drugs. Decreases in tear-film break-up time were noted with travoprost/timolol and latanoprost/timolol. An increase in the Lissamine green score was noted with travoprost/timolol and bimatoprost/timolol. The Ocular Surface Disease Index score increased after treatment in the travoprost/timolol group. Impression cytology revealed a significant difference in cell-to-cell contact in the same group, an increase in cellularity in all of the groups and an increase in the number of goblet cells in all of the groups. The fixed combinations induced an increase in IL-6 expression in the travoprost/timolol group, in which there was also an increase in HLA-DR expression. CONCLUSIONS: All of the fixed combinations induced a significant reduction in intraocular pressure, and the travoprost/timolol group showed increased expression of the inflammatory markers HLA-DR and interleukin-6. All three tested medications resulted in some degree of deterioration in the ocular surface after three months

  12. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2007-05-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issues focuses on the following selection of drugs: (-)-Epigallocatechin gallate, 101M, AAV-AADC, AGN-201904-Z; Agomelatine, AN-0128, AN-2690, Arginine butyrate, Asenapine maleate; Belinostat, Bortezomib, BQ-123, BQ-788; Bucindolol hydrochloride; Certolizumab pegol; Dasatinib, Denosumab, Desvenlafaxine succinate; Ecogramostim, Esomeprazole magnesium; Homoharringtonine; huN901-DM1, Hyaluronic acid; Incyclinide; L-Arginine hydrochloride; Mepolizumab; Nematode anticoagulant protein c2, Nilotinib; Oblimersen sodium; R-115866, Raltegravir potassium, Retapamulin, Romidepsin, Rusalatide acetate; Sarcosine, SCIO-469, Soblidotin, Sorivudine; Tilarginine hydrochloride, Tipifarnib; Uracil; Vildagliptin. (c) 2007 Prous Science. All rights reserved.

  13. Alzheimer Disease Biomarkers as Outcome Measures for Clinical Trials in MCI.

    PubMed

    Caroli, Anna; Prestia, Annapaola; Wade, Sara; Chen, Kewei; Ayutyanont, Napatkamon; Landau, Susan M; Madison, Cindee M; Haense, Cathleen; Herholz, Karl; Reiman, Eric M; Jagust, William J; Frisoni, Giovanni B

    2015-01-01

    The aim of this study was to compare the performance and power of the best-established diagnostic biological markers as outcome measures for clinical trials in patients with mild cognitive impairment (MCI). Magnetic resonance imaging, F-18 fluorodeoxyglucose positron emission tomography markers, and Alzheimer's Disease Assessment Scale-cognitive subscale were compared in terms of effect size and statistical power over different follow-up periods in 2 MCI groups, selected from Alzheimer's Disease Neuroimaging Initiative data set based on cerebrospinal fluid (abnormal cerebrospinal fluid Aβ1-42 concentration-ABETA+) or magnetic resonance imaging evidence of Alzheimer disease (positivity to hippocampal atrophy-HIPPO+). Biomarkers progression was modeled through mixed effect models. Scaled slope was chosen as measure of effect size. Biomarkers power was estimated using simulation algorithms. Seventy-four ABETA+ and 51 HIPPO+ MCI patients were included in the study. Imaging biomarkers of neurodegeneration, especially MR measurements, showed highest performance. For all biomarkers and both MCI groups, power increased with increasing follow-up time, irrespective of biomarker assessment frequency. These findings provide information about biomarker enrichment and outcome measurements that could be employed to reduce MCI patient samples and treatment duration in future clinical trials.

  14. Minimal clinically important difference in Parkinson's disease as assessed in pivotal trials of pramipexole extended release.

    PubMed

    Hauser, Robert A; Gordon, Mark Forrest; Mizuno, Yoshikuni; Poewe, Werner; Barone, Paolo; Schapira, Anthony H; Rascol, Olivier; Debieuvre, Catherine; Fräßdorf, Mandy

    2014-01-01

    Background. The minimal clinically important difference (MCID) is the smallest change in an outcome measure that is meaningful for patients. Objectives. To calculate the MCID for Unified Parkinson's Disease Rating Scale (UPDRS) scores in early Parkinson's disease (EPD) and for UPDRS scores and "OFF" time in advanced Parkinson's disease (APD). Methods. We analyzed data from two pivotal, double-blind, parallel-group trials of pramipexole ER that included pramipexole immediate release (IR) as an active comparator. We calculated MCID as the mean change in subjects who received active treatment and rated themselves "a little better" on patient global impression of improvement (PGI-I) minus the mean change in subjects who received placebo and rated themselves unchanged. Results. MCIDs in EPD (pramipexole ER, pramipexole IR) for UPDRS II were -1.8 and -2.0, for UPDRS III -6.2 and -6.1, and for UPDRS II + III -8.0 and -8.1. MCIDs in APD for UPDRS II were -1.8 and -2.3, for UPDRS III -5.2 and -6.5, and for UPDRS II + III -7.1 and -8.8. MCID for "OFF" time (pramipexole ER, pramipexole IR) was -1.0 and -1.3 hours. Conclusions. A range of MCIDs is emerging in the PD literature that provides the basis for power calculations and interpretation of clinical trials.

  15. Alzheimer's disease biomarkers as outcome measures for clinical trials in MCI

    PubMed Central

    Caroli, Anna; Prestia, Annapaola; Wade, Sara; Chen, Kewei; Ayutyanont, Napatkamon; Landau, Susan M.; Madison, Cindee M.; Haense, Cathleen; Herholz, Karl; Reiman, Eric M.; Jagust, William J.; Frisoni, Giovanni B.

    2014-01-01

    Background Aim of this study was to compare the performance and power of the best-established diagnostic biological markers as outcome measures for clinical trials in patients with mild cognitive impairment (MCI). Methods MRI, FDG-PET markers, and ADAS-COG were compared in terms of effect size and statistical power over different followup periods in two MCI groups, selected from ADNI dataset based on CSF (abnormal CSF Aβ1-42 concentration - ABETA+) or MRI evidence of Alzheimer's Disease (AD) (positivity to hippocampal atrophy - HIPPO+). Biomarkers progression was modeled through mixed effect models. Scaled slope was chosen as measure of effect size. Biomarkers power was estimated using simulation algorithms. Results Seventy-four ABETA+ and 51 HIPPO+ MCI patients were included in the study. Imaging biomarkers of neurodegeneration, especially MR measurements, showed highest performance. For all biomarkers and both MCI groups, power increased with increasing follow-up time, irrespective of biomarker assessment frequency. Conclusions These findings provide information about biomarker enrichment and outcome measurements that could be employed to reduce MCI patient samples and treatment duration in future clinical trials. PMID:25437302

  16. Participating in Clinical Trials

    MedlinePlus Videos and Cool Tools

    ... lifestyle changes, such as exercising more, getting more sleep, keeping mentally active, or eating nutritious foods, can ... become clear until more people have taken it over a longer period of time. home | health topics ...

  17. "They should take time": disclosure of clinical trial results as part of a social relationship.

    PubMed

    Sarradon-Eck, Aline; Sakoyan, Juliette; Desclaux, Alice; Mancini, Julien; Genre, Dominique; Julian-Reynier, Claire

    2012-09-01

    Disclosing overall scientific results to clinical trial participants has become an ethical obligation. Here we studied how participants understand these results in view of their experience of clinical trials and illness in general and what modes of disclosure they preferred. Interviews were conducted with 29 breast cancer patients in France during 2009, using an in-depth qualitative approach. The findings obtained show that the "results" of research are understood quite differently by various patients depending on their expectations about clinical trials. Most of the women interviewed expected to receive personally tailored results at an individual encounter with their own clinical oncologist. Their preferred mode of disclosure was a consultation with their doctors because personal encounters promote mutual recognition and set up a symbolic process of exchange. The results of this study show that medical interventions should not be regarded solely from the technical point of view, but also in terms of the social relationships involved.

  18. [Topics in clinical dentistry. Trends in the Dutch dental literature].

    PubMed

    van der Sanden, W J; Mettes, T G; Grol, R; Plasschaert, A J; Verdonschot, E H

    1999-10-01

    Aim of the study was to evaluate a method for selecting topics suitable for developing dental clinical practice guidelines in the Netherlands, based on an analysis of Dutch dental journals. A search for dental clinical topics was conducted by analysing Dutch dental journals, magazines and series over the period 1992-1997. The numbers of publications per topic were plotted against the publication years. The number of publications as well as the value of the slope of the linear regression were considered to be indicators of the importance of a topic. 'Dental implants (indication)' had the highest number of publications, followed by 'orthodontic treatment planning' and 'periodontology (indication)'. The topic 'practice hygiene' showed the highest value of the slope of the linear regression, followed by 'TMJ dysfunction' and 'dental implants (indication)'. With this method, it is feasible to detect changes and tendencies in the Dutch dental literature. It permits a selection of clinically relevant topics over a time span. It was concluded that this method may be very useful in the selection of a topic, but should probably be combined with other methods.

  19. Neutropenia as an Adverse Event following Vaccination: Results from Randomized Clinical Trials in Healthy Adults and Systematic Review

    PubMed Central

    Muturi-Kioi, Vincent; Lewis, David; Launay, Odile; Leroux-Roels, Geert; Anemona, Alessandra; Loulergue, Pierre; Bodinham, Caroline L.; Aerssens, Annelies; Groth, Nicola; Saul, Allan; Podda, Audino

    2016-01-01

    Background In the context of early vaccine trials aimed at evaluating the safety profile of novel vaccines, abnormal haematological values, such as neutropenia, are often reported. It is therefore important to evaluate how these trials should be planned not to miss potentially important safety signals, but also to understand the implications and the clinical relevance. Methodology We report and discuss the results from five clinical trials (two with a new Shigella vaccine in the early stage of clinical development and three with licensed vaccines) where the absolute neutrophil counts (ANC) were evaluated before and after vaccination. Additionally, we have performed a systematic review of the literature on cases of neutropenia reported during vaccine trials to discuss our results in a more general context. Principal Findings Both in our clinical trials and in the literature review, several cases of neutropenia have been reported, in the first two weeks after vaccination. However, neutropenia was generally transient and had a benign clinical outcome, after vaccination with either multiple novel candidates or well-known licensed vaccines. Additionally, the vaccine recipients with neutropenia frequently had lower baseline ANC than non-neutropenic vaccinees. In many instances neutropenia occurred in subjects of African descent, known to have lower ANC compared to western populations. Conclusions It is important to include ANC and other haematological tests in early vaccine trials to identify potential safety signals. Post-vaccination neutropenia is not uncommon, generally transient and clinically benign, but many vaccine trials do not have a sampling schedule that allows its detection. Given ethnic variability in the level of circulating neutrophils, normal ranges taking into account ethnicity should be used for determination of trial inclusion/exclusion criteria and classification of neutropenia related adverse events. Trial registration ClinicalTrials.gov NCT02017899

  20. Clinical trials as treatment option: bioethics and health care disparities in substance dependency.

    PubMed

    Timmermans, Stefan; McKay, Tara

    2009-12-01

    Bioethicists have warned against the dangers of mixing research with treatment. They are concerned that research priorities may take precedence over individual patient needs and that research subjects tend to misunderstand the purpose of research or overestimate the direct medical benefits of participating in studies. Yet, other work has questioned whether clinical research can always be separated from therapeutic benefit for participants. Using in-depth interviews with participants in two phase III randomized U.S. clinical trials for methamphetamine dependency, we examine the treatment options available to participants, their experiences with participating in the trials, and potential problems of trial participation. We find that while participants have experience with four alternative treatment modalities - quitting alone, support groups, in-patient treatment facilities, and consulting primary care physicians - the randomized clinical trials compare favorably to alternatives because they provide access to evidence-based behavioral treatments, specialized medical professionals, non-judgmental staff, and the possibility of receiving an experimental drug. We conclude that while randomized clinical trials are imperfect substitutes for clinical care, they constitute a fragile and sporadic therapeutic niche in a country with fundamental problems in access to health care, a mixed punitive-therapeutic drug addiction policy, and a profit-driven pharmaceutical development and approval process.

  1. Comparison of pain perception during miniscrew placement in orthodontic patients with a visual analog scale survey between compound topical and needle-injected anesthetics: A crossover, prospective, randomized clinical trial.

    PubMed

    Lamberton, Jordan A; Oesterle, Larry J; Shellhart, W Craig; Newman, Sheldon M; Harrell, Ricky E; Tilliss, Terri; Singh, Neha; Carey, Clifton M

    2016-01-01

    The use of a compound topical anesthetic (CTA) instead of an injection of a local anesthetic for placing miniscrew implants offers advantages to both the clinician and the patient. The purpose of this crossover, prospective, randomized clinical trial was to compare the clinical effectiveness of a CTA with that of a needle injection of local anesthetic for miniscrew placement. Twenty-four orthodontic patients in a university clinic were recruited; they required bilateral buccal miniscrews for orthodontic anchorage. Eligibility criteria included healthy patients with no special needs; over 8 years of age and 25 pounds; not taking sulfonamides, monoamine oxidase inhibitors, tricyclic antidepressants, or phenothiazines; and not allergic to ester-type local anesthetics or any of the other materials used in the study. A computer generated a randomization list. The allocation was randomized by anesthetic protocol and side of the mouth, and was restricted to achieve balance by treatment and side of the mouth. No allocation concealment was applied. Associated with each randomized number was the subjects' assignment into 1 of 4 groups divided by the side of first miniscrew placement and the type of anesthetic. Blinding was done only for data analysis because of clinical limitations. Each patient received a CTA on one side and an injection of anesthetic on the other before miniscrew placement in a crossover study design. The outcome was assessed by measuring pain levels with a 100-mm visual analog scale at 5 time points. Anesthetic failures occurred when the miniscrew could not be fully comfortably placed with a given anesthetic. Data were organized by visual analog scale time points, and descriptive statistics were calculated. A factorial repeated-measures analysis of variance was used to determine any differences. Twenty-seven patients were assessed for eligibility, and 24 agreed to participate in the study. Patients did not distinguish any differences in pain between the

  2. Efficacy of egg yolk and nitroglycerin ointment as treatments for acute anal fissures: A randomized clinical trial study.

    PubMed

    Salari, Masoumeh; Salari, Roshanak; Dadgarmoghadam, Maliheh; Khadem-Rezaiyan, Majid; Hosseini, Mousalreza

    2016-10-01

    Acute anal fissure as a common disease in society has several etiologies and manifestations such as severe anal pain and bleeding. Nitroglycerin ointment 0.2% is the most common topical treatment used. The most common side effect of nitroglycerin is headache, which is annoying for patients and often leads to discontinuation of the drug. Comparison of egg yolk as a natural substance with analgesic and anti-inflammatory properties and minimal side effects with nitroglycerin ointment in the treatment of acute anal fissure. This randomized clinical trial was carried out during a 10-day period in the Gastroenterology clinic of Ghaem Hospital, Mashhad, Iran (year 2015). 126 patients who filled the inclusion criteria were enrolled. The patients were randomly divided into two groups. Nitroglycerin ointment (0.2%) was applied by patients in the first group, twice daily for 10 days. For the second group, one egg yolk once a day was administered rectally up to 10 days. The pain and bleeding severity were recorded every two days up to 10 days after finishing the treatment course, based on visual scale. The results showed that egg yolk caused a significant reduction in pain and bleeding compared with nitroglycerin (p<0.05). At the beginning of the study, the difference in pain intensity between the two groups was not statistically significant (p-value = 0.25). However, it became significant in the following days. Changes in the frequency of rectorrhagia were also significant in both groups, showing a major decrease in the number of rectorrhagia cases (p<0.001). Egg yolk is more efficient than nitroglycerin in the treatment of acute anal fissure. In addition, lack of any side effects results in the completion of the treatment course by the patients. The trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the Irct ID: IRCT2015050718915N3. This work was supported by a grant from the Vice Chancellor of Research of Mashhad University of Medical

  3. Clinical trial design in cancer.

    PubMed

    Mould, R F

    1979-07-01

    The design of clinical trials in cancer is a subject which features reasonably often among FRCR (Part 1) examination questions, and as such should be of more than passing interest to oncologists. It is also a subject which is gaining in relevance since the number of trials is increasing annually due in part to the many chemotherapeutic regimes which are being proposed. This paper which is based on a lecture given in Cambridge at the Hospital Physicists' Association Annual Conference in September 1978, is intended to act as an introduction to clinical trial design. References for further reading are given and, in particular, the extensive report on randomised clinical trials to the Medical Research Council's Leukaemia Steering Committee (Peto et al., 1977, 1978) is recommended.

  4. Clinical Trials Corner: September 2017.

    PubMed

    Rodrigues, Filipe B; Wild, Edward J

    2017-01-01

    Clinical Trials Corner of Journal of Huntington's Disease will regularly review ongoing and recently completed clinical trials in Huntington's disease. In this inaugural issue, we list all currently registered and ongoing clinical trials, expand on LEGATO-HD and IONIS-HTTRx, and cover two recently finished trials: Amaryllis and Pride-HD.

  5. Clinical Trials: CSDRG Overview

    ERIC Educational Resources Information Center

    Logemann, Jeri A.

    2004-01-01

    Recent importance placed upon efficacy research has spawned the development of the Communication Sciences and Disorders Clinical Trials Research Group (CSDRG). This group, funded by the National Institutes of Health (NIH), was organized by the American Speech Language and Hearing Association to address the need for more treatment efficacy research…

  6. The effect of topical application of lavender essential oil on the intensity of pain caused by the insertion of dialysis needles in hemodialysis patients: A randomized clinical trial.

    PubMed

    Ghods, Ali Asghar; Abforosh, Neda Hoseini; Ghorbani, Raheb; Asgari, Mohammad Reza

    2015-06-01

    Patients undergoing hemodialysis experience constant fear and anxiety due to the pain of the insertion of dialysis needles, which might lead to certain physiological and psychological complications for them in the long term. It is therefore essential to control their pain through a simple, safe method. The present study was conducted to determine the effect of the topical application of lavender essential oil on the intensity of pain during the insertion of dialysis needles in hemodialysis patients. This open crossover study was conducted on 34 hemodialysis patients with arteriovenous fistula (AVF) admitted to the dialysis unit of one of the hospitals of Semnan University of Medical Sciences in 2013. The intensity of pain was measured in all the patients in three different states during the insertion of arterial needles for hemodialysis: (1) The topical application of 100% lavender essential oil, (2) no intervention, (3) placebo (with water). Pain intensity was measured in this study through the numeric rating scale (NRS) of pain. The findings showed that the mean±SD of pain intensity was 2.91±1.69 with the topical application of lavender, 4.59±2.02 in the no intervention state and 4.18±1.66 with the placebo state. Statistical tests showed a significant difference between the patients' intensity of pain in the three different states (p=0.001). Based on the findings of the study, the topical application of lavender decreases moderate intensities of pain during the insertion of dialysis needles. Accordingly, lavender oil may be an option to reduce pain by insertion of hemodialysis needles. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Anaesthetic Efficacy of Topical Benzocaine Gel Combined with Hyaluronidase for Supplemental Intrapulpal Injection in Teeth with Irreversible Pulpitis- A Double Blinded Clinical Trial

    PubMed Central

    Sooraparaju, Sujatha Gopal; Abarajithan, M.; Sathish, Emmanuel Solomon; Suryakumari, Nujella Bhaskara Padma; Gade, Winner

    2015-01-01

    Objective Intrapulpal injection technique is one of the most commonly employed method to achieve profound pulpal anaesthesia during an endodontic procedure. To determine if the topical application of benzocaine gel along with hyaluronidase to the pulp chamber could reduce the pain felt with the intrapulpal injection technique. Materials and Methods Two hundred patients with chronic irreversible pulpitis undergoing endodontic treatment for mandibular first molars in which the primary anaesthetic technique failed were selected and randomly divided into 2 groups. In the control group intrapulpal injection was administered with backpressure. In the experimental group topical application of 20% benzocaine gel mixed with hyaluronidase was done over the exposed pulp following which intrapulpal injection was administered with backpressure. Pain assessment was done on a visual analogue scale. Results There was statistically significant difference (p<0.001) between the two groups. The mean value in the control group corresponded to the pain perception "strong”, whereas that of the experimental group corresponded to the pain perception "weak”. Conclusion Topical application of 20% benzocaine gel mixed with hyaluronidase to the exposed pulp reduces the pain encountered with the intrapulpal injection. PMID:26436058

  8. Neutropenia as an Adverse Event following Vaccination: Results from Randomized Clinical Trials in Healthy Adults and Systematic Review.

    PubMed

    Muturi-Kioi, Vincent; Lewis, David; Launay, Odile; Leroux-Roels, Geert; Anemona, Alessandra; Loulergue, Pierre; Bodinham, Caroline L; Aerssens, Annelies; Groth, Nicola; Saul, Allan; Podda, Audino

    2016-01-01

    In the context of early vaccine trials aimed at evaluating the safety profile of novel vaccines, abnormal haematological values, such as neutropenia, are often reported. It is therefore important to evaluate how these trials should be planned not to miss potentially important safety signals, but also to understand the implications and the clinical relevance. We report and discuss the results from five clinical trials (two with a new Shigella vaccine in the early stage of clinical development and three with licensed vaccines) where the absolute neutrophil counts (ANC) were evaluated before and after vaccination. Additionally, we have performed a systematic review of the literature on cases of neutropenia reported during vaccine trials to discuss our results in a more general context. Both in our clinical trials and in the literature review, several cases of neutropenia have been reported, in the first two weeks after vaccination. However, neutropenia was generally transient and had a benign clinical outcome, after vaccination with either multiple novel candidates or well-known licensed vaccines. Additionally, the vaccine recipients with neutropenia frequently had lower baseline ANC than non-neutropenic vaccinees. In many instances neutropenia occurred in subjects of African descent, known to have lower ANC compared to western populations. It is important to include ANC and other haematological tests in early vaccine trials to identify potential safety signals. Post-vaccination neutropenia is not uncommon, generally transient and clinically benign, but many vaccine trials do not have a sampling schedule that allows its detection. Given ethnic variability in the level of circulating neutrophils, normal ranges taking into account ethnicity should be used for determination of trial inclusion/exclusion criteria and classification of neutropenia related adverse events. ClinicalTrials.gov NCT02017899, NCT02034500, NCT01771367, NCT01765413, NCT02523287.

  9. Ethics and clinical trials.

    PubMed

    Chassany, O; Duracinský, M

    1999-01-01

    The current reference guideline about ethics in clinical trials is the Declaration of Helsinki of human rights in medical research. Three major principles are emphasised: respect of the patient to accept or not to participate in a trial, the constraints and the presumed risks must be acceptable for patients included in a study, and vulnerable subjects should not participate in studies. The investigator is responsible for obtaining a free and well-informed consent from patients before their inclusion in a study. Where possible, a new drug should always first be compared to placebo in order to prove its superiority. Else, a small-sized trial comparing a new drug versus a reference treatment can lead to an erroneous conclusion of absence of difference. Moreover, good results or improvement are obtained in at least 30% of cases with placebo, whatever the disease. The use of placebo is unethical in life-threatening diseases and when an effective proved drug exists. The use of placebo is ethical in severe diseases with no efficient drug, in some severe diseases even when an active reference treatment is available, and in all moderate and functional diseases. In order to detect flawed studies, most journals now ask for any manuscript submitted and reporting results of a randomised clinical trial to join a checklist in order to verify the quality of the trial. Finally, it remains the responsibility of the doctor to decide whether or not a protocol is ethical, to participate or not and to include patients or not.

  10. Effect of socioeconomic status as measured by education level on survival in breast cancer clinical trials.

    PubMed

    Herndon, James E; Kornblith, Alice B; Holland, Jimmie C; Paskett, Electra D

    2013-02-01

    This paper aims to investigate the effect of socioeconomic status, as measured by education, on the survival of breast cancer patients treated on 10 studies conducted by the Cancer and Leukemia Group B. Sociodemographic data, including education, were reported by the patient at trial enrollment. Cox proportional hazards model stratified by treatment arm/study was used to examine the effect of education on survival among patients with early stage and metastatic breast cancer, after adjustment for known prognostic factors. The patient population included 1020 patients with metastatic disease and 5146 patients with early stage disease. Among metastatic patients, factors associated with poorer survival in the final multivariable model included African American race, never married, negative estrogen receptor status, prior hormonal therapy, visceral involvement, and bone involvement. Among early stage patients, significant factors associated with poorer survival included African American race, separated/widowed, post/perimenopausal, negative/unknown estrogen receptor status, negative progesterone receptor status, >4 positive nodes, tumor diameter >2 cm, and education. Having not completed high school was associated with poorer survival among early stage patients. Among metastatic patients, non-African American women who lacked a high school degree had poorer survival than other non-African American women, and African American women who lacked a high school education had better survival than educated African American women. Having less than a high school education is a risk factor for death among patients with early stage breast cancer who participated in a clinical trial, with its impact among metastatic patients being less clear. Post-trial survivorship plans need to focus on women with low social status, as measured by education. Copyright © 2011 John Wiley & Sons, Ltd.

  11. PI3K inhibitors as new cancer therapeutics: implications for clinical trial design

    PubMed Central

    Massacesi, Cristian; Di Tomaso, Emmanuelle; Urban, Patrick; Germa, Caroline; Quadt, Cornelia; Trandafir, Lucia; Aimone, Paola; Fretault, Nathalie; Dharan, Bharani; Tavorath, Ranjana; Hirawat, Samit

    2016-01-01

    The PI3K–AKT–mTOR pathway is frequently activated in cancer. PI3K inhibitors, including the pan-PI3K inhibitor buparlisib (BKM120) and the PI3Kα-selective inhibitor alpelisib (BYL719), currently in clinical development by Novartis Oncology, may therefore be effective as anticancer agents. Early clinical studies with PI3K inhibitors have demonstrated preliminary antitumor activity and acceptable safety profiles. However, a number of unanswered questions regarding PI3K inhibition in cancer remain, including: what is the best approach for different tumor types, and which biomarkers will accurately identify the patient populations most likely to benefit from specific PI3K inhibitors? This review summarizes the strategies being employed by Novartis Oncology to help maximize the benefits of clinical studies with buparlisib and alpelisib, including stratification according to PI3K pathway activation status, selective enrollment/target enrichment (where patients with PI3K pathway-activated tumors are specifically recruited), nonselective enrollment with mandatory tissue collection, and enrollment of patients who have progressed on previous targeted agents, such as mTOR inhibitors or endocrine therapy. An overview of Novartis-sponsored and Novartis-supported trials that are utilizing these approaches in a range of cancer types, including breast cancer, head and neck squamous cell carcinoma, non-small cell lung carcinoma, lymphoma, and glioblastoma multiforme, is also described. PMID:26793003

  12. Change in sweat chloride as a clinical end point in cystic fibrosis clinical trials: the ivacaftor experience.

    PubMed

    Durmowicz, Anthony G; Witzmann, Kimberly A; Rosebraugh, Curtis J; Chowdhury, Badrul A

    2013-01-01

    Cystic fibrosis (CF) is a life-shortening inherited disease caused by mutations in the CF transmembrane conductance regulator gene (CFTR), which encodes for the CF transmembrane conductance regulator (CFTR) ion channel that regulates chloride and water transport across the surface of epithelial cells. Ivacaftor, a drug recently approved by the US Food and Drug Administration, represents the first mutation-specific therapy for CF. It is a CFTR channel modulator and improves CFTR function in patients with CF who have a G551D mutation. A clinical trial performed to support ivacaftor dose selection demonstrated a dose-response relationship between improvement in FEV(1) and decrease in sweat chloride, a measure of CFTR function. Validation of such a relationship between FEV(1) and sweat chloride would facilitate development of new drugs that target the defective CFTR. Subsequently, in phase 3 studies, ivacaftor 150 mg bid resulted in significant improvements in FEV(1) (10%-12%) and reduction in sweat chloride (approximately 50 mmol/L). However, a decrease in sweat chloride did not correlate with improvement in FEV(1), nor did there appear to be a threshold level for change in sweat chloride above which an improvement in FEV(1) was apparent. The lack of correlation of sweat chloride with improvement in FEV(1) speaks to the multiplicity of factors, physiologic, environmental, and genetic, that likely modulate CF disease severity. Future clinical trials of drugs that are directed to the defective CFTR will need take into account the uncertainty of using even established measurements, such as sweat chloride, as clinical end points.

  13. Potential bias in ophthalmic pharmaceutical clinical trials

    PubMed Central

    Varner, Paul

    2008-01-01

    To make clinicians aware of potential sources of error in ophthalmic pharmaceutical clinical trials that can lead to erroneous interpretation of results, a critical review of the study design of various pharmaceutical ophthalmic clinical trials was completed. Discrepancies as a result of study shortcomings may explain observed differences between reported ophthalmic trial data and observed clinical results. PMID:19668731

  14. Overcoming Challenges to Initiating Cell Therapy Clinical Trials in Rapidly Developing Countries: India as a Model

    PubMed Central

    Rao, Mahendra; Keating, Armand; Srivastava, Alok

    2013-01-01

    Increasingly, a number of rapidly developing countries, including India, China, Brazil, and others, are becoming global hot spots for the development of regenerative medicine applications, including stem cell-based therapies. Identifying and overcoming regulatory and translational research challenges and promoting scientific and ethical clinical trials with cells will help curb the growth of stem cell tourism for unproven therapies. It will also enable academic investigators, local regulators, and national and international biotechnology and biopharmaceutical companies to accelerate stem cell-based clinical research that could lead to effective innovative treatments in these regions. Using India as a model system and obtaining input from regulators, clinicians, academics, and industry representatives across the stem cell field in India, we reviewed the role of key agencies and processes involved in this field. We have identified areas that need attention and here provide solutions from other established and functioning models in the world to streamline and unify the regulatory and ethics approval processes for cell-based therapies. We also make recommendations to check the growth and functioning of clinics offering unproven treatments. Addressing these issues will remove considerable hurdles to both local and international investigators, accelerate the pace of research and development, and create a quality environment for reliable products to emerge. By doing so, these countries would have taken one important step to move to the forefront of stem cell-based therapeutics. PMID:23836804

  15. Overcoming challenges to initiating cell therapy clinical trials in rapidly developing countries: India as a model.

    PubMed

    Viswanathan, Sowmya; Rao, Mahendra; Keating, Armand; Srivastava, Alok

    2013-08-01

    Increasingly, a number of rapidly developing countries, including India, China, Brazil, and others, are becoming global hot spots for the development of regenerative medicine applications, including stem cell-based therapies. Identifying and overcoming regulatory and translational research challenges and promoting scientific and ethical clinical trials with cells will help curb the growth of stem cell tourism for unproven therapies. It will also enable academic investigators, local regulators, and national and international biotechnology and biopharmaceutical companies to accelerate stem cell-based clinical research that could lead to effective innovative treatments in these regions. Using India as a model system and obtaining input from regulators, clinicians, academics, and industry representatives across the stem cell field in India, we reviewed the role of key agencies and processes involved in this field. We have identified areas that need attention and here provide solutions from other established and functioning models in the world to streamline and unify the regulatory and ethics approval processes for cell-based therapies. We also make recommendations to check the growth and functioning of clinics offering unproven treatments. Addressing these issues will remove considerable hurdles to both local and international investigators, accelerate the pace of research and development, and create a quality environment for reliable products to emerge. By doing so, these countries would have taken one important step to move to the forefront of stem cell-based therapeutics.

  16. Patient safety and efficacy as measured by clinical trials and regulatory policy.

    PubMed

    Harvey, B E; Alpert, S

    1997-01-01

    Virtual Reality and other technological innovations in medicine provide new challenges to the regulatory framework of the premarket review process for medical devices. By reinventing the government-academia-industry partnership, clinical trial data necessary for a medical device to enter the market can be more efficiently obtained.

  17. Phimosis and topical steroids: new clinical findings.

    PubMed

    Zampieri, Nicola; Corroppolo, Michele; Zuin, Veronica; Bianchi, Sanzio; Camoglio, Francesco Saverio

    2007-04-01

    Phimosis has been defined as unretractable foreskin without adherences and/or a circular band of tight prepuce preventing full retraction. The aim of this study is to evaluate the efficacy (response rate) of topical steroids for the treatment of tight phimosis at different age stages. After using the same medication with different dosage schemes, a retrospective analysis was carried out to assess the efficacy of topical steroids in the treatment of tight phimosis. Patients were divided into three groups: group A (betamethasone scheme A), group B (betamethasone scheme B) and group C (control group). Remission of phimosis, with a complete exposure and without a narrowing behind the glans, was considered a complete response to treatment. The outcomes were then related to dosage scheme and patient's age. The dosage for group A was more effective than the dosage for groups B and C (control group). Phimosis resolved in 90% (group A), 72% (group B) and 56% (group C) of cases. A successful treatment was closely related to the age of patients at the beginning of steroid application. The results showed that treatment with topical steroids, which in general gives good results, proved to be much more successful in patients aged between 4 and 8 years, suggesting the efficacy of an early beginning of the treatment.

  18. Honey as a topical treatment for wounds.

    PubMed

    Jull, Andrew B; Walker, Natalie; Deshpande, Sohan

    2013-02-28

    Honey is a viscous, supersaturated sugar solution derived from nectar gathered and modified by the honeybee, Apis mellifera. Honey has been used since ancient times as a remedy in wound care. Evidence from animal studies and some trials has suggested that honey may accelerate wound healing. The objective was to determine whether honey increases the rate of healing in acute wounds (e.g. burns, lacerations) and chronic wounds (e.g. skin ulcers, infected surgical wounds). For this first update of the review we searched the Cochrane Wounds Group Specialised Register (searched 13 June 2012); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 5); Ovid MEDLINE (2008 to May Week 5 2012); Ovid MEDLINE (In-Process & Other Non-Indexed Citations 12 June 2012); Ovid EMBASE (2008 to 2012 Week 23); and EBSCO CINAHL (2008 to 8 June 2012). Randomised and quasi-randomised trials that evaluated honey as a treatment for any sort of acute or chronic wound were sought. There was no restriction in terms of source, date of publication or language. Wound healing was the primary endpoint. Data from eligible trials were extracted and summarised by one review author, using a data extraction sheet, and independently verified by a second review author. We identified 25 trials (with a total of 2987 participants) that met the inclusion criteria, including six new trials that were added to this update. In acute wounds, three trials evaluated the effect of honey in acute lacerations, abrasions or minor surgical wounds and 12 trials evaluated the effect of honey in burns. In chronic wounds, two trials evaluated the effect of honey in venous leg ulcers, and single trials investigated its effect in infected post-operative wounds, pressure injuries, cutaneous Lieshmaniasis, diabetic foot ulcers and Fournier's gangrene. Three trials recruited people into mixed groups of chronic or acute wounds. Most trials were at high or unclear risk of bias. In acute wounds

  19. Clinical trials in pulmonary hypertension.

    PubMed

    Badesch, D B

    1997-01-01

    Progress in treatment of pulmonary hypertension has been impaired by the lack of formal clinical trials. This is now beginning to change, and the impact on our approach to treating patients with pulmonary hypertension in substantial. As with other relatively uncommon medical disorders, randomized, controlled, multi-center trials are needed to assess the safety and efficacy of potential therapeutic modalities. Treatments showing promise at the level of small pilot studies within a single center should be studied more rigorously.

  20. Effectiveness of spirometry as a motivational tool for smoking cessation: a clinical trial, the ESPIMOAT study

    PubMed Central

    2013-01-01

    Background Smoking is the main preventable cause of morbidity and mortality in our region, it being the main causative agent of chronic obstructive pulmonary disease. There still is no consensus on the use of spirometry as a strategy for smoking cessation, given that there is insufficient scientific evidence from high quality studies to recommend the use of this technique. Methods/Design This is to be a randomized, multicentre, open-label clinical trial. A total of 444 smokers over 40 years of age will be recruited by 39 general practitioners from 22 health centers. Primary objective of this study is to assess the effectiveness of spirometry together with information regarding the test for smoking cessation after 1 year in smokers over 40 years of age with a more than 10 pack-year history and no previous diagnosis of chronic obstructive pulmonary disease. Groups of 45 patients who smoke will be randomly selected from the lists of the participating doctors. The names will be sent to the corresponding doctors who will contact candidate patients and assess whether they meet the selection criteria. Patients who meet these criteria will be randomly allocated to an intervention or control group. For patients in both groups, a nurse will conduct an interview and perform a spirometry test to measure forced vital capacity. Then, all patients will be referred for an appointment with their doctor for brief anti-smoking intervention, patients from the intervention group additionally being informed about the result of the spirometry test. After 1 year, smoking status will be assessed and, in those who report that they have quit smoking, abstinence will be confirmed by co-oximetry. Data will be analyzed on an intention-to-treat basis using the chi-squared test for outcomes and binary logistic regression if it is considered to be necessary to adjust for confounding variables. Discussion Performing a spirometry test and providing information on pulmonary function may increase

  1. Eslicarbazepine acetate: its effectiveness as adjunctive therapy in clinical trials and open studies.

    PubMed

    Shorvon, S D; Trinka, E; Steinhoff, B J; Holtkamp, M; Villanueva, V; Peltola, J; Ben-Menachem, E

    2017-03-01

    Eslicarbazepine acetate (ESL) is a once-daily antiepileptic drug that is approved as adjunctive therapy in adults with focal-onset seizures. Following oral administration, ESL is rapidly metabolized to its active metabolite, eslicarbazepine, which acts primarily by enhancing slow inactivation of voltage-gated sodium channels. The efficacy and safety/tolerability of ESL in the adjunctive setting were established in a comprehensive Phase III program (n = 1702 randomized patients) and this evidence has been supported by several open studies (n = 864). ESL treatment has demonstrated improvements in health-related quality of life, in both randomized clinical trials and open studies. ESL has also been shown to be usually well tolerated and efficacious when used in the adjunctive setting in elderly patients. The effectiveness of ESL as the only add-on to antiepileptic drug monotherapy has been demonstrated in a multinational study (n = 219), subgroup analyses of which have also shown it to be efficacious and generally well tolerated in patients who had previously not responded to carbamazepine therapy. Open studies have also demonstrated improvements in tolerability in patients switched overnight from oxcarbazepine to ESL. Due to differences in pharmacokinetics, pharmacodynamics, and metabolism, there may be clinical situations in which it is appropriate to consider switching patients from oxcarbazepine or carbamazepine to ESL.

  2. Clinical trials. A pending subject.

    PubMed

    Gil-Extremera, B; Jiménez-López, P; Mediavilla-García, J D

    2017-07-31

    Clinical trials are essential tools for the progress of clinical medicine in its diagnostic and therapeutic aspects. Since the first trial in 1948, which related tobacco use with lung cancer, there have been more than 150,000 clinical trials to date in various areas (paediatrics, cardiology, oncology, endocrinology, etc.). This article highlights the importance for all physicians to participate, over the course of their professional career, in a clinical trial, due to the inherent benefits for patients, the progress of medicine and for curricular prestige. The authors have created a synthesis of their experience with clinical trials on hypertension, diabetes, dyslipidaemia and ischaemic heart disease over the course of almost 3 decades. Furthermore, a brief reference has been made to the characteristics of a phase I unit, as well as to a number of research studies currently underway. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  3. Innovative Clinical Trial Designs

    PubMed Central

    Lavori, Philip W.

    2015-01-01

    Whereas the 20th-century health care system sometimes seemed to be inhospitable to and unmoved by experimental research, its inefficiency and unaffordability have led to reforms that foreshadow a new health care system. We point out certain opportunities and transformational needs for innovations in study design offered by the 21st-century health care system, and describe some innovative clinical trial designs and novel design methods to address these needs and challenges. PMID:26140056

  4. Types of Treatment: Clinical Trials

    MedlinePlus

    ... Initiative Grant Finder Therapy Acceleration Program Academic Concierge Biotechnology Accelerator Clinical Trials Division Special Projects Beat AML ... Initiative Grant Finder Therapy Acceleration Program Academic Concierge Biotechnology Accelerator Clinical Trials Division Special Projects Beat AML ...

  5. Clinical Trials in Vision Research

    MedlinePlus

    ... the right choice for you. What are the costs of a clinical trial? All medical care provided ... Clinical trials conducted at other locations may involve costs related to standard medical care. These may or ...

  6. Nurses' unique roles in randomized clinical trials.

    PubMed

    Sadler, G R; Lantz, J M; Fullerton, J T; Dault, Y

    1999-01-01

    Nurses are in an ideal position to promote patients' awareness of the role played by clinical trials in the advancement of health science and the subsequent improvement of patient care. The history of clinical trials and the four phases of clinical trials are described. Nurses' professional roles in clinical trial participation, such as helping the patient to identify open clinical trials and acting as clinical interpreter and patient advocate during the patient's participation in a trial, are detailed. Professional considerations that must be addressed by the nurse are reviewed and include ensuring that the trial has received approval from an Institutional Review Board for the participation of human subjects; that the responsibilities of participation are congruent with the nurse's personal values and workplace obligations; and that once engaged, the nurse can make the commitment to sustain participation in the trial. Most important, the nurse must keep the patient's needs and values uppermost in mind during the evaluation of potential clinical trials. Nurses have a critical role to play in the promotion of clinical trials, the recruitment of patients for clinical trial participation, the education of the patient and family, and the clinical care and support of patients throughout their participation in clinical trials.

  7. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2005-05-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 3-AP, Adalimumab, adefovir dipivoxil, AeroDose albuterol inhaler, agalsidase alfa, alemtuzumab, aminolevulinic acid methyl ester, anidulafungin, anthrax vaccine, anti-CTLA-4 MAb, azimilide hydrochloride; Bevacizumab, BG-12, bimatoprost, bortezomib, bosentan, botulinum toxin type B; Caspofungin acetate, ceftobiprole, certolizumab pegol, CG-53135, cilansetron; Darbepoetin alfa, degarelix acetate, dimethylfumarate, duloxetine hydrochloride, dutasteride; Eicosapentaenoic acid/docosahexaenoic acid, eletriptan, entecavir, esomeprazole magnesium, exatecan mesilate, exenatide, ezetimibe; Falecalcitriol, fampridine, fondaparinux sodium, fontolizumab; Gefitinib, gepirone hydrochloride; Human insulin; IDEA-070, imatinib mesylate, iodine (I131) tositumomab; Lanthanum carbonate, lubiprostone; Mafosfamide cyclohexylamine salt, melatonin; NC-531, nemifitide ditriflutate, neridronic acid, nolatrexed dihydrochloride; Oral insulin; Palifermin, parecoxib sodium, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, plerixafor hydrochloride, posaconazole, pramlintide acetate, pregabalin, PT-141; Quercetin; Ranibizumab, renzapride hydrochloride, RSD-1235; Sabarubicin hydrochloride, semapimod hydrochloride, Semax, SHL-749; Tegaserod maleate, tenatoprazole, tetrodotoxin, tolevamer sodium, trabectedin, travoprost, travoprost/timolol; Valdecoxib, visilizumab, Xcellerated T cells, XP-828L; Zoledronic acid monohydrate. Copyright 2005 Prous Science. All rights reserved.

  8. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2007-01-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issues focuses on the following selection of drugs: 4'-Thio-ara-C, 5-methyltetrahydrofolate; ABT-089, AD-237, AF-37702, alvocidib hydrochloride, apricitabine, armodafinil, atrasentan, AVE-5883, avian influenza vaccine, azimilide hydrochloride; Banoxantrone, BIBF-1120; CD34+ cells, certolizumab pegol, CHIR-258, cilansetron, CoFactor, CX-3543, cystemustine; D-003, dexloxiglumide, DMXB-anabaseine; Ecogramostim, elcometrine, elcometrine/ethinylestradiol, etravirine; Fenretinide, fingolimod hydrochloride, fospropofol disodium; Gaboxadol, gestodene, glutamine; Human insulin, hyaluronic acid; Incyclinide, indacaterol, ispronicline, istradefylline; Labradimil, lamifiban, lapatinib, L-arginine hydrochloride, liposomal cisplatin, liposome encapsulated paclitaxel, LY-517717; Manidipine hydrochloride/delapril hydrochloride, maraviroc, MBP(82-98), MD-0727, MDX-214, melanotan I, MMR vaccine; Nacystelyn, nalfurafine hydrochloride, nibentan, nilotinib, NK-105; OBI-1, oblimersen sodium, olmesartan medoxomil, olmesartan medoxomil/hydrochlorothiazide, oregovomab; Pexelizumab, PG-116800, PG-CPT, PHA-794428, prasugrel; RC-3095, rDNA insulin, RFB4(dsFv)-PE38, rhEndostatin, rhenium Re-186 etidronate, rhGM-CSF, roflumilast, romidepsin; Sarcosine, SGLU1, SGN-40, succinobucol; TAU, teduglutide, telatinib, tesofensine, tipifarnib, tirapazamine, TKA-731, tolvaptan, trabectedin; Vaccimel, vatalanib succinate, velafermin, vildagliptin, vinflunine; XP-19986; YM-155.

  9. Topical ozonated oil versus hyaluronic gel for the treatment of partial- to full-thickness second-degree burns: A prospective, comparative, single-blind, non-randomised, controlled clinical trial.

    PubMed

    Campanati, A; De Blasio, S; Giuliano, A; Ganzetti, G; Giuliodori, K; Pecora, T; Consales, V; Minnetti, I; Offidani, A

    2013-09-01

    Several studies have demonstrated that ozonated oil is effective on cutaneous wound healing. This in vivo study has been conducted to evaluate the clinical effect of the topical application of ozonated oil for 12 weeks on second-degree skin burns. A total of 30 patients suffering from second-degree skin burns in the phase of re-epithelisation were included in this study. Every skin burn was subdivided in two symmetrical parts. One part was treated with occlusive application of ozonated oil; the contralateral part of the lesion was treated with topical application of hyaluronic acid gel, once a day for 12 weeks. A clinical evaluation and an intra-vital video-capillaroscopy were performed on every patient at baseline, 6 and 12 weeks after. All treated lesions improved regardless of the treatment used. Ozonated oil was as effective as hyaluronic acid in improving erythema, tension, itching and burning sensation reported by patients, and it does not exert a specific anti-angiogenic effect compared to hyaluronic acid. However it seems more effective than hyaluronic acid in reducing post-lesional hyperpigmentation. Ozonated oil, topically applied for 12 weeks, seems to be as effective as hyaluronic acid in reducing symptoms related to skin burns, but it could be more effective in preventing the post-lesional hyperpigmentation. Copyright © 2013 Elsevier Ltd and ISBI. All rights reserved.

  10. The ethics of clinical trials.

    PubMed Central

    Wing, J K

    1975-01-01

    In summary, the discussion by Professors Helmchen and Müller-Oerlinghausen of the morality of clinical trials has emphasized a point that is frequently overlooked. It is an essential to consider those situations in which it might be unethical not to conduct a trial as it is to be concerned about the ways in which trials might restrict the rights of the individuals taking part in them. They and I have dealt mainly with the first of these two issues because it has been relatively neglected. The second is, of course, equally important and has rightly received much attention. Both matters deserve further public discussion. PMID:775090

  11. The ethics of clinical trials.

    PubMed

    Wing, J K

    1975-12-01

    In summary, the discussion by Professors Helmchen and Müller-Oerlinghausen of the morality of clinical trials has emphasized a point that is frequently overlooked. It is an essential to consider those situations in which it might be unethical not to conduct a trial as it is to be concerned about the ways in which trials might restrict the rights of the individuals taking part in them. They and I have dealt mainly with the first of these two issues because it has been relatively neglected. The second is, of course, equally important and has rightly received much attention. Both matters deserve further public discussion.

  12. Importance of SPP1 genotype as a covariate in clinical trials in Duchenne muscular dystrophy

    PubMed Central

    Bello, Luca; Piva, Luisa; Barp, Andrea; Taglia, Antonella; Picillo, Esther; Vasco, Gessica; Pane, Marika; Previtali, Stefano C.; Torrente, Yvan; Gazzerro, Elisabetta; Chiara Motta, Maria; Grieco, Gaetano S.; Napolitano, Sara; Magri, Francesca; D'Amico, Adele; Astrea, Guja; Messina, Sonia; Sframeli, Maria; Luca Vita, Gian; Boffi, Patrizia; Mongini, Tiziana; Ferlini, Alessandra; Gualandi, Francesca; Soraru', Gianni; Ermani, Mario; Vita, Giuseppe; Battini, Roberta; Bertini, Enrico; Comi, Giacomo P.; Berardinelli, Angela; Minetti, Carlo; Bruno, Claudio; Mercuri, Eugenio; Politano, Luisa; Angelini, Corrado; Hoffman, Eric P.

    2012-01-01

    Objective: To test the effect of the single nucleotide polymorphism −66 T>G (rs28357094) in the osteopontin gene (SPP1) on functional measures over 12 months in Duchenne muscular dystrophy (DMD). Methods: This study was conducted on a cohort of ambulatory patients with DMD from a network of Italian neuromuscular centers, evaluated longitudinally with the North Star Ambulatory Assessment (NSAA) and the 6-Minute Walk Test (6MWT) at study entry and after 12 months. Genotype at rs28357094 was determined after completion of the clinical evaluations. Patients were stratified in 2 groups according to a dominant model (TT homozygotes vs TG heterozygotes and GG homozygotes) and clinical data were retrospectively compared between groups. Results: Eighty patients were selected (age 4.1–19.3 years; mean 8.3 ± 2.7 SD). There were no differences in age or steroid treatment between the 2 subgroups. Paired t test showed a significant difference in both NSAA (p = 0.013) and 6MWT (p = 0.03) between baseline and follow-up after 12 months in patients with DMD carrying the G allele. The difference was not significant in the T subgroup. The analysis of covariance using age and baseline values as covariate and SPP1 genotype as fixed effect showed that these parameters are significantly correlated with the 12-month values. Conclusions: These data provide evidence of the role of SPP1 genotype as a disease modifier in DMD and support its relevance in the selection of homogeneous groups of patients for future clinical trials. PMID:22744661

  13. Placebo Devices as Effective Control Methods in Acupuncture Clinical Trials: A Systematic Review

    PubMed Central

    Zhang, Claire Shuiqing; Tan, Hsiewe Ying; Zhang, George Shengxi; Zhang, Anthony Lin; Xue, Charlie Changli; Xie, Yi Min

    2015-01-01

    While the use of acupuncture has been recognised by the World Health Organisation, its efficacy for many of the common clinical conditions is still undergoing validation through randomised controlled trials (RCTs). A credible placebo control for such RCTs to enable meaningful evaluation of its efficacy is to be established. While several non-penetrating acupuncture placebo devices, namely the Streitberger, the Park and the Takakura Devices, have been developed and used in RCTs, their suitability as inert placebo controls needs to be rigorously determined. This article systematically reviews these devices as placebo interventions. Electronic searches were conducted on four English and two Chinese databases from their inceptions to July 2014; hand searches of relevant references were also conducted. RCTs, in English or Chinese language, comparing acupuncture with one of the aforementioned devices as the control intervention on human participants with any clinical condition and evaluating clinically related outcomes were included. Thirty-six studies were included for qualitative analysis while 14 were in the meta-analysis. The meta-analysis does not support the notion of either the Streitberger or the Park Device being inert control interventions while none of the studies involving the Takakura Device was included in the meta-analysis. Sixteen studies reported the occurrence of adverse events, with no significant difference between verum and placebo acupuncture. Author-reported blinding credibility showed that participant blinding was successful in most cases; however, when blinding index was calculated, only one study, which utilised the Park Device, seemed to have an ideal blinding scenario. Although the blinding index could not be calculated for the Takakura Device, it was the only device reported to enable practitioner blinding. There are limitations with each of the placebo devices and more rigorous studies are needed to further evaluate their effects and

  14. The clinical anti-aging effects of topical kinetin and niacinamide in Asians: a randomized, double-blind, placebo-controlled, split-face comparative trial.

    PubMed

    Chiu, Pin-Chi; Chan, Chih-Chieh; Lin, Hui-Min; Chiu, Hsien-Ching

    2007-12-01

    Kinetin and niacinamide are used in the cosmetic industry as anti-aging agents. Neither the interactive/additive effects of these compounds nor the anti-aging efficacy on Asian skin has been studied. Objective To assess the clinical anti-aging effects and efficacy differences between kinetin plus niacinamide and niacinamide alone vs. vehicle placebo in an Asian cohort. Fifty-two Taiwanese subjects were enrolled in a randomized, double-blind, placebo-controlled, split-face comparative study. Group 1 subjects were treated with kinetin 0.03% plus niacinamide 4%, whereas group 2 subjects received niacinamide 4%. The treatment formulation was applied on one side of the face, whereas a placebo was applied on the other for a period of 12 weeks. We used noninvasive biometrological instruments to evaluate a variety of skin parameters at baseline and at weeks 4, 8, and 12. Persistent and significant reductions in spot, pore, wrinkle, and evenness counts were found at weeks 8 and 12 in group 1. A significant increase in corneal hydration status was also evident at week 12, whereas persistent decreases in erythema index were apparent at 8 and 12 weeks. In group 2, significant reductions in pore and evenness counts at week 8 and wrinkle counts at week 12 were noted. We found kinetin and niacinamide exert a synergistic anti-aging effect. Our data suggest that these compounds have multiactive, multifunctional, and pluripotent effects on skin. They are also both promising to be included in the cutaneous anti-aging cosmeceuticals in the future.

  15. Dopamine Transporter Neuroimaging as an Enrichment Biomarker in Early Parkinson's Disease Clinical Trials: A Disease Progression Modeling Analysis.

    PubMed

    Conrado, Daniela J; Nicholas, Timothy; Tsai, Kuenhi; Macha, Sreeraj; Sinha, Vikram; Stone, Julie; Corrigan, Brian; Bani, Massimo; Muglia, Pierandrea; Watson, Ian A; Kern, Volker D; Sheveleva, Elena; Marek, Kenneth; Stephenson, Diane T; Romero, Klaus

    2017-07-27

    Given the recognition that disease-modifying therapies should focus on earlier Parkinson's disease stages, trial enrollment based purely on clinical criteria poses significant challenges. The goal herein was to determine the utility of dopamine transporter neuroimaging as an enrichment biomarker in early motor Parkinson's disease clinical trials. Patient-level longitudinal data of 672 subjects with early-stage Parkinson's disease in the Parkinson's Progression Markers Initiative (PPMI) observational study and the Parkinson Research Examination of CEP-1347 Trial (PRECEPT) clinical trial were utilized in a linear mixed-effects model analysis. The rate of worsening in the motor scores between subjects with or without a scan without evidence of dopamine transporter deficit was different both statistically and clinically. The average difference in the change from baseline of motor scores at 24 months between biomarker statuses was -3.16 (90% confidence interval [CI] = -0.96 to -5.42) points. Dopamine transporter imaging could identify subjects with a steeper worsening of the motor scores, allowing trial enrichment and 24% reduction of sample size. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  16. [PRIMER FOR SURGICAL CLINICAL TRIALS].

    PubMed

    Sakamaki, Kentaro; Yamanaka, Takeharu

    2016-01-01

    Clinical trials are conducted based on the development of surgical technology and are designed to answer specific research questions. In planning clinical trials population, intervention, comparison, and outcome are important elements. Sample size calculation is also central to the design of clinical trials, especially randomized, controlled ones. This article outlines study phases, four important elements of design, and sample size calculation.

  17. Antiepileptic drug trials: the view from the clinic.

    PubMed

    Faught, Edward

    2012-06-01

    A golden age of antiepileptic drug development has yielded over a dozen useful new compounds, but the nature of clinical trials has made translation to practical use in the clinic difficult. Most clinical trials are designed for regulatory purposes and fail to answer critical clinical questions. These questions include: which drug is best as initial therapy, which drugs work as monotherapy, what are good drug combinations, what is the best starting dose and titration schedule, what is a reasonable target dose, what is the shape of the dose-response curve and does it vary significantly between patients, what is the true incidence of side effects, and what is the long-term efficacy of the drug? Most of these questions could be answered by changing trial designs, but many changes would entail additional time and money. There are encouraging signs that trials with procedures more directly applicable to the clinic are becoming common. These include direct comparative trials, longer trials with emphasis on seizure freedom, and trials with more flexible dosing schedules. In the past, funding of longer and more naturalistic trials has fallen to government agencies, but commercial funding has been obtained for several recent studies. Better quality control, innovative endpoints, structured searching for side effects, and standardisation of data collection are also promising topics for development.

  18. 3M Cavilon No-Sting Barrier Film or topical corticosteroid (mometasone furoate) for protection against radiation dermatitis: A clinical trial.

    PubMed

    Shaw, Su-Zun; Nien, Hsin-Hua; Wu, Ching-Jung; Lui, Louis Tak; Su, Jui-Fen; Lang, Chin-Hsin

    2015-05-01

    Evidence on the prevention of radiation dermatitis is lacking. The aim of this study was to investigate the effect of 3M Cavilon No Sting Barrier Film and topical corticosteroids on irradiated skin. Thirty-nine postoperative breast cancer patients were randomized into three groups for intraindividual comparison (skin to be irradiated was divided into 2 parts): (1) 3M No Sting Barrier Film versus no treatment; (2) corticosteroid versus no treatment; and (3) corticosteroid versus 3M No Sting Barrier Film. The primary end points monitored were the time to first occurrence of grade 1 pruritus, pain score of 3 and grade 2 radiation dermatitis. The secondary end points studied were the incidence of grade 3 radiation dermatitis and total pain scores. Data analysis was done using the SPSS software version 10. Skin given the 3M barrier film experienced a later occurrence of pruritus compared to both corticosteroids and untreated, although this was statistically insignificant. Corticosteroids delayed the time to occurrence of grade 2 dermatitis compared to both untreated skin and 3M barrier film, (mean day of onset = corticosteroid: 52 vs. untreated: 43, p = 0.092; corticosteroid: 53.4 vs. 3M barrier film: 44.5, p = 0.002, t test). Skin given corticosteroids had the lowest incidence of grade 3 dermatitis among all three conditions, although the differences were statistically insignificant. No statistically significant differences were noted in total pain scores. The 3M barrier film may be helpful against dermatitis associated pruritus. Corticosteroids may delay the time of onset of severe skin reactions and also reduce the incidence of severe radiation dermatitis. Copyright © 2013. Published by Elsevier B.V.

  19. Patient-reported outcomes as end points in clinical trials in rheumatoid arthritis

    PubMed Central

    Gossec, Laure; Dougados, Maxime; Dixon, William

    2015-01-01

    There is a growing interest in patient-reported outcomes (PROs) in rheumatology, which goes with a global trend for more ‘patient-centred care’. This review considers the use of PROs in trials, including their strengths and limitations. In rheumatoid arthritis (RA) trials, the most frequently used PROs to assess treatments include pain, patient global assessment, assessment of functional status, but also health-related quality of life and less commonly fatigue. Other aspects of importance for patients, such as sleep, psychological well-being or ability to cope, are rarely assessed. PROs as outcome measures in RA trials have strengths as well as limitations. PROs have face validity, they are reproducible and sensitive to change and they bring additional information beyond joint counts or acute phase reactants. However, their predictive validity for later outcomes has been little explored, some PROs show redundancy (they bring similar information) and, due to the apparently moderate link between some PROs such as fatigue and the disease process, the use of some PROs to inform treatment choices has been questioned. We suggest the choice of PROs for trials depends on the study objective and on the viewpoint of the stakeholder. There needs to be agreed prioritisation across all stakeholders about what is most important to collect in a trial, which is why a prioritisation and selection process is necessary. Trials in RA will continue to include PROs and their interpretation will become easier as our knowledge progresses. PMID:26509052

  20. Suboptimal Dosing Parameters as Possible Factors in the Negative Phase III Clinical Trials of Progesterone for Traumatic Brain Injury.

    PubMed

    Howard, Randy B; Sayeed, Iqbal; Stein, Donald G

    2017-06-01

    To date, outcomes for all Phase III clinical trials for traumatic brain injury (TBI) have been negative. The recent disappointing results of the Progesterone for the Treatment of Traumatic Brain Injury (ProTECT) and Study of a Neuroprotective Agent, Progesterone, in Severe Traumatic Brain Injury (SyNAPSe) Phase III trials for progesterone in TBI have triggered considerable speculation about the reasons for the negative outcomes of these two studies in particular and for those of all previous Phase III TBI clinical trials in general. Among the factors proposed to explain the ProTECT III and SyNAPSe results, the investigators themselves and others have cited: 1) the pathophysiological complexity of TBI itself; 2) issues with the quality and clinical relevance of the preclinical animal models; 3) insufficiently sensitive clinical endpoints; and 4) inappropriate clinical trial designs and strategies. This paper highlights three critical trial design factors that may have contributed substantially to the negative outcomes: 1) suboptimal doses and treatment durations in the Phase II studies; 2) the strategic decision not to perform Phase IIB studies to optimize these variables before initiating Phase III; and 3) the lack of incorporation of the preclinical and Chinese Phase II results, as well as allometric scaling principles, into the Phase III designs. Given these circumstances and the exceptional pleiotropic potential of progesterone as a TBI (and stroke) therapeutic, we are advocating a return to Phase IIB testing. We advocate the incorporation of dose and schedule optimization focused on lower doses and a longer duration of treatment, combined with the addressing of other potential trial design problems raised by the authors in the recently published trial results.

  1. Stem cells clinical trials for cardiac repair: regulation as practical accomplishment.

    PubMed

    Wilson-Kovacs, Dana M; Weber, Susanne; Hauskeller, Christine

    2010-01-01

    Macro-analyses on the regulation of new biomedical objects tend to focus on discursive structures and legislative categories in science policy debates at national and cross-national levels, but overlook how actors engage in regulatory practices on an everyday basis. Based on data from ethnographic fieldwork in British and German clinics, and 32 interviews with medical staff, this article provides an insight into the regulation of adult stem cell research and its clinical implementation. The argument illustrates the enactment of regulation at different stages and highlights the accompanying interpretative strategies employed by the medical personnel involved in the management of clinical trials using patients' own (autologous) stem cells to regenerate damaged cardiac tissue. We argue that the implementation of regulation is a practical accomplishment in both national contexts. The complexities present in this process are instanced by the gradual crystallisation of practices within the organisation of clinical trials. This crystallisation is dependent on exchanges between members of medical teams and external agencies, and is set within a strategic ordering of regulatory measures that are mobilised to legitimise clinical research and reinforce professional interests.

  2. Credentialing for participation in clinical trials

    PubMed Central

    Followill, David S.; Urie, Marcia; Galvin, James M.; Ulin, Kenneth; Xiao, Ying; FitzGerald, Thomas J.

    2012-01-01

    The National Cancer Institute (NCI) clinical cooperative groups have been instrumental over the past 50 years in developing clinical trials and evidence-based clinical trial processes for improvements in patient care. The cooperative groups are undergoing a transformation process to launch, conduct, and publish clinical trials more rapidly. Institutional participation in clinical trials can be made more efficient and include the expansion of relationships with international partners. This paper reviews the current processes that are in use in radiation therapy trials and the importance of maintaining effective credentialing strategies to assure the quality of the outcomes of clinical trials. The paper offers strategies to streamline and harmonize credentialing tools and processes moving forward as the NCI undergoes transformative change in the conduct of clinical trials. PMID:23272300

  3. Microbicide clinical trial adherence: insights for introduction

    PubMed Central

    Woodsong, Cynthia; MacQueen, Kathleen; Amico, K Rivet; Friedland, Barbara; Gafos, Mitzy; Mansoor, Leila; Tolley, Elizabeth; McCormack, Sheena

    2013-01-01

    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. PMID:23561044

  4. Predicting Product Adherence in a Topical Microbicide Safety Trial in Pune, India

    PubMed Central

    Tolley, Elizabeth E.; Tsui, Sharon; Mehendale, Sanjay; Weaver, Mark A.; Kohli, Rewa

    2012-01-01

    The inconclusive results of past trials and recent findings of partial protection of Tenofovir 1% gel underscore the need to better understand product adherence in microbicide trials. This study aimed to identify factors predicting couples’ ability to sustain topical gel and condom use during clinical trial participation. We enrolled 100 Indian participants of a randomized, controlled safety trial of Tenofovir 1% gel (CT cohort) and 100 similar women who were ineligible or declined trial participation (NCT cohort). Compared to the NCT cohort, CT women reported higher baseline condom use, more positive attitudes towards condoms and higher levels of protection efficacy. While NCT condom use remained low, CT condom use increased dramatically during the study. Reported gel consistency was higher than condom consistency. Individual and couple-related factors predicted condom consistency and interest in future gel use, but not gel consistency. Findings could inform trial recruitment strategies and product introduction. PMID:21877203

  5. Predicting product adherence in a topical microbicide safety trial in Pune, India.

    PubMed

    Tolley, Elizabeth E; Tsui, Sharon; Mehendale, Sanjay; Weaver, Mark A; Kohli, Rewa

    2012-10-01

    The inconclusive results of past trials and recent findings of partial protection of Tenofovir 1% gel underscore the need to better understand product adherence in microbicide trials. This study aimed to identify factors predicting couples' ability to sustain topical gel and condom use during clinical trial participation. We enrolled 100 Indian participants of a randomized, controlled safety trial of Tenofovir 1% gel (CT cohort) and 100 similar women who were ineligible or declined trial participation (NCT cohort). Compared to the NCT cohort, CT women reported higher baseline condom use, more positive attitudes towards condoms and higher levels of protection efficacy. While NCT condom use remained low, CT condom use increased dramatically during the study. Reported gel consistency was higher than condom consistency. Individual and couple-related factors predicted condom consistency and interest in future gel use, but not gel consistency. Findings could inform trial recruitment strategies and product introduction.

  6. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2002-01-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses, which has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the world's first drug discovery and development portal, providing information on study design, treatments, conclusions and references. This issue focuses on the following selection of drugs: Abacavir sulfate; abciximab; abetimus sodium; adalimumab; aldesleukin; almotriptan; alteplase; amisulpride; amitriptyline hydrochloride; amoxicillin trihydrate; atenolol; atorvastatin calcium; atrasentan; Beclometasone dipropionate; bosentan; Captopril; ceftriaxone sodium; cerivastatin sodium; cetirizine hydrochloride; cisplatin; citalopram hydrobromide; Dalteparin sodium; darusentan; desirudin; digoxin; Efalizumab; enoxaparin sodium; ertapenem sodium; esomeprazole magnesium; estradiol; ezetimibe; Famotidine; farglitazar; fluorouracil; fluticasone propionate; fosamprenavir sodium; Glibenclamide; glucosamine sulfate; Heparin sodium; HSPPC-96; hydrochlorothiazide; Imatinib mesilate; implitapide; Lamivudine; lansoprazole; lisinopril; losartan potassium; l-Propionylcarnitine; Melagatran; metformin hydrochloride; methotrexate; methylsulfinylwarfarin; Nateglinide; norethisterone; Olmesartan medoxomil; omalizumab; omapatrilat; omeprazole; oseltamivir phosphate; oxatomide; Pantoprazole; piperacillin sodium; pravastatin sodium; Quetiapine hydrochloride; Rabeprazole sodium; raloxifene hydrochloride; ramosetron hydrochloride; ranolazine; rasburicase; reboxetine mesilate; recombinant somatropin; repaglinide; reteplase; rosiglitazone; rosiglitazone maleate; rosuvastatin calcium; Sertraline; simvastatin; sumatriptan succinate; Tazobactam sodium; tenecteplase; tibolone; tinidazole; tolterodine tartrate; troglitazone; Uniprost; Warfarin sodium; Ximelagatran.

  7. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2002-05-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables can be retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abacavir sulfate, abarelix, abciximab, acarbose, alefacept, alteplase, amisulpride, amoxicillin trihydrate, apomorphine hydrochloride, aprepitant, argatroban monohydrate, aspirin, atenolol; Betamethasone dipropionate, betamethasone valerate, bicalutamide, bleomycin sulfate; Calcium carbonate, candesartan cilexetil, celecoxib, cetirizine hydrochloride, cisplatin, clarithromycin, clavulanate potassium, clomethiazole edisilate, clopidogrel hydrogensulfate, cyclophosphamide, chorionic gonadotropin (human); Dalteparin sodium, desloratadine, dexamethasone, doxorubicin, DPC-083; Efalizumab, efavirenz, enoxaparin sodium, eprosartan mesilate, etanercept, etoposide, ezetimibe; Faropenem daloxate, fenofibrate, fluocinolone acetonide, flutamide, fluvastatin sodium, follitropin beta, fondaparinux sodium; Gabapentin, glibenclamide, goserelin, granisetron hydrochloride; Haloperidol, hydrochlorothiazide; Imiquimod, interferon beta-1a, irbesartan, iseganan hydrochloride; L-758298, lamivudine, lanoteplase, leflunomide, leuprorelin acetate, loratadine, losartan potassium; Melagatran, metformin hydrochloride, methotrexate, metronidazole, micafungin sodium, mitoxantrone hydrochloride; Nelfinavir mesilate, neutral insulin injection, nizatidine; Olopatadine hydrochloride, omeprazole, ondansetron hydrochloride; Pamidronate sodium, paracetamol, paroxetine hydrochloride, perindopril, pimecrolimus, pioglitazone hydrochloride, piroxicam, pleconaril, pralmorelin, pravastatin sodium, prednisolone, prednisone, propofol; Raloxifene hydrochloride, ranpirnase, remifentanil hydrochloride, risedronate sodium, risperidone, rofecoxib, ropinirole

  8. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2003-12-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abetimus sodium, adalimumab, alefacept, alemtuzumab, almotriptan, AMGN-0007, anakinra, anti-CTLA-4 Mab, L-arginine hydrochloride, arzoxifene hydrochloride, astemizole, atazanavir sulfate, atlizumab; Belimumab, BG-9928, binodenoson, bosentan, botulinum toxin type B, bovine lactoferrin, BufferGel; Caspofungin acetate, ciclesonide,cilomilast, ciluprevir, clofarabine, CVT-3146; Darbepoetin alfa, desloratadine, diflomotecan, doripenem, dronedarone hydrochloride, drotrecogin alfa (activated), DT388-GM-CSF, duloxetine hydrochloride, E-5564, efalizumab, enfuvirtide, esomeprazole magnesium, estradiol acetate, ETC-642, exenatide, exisulind, ezetimib; Febuxostat; Gallium maltolate, ganirelix acetate, garenoxacin mesilate, gefitinib; H11, HuMax; IL-15, IDD-1, IGIV-C, imatinib mesylate, ISIS-14803, ITF-1697, ivabradine hydrochloride; KRN-5500; L-365260, levetiracetam, levosimendan, licofelone, linezolid, LJP-1082, lopinavir lumiracoxib; MCC-478, melatonin, morphine hydrochloride, morphine-6-glucuronide, moxidectin; N-Acetylcarnosine, natalizumab, NM-702, NNC-05-1869, NSC-703940; Ocinaplon OM-89, omalizumab, omeprazole/ sodium bicarbonate, OPC-28326, ospemifene; PEG-filgrastim peginterferon alfa-2a, pegsunercept, pirfenidone, pralmorelin, pregabalin; Recombinant glucagon-like peptide-1 (7-36) amide, repifermin, RSD-1235; S-8184, selodenoson, sodium dichloroacetate, suberanilohydroxamic acid; TAS-102, terfenadine, teriparatide, tipranavir troxacitabine; Ximelagatran; YM-337. (c) 2003 Prous Science

  9. Gateways to Clinical Trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2002-09-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Adalimumab, aeroDose insulin inhaler, agomelatine, alendronic acid sodium salt, aliskiren fumarate, alteplase, amlodipine, aspirin, atazanavir; Bacillus Calmette-Guérin, basiliximab, BQ-788, bupropion hydrochloride; Cabergoline, caffeine citrate, carbamazepine, carvedilol, celecoxib, cyclosporine, clopidogrel hydrogensulfate, colestyramine; Dexamethasone, diclofenac sodium, digoxin, dipyridamole, docetaxel, dutasteride; Eletriptan, enfuvirtidie, eplerenone, ergotamine tartrate, esomeprazole magnesium, estramustine phosphate sodium; Finasteride, fluticasone propionate, fosinopril sodium; Ganciclovir, GBE-761-ONC, glatiramer acetate, gliclazide, granulocyte-CSF; Heparin sodium, human isophane insulin (pyr), Hydrochlorothiazide; Ibuprofen, inhaled insulin, interferon alfa, interferon beta-1a; Laminvudine, lansoprazole, lisinopril, lonafarnib, losartan potassium, lumiracoxib; MAb G250, meloxicam methotrexate, methylprednisolone aceponate, mitomycin, mycophenolate mofetil; Naproxen sodium, natalizumab, nelfinavir mesilate, nemifitide ditriflutate, nimesulide; Omalizumab, omapatrilat, omeprazole, oxybutynin chloride; Pantoprazole sodium, paracetamol, paroxetine, pentoxifylline, pergolide mesylate, permixon, phVEGF-A165, pramipexole hydrochloride, prasterone, prednisone, probucol, propiverine hydrochloride; Rabeprazole sodium, resiniferatoxin, risedronate sodium, risperidone, rofecoxib rosiglitazone maleate, ruboxistaurin mesilate hydrate; Selegiline transdermal system, sertraline, sildenafil citrate, streptokinase; Tadalafil, tamsulosin hydrochloride, technosphere/Insulin, tegaserod maleate, tenofovir disoproxil

  10. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2003-05-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 2F5, 2G12, abetimus sodium, ABI-007, adalimumab, adefovir dipivoxil, AE-941, alefacept, altropane, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, aminopterin, anakinra, aprinocarsen sodium, atazanavir, atlizumab, atomoxetine hydrochloride; B7-1 vaccine, bevacizumab, biricodar dicitrate, BMS-188667, brasofensine sulfate, bryostatin 1; cantuzumab mertansine, CHS-828, cinacalcet hydrochloride, cipamfylline, creatine, CVT-3146; darbepoetin alfa, DITPA, drotrecogin alfa (activated), duloxetine hydrochloride; edatrexate, efalizumab, ENMD-0997, epoetin, erlosamide, esomeprazole magnesium, etiprednol dicloacetate, etoricoxib, everolimus, ezetimibe; fampridine, fenretinide, FTY-720; IGF-I/IGFBP-3, IL-1 cytokine trap, ilodecakin, interferon beta, ISIS-104838, ISIS-2503, ISIS-5132, ivabradine hydrochloride; lafutidine, lanthanum carbonate, l-Arginine hydrochloride, LEA29Y, lerdelimumab, levetiracetam, levobupivacaine hydrochloride, levosimendan, lopinavir; melagatran, mibefradil hydrochloride, miglustat, morphine-6-glucuronide; nesiritide; omalizumab, omapatrilat; p24-VLP, parecoxib sodium, peginterferon alfa-2a, peginterferon alfa-2b, pegsunercept, pitavastatin calcium, plevitrexed, prasterone, pregabalin, PRO-2000, prucalopride; rapacuronium bromide, rebimastat, RGA-0853, rubitecan, ruboxistaurin mesilate hydrate, RWJ-67657; S-16020-2, sarizotan, SLV-306, stiripentol; TA-CIN, tenecteplase, teriparatide, tezacitabine, tipifarnib, trabectedin, troglitazone; valdecoxib, vardenafil; Z-338, ziconotide.

  11. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2003-06-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: AdGVVEGF121.10, anakinra, andolast, anidulafungin, APC-2059, l-arginine hydrochloride, aripiprazole, arzoxifene hydrochloride, asimadoline; Bexarotene, bimatoprost, bimosiamose, bizelesin, BMS-188667, botulinum toxin type B, bromfenac sodium, bryostatin 1; Cannabidiol, cariporide mesilate, CCI-1004, CDP-571, cerivastatin sodium, clevudine; Dalbavancin, darbepoetin alfa, decitabine, deligoparin sodium, diethylnorspermine, drotrecogin alfa (activated), DTaP-HBV-IPV/Hib-vaccine; E-5564, eculizumab, edodekin alfa, emtricitabine, enfuvirtide, (-)-epigallocatechin gallate, eplerenone, esomeprazole magnesium, etaquine, etoricoxib, ezetimibe; Fesoterodine, fipamezole hydrochloride, fondaparinux sodium, fosamprenavir calcium, frovatriptan, fulvestrant; Gadofosveset sodium, galiximab, ghrelin (human), glufosfamide; Homoharringtonine; Idraparinux sodium, imatinib mesylate, INS-37217; KRN-7000; L-651582, lafutidine, lanthanum carbonate, lenercept, levetiracetam, lusupultide; Magnesium sulfate, melatonin, mepolizumab, midostaurin, morphine hydrochloride, mozavaptan; Natalizumab, nesiritide; OPC-51803, oregovomab, oritavancin; Peginterferon alfa-2(a), pleconaril, plevitrexed, prasterone, pregabalin; Ranibizumab, Ro-31-7453, roxifiban acetate, rubitecan; SCV-07, SHL-749, sho-saiko-to, soblidotin, solifenacin succinate; Tegaserod maleate, telithromycin, tenecteplase, theraCIM, tipifarnib, travoprost; Valdecoxib, vardenafil hydrochloride hydrate, voriconazole; Ximelagatran; Ziprasidone hydrochloride, ZYC-00101. (c) 2003 Prous Science. All rights reserved.

  12. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2002-10-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abacavir sulfate, abciximab, acetylcysteine, adefovir dipivoxil, alfuzosin hydrochloride, aliskiren fumarate, alosetron hydrochloride, amlodipine besilate, apomorphine hydrochloride, atazanavir, atorvastatin, atorvastatin calcium, atrasentan; Basiliximab, beraprost sodium, bevacizumab, bivalirudin, botulinum toxin type A, botulinum toxin type B; Celecoxib, cetuximab, cilansetron, cilomilast; Daclizumab, darbepoetin alfa, docetaxel, duloxetine hydrochloride; Efalizumab, efavirenz, eletriptan,, entecavir, eplerenone, epoetin alfa, eptifibatide, esomeprazole magnesium. ezetimibe; Filgrastim, finasteride, fluvastatin sodium, follitropin alfa; Gemcitabine, gemeprost, ghrelin (human); HE-2000; Infliximab, 111In-Pentetreotide, interferon alfa-2 alpha, interferon alfa-2 beta, interferon beta-1 alpha, irbesartan, irinotecan hydrochloride; Ketamine hydrochloride; L-778123, lafutidine, lamivudine, lamivudine/zidovudine, latanoprost, letrozole, licofelone, lopinavir, losartan potassium, loxiglumide, lubeluzole; Magnesium sulfate, MeGLA, meloxicam, mycophenolate mofetil; NBI-6024, nelfinavir mesilate, nesiritide, nevirapine, niacin, NN-2211; Octreotide, orlistat; PC-515, peginterferon alfa-2 alpha, peginterferon alfa-2b, pemetrexed disodium, pibrozelesin hydrochloride, pimagedine, pirfenidone, pitavastatin calcium, premarin/trimegestone, prucalopride; Rabeprazole sodium; reboxetine, risedronate sodium, ritonavir, rituximab, rofecoxib, roflumilast, rosuvastatin calcium; Sertraline, sibutramine hydrochloride monohydrate, sildenafil citrate, spironolactone, stavudine; Tacrolimus, tadalafil, tamsulosin hydrochloride

  13. Stopping clinical trials by design.

    PubMed

    Whitehead, John

    2004-11-01

    Before any clinical trial begins, a detailed trial protocol must be prepared. The authority of the trial results will depend on the quality of this document. In many protocols, a key component is a plan for a series of interim analyses of the accumulating trial data, and a 'stopping rule' based on them. Such a rule might be intended to prevent participants from continuing to receive a drug that already seems to be unsafe, or to allow a successful drug to become generally available as soon as sufficient evidence of its advantages has been collected. There has been considerable misunderstanding of these rules, and controversies associated with them. Here, I discuss why this might be, and what can be done to promote their successful and beneficial use in the future.

  14. Comparing community and specialty provider-based recruitment in a randomized clinical trial: clinical trial in fecal incontinence.

    PubMed

    Whitebird, Robin R; Bliss, Donna Zimmaro; Savik, Kay; Lowry, Ann; Jung, Hans-Joachim G

    2010-12-01

    Recruitment of participants to clinical trials remains a significant challenge, especially for research addressing topics of a sensitive nature such as fecal incontinence (FI). In the Fiber Study, a randomized controlled trial on symptom management for FI, we successfully enrolled 189 community-living adults through collaborations with specialty-based and community-based settings, each employing methods tailored to the organizational characteristics of their site. Results show that using the two settings increased racial and ethnic diversity of the sample and inclusion of informal caregivers. There were no differential effects on enrollment, final eligibility, or completion of protocol by site. Strategic collaborations with complementary sites can achieve sample recruitment goals for clinical trials on topics that are sensitive or known to be underreported.

  15. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2005-10-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: (-)-Epigallocatechin gallate, (Z)-4-hydroxytamoxifen; Ad.muIFN-beta AD-237, adalimumab, adefovir dipivoxil, agalsidase alfa, alemtuzumab, almotriptan, ALVAC vCP1452, alvimopan hydrate, ambrisentan, anakinra, anti-IFN-gamma MAb; Bimatoprost, BMS-188797, BMS-214662, bortezomib, bosentan, bovine lactoferrin; Caffeine, canertinib dihydrochloride, canfosfamide hydrochloride, cannabidiol, caspofungin acetate, cetuximab, cH36, ChimeriVax-JE, ciclesonide, cilansetron, cinacalcet hydrochloride, clopidogrel, CpG-7909, Cypher; Daptomycin, darbepoetin alfa, darifenacin hydrobromide, decitabine, denufosol tetrasodium, Dexamet, diindolemethane, drotrecogin alfa (activated), duloxetine hydrochloride, DX-9065a; E-7010, edaravone, efalizumab, eicosapentaenoic acid/docosahexaenoic acid, elacridar, eletriptan, emtricitabine, epratuzumab, erlotinib hydrochloride, ertapenem sodium, eszopiclone, everolimus, ezetimibe; Fludarabine, fondaparinux sodium; gamma-Hydroxybutyrate sodium, gavestinel sodium, gefitinib, granisetron-Biochronomer; Human Albumin, human insulin; Imatinib mesylate, indiplon, interleukin-2 XL, isatoribine, ISS-1018, i.v. gamma-globulin, ivabradine hydrochloride, ixabepilone; Lanthanum carbonate, L-arginine hydrochloride, liposomal doxorubicin, LY-450139; Magnesium sulfate, melatonin, motexafin gadolinium, mycophenolic acid sodium salt; Natalizumab, nesiritide, niacin/lovastatin; OGX-011, olmesartan medoxomil, omalizumab, ospemifene; PACAP38, panitumumab, parathyroid hormone (human recombinant), parecoxib sodium, patupilone, pegfilgrastim, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b

  16. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-09-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: AAV1/SERCA2a, Abacavir sulfate/lamivudine, Adalimumab, Aliskiren fumarate, Ambrisentan, Aripiprazole, AT-7519, Atazanavir sulfate, Atomoxetine hydrochloride, Azacitidine, Azelnidipine; Besifloxacin hydrochloride, Bevacizumab, Bioabsorbable everolimus-eluting coronary stent, Bortezomib, Bosentan, Budesonide/formoterol fumarate; CAIV-T, Carisbamate, Casopitant mesylate, Certolizumab pegol, Cetuximab, Ciclesonide, Ciprofloxacin/dexamethasone, CTCE-9908; Dalcetrapib, Darunavir, Deferasirox, Desloratadine, Disitertide, Drotrecogin alfa (activated), DTA-H19, Duloxetine hydrochloride, Dutasteride; Ecogramostim, Efalizumab, Emtricitabine, Eribulin mesilate, Escitalopram oxalate, Eszopiclone, EUR-1008, Everolimus-eluting coronary stent, Exenatide; Fampridine, Fluticasone furoate, Formoterol fumarate/fluticasone propionate, Fosamprenavir calcium, Fulvestrant; Gabapentin enacarbil, GS-7904L; HPV-6/11/16/18, Human Secretin, Hydralazine hydrochloride/isosorbide dinitrate; Imatinib mesylate, Imexon, Inalimarev/Falimarev, Indacaterol, Indacaterol maleate, Inhalable human insulin, Insulin detemir, Insulin glargine, Ixabepilone; L-Alanosine, Lapatinib ditosylate, Lenalidomide, Levocetirizine dihydrochloride, Liraglutide, Lisdexamfetamine mesilate, Lopinavir, Loratadine/montelukast sodium, Lutropin alfa; MeNZB, Mepolizumab, Micafungin sodium, Morphine hydrochloride; Nabiximols, Nikkomycin Z; Olmesartan medoxomil, Omalizumab; Paclitaxel-eluting stent, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Perifosine, PF-489791, Plitidepsin, Posaconazole, Pregabalin; QAX-576; Raltegravir potassium, Ramelteon, Rasagiline

  17. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2005-04-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity. prous.com. This issue focuses on the following selection of drugs: ABX-IL-8, Acclaim, adalimumab, AGI-1067, alagebrium chloride, alemtuzumab, Alequel, Androgel, anti-IL-12 MAb, AOD-9604, aripiprazole, atomoxetine hydrochloride; Biphasic insulin aspart, bosentan, botulinum toxin type B, bovine lactoferrin, brivudine; Cantuzumab mertansine, CB-1954, CDB-4124, CEA-TRICOM, choriogonadotropin alfa, cilansetron, CpG-10101, CpG-7909, CTL-102, CTL-102/CB-1954; DAC:GRF, darbepoetin alfa, davanat-1, decitabine, del-1 Genemedicine, dexanabinol, dextofisopam, dnaJP1, dronedarone hydrochloride, dutasteride; Ecogramostim, eletriptan, emtricitabine, EPI-hNE-4, eplerenone, eplivanserin fumarate, erlotinib hydrochloride, ertapenem sodium, escitalopram oxalate, esomeprazole magnesium, etoricoxib, ezetimibe; Falecalcitriol, fingolimod hydrochloride; Gepirone hydrochloride; HBV-ISS, HSV-2 theracine, human insulin; Imatinib mesylate, Indiplon, insulin glargine, ISAtx-247; L612 HuMAb, levodopa/carbidopa/entacapone, lidocaine/prilocaine, LL-2113AD, lucinactant, LY-156735; Meclinertant, metelimumab, morphine hydrochloride, morphine-6-glucuronide; Natalizumab, nimotuzumab, NX-1207, NYVAC-HIV C; Omalizumab, onercept, osanetant; PABA, palosuran sulfate, parathyroid hormone (human recombinant), parecoxib sodium, PBI-1402, PCK-3145, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pemetrexed disodium, pimecrolimus, PINC, pregabalin; Ramelteon, rasagiline mesilate, rasburicase, rimonabant hydrochloride, RO-0098557, rofecoxib, rosiglitazone maleate/metformin hydrochloride; Safinamide mesilate, SHL-749, sitaxsentan sodium, sparfosic acid, SprayGel, squalamine, St. John's Wort

  18. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2010-12-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Thomson Reuters Integrity(SM), the drug discovery and development portal, http://www.thomsonreutersintegrity.com. This issue focuses on the following selection of drugs: 17-Hydroxyprogesterone caproate; Abacavir sulfate/lamivudine, Aclidinium bromide, Adalimumab, Adefovir, Alemtuzumab, Alkaline phosphatase, Amlodipine, Apilimod mesylate, Aripiprazole, Axitinib, Azacitidine; Belotecan hydrochloride, Berberine iodide, Bevacizumab, Bortezomib, Bosentan, Bryostatin 1; Calcipotriol/hydrocortisone, Carglumic acid, Certolizumab pegol, Cetuximab, Cinacalcet hydrochloride, Cixutumumab, Coumarin, Custirsen sodium; Darbepoetin alfa, Darifenacin hydrobromide, Darunavir, Dasatinib, Denibulin hydrochloride, Denosumab, Diacetylmorphine, Dulanermin, Duloxetine hydrochloride; Ecogramostim, Enfuvirtide, Entecavir, Enzastaurin hydrochloride, Eplerenone, Escitalopram oxalate, Esomeprazole sodium, Etravirine, Everolimus, Ezetimibe; Fenofibrate/pravastatin sodium, Ferric carboxymaltose, Flavangenol, Fondaparinux sodium; Glutamine, GSK-1024850A; Hepatitis B hyperimmunoglobulin, Hib-MenC, HIV-LIPO-5; Immunoglobulin intravenous (human), Indacaterol maleate, Indibulin, Indium 111 (¹¹¹In) ibritumomab tiuxetan, Influenza A (H1N1) 2009 Monovalent vaccine, Inhalable human insulin, Insulin glulisine; Lapatinib ditosylate, Leucovorin/UFT; Maraviroc, Mecasermin, MMR-V, Morphine hydrochloride, Morphine sulfate/naltrexone hydrochloride, Mycophenolic acid sodium salt; Naproxen/esomeprazole magnesium, Natalizumab; Oncolytic HSV; Paliperidone, PAN-811, Paroxetine, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b/ribavirin, Pegvisomant, Pemetrexed disodium, Pimecrolimus, Posaconazole, Pregabalin; Raltegravir potassium, Ranelic acid distrontium salt, Rasburicase, Rilpivirine

  19. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2006-12-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 5-Methyltetrahydrofolate, 9-aminocamptothecin; AdPEDF.11, AE-37, albumin interferon alfa, alicaforsen sodium, alvocidib hydrochloride, AMG-706, arginine butyrate, avanafil, axitinib, azimilide hydrochloride; BAY-579352, belagenpumatucel-L, beta-lapachone, BHT-3009, BIBW-2992, bremelanotide, BX-471; Casopitant mesylate, cediranib, certolizumab pegol, CH-1504, ChimeriVax-West Nile, clofazimine, CpG-7909, curcumin, Cypher; Dapoxetine hydrochloride, darusentan, diflomotecan, D-methionine, dnaJP1, D-serine, DTPw-HB Hib-MenAC, DTPw-HepB-Hib; E-7010, ecogramostim, edodekin alfa, EGFRvlll peptide vaccine, elcometrine, elcometrine/ethinylestradiol, elsilimomab, enrasentan, ertumaxomab, etalocib sodium, exisulind; Fenretinide, fesoterodine, fingolimod hydrochloride, fontolizumab; Gefitinib, gemtuzumab ozogamicin, ghrelin (human), GV-1001; HTU-PA, human papillomavirus vaccine; Indacaterol, indiplon, interleukin-21, intranasal insulin, irinotecan hydrochloride/floxuridine, ISIS-301012, ispinesib mesylate, ixabepilone; K562/GM-CSF; Lapatinib, L-BLP-25, linezolid, liposome encapsulated paclitaxel, LY-2124275; MC-1, MC-1/lisinopril, MDX-066, melanoma vaccine, MMR-V, multivalent (ACYW) meningitis vaccine; Nilotinib, nobori, nociceptin; Oblimersen sodium, orbofiban acetate, ospemifene; Paliperidone, panitumumab, PEG-filgrastim, PEGylated interferon alfacon-1, perflubutane, pertuzumab, phenserine tartrate, phVEGF-A165, pleconaril, prasugrel, prednisolone sodium metasulfobenzoate; R-411, recombinant malaria vaccine, rhGM-CSF, roflumilast, romidepsin, ruboxistaurin mesilate hydrate; Sirolimus-eluting stent, SR-4554, St. John

  20. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2004-01-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Know- ledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: ABI-007, Ad.Egr.TNF.11D, adefovir dipivoxil, AdPEDF.11, AES-14, albumex, alefacept, alemtuzumab, aliskiren fumarate, alvimopan hydrate, aAminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, anakinra, anti-IL-12 MAb, aprepitant, atazanavir sulfate, atrasentan, avanafil; Banoxantrone, BG-12, bimatoprost, bortezomib, bosentan; Calcipotriol/betamethasone dipropionate, caspofungin acetate, CBT-1, ciclesonide, clofarabine, conivaptan hydrochloride, CpG-7909, C-Vax, Cypher; DA-8159, DAC:GLP-1, darbepoetin alfa, darifenacin, duloxetine hydrochloride; Eculizumab, efalizumab, efaproxiral sodium, EGF vaccine, eletriptan, epratuzumab, erlotinib hydrochloride, escitalopram oxalate, ETC-642, etoricoxib, everolimus, exenatide; Gefitinib, IV gamma-globulin; Human insulin, gamma-hydroxybutyrate sodium; IDN-6556, iguratimod, imatinib mesylate, indiplon, ixabepilone; Laquinimod, LB-80380, lidocaine/prilocaineliraglutide, lopinavir, lopinavir/ritonavir, lucinactant; MAb-14.18, melatonin, MLN-591-DM1; NC-531, neridronic acid, nesiritide, neutrophil-inhibitory factor, niacin/lovastatin; Oblimersen sodium, olcegepant, oral Insulin, ORV-105; Palonosetron hydrochloride, PAmAb, pegaptanib sodium, peginterferon alfa-2a, pegvisomant, perifosine, pexelizumab, phenoxodiol, phenserine tartrate, pimecrolimus, pramlintide acetate, pregabalin, PRO-542, prostate cancer vaccine, PT-141; Ramelteon, rasagiline mesilate, rDNA insulin, reslizumab, rh-Lactoferrin, ribamidine hydrochloride, rosuvastatin calcium; S-8184l, SC-1, sorafenib, St. John's Wort extract, SU-11248; Taxus, telbivudine, tenofovir disoproxil fumarate, teriparatide

  1. Likelihood and clinical trials.

    PubMed

    Hill, G; Forbes, W; Kozak, J; MacNeill, I

    2000-03-01

    The history of the application of statistical theory to the analysis of clinical trials is reviewed. The current orthodoxy is a somewhat illogical hybrid of the original theory of significance tests of Edgeworth, Karl Pearson, and Fisher, and the subsequent decision theory approach of Neyman, Egon Pearson, and Wald. This hegemony is under threat from Bayesian statisticians. A third approach is that of likelihood, stemming from the work of Fisher and Barnard. This approach is illustrated using hypothetical data from the Lancet articles by Bradford Hill, which introduced clinicians to statistical theory.

  2. Deuterium oxide as a tracer for measurement of compliance in pediatric clinical drug trials

    SciTech Connect

    Rodewald, L.E.; Maiman, L.A.; Foye, H.R.; Borch, R.F.; Forbes, G.B.

    1989-05-01

    We tested the hypothesis that a deuterium oxide (D/sub 2/O) tracer could discriminate among patterns of clinically significant, imperfect compliance during drug trials. A model was developed to predict deuterium concentration during multiple dose regimens. After developing a regression equation to predict one of the model parameters for children, we selected healthy children (N = 20) at random to receive one of five 10-day D/sub 2/O regimens. Five urine samples were obtained from each child during 15 days and analyzed for deuterium level by mass spectrometry. Each child's height, weight, age, and the first four urinary deuterium levels were used to estimate the amount and timing of deuterium administration. These estimates were compared with the five regimens to determine the closest match between estimate and regimen. The closest matching regimen was the regimen actually administered to 19 (95%) of the 20 children. Two of these children had D/sub 2/O administration estimates that could be confused with another regimen. The correlation between the model's predicted levels and the measured levels of all urine samples was 0.96. We conclude that a D/sub 2/O tracer shows excellent promise as a quantitative method of assessing compliance with liquid medications under specified conditions.

  3. Clinical trials for predictive medicine.

    PubMed

    Simon, Richard

    2012-11-10

    Developments in biotechnology and genomics are providing a biological basis for the heterogeneity of clinical course and response to treatment that have long been apparent to clinicians. The ability to molecularly characterize human diseases presents new opportunities to develop more effective treatments and new challenges for the design and analysis of clinical trials. In oncology, treatment of broad populations with regimens that benefit a minority of patients is less economically sustainable with expensive molecularly targeted therapeutics. The established molecular heterogeneity of human diseases requires the development of new paradigms for the design and analysis of randomized clinical trials as a reliable basis for predictive medicine. We review prospective designs for the development of new therapeutics and predictive biomarkers to inform their use. We cover designs for a wide range of settings. At one extreme is the development of a new drug with a single candidate biomarker and strong biological evidence that marker negative patients are unlikely to benefit from the new drug. At the other extreme are Phase III clinical trials involving both genome-wide discovery of a predictive classifier and internal validation of that classifier. We have outlined a prediction-based approach to the analysis of randomized clinical trials that both preserves the Type I error and provides a reliable internally validated basis for predicting which patients are most likely or unlikely to benefit from the new regimen.

  4. Repurposing celecoxib as a topical antimicrobial agent

    PubMed Central

    Thangamani, Shankar; Younis, Waleed; Seleem, Mohamed N.

    2015-01-01

    There is an urgent need for new antibiotics and alternative strategies to combat multidrug-resistant bacterial pathogens, which are a growing clinical issue. Repurposing existing approved drugs with known pharmacology and toxicology is an alternative strategy to accelerate antimicrobial research and development. In this study, we show that celecoxib, a marketed inhibitor of cyclooxygenase-2, exhibits broad-spectrum antimicrobial activity against Gram-positive pathogens from a variety of genera, including Staphylococcus, Streptococcus, Listeria, Bacillus, and Mycobacterium, but not against Gram-negative pathogens. However, celecoxib is active against all of the Gram-negative bacteria tested, including strains of, Acinetobacter, and Pseudomonas, when their intrinsic resistance is artificially compromised by outer membrane permeabilizing agents such as colistin. The effect of celecoxib on incorporation of radioactive precursors into macromolecules in Staphylococcus aureus was examined. The primary antimicrobial mechanism of action of celecoxib was the dose-dependent inhibition of RNA, DNA, and protein synthesis. Further, we demonstrate the in vivo efficacy of celecoxib in a methicillin-resistant S. aureus (MRSA) infected Caenorhabditis elegans whole animal model. Topical application of celecoxib (1 and 2%) significantly reduced the mean bacterial count in a mouse model of MRSA skin infection. Further, celecoxib decreased the levels of all inflammatory cytokines tested, including tumor necrosis factor-α, interleukin-6, interleukin-1 beta, and monocyte chemo attractant protein-1 in wounds caused by MRSA infection. Celecoxib also exhibited synergy with many conventional antimicrobials when tested against four clinical isolates of S. aureus. Collectively, these results demonstrate that celecoxib alone, or in combination with traditional antimicrobials, has a potential to use as a topical drug for the treatment of bacterial skin infections. PMID:26284040

  5. The state of infectious diseases clinical trials: a systematic review of ClinicalTrials.gov.

    PubMed

    Goswami, Neela D; Pfeiffer, Christopher D; Horton, John R; Chiswell, Karen; Tasneem, Asba; Tsalik, Ephraim L

    2013-01-01

    There is a paucity of clinical trials informing specific questions faced by infectious diseases (ID) specialists. The ClinicalTrials.gov registry offers an opportunity to evaluate the ID clinical trials portfolio. We examined 40,970 interventional trials registered with ClinicalTrials.gov from 2007-2010, focusing on study conditions and interventions to identify ID-related trials. Relevance to ID was manually confirmed for each programmatically identified trial, yielding 3570 ID trials and 37,400 non-ID trials for analysis. The number of ID trials was similar to the number of trials identified as belonging to cardiovascular medicine (n = 3437) or mental health (n = 3695) specialties. Slightly over half of ID trials were treatment-oriented trials (53%, vs. 77% for non-ID trials) followed by prevention (38%, vs. 8% in non-ID trials). ID trials tended to be larger than those of other specialties, with a median enrollment of 125 subjects (interquartile range [IQR], 45-400) vs. 60 (IQR, 30-160) for non-ID trials. Most ID studies are randomized (73%) but nonblinded (56%). Industry was the funding source in 51% of ID trials vs. 10% that were primarily NIH-funded. HIV-AIDS trials constitute the largest subset of ID trials (n = 815 [23%]), followed by influenza vaccine (n = 375 [11%]), and hepatitis C (n = 339 [9%]) trials. Relative to U.S. and global mortality rates, HIV-AIDS and hepatitis C virus trials are over-represented, whereas lower respiratory tract infection trials are under-represented in this large sample of ID clinical trials. This work is the first to characterize ID clinical trials registered in ClinicalTrials.gov, providing a framework to discuss prioritization, methodology, and policy.

  6. International Clinical Trial Day and clinical trials in Ethiopia and Africa.

    PubMed

    Fekadu, Abebaw; Teferra, Solomon; Hailu, Asrat; Gebre-Mariam, Tsige; Addissie, Adamu; Deressa, Wakgari; Yimer, Getnet; Reja, Ahmed

    2014-12-19

    Low income countries like Ethiopia are underrepresented in clinical research. As a major public commitment to clinical research, Ethiopia celebrated the International Clinical Trial Day (ICTD) for the first time on 20 May 2014 under the auspices of Addis Ababa University. The motto for the day was 'Clinical Trials for Excellence in Patient Care'. The celebration offered an opportunity to inform academic staff, researchers, students and the leadership about clinical trials being conducted and to discuss the future of clinical trials in the country. Although clear challenges to the conduct of trials abound, clinical trials registered from Ethiopia in trial registration databases is increasing. Cross-country collaborations, international funding support, motivation of academic staff to conduct clinical trials and the commitment and engagement of the leadership in research are all improving. The overall impact of clinical trials is also encouraging. For example, some of the trials conducted in Ethiopia have informed treatment guidelines. However, administrative capacity, research infrastructure as well as financial support remain weak. There is a need for enhanced university-industry linkage and translation of research findings into locally relevant evidence. Ethiopia, as well as the whole of Africa, has an unparalleled opportunity to lead the way in clinical trials, given its prospect of development and the need to have locally relevant evidence for its growing population. In this commentary we reflect on the celebration of ICTD, the status and opportunities for conducting clinical trials and the way forward for facilitating clinical trials in Ethiopia and Africa.

  7. Statins as Anti-Inflammatory Agents in Atherogenesis: Molecular Mechanisms and Lessons from the Recent Clinical Trials

    PubMed Central

    Antonopoulos, Alexios S; Margaritis, Marios; Lee, Regent; Channon, Keith; Antoniades, Charalambos

    2012-01-01

    Ample evidence exists in support of the potent anti-inflammatory properties of statins. In cell studies and animal models statins exert beneficial cardiovascular effects. By inhibiting intracellular isoprenoids formation, statins suppress vascular and myocardial inflammation, favorably modulate vascular and myocardial redox state and improve nitric oxide bioavailability. Randomized clinical trials have demonstrated that further to their lipid lowering effects, statins are useful in the primary and secondary prevention of coronary heart disease (CHD) due to their anti-inflammatory potential. The landmark JUPITER trial suggested that in subjects without CHD, suppression of low-grade inflammation by statins improves clinical outcome. However, recent trials have failed to document any clinical benefit with statins in high risk groups, such in heart failure or chronic kidney disease patients. In this review, we aim to summarize the existing evidence on statins as an anti-inflammatory agent in atherogenesis. We describe the molecular mechanisms responsible for the anti-inflammatory effects of statins, as well as clinical data on the non lipid-lowering, anti-inflammatory effects of statins on cardiovascular outcomes. Lastly, the controversy of the recent large randomized clinical trials and the issue of statin withdrawal are also discussed. PMID:22364136

  8. The remote prayer delusion: clinical trials that attempt to detect supernatural intervention are as futile as they are unethical.

    PubMed

    Paul, G

    2008-09-01

    Extreme rates of premature death prior to the advent of modern medicine, very low rates of premature death in First World nations with low rates of prayer, and the least flawed of a large series of clinical trials indicate that remote prayer is not efficacious in treating illness. Mass contamination of sample cohorts renders such clinical studies inherently ineffectual. The required supernatural and paranormal mechanisms render them implausible. The possibility that the latter are not benign, and the potentially adverse psychological impact of certain protocols, renders these medical trials unethical. Resources should no longer be wasted on medical efforts to detect the supernatural and paranormal.

  9. The effect of topical virgin coconut oil on SCORAD index, transepidermal water loss, and skin capacitance in mild to moderate pediatric atopic dermatitis: a randomized, double-blind, clinical trial.

    PubMed

    Evangelista, Mara Therese Padilla; Abad-Casintahan, Flordeliz; Lopez-Villafuerte, Lillian

    2014-01-01

    Atopic dermatitis (AD) is a chronic skin disease characterized by defects in the epidermal barrier function and cutaneous inflammation, in which transepidermal water loss (TEWL) is increased and the ability of the stratum corneum to hold water is impaired, causing decreased skin capacitance and hydration. This study investigated the effects of topical virgin coconut oil (VCO) and mineral oil, respectively, on SCORAD (SCORing of Atopic Dermatitis) index values, TEWL, and skin capacitance in pediatric patients with mild to moderate AD, using a randomized controlled trial design in which participants and investigators were blinded to the treatments allocated. Patients were evaluated at baseline, and at 2, 4, and 8 weeks. A total of 117 patients were included in the analysis. Mean SCORAD indices decreased from baseline by 68.23% in the VCO group and by 38.13% in the mineral oil group (P < 0.001). In the VCO group, 47% (28/59) of patients achieved moderate improvement and 46% (27/59) showed an excellent response. In the mineral oil group, 34% (20/58) of patients showed moderate improvement and 19% (11/58) achieved excellent improvement. The VCO group achieved a post-treatment mean TEWL of 7.09 from a baseline mean of 26.68, whereas the mineral oil group demonstrated baseline and post-treatment TEWL values of 24.12 and 13.55, respectively. In the VCO group, post-treatment skin capacitance rose to 42.3 from a baseline mean of 32.0, whereas that in the mineral oil group increased to 37.49 from a baseline mean of 31.31. Thus, among pediatric patients with mild to moderate AD, topical application of VCO for eight weeks was superior to that of mineral oil based on clinical (SCORAD) and instrumental (TEWL, skin capacitance) assessments.

  10. Randomized phase II clinical trials.

    PubMed

    Jung, Sin-Ho; Sargent, Daniel J

    2014-01-01

    Traditionally, Phase II trials have been conducted as single-arm trials to compare the response probabilities between an experimental therapy and a historical control. Historical control data, however, often have a small sample size, are collected from a different patient population, or use a different response assessment method, so that a direct comparison between a historical control and an experimental therapy may be severely biased. Randomized Phase II trials entering patients prospectively to both experimental and control arms have been proposed to avoid any bias in such cases. The small sample sizes for typical Phase II clinical trials imply that the use of exact statistical methods for their design and analysis is appropriate. In this article, we propose two-stage randomized Phase II trials based on Fisher's exact test, which does not require specification of the response probability of the control arm for testing. Through numerical studies, we observe that the proposed method controls the type I error accurately and maintains a high power. If we specify the response probabilities of the two arms under the alternative hypothesis, we can identify good randomized Phase II trial designs by adopting the Simon's minimax and optimal design concepts that were developed for single-arm Phase II trials.

  11. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2008-10-01

    Gateways to clinical trials is a guide to the most recent trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: (+)-Dapoxetine hydrochloride, (S)-Tenatoprazole sodium salt monohydrate 19-28z, Acotiamide hydrochloride hydrate, ADV-TK, AE-37, Aflibercept, Albinterferon alfa-2b, Aliskiren fumarate, Asenapine maleate, Axitinib; Bavituximab, Becatecarin, beta-1,3/1,6-Glucan, Bevacizumab, Bremelanotide; Calcipotriol/betamethasone dipropionate, Casopitant mesylate, Catumaxomab, CDX-110, Cediranib, CMD-193, Cositecan; Darinaparsin, Denosumab, DP-b99, Duloxetine hydrochloride; E75, Ecogramostim, Elacytarabine, EMD-273063, EndoTAG-1, Enzastaurin hydrochloride, Eplerenone, Eribulin mesilate, Esomeprazole magnesium, Etravirine, Everolimus, Ezetimibe; Faropenem daloxate, Febuxostat, Fenretinide; Ghrelin (human); I-131 ch-TNT-1/B, I-131-3F8, Iclaprim, Iguratimod, Iloperidone, Imatinib mesylate, Inalimarev/Falimarev, Indacaterol, Ipilimumab, Iratumumab, Ispinesib mesylate, Ixabepilone; Lapatinib ditosylate, Laquinimod sodium, Larotaxel dehydrate, Linezolid, LOR-2040; Mapatumumab, MKC-1, Motesanib diphosphate, Mycophenolic acid sodium salt; NK-012; Olanzapine pamoate, Oncolytic HSV, Ortataxel; Paclitaxel nanoparticles, Paclitaxel poliglumex, Paliperidone palmitate, Panitumumab, Patupilone, PCV-9, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Pertuzumab, Picoplatin, Pimavanserin tartrate, Pimecrolimus, Plerixafor hydrochloride, PM-02734, Poly I:CLC, PR1, Prasugrel, Pregabalin, Progesterone caproate, Prucalopride, Pumosetrag hydrochloride; RAV-12, RB-006, RB-007, Recombinant human erythropoietin alfa, Rimonabant, Romidepsin; SAR-109659, Satraplatin, Sodium butyrate; Tadalafil, Talampanel, Tanespimycin, Tarenflurbil, Tariquidar

  12. Evaluation of Short-Term Changes in Serum Creatinine Level as a Meaningful End Point in Randomized Clinical Trials.

    PubMed

    Coca, Steven G; Zabetian, Azadeh; Ferket, Bart S; Zhou, Jing; Testani, Jeffrey M; Garg, Amit X; Parikh, Chirag R

    2016-08-01

    Observational studies have shown that acute change in kidney function (specifically, AKI) is a strong risk factor for poor outcomes. Thus, the outcome of acute change in serum creatinine level, regardless of underlying biology or etiology, is frequently used in clinical trials as both efficacy and safety end points. We performed a meta-analysis of clinical trials to quantify the relationship between positive or negative short-term effects of interventions on change in serum creatinine level and more meaningful clinical outcomes. After a thorough literature search, we included 14 randomized trials of interventions that altered risk for an acute increase in serum creatinine level and had reported between-group differences in CKD and/or mortality rate ≥3 months after randomization. Seven trials assessed interventions that, compared with placebo, increased risk of acute elevation in serum creatinine level (pooled relative risk, 1.52; 95% confidence interval, 1.22 to 1.89), and seven trials assessed interventions that, compared with placebo, reduced risk of acute elevation in serum creatinine level (pooled relative risk, 0.57; 95% confidence interval, 0.44 to 0.74). However, pooled risks for CKD and mortality associated with interventions did not differ from those with placebo in either group. In conclusion, several interventions that affect risk of acute, mild to moderate, often temporary elevation in serum creatinine level in placebo-controlled randomized trials showed no appreciable effect on CKD or mortality months later, raising questions about the value of using small to moderate changes in serum creatinine level as end points in clinical trials. Copyright © 2016 by the American Society of Nephrology.

  13. Evaluation of Short-Term Changes in Serum Creatinine Level as a Meaningful End Point in Randomized Clinical Trials

    PubMed Central

    Zabetian, Azadeh; Ferket, Bart S.; Zhou, Jing; Testani, Jeffrey M.; Garg, Amit X.; Parikh, Chirag R.

    2016-01-01

    Observational studies have shown that acute change in kidney function (specifically, AKI) is a strong risk factor for poor outcomes. Thus, the outcome of acute change in serum creatinine level, regardless of underlying biology or etiology, is frequently used in clinical trials as both efficacy and safety end points. We performed a meta-analysis of clinical trials to quantify the relationship between positive or negative short–term effects of interventions on change in serum creatinine level and more meaningful clinical outcomes. After a thorough literature search, we included 14 randomized trials of interventions that altered risk for an acute increase in serum creatinine level and had reported between–group differences in CKD and/or mortality rate ≥3 months after randomization. Seven trials assessed interventions that, compared with placebo, increased risk of acute elevation in serum creatinine level (pooled relative risk, 1.52; 95% confidence interval, 1.22 to 1.89), and seven trials assessed interventions that, compared with placebo, reduced risk of acute elevation in serum creatinine level (pooled relative risk, 0.57; 95% confidence interval, 0.44 to 0.74). However, pooled risks for CKD and mortality associated with interventions did not differ from those with placebo in either group. In conclusion, several interventions that affect risk of acute, mild to moderate, often temporary elevation in serum creatinine level in placebo–controlled randomized trials showed no appreciable effect on CKD or mortality months later, raising questions about the value of using small to moderate changes in serum creatinine level as end points in clinical trials. PMID:26712525

  14. A new role for evoked potentials in MS? Repurposing evoked potentials as biomarkers for clinical trials in MS.

    PubMed

    Hardmeier, Martin; Leocani, Letizia; Fuhr, Peter

    2017-09-01

    Evoked potentials (EP) characterize signal conduction in selected tracts of the central nervous system in a quantifiable way. Since alteration of signal conduction is the main mechanism of symptoms and signs in multiple sclerosis (MS), multimodal EP may serve as a representative measure of the functional impairment in MS. Moreover, EP have been shown to be predictive for disease course, and thus might help to select patient groups at high risk of progression for clinical trials. EP can detect deterioration, as well as improvement of impulse propagation, independently from the mechanism causing the change. Therefore, they are candidates for biomarkers with application in clinical phase-II trials. Applicability of EP in multicenter trials has been limited by different standards of registration and assessment.

  15. Effects of Topical Bimatoprost 0.01% and Timolol 0.5% on Circadian IOP, Blood Pressure and Perfusion Pressure in Patients with Glaucoma or Ocular Hypertension: A Randomized, Double Masked, Placebo-Controlled Clinical Trial

    PubMed Central

    Tanga, Lucia; Berardo, Francesca; Ferrazza, Manuela; Michelessi, Manuele; Roberti, Gloria

    2015-01-01

    Purpose To compare the 24-hour (24h) effects on intraocular pressure (IOP) and cardiovascular parameters of timolol 0.5% and bimatoprost 0.01% in open angle glaucoma and ocular hypertensive subjects. Methods In this prospective, randomized, double masked, crossover, clinical trial, after washout from previous medications enrolled subjects underwent 24h IOP, blood pressure (BP) and heart rate (HR) measurements and were randomized to either topical bimatoprost 0.01% at night plus placebo in the morning or to timolol 0.5% bid. After 8 weeks of treatment a second 24h assessment of IOP, BP and HR was performed and then subjects switched to the opposite treatment for additional 8 weeks when a third 24h assessment was performed. The primary endpoint was the comparison of the mean 24h IOP after each treatment. Secondary endpoints included the comparisons of IOP at each timepoint of the 24h curve and the comparison of BP, HR, ocular perfusion pressure and tolerability. Results Mean untreated 24h IOP was 20.3 mmHg (95%CI 19.0 to 21.6). Mean 24h IOP was significantly lower after 8 weeks of treatment with bimatoprost 0.01% than after 8 weeks of treatment with timolol 0.5% bid (15.7 vs 16.8 mmHg, p = 0.0003). Mean IOP during the day hours was significantly reduced from baseline by both drugs while mean IOP during the night hours was reduced by -2.3 mmHg (p = 0.0002) by bimatoprost 0.01% plus placebo and by -1.1 mmHg by timolol 0.5% bid (p = 0.06). Timolol 0.5% significantly reduced the mean 24h systolic BP from baseline, the diastolic BP during the day hours, the HR during the night hours, and the mean 24h systolic ocular perfusion pressure. Conclusion Both Bimatoprost 0.01% and Timolol 0.5% are effective in reducing the mean 24h IOP from an untreated baseline but Bimatoprost 0.01% is more effective than timolol 0.5% throughout the 24h. Timolol 0.5% effect on IOP is reduced during the night hours and is associated with reduced BP, HR and ocular perfusion pressure. Trial

  16. Topical monotherapy with clobetasol propionate spray 0.05% in the COBRA trial.

    PubMed

    Menter, Alan

    2007-11-01

    The Clobex Spray Community-Based Research Assessment (COBRA) trial, a large, 4-week, open-label, observational trial, evaluated the use of twice-daily clobetasol propionate spray 0.05% in subjects with moderate to severe plaque psoriasis affecting 3% to 20% body surface area (BSA). The study was designed to augment existing phase 3 clinical trial data. In this trial, 1254 subjects in the effectiveness-evaluable (EE) population were treated with clobetasol propionate spray 0.05% as monotherapy. Clinical effectiveness was evaluated at weeks 2 and 4 using a 6-point target plaque severity (TPS) scale and 7-point investigators' global assessment of improvement (GAI) scale. Psoriasis TPS at week 0 (baseline) was rated as moderate to severe in more than 90% of subjects. After 2 weeks of clobetasol propionate spray 0.05% monotherapy, statistically significant improvement in TPS was seen at weeks 2 and 4 (P < .001). In addition, statistically significant improvement was seen at week 4 versus week 2 (P < .001) using the GAI scale. Clobetasol propionate spray 0.05% monotherapy was well-tolerated as assessed by erythema, peeling/scaling, dryness, stinging/burning, telangiectasia, skin atrophy, pruritus, and folliculitis. Skin and subcutaneous tissue disorders as well as general disorders and application-site conditions defined as possibly or probably related to therapy occurred in 1.0% and less than 1.0% of subjects, respectively. In addition, more than 90% of subjects were reported by investigators as being very satisfied or somewhat satisfied with their treatment at week 4. Based on these data, clobetasol propionate spray 0.05% is an effective and convenient topical monotherapy for moderate to severe plaque psoriasis.

  17. Skeletal Muscle Quantitative Nuclear Magnetic Resonance Imaging and Spectroscopy as an Outcome Measure for Clinical Trials

    PubMed Central

    Carlier, Pierre G.; Marty, Benjamin; Scheidegger, Olivier; Loureiro de Sousa, Paulo; Baudin, Pierre-Yves; Snezhko, Eduard; Vlodavets, Dmitry

    2016-01-01

    Recent years have seen tremendous progress towards therapy of many previously incurable neuromuscular diseases. This new context has acted as a driving force for the development of novel non-invasive outcome measures. These can be organized in three main categories: functional tools, fluid biomarkers and imagery. In the latest category, nuclear magnetic resonance imaging (NMRI) offers a considerable range of possibilities for the characterization of skeletal muscle composition, function and metabolism. Nowadays, three NMR outcome measures are frequently integrated in clinical research protocols. They are: 1/ the muscle cross sectional area or volume, 2/ the percentage of intramuscular fat and 3/ the muscle water T2, which quantity muscle trophicity, chronic fatty degenerative changes and oedema (or more broadly, “disease activity”), respectively. A fourth biomarker, the contractile tissue volume is easily derived from the first two ones. The fat fraction maps most often acquired with Dixon sequences have proven their capability to detect small changes in muscle composition and have repeatedly shown superior sensitivity over standard functional evaluation. This outcome measure will more than likely be the first of the series to be validated as an endpoint by regulatory agencies. The versatility of contrast generated by NMR has opened many additional possibilities for characterization of the skeletal muscle and will result in the proposal of more NMR biomarkers. Ultra-short TE (UTE) sequences, late gadolinium enhancement and NMR elastography are being investigated as candidates to evaluate skeletal muscle interstitial fibrosis. Many options exist to measure muscle perfusion and oxygenation by NMR. Diffusion NMR as well as texture analysis algorithms could generate complementary information on muscle organization at microscopic and mesoscopic scales, respectively. 31P NMR spectroscopy is the reference technique to assess muscle energetics non-invasively during and

  18. Efficacy and safety of topical alprostadil cream for the treatment of female sexual arousal disorder (FSAD): a double-blind, multicenter, randomized, and placebo-controlled clinical trial.

    PubMed

    Padma-Nathan, Harin; Brown, Candace; Fendl, Jane; Salem, Shawki; Yeager, James; Harningr, Ronald

    2003-01-01

    We evaluated the efficacy and safety of three doses of a novel alprostadil cream in a randomized, double-blind, placebo-controlled study in 94 women presenting with female sexual arousal disorder of at least 6 month s duration. We sent the subjects home with 10 premeasured doses of 500 g, 1000 g, or 1500 g alprostadil or a placebo cream to be applied to the vulvar area prior to vaginal intercourse over a period of 6 weeks. The primary efficacy parameter, the arousal success rate (as measured by diary responses to the Female Sexual Encounter Profile [FSEP]), was highest in the alprostadil 1000 g group and lowest in the 500 g group, but the responses were not different from that of the placebo cream, at the p = 0.05 level, for any of the three alprostadil doses. However, the change from baseline for Item 6 of the Female Sexual Function Index (FSFI; Rosen et al., 2000; satisfaction with arousal during sexual activity) suggested an important dose-related trend (p = 0.173; 1500 g versus placebo). The mean percent responder rate (responder = > 50% arousal success rate with > 3 sexual attempts) suggested a dose-response effect (p = 0.157; 1500 g versus placebo). Adverse events were generally mild or moderate in intensity and mainly involved localized reactions in the genital area.

  19. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2003-09-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abetimus sodium, adefovir dipivoxil, AGI-1067, alefacept, alemtuzumab, ALVAC-p53, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, Anti-CTLA-4 Mab, AOD-9604, apafant, aprinocarsen sodium, arsenic trioxide; Balaglitazone, BIM-23190, bimatoprost, bortezomib, bosentan, BR-1; Canertinib dihydrochloride, CDP-850, cevimeline hydrochloride, cinacalcet hydrochloride, clenoliximab, clevudine, CN-787; D-003, darusentan, deferasirox, desloratadine dexanabinol, duloxetine hydrochloride; E-5564, edaravone, efaproxiral sodium, elvucitabine emfilermin, EN-101, enfuvirtide, entecavir, epithalon, eplerenone, erlotinib hydrochloride, escitalopram oxalate, esomeprazole magnesium, eszopiclone, etilefrine pivalate hydrochloride etoricoxib, everolimus, exenatide; Fidarestat, fondaparinux sodium; Ganstigmine hydrochloride; Homoharringtonine, HuMax-IL-15, hyperimmune IVIG; Imatinib mesylate, IMC-1C11, Inhaled insulin, irofulven, iseganan hydrochloride, ISIS-14803, ISIS-5132, ivabradine hydrochloride; Keratinocyte growth factor; Lafutidine, lanthanum carbonate, LAS-34475, levocetirizine, liraglutide, LY-307161 SR; Magnesium sulfate, maribavir, melatonin, mycobacterium cell wall complex; NN-414, NO-aspirin, nociceptin, nolomirole hydrochloride; Olmesartan medoxomil oral insulin, ospemifene; PDX, perillyl alcohol, pimecrolimus, pitavastatin calcium, pramlintide acetate, prasterone, pregabalin, PRO-542, PV-701, pyrazoloacridine; R-744, ranelic acid distrontium salt, rasburicase, rDNA insulin, resiniferatoxin, reslizumab, ridogrel, riplizumab ropivacaine, rosuvastatin calcium, roxifiban acetate, ruboxistaurin mesilate

  20. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2004-03-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Activated protein C concentrate, Ad-CD154, Adeno-Interferon gamma, alemtuzumab, APC-8024, 9-aminocamptothecin, aprepitant, l-arginine hydrochloride, aripiprazole, arsenic trioxide, asimadoline; O6-Benzylguanine, bevacizumab, Bi-20, binodenoson, biphasic insulin aspart, bivatuzumab, 186Re-bivatuzumab, BMS-181176, bosentan, botulinum toxin type B, BQ-123, bryostatin 1; Carboxy- amidotriazole, caspofungin acetate, CB-1954, CC-4047, CDP-860, cerivastatin sodium, clevidipine, CTL-102; 3,4-DAP, darbepoetin alfa, decitabine, desloratadine, DHA-paclitaxel, duloxetine hydrochloride; Efalizumab, EGF vaccine, eletriptan, eniluracil, ENMD-0997, eplerenone, eplivanserin, erlosamide, ertapenem sodium, escitalopram oxalate, esomeprazole magnesium, eszopiclone, everolimus, exatecan mesilate, exenatide, ezetimibe; Fondaparinux sodium, FR-901228, FTY-720; Gefitinib, gemtuzumab ozogamicin, gepirone hydrochloride; Hexyl insulin M2, human insulin; Imatinib mesylate, insulin detemir, insulin glargine, iodine (I131) tositumomab, ISV-205, ivabradine hydrochloride, ixabepilone; Levetiracetam, levocetirizine, linezolid, liposomal NDDP, lonafarnib, lopinavir, LY-156735; Mafosfamide cyclohexylamine salt, magnesium sulfate, maxacalcitol, meclinertant, melagatran, melatonin, MENT, mepolizumab, micafungin sodium, midostaurin, motexafin gadolinium; Nesiritide, NS-1209, NSC-601316, NSC-683864; Osanetant; Palonosetron hydrochloride, parecoxib sodium, pegaptanib sodium, peginterferon alfa-2a, peginterferon alfa-2b, pegylated OB protein, pemetrexed disodium, perillyl alcohol, picoplatin, pimecrolimus, pixantrone maleate, plevitrexed

  1. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2004-04-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: ABI-007, adalimumab, adefovir dipivoxil, alefacept, alemtuzumab, 3-AP, AP-12009, APC-8015, L-Arginine hydrochloride, aripiprazole, arundic acid, avasimibe; Bevacizumab, bivatuzumab, BMS-181176, BMS-184476, BMS-188797, bortezomib, bosentan, botulinum toxin type B, BQ-123, BRL-55730, bryostatin 1; CEP-1347, cetuximab, cinacalcet hydrochloride, CP-461, CpG-7909; D-003, dabuzalgron hydrochloride, darbepoetin alfa, desloratadine, desoxyepothilone B, dexmethylphenidate hydrochloride, DHA-paclitaxel, diflomotecan, DN-101, DP-b99, drotrecogin alfa (activated), duloxetine hydrochloride, duramycin; Eculizumab, Efalizumab, EKB-569, elcometrine, enfuvirtide, eplerenone, erlotinib hydrochloride, ertapenem sodium, eszopiclone, everolimus, exatecan mesilate, ezetimibe; Fenretinide, fosamprenavir calcium, frovatriptan; GD2L-KLH conjugate vaccine, gefitinib, glufosfamide, GTI-2040; Hexyl insulin M2, human insulin, hydroquinone, gamma-Hydroxybutyrate sodium; IL-4(38-37)-PE38KDEL, imatinib mesylate, indisulam, inhaled insulin, ixabepilone; KRN-5500; LY-544344; MDX-210, melatonin, mepolizumab, motexafin gadolinium; Natalizumab, NSC-330507, NSC-683864; 1-Octanol, omalizumab, ortataxel; Pagoclone, peginterferon alfa-2a, peginterferon alfa-2b, pemetrexed disodium, phenoxodiol, pimecrolimus, plevitrexed, polyphenon E, pramlintide acetate, prasterone, pregabalin, PX-12; QS-21; Ragaglitazar, ranelic acid distrontium salt, RDP-58, recombinant glucagon-like peptide-1 (7-36) amide, repinotan hydrochloride, rhEndostatin, rh-Lactoferrin, (R)-roscovitine; S-8184, semaxanib, sitafloxacin hydrate, sitaxsentan sodium, sorafenib, synthadotin

  2. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2003-01-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 81C6; Adefovir dipivoxil, Agalsidase alfa, AGM-1470, albumin interferon alfa, alefacept, alosetron hydrochloride, anakinra, anti-CTLA-4 Mab, aprepitant, aripiprazole, atazanavir; BAY-43-9006, BBR-3438, beta-L-Fd4C, bimatoprost, bortezomib, bosentanBR96-doxorubicin; Caspofungin acetate, ciclesonide, cilengitide, cilomilast, COL-1621, COL-3, CpG-7909, cyclosporine; DCVax-Brain, dexmethylphenidate hydrochloride, dexosome vaccine (melanoma), donepezil hydrochloride, drotrecogin alfa (activated), DTI-015, [99Tc]-DTPA-mannosyldextran, duloxetine hydrochloride; Emivirine, emtricitabine, entecavir, epothilone B, estradiol-MNP, etonogestrel/etonogestrel/ethinylestradiol, etoricoxib; Febuxostat, fondaparinux sodium, fosamprenavir calcium; Gefitinib, GVS-111; Heparinase I, HspE7, human alpha-glucosidase, human insulin; Imatinib mesylate, INGN-241, interferon alfa B/D hybrid, interferon alfa Biphasix, ISIS-14803; Lanicemine hydrochloride, 1311-lipiodol, liposome-encapsulated mitoxantrone, lixivaptan, lumiracoxib, lupus-AHP, LY-466700; Marimastat, MEN-10755, micafungin sodium; Nitronaproxen, NSC-683864 Omalizumab, oral insulin; Palonosetron hydrochloride, peginterferon alfa-2a, pimecrolimus, pralnacasan, pramlintide acetate, pregabalin, pyrazoloacridine; R-165335, ranolazine, risperidone, RPR-109881;, RSD-1235, Satraplatin, seocalcitol, sertindole, SMART anti-interferon gamma antibody, sulfasalazine; T-138067, TAK-013, tegaserod maleate, telithromycin, tenofovir disoproxil fumarate, teriparatide, tiotropium bromide, tipifarnib, TP-38; Valdecoxib, vatalanib succinate, voriconazole; ZD-9331.

  3. Gateways to Clinical Trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2002-04-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the world's first drug discovery and development portal, and provides information on study design, treatments, conclusions and references. This issue focuses on the following selection of drugs: Abiciximab, acetylcholine chloride, acetylcysteine, alefacept, alemtuzumab, alicaforsen, alteplase, aminopterin, amoxicillin sodium, amphotericin B, anastrozole, argatroban monohydrate, arsenic trioxide, aspirin, atazanavir, atorvastatin, augmerosen, azathioprine; Benzylpenicillin, BMS-284756, botulinum toxin type A, botulinum toxin type B, BQ-123, budesonide, BXT-51072; Calcium folinate, carbamazepine, carboplatin, carmustine, ceftriaxone sodium, cefuroxime axetil, chorionic gonadotropin (human), cimetidine, ciprofloxacin hydrochloride, cisplatin, citalopram hydrobromide, cladribine, clarithromycin, clavulanic acid, clofarabine, clopidogrel hydrogensulfate, clotrimazole, CNI-1493, colesevelam hydrochloride, cyclophosphamide, cytarabine; Dalteparin sodium, daptomycin, darbepoetin alfa, debrisoquine sulfate, dexrazoxane, diaziquone, didanosine, docetaxel, donezepil, doxorubicin hydrochloride liposome injection, DX-9065a; Eberconazole, ecogramostim, eletriptan, enoxaparin sodium, epoetin, epoprostenol sodium, erlizumab, ertapenem sodium, ezetimibe; Fampridine, fenofibrate, filgrastim, fluconazole, fludarabine phosphate, fluorouracil, 5-fluorouracil/epinephrine, fondaparinux sodium, formoterol fumarate; Gabapentin, gemcitabine, gemfibrozil, glatiramer; Heparin sodium, homoharringtonine; Ibuprofen, iloprost, imatinib mesilate, imiquimod, interferon alpha-2b, interferon alpha-2c, interferon-beta; KW-6002; Lamotrigine, lanoteplase, metoprolol tartrate, mitoxantrone hydrochloride; Naproxen sodium, naratriptan, Natalizumab, nelfinavir mesilate

  4. Phase I clinical trial of recombinant human endostatin administered as a short intravenous infusion repeated daily.

    PubMed

    Eder, Joseph P; Supko, Jeffrey G; Clark, Jeffrey W; Puchalski, Thomas A; Garcia-Carbonero, Rocio; Ryan, David P; Shulman, Lawrence N; Proper, Joann; Kirvan, Moira; Rattner, Barbara; Connors, Susan; Keogan, Mary T; Janicek, Milos J; Fogler, William E; Schnipper, Lowell; Kinchla, Nancy; Sidor, Carolyn; Phillips, Eric; Folkman, Judah; Kufe, Donald W

    2002-09-15

    To perform a phase I trial of recombinant human endostatin (rhEndostatin; EntreMed, Rockville, MD) given as a daily 20-minute intravenous (IV) injection in adult patients with refractory solid tumors. The daily dose was increased from 15 to 240 mg/m(2) by a factor of 100% in cohorts of three patients. In the absence of dose-limiting toxicity, uninterrupted treatment was continued until the tumor burden increased by more than 50% from baseline. Correlative studies included dynamic contrast-enhanced magnetic resonance imaging of tumor blood flow, urinary vascular endothelial growth factor and basic fibroblast growth factor levels, rhEndostatin serum pharmacokinetics, and monitoring of circulating antibodies to rhEndostatin. There were no notable treatment related toxicities among 15 patients receiving a total of 50 monthly cycles of rhEndostatin. One patient with a pancreatic neuroendocrine tumor had a minor response and two patients showed disease stabilization. Linearity in the pharmacokinetics of rhEndostatin was indicated by dose-proportionate increases in the area under the curve for the first dose and the peak serum concentration at steady state. Daily systemic exposure to rhEndostatin in patients receiving 240 mg/m(2)/d was approximately 50% lower than that provided by the therapeutically optimal dose in preclinical studies. rhEndostatin administered as a 20-minute daily IV injection at doses up to 240 mg/m(2) showed no significant toxicities. Evidence of clinical benefit was observed in three patients. Due to high variability between the peak and trough serum concentrations associated with the repeated short IV infusion schedule, daily serum drug levels only briefly exceeded concentrations necessary for in vitro antiangiogenic effects.

  5. Efficacy and Safety of Basimglurant as Adjunctive Therapy for Major Depression: A Randomized Clinical Trial.

    PubMed

    Quiroz, Jorge A; Tamburri, Paul; Deptula, Dennis; Banken, Ludger; Beyer, Ulrich; Rabbia, Michael; Parkar, Nikhat; Fontoura, Paulo; Santarelli, Luca

    2016-07-01

    Antagonism of the postsynaptic metabotropic glutamate subtype 5 receptor is a novel approach to modulate glutamatergic function and has proven efficacy in a number of preclinical behavioral models of depression. To evaluate the safety and efficacy of basimglurant modified-release (MR) vs placebo as adjunctive therapy to ongoing antidepressant medication therapy in patients with MDD who had inadequate response within the current episode. In this phase 2b, double blind, randomized clinical trial of 333 adult patients with a DSM-IV-TR diagnosis of MDD across 59 research clinics globally, patients were assigned to 1 of 2 doses of basimglurant MR (0.5 or 1.5 mg) or placebo once daily, adjunctive to ongoing antidepressant medication therapy (selective serotonin reuptake inhibitor or serotonin and norepinephrine reuptake inhibitor). Patients were enrolled from October 5, 2011, through July 26, 2013. Six-week treatment with 0.5 mg of basimglurant MR, 1.5-mg basimglurant MR, or placebo once daily, adjunctive to ongoing antidepressant medication therapy. The primary end point was the mean change from baseline score on the Montgomery-Åsberg Depression Rating Scale (MADRS), as rated by the clinician at week 6. Other measures included patient-rated MADRS, Quick Inventory of Depressive Symptomatology-Self-Report, Clinical Global Impression-Improvement, Patient Global Impression-Improvement, and Clinical Global Impression-Severity Scales and adverse events. A total of 596 patients were screened, and 333 were randomized into the study (mean [SD] age, 47 [11.2] years; 216 female [65.1%]). The primary end point (mean change in clinician-rated MADRS score from baseline to end of treatment) was not met (effect size [ES] = 0.16, P = .42; intent-to-treat [ITT] mixed-effects model for repeated measures [MMRM] analysis for comparing 1.5-mg basimglurant MR and placebo). Across secondary and exploratory end points, 1.5-mg basimglurant MR revealed larger improvements vs placebo on

  6. Intricacy of missing data in clinical trials: Deterrence and management.

    PubMed

    Singhal, Richa; Rana, Rakesh

    2014-09-01

    Missing data is frequently encountered in clinical studies. Unfortunately, they are often neglected or not properly handled during data analysis and this may significantly bias the results of the study, reduce study power and lead to invalid conclusions. Substantial instances of missing data are a serious problem that undermines the scientific trustworthiness of causal conclusions from clinical trials. The assumption that statistical analysis methods can compensate for such missing data is not justified. Hence aspects of clinical trial design that limit the probability of missing data should be an important objective, while planning a clinical trial. In addition to specific aspects of trial design, many components of clinical trial conduct can also limit the extent of missing data. The topic of missing data is often not a major concern until it is time for data collection and data analysis. This article discusses some basic issues about missing data as well as prospective "watch outs" which could reduce the occurrence of missing data. It provides some possible design considerations that should be considered in order to alleviate patients from dropping out of a clinical trial. In addition to these the concept of the missing data mechanism has also been discussed. Three types of missing data mechanisms missing completely at random, missing at random and not missing at random have been discussed in detail.

  7. Rationale and design of the randomised clinical trial comparing early medication change (EMC) strategy with treatment as usual (TAU) in patients with Major Depressive Disorder - the EMC trial

    PubMed Central

    2010-01-01

    Background In Major Depressive Disorder (MDD), the traditional belief of a delayed onset of antidepressants' effects has lead to the concept of current guidelines that treatment durations should be between 3-8 weeks before medication change in case of insufficient outcome. Post hoc analyses of clinical trials, however, have shown that improvement usually occurs within the first 10-14 days of treatment and that such early improvement (Hamilton Depression Rating Scale [HAMD] decrease ≥20%) has a substantial predictive value for final treatment outcome. Even more important, non-improvement (HAMD decrease <20%) after 14 days of treatment was found to be highly predictive for a poor final treatment outcome. Methods/Design The EMC trial is a phase IV, multi-centre, multi-step, randomized, observer-blinded, actively controlled parallel-group clinical trial to investigate for the first time prospectively, whether non-improvers after 14 days of antidepressant treatment with an early medication change (EMC) are more likely to attain remission (HAMD-17 ≤7) on treatment day 56 compared to patients treated according to current guideline recommendation (treatment as usual; TAU). In level 1 of the EMC trial, non-improvers after 14 days of antidepressant treatment will be randomised to an EMC strategy or TAU. The EMC strategy for this study schedules a first medication change on day 15; in case of non-improvement between days 15-28, a second medication change will be performed. TAU schedules the first medication change after 28 days in case of non-response (HAMD-17 decrease <50%). Both interventions will last 42 days. In levels 2 and 3, EMC strategies will be compared with TAU strategies in improvers on day 14, who experience a stagnation of improvement during the course of treatment. The trial is supported by the German Federal Ministry of Education and Research (BMBF) and will be conducted in cooperation with the BMBF funded Interdisciplinary Centre Clinical Trials (IZKS) at

  8. June 6—7, 2011 Clinical Trials Conference: New Challenges & Opportunities | NIH MedlinePlus the Magazine

    MedlinePlus

    ... on. June 6–7, 2011 Clinical Trials Conference: New Challenges & Opportunities Past Issues / Spring 2011 Table of ... the important topic of clinical trials: “Clinical Trials: New Challenges and Opportunities.” On Monday and Tuesday, June ...

  9. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2005-01-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: (-)-Epigallocatechin gallate; ACP-103, Ad.Egr.TNF.11 D, adalimumab, AF-IL 12, AIDSVAX gp120 B/B, alefacept, alemtuzumab, a-Galactosylceramide, ALVAC vCP 1452, alvimopan hydrate, alvocidib hydrochloride, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, anakinra, anidulafungin, antarelix, aprepitant, aripiprazole, arsenic sulfide, asoprisnil, atazanavir sulfate, atomoxetine hydrochloride; Bevacizumab, bimatoprost, BMS-184476, bortezomib, bosentan, botulinum toxin type B, BrachySil, brivudine; Caffeine, calcipotriol/betamethasone dipropionate, cannabidiol, capsaicin for injection, caspofungin acetate, CC-4047, cetuximab, CGP-36742, clofazimine, CpG-7909, Cypher; Darbepoetin alfa, dextromethorphan/quinidine sulfate, dimethylfumarate, dronabinol/cannabidiol, drotrecogin alfa (activated), duloxetine hydrochloride, dutasteride; Ecogramostim, efalizumab, eletriptan, emtricitabine, enfuvirtide, eplerenone, esomeprazole magnesium, estradiol acetate, eszopiclone, etoricoxib, exenatide, ezetimibe, ezetimibe/simvastatin; Fampridine, fondaparinux sodium, fosamprenavir calcium; Gefitinib, GPI-0100; hA 20, HTU-PA, human insulin, HuOKT 3 gamma 1(Ala 234-Ala 235), hyaluronic acid; Icatibant, imatinib mesylate, Indiplon, INKP-100, INKP-102, iodine (I131) tositumomab, istradefylline, IV gamma-globulin, ivabradine hydrochloride, ixabepilone; Lacosamide, landiolol, lanthanum carbonate, lasofoxifene tartrate, LB-80380, lenalidomide, lidocaine/tetracaine, linezolid, liposomal doxorubicin, liposomal vincristine sulfate, lopinavir, lopinavir/ritonavir, lumiracoxib, lurtotecan; Maribavir, morphine glucuronide, MVA-5 T

  10. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2008-09-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com.This issue focuses on the following selection of drugs: ABT-263, AC-2307, Aclidinium bromide, Adefovir dipivoxil, ADH-1, Agatolimod sodium, Alefacept, Aliskiren fumarate, Aminolevulinic acid methyl ester, Anakinra, Apaziquone, Aprepitant, Aripiprazole, ASM-8, Atiprimod hydrochloride, AVE-0277, AVE-1642, AVE-8062, Axitinib, Azacitidine, AZD-0530; Bazedoxifene acetate, Bevacizumab, Bexarotene, BI-2536, Biphasic insulin aspart, BMS-387032, BMS-663513, Bortezomib, BQ-123, Brivanib alaninate, BSI-201; Caspofungin acetate, CDX-110, Cetuximab, Ciclesonide, CR-011, Cypher; Daptomycin, Darbepoetin alfa, Dasatinib, Decitabine, Deferasirox, Denosumab, Dexlansoprazole, Dexmethylphenidate hydrochloride, DNA-Hsp65 vaccine, Dovitinib, Drotrecogin alfa (activated), DTaP-HBV-IPV/Hibvaccine, DTaP-IPV-HB-PRP-T, Duloxetine hydrochloride, Dutasteride; Ecogramostim, Elacytarabine, Emtricitabine, Endothelin, Entecavir, Eplivanserin fumarate, Escitalopram oxalate, Everolimus, Ezetimibe, Ezetimibe/simvastatin; Farletuzumab, Fesoterodine fumarate, Fibrin sealant (human), Fulvestrant; Gefitinib, Gemtuzumab ozogamicin, Glufosfamide, GSK-1562902A; Hib-TT; Imatinib mesylate, IMC-11F8, Imidazoacridinone, IMP-321, INCB-18424, Indiplon, Indisulam, INNO-406, Irinotecan hydrochloride/Floxuridine, ITF-2357, Ixabepilone; KRN-951; Lasofoxifene tartrate; Lenalidomide, LGD-4665, Lonafarnib, Lubiprostone, Lumiliximab; MDX-1100, Melan-A/MART-1/gp100/IFN-alfa, Methyl-CDDO, Metreleptin, MLN-2704, Mycophenolic acid sodium salt; Na-ASP-2, Naproxcinod, Nilotinib hydrochloride monohydrate, NPI-2358; Oblimersen sodium, Odanacatib; Paclitaxel nanoparticles, PAN-811, Panobinostat, PBI-1402, PC-515, Peginterferon alfa

  11. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2006-03-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 131I-labetuzumab; Abacavir sulfate, abatacept, adalimumab, ademetionine, adjuvanted influenza vaccine, alefacept, alemtuzumab, amlodipine, amphotericin B, anakinra, aripiprazole, aspirin, axitinib; Betamethasone dipropionate, bevacizumab, biphasic insulin aspart, bortezomib, bosentan, botulinum toxin type B, BQ-123; Calcium folinate, canertinib dihydrochloride, carboplatin, carmustine, cetirizine hydrochloride, cetuximab, cholecalciferol, ciclesonide, ciclosporin, cinacalcet hydrochloride, cisplatin, clarithromycin, clofazimine, cold-adapted influenza vaccine trivalent, CpG-7909; Darbepoetin alfa, darifenacin hydrobromide, DB-289, desloratadine, Dexamet, dicycloverine hydrochloride, dimethyl fumarate, docetaxel, dolastatin 10, drospirenone, drospirenone/estradiol, duloxetine hydrochloride; Ecogramostim, edotecarin, efaproxiral sodium, enalapril maleate, epoetin beta, epoprostenol sodium, epratuzumab, erlotinib hydrochloride, escitalopram oxalate, estradiol, etanercept; Fluconazole, fludarabine phosphate, fluorouracil; Gefitinib, gemcitabine, Ghrelin (human), glibenclamide, glimepiride, GTI-2040; Haloperidol, human insulin, hydrocortisone probutate; Imatinib mesylate, indisulam, influenza vaccine, inhaled insulin, insulin aspart, insulin glulisine, insulin lispro, irinotecan, ispronicline; Lamivudine, lamivudine/zidovudine/abacavir sulfate, lapatinib, letrozole, levocetirizine, lomustine, lonafarnib, lumiracoxib;Magnesium sulfate, MD-1100, melphalan, metformin hydrochloride, methotrexate, metoclopramide hydrochloride, mitiglinide calcium hydrate, monophosphoryl lipid A, montelukast sodium, motexafin gadolinium

  12. Gender and Ethnicity as Moderators: Integrative Data Analysis of Multidimensional Family Therapy Randomized Clinical Trials

    PubMed Central

    Greenbaum, Paul E.; Wang, Wei; Hall, Kristin; Henderson, Craig E.; Kan, Lisa; Dakof, Gayle A.; Liddle, Howard A.

    2015-01-01

    This study examined gender and ethnicity as moderators of Multidimensional Family Therapy (MDFT) effectiveness for adolescent drug abuse and illustrated the utility of integrative data analysis (IDA, Bauer & Hussong, 2009) for assessing moderation. By pooling participant data from five independent MDFT randomized clinical trials (RCTs), IDA increased power to test moderation. Participants were 646 adolescents receiving treatment for drug use, aged 11 to 17 years (M = 15.31, SD = 1.30), with 19% female (n = 126), 14% (n = 92) European American, 35% (n = 225) Hispanic, and 51% (n = 329) African American. Participants were randomized to MDFT or active comparison treatments, which varied by study. Drug use involvement (i.e., frequency and consequences) was measured at study entry, 6-, and 12-months by a four-indicator latent variable. Growth curve change parameters from multiple calibration samples were regressed on treatment effects overall and by moderator subgroups. MDFT reduced drug use involvement (p < .05) for all participant groups. Pooled comparison groups reduced drug use involvement only for females and Hispanics (ps < .05). MDFT was more effective than comparisons for males, African Americans, and European Americans (ps <.05; Cohen's d = 1.17, 1.95, and 1.75, respectively). For females and Hispanics, there were no significant differences between MDFT and pooled comparison treatments, Cohen's d = 0.63 and 0.19, respectively. MDFT is an effective treatment for drug use among adolescents of both genders and varied ethnicity with males, African American, and White Non-Hispanic adolescents benefitting most from MDFT. PMID:26213796

  13. Immunotherapy Shown Safe in Type 1 Diabetes Clinical Trial

    MedlinePlus

    ... fullstory_167692.html Immunotherapy Shown Safe in Type 1 Diabetes Clinical Trial Next step is to see if ... and Human Services. More Health News on Diabetes Diabetes Type 1 Recent Health News Related MedlinePlus Health Topics Diabetes ...

  14. Systematic review of clinical efficacy of topical treatments for head lice.

    PubMed Central

    Vander Stichele, R. H.; Dezeure, E. M.; Bogaert, M. G.

    1995-01-01

    OBJECTIVES--To collect and evaluate all trials on clinical efficacy of topical treatments for head lice. DESIGN--Systematic review of randomised trials identified from following data sources: Medline, International Pharmaceutical Abstracts, Science Citation Index, letters to key authors and companies, and hand search of journals. SETTING--Trials in schools or communities. SUBJECTS--Patients infested with lice. MAIN OUTCOME MEASURE--Cure rate (absence of live lice and viable nits) on day 14 after treatment. RESULTS--Total of 28 trials were identified and evaluated according to eight general and 18 lice specific criteria. Of the 14 trials rated as having low to moderate risk of bias, seven were selected as they used the main outcome measure. These seven trials described 21 evaluations of eight different compounds and placebo (all but two evaluations were of single applications). Only permethrin 1% creme rinse showed efficacy in more than two studies with the lower 95% confidence limit of cure rate above 90%. CONCLUSIONS--Only for permethrin has sufficient evidence been published to show efficacy. Less expensive treatments such as malathion and carbaryl need more evidence of efficacy. Lindane and the natural pyrethrines are not sufficiently effective to justify their use. PMID:7545045

  15. Clinical Trials Information for Patients and Caregivers

    MedlinePlus

    ... Trials Phases of Clinical Trials Randomization Use of Placebos Research Team Members Paying for Clinical Trials Insurance ... types of clinical trials. Also, explains phases, randomization, placebo, and members of the research team. Paying for ...

  16. Adaptive clinical trial designs in oncology

    PubMed Central

    Zang, Yong; Lee, J. Jack

    2015-01-01

    Adaptive designs have become popular in clinical trial and drug development. Unlike traditional trial designs, adaptive designs use accumulating data to modify the ongoing trial without undermining the integrity and validity of the trial. As a result, adaptive designs provide a flexible and effective way to conduct clinical trials. The designs have potential advantages of improving the study power, reducing sample size and total cost, treating more patients with more effective treatments, identifying efficacious drugs for specific subgroups of patients based on their biomarker profiles, and shortening the time for drug development. In this article, we review adaptive designs commonly used in clinical trials and investigate several aspects of the designs, including the dose-finding scheme, interim analysis, adaptive randomization, biomarker-guided randomization, and seamless designs. For illustration, we provide examples of real trials conducted with adaptive designs. We also discuss practical issues from the perspective of using adaptive designs in oncology trials. PMID:25811018

  17. Searching ClinicalTrials.gov did not change the conclusions of a systematic review.

    PubMed

    Wilson, Lisa M; Sharma, Ritu; Dy, Sydney M; Waldfogel, Julie M; Robinson, Karen A

    2017-07-27

    We assessed the effect of searching ClinicalTrials.gov on the conclusions of a systematic review. We conducted this case study concurrently with a systematic review. We searched ClinicalTrials.gov on March 9, 2016, to identify trial records eligible for inclusion in the review. Two independent reviewers screened ClinicalTrials.gov records. We compared conclusions and strength of evidence grade with and without ClinicalTrials.gov records for 31 comparisons and 2 outcomes. We identified 106 trials (53 in the peer-reviewed literature only, 23 in ClinicalTrials.gov only, and 30 in both sources). For one comparison, the addition of results identified through ClinicalTrials.gov reduced the pooled effect size. We found evidence of selective outcome reporting for two comparisons and suspected publication bias for another two comparisons. For all other comparisons, searching ClinicalTrials.gov did not change conclusions or the strength of evidence grading for the two outcomes. Our search of ClinicalTrials.gov bolstered suspicions of reporting biases but did not change either the conclusions or the strength of evidence grading. Further research is needed to determine the effect of searching ClinicalTrials.gov on the conclusions of systematic reviews in different topic areas and as the new rules for registration of trial results take effect. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Improving transparency of clinical trials.

    PubMed

    Dal-Ré, Rafael

    2015-06-01

    Recent data reveal that subtle selective publication affects critical aspects of trial reporting, in some cases altering the interpretation of results. Timely prospective registration could help deter selective reporting and clinical trial stakeholders from government authorities to journal editors should work together to foster prospective registration of trials.

  19. Topical diclofenac therapy for osteoarthritis: a meta-analysis of randomized controlled trials.

    PubMed

    Deng, Zhen-Han; Zeng, Chao; Yang, Ye; Li, Yu-Sheng; Wei, Jie; Yang, Tuo; Li, Hui; Lei, Guang-Hua

    2016-05-01

    The objective of this study was to evaluate the efficacy and safety of topical diclofenac therapy for osteoarthritis (OA). A meta-analysis of randomized controlled trials was conducted. A comprehensive literature search, covering the databases of Medline, the Cochrane Central Register of Controlled Trials, and EMBASE, was conducted in September 2014 to identify the randomized controlled trials which adopted the topical diclofenac therapy for OA. A total of nine papers were included in this meta-analysis. Topical diclofenac appears to be effective in both pain relief (standard mean differences (SMD) = 0.40; 95 % confidence interval (CI) 0.19 to 0.62; P = 0.0003) and function improvement (SMD = 0.23; 95 % CI 0.03 to 0.43; P = 0.03) when compared with the control group. The sensitivity analysis and subgroup analysis showed that the result of pain intensity was stable and reliable, while the result of physical function improvement was vague. With respect to safety, topical diclofenac demonstrated a higher incidence of adverse events such as dry skin, rash, dermatitis, neck pain, and withdrawal. Topical diclofenac is effective in pain relief as a treatment of OA. It may also have a potential effect in function improvement, which needs further studies to be explored. Although, some adverse effects were observed in the application of topical diclofenac, none of them was serious.

  20. Clinical trial for evaluation of Ricinus communis and sodium hypochlorite as denture cleanser.

    PubMed

    Badaró, Maurício Malheiros; Salles, Marcela Moreira; Leite, Vanessa Maria Fagundes; Arruda, Carolina Noronha Ferraz de; Oliveira, Viviane de Cássia; Nascimento, Cássio do; Souza, Raphael Freitas de; Paranhos, Helena de Freitas de Oliveira; Silva-Lovato, Cláudia Helena

    2017-01-01

    This study evaluated Ricinus communis and sodium hypochlorite solutions in terms of biofilm removal ability, remission of candidiasis, antimicrobial activity, and participant satisfaction. It was conducted a controlled clinical trial, randomized, double-blind, and crossover. Sixty-four denture wearers with (n=24) and without candidiasis (n=40) were instructed to brush (3 times/day) and immerse their dentures (20 min/day) in different storage solutions (S1 / S2: 0.25% / 0.5% sodium hypochlorite; S3: 10% R. communis; S4: Saline).The trial period for each solution was seven days and a washout period of seven days was used before starting the use of another solution. The variables were analyzed at baseline and after each trial period. The biofilm of inner surfaces of maxillary dentures was disclosed, photographed, and total and dyed areas were measured (Image Tool software). The percentage of biofilm was calculated. Remission of candidiasis was assessed by visual scale and score were attributed. Antimicrobial activity was assessed by the DNA-Checkerboard hybridization method. Patient satisfaction was measured using a questionnaire. S1 (4.41±7.98%) and S2 (2.93±5.23%) were more effective then S3 (6.95±10.93%) in biofilm remotion(P<0.0001). All solutions were different from the control (11.07±11.99%). S3 was the most effective solution in remission of candidiasis (50%), followed by S1 (46%). Concerning antimicrobial action, S1/S2 were similar and resulted in the lowest microorganism mean count (P=0.04), followed by S3. No significant differences were found with patient's satisfaction. 10% R. communis and 0.25% sodium hypochlorite were effective in biofilm removal, causing remission of candidiasis and reducing the formation of microbial colonies in denture surfaces. All solutions were approved by patients.

  1. Internet based clinical trial protocols -- as applied to a study of warfarin pharmacogenetics.

    PubMed

    Lindh, Jonatan D; Kublickas, Marius; Westgren, Magnus; Rane, Anders

    2004-11-01

    To describe and evaluate the use of an Internet-based study protocol in a multicentre study of genetic risk factors in anticoagulant treatment. A web-based study protocol, similar to existing anticoagulation medical record systems, was developed for entry of clinical data. It was also supplied with a separate interface for study monitoring. Measures were taken to assure the confidentiality of transferred data. In addition, software modifications were made to enable automated transfer of clinical data from an existing medical record system to the study database. The system has been in use since March 2002, and at present 39 centres have included 909 patients with a dropout rate of 2.8%. The need for education of participating clinicians has been satisfactorily provided for by means of written instructions and telephone support. Our study demonstrates the usability of Internet-based data acquisition techniques in a full-scale multicentre clinical trial. The main advantages of such a protocol are automated data validation and standardization, fast data transfer independent of geographical distance, user feedback, synchronization of protocol updates and automatic data formatting facilitating statistical analyses. Safety and accessibility are possibly cumbersome areas and should be addressed duly.

  2. Spine device clinical trials: design and sponsorship.

    PubMed

    Cher, Daniel J; Capobianco, Robyn A

    2015-05-01

    Multicenter prospective randomized clinical trials represent the best evidence to support the safety and effectiveness of medical devices. Industry sponsorship of multicenter clinical trials is purported to lead to bias. To determine what proportion of spine device-related trials are industry-sponsored and the effect of industry sponsorship on trial design. Analysis of data from a publicly available clinical trials database. Clinical trials of spine devices registered on ClinicalTrials.gov, a publicly accessible trial database, were evaluated in terms of design, number and location of study centers, and sample size. The relationship between trial design characteristics and study sponsorship was evaluated using logistic regression and general linear models. One thousand six hundred thrity-eight studies were retrieved from ClinicalTrials.gov using the search term "spine." Of the 367 trials that focused on spine surgery, 200 (54.5%) specifically studied devices for spine surgery and 167 (45.5%) focused on other issues related to spine surgery. Compared with nondevice trials, device trials were far more likely to be sponsored by the industry (74% vs. 22.2%, odds ratio (OR) 9.9 [95% confidence interval 6.1-16.3]). Industry-sponsored device trials were more likely multicenter (80% vs. 29%, OR 9.8 [4.8-21.1]) and had approximately four times as many participating study centers (p<.0001) and larger sample sizes. There were very few US-based multicenter randomized trials of spine devices not sponsored by the industry. Most device-related spine research is industry-sponsored. Multicenter trials are more likely to be industry-sponsored. These findings suggest that previously published studies showing larger effect sizes in industry-sponsored vs. nonindustry-sponsored studies may be biased as a result of failure to take into account the marked differences in design and purpose. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Setting a Minimum Standard of Care in Clinical Trials: Human Rights and Bioethics as Complementary Frameworks.

    PubMed

    Marouf, Fatma E; Esplin, Bryn S

    2015-06-11

    For the past few decades, there has been intense debate in bioethics about the standard of care that should be provided in clinical trials conducted in developing countries. Some interpret the Declaration of Helsinki to mean that control groups should receive the best intervention available worldwide, while others interpret this and other international guidelines to mean the best local standard of care. Questions of justice are particularly relevant where limited resources mean that the local standard of care is no care at all. Introducing human rights law into this complex and longstanding debate adds a new and important perspective. Through non-derogable rights, including the core obligations of the right to health, human rights law can help set a minimum standard of care.

  4. Trimethoprim as adjuvant treatment in schizophrenia: a double-blind, randomized, placebo-controlled clinical trial.

    PubMed

    Shibre, Teshome; Alem, Atalay; Abdulahi, Abdulreshid; Araya, Mesfin; Beyero, Teferra; Medhin, Girmay; Deyassa, Negusse; Negash, Alemayehu; Nigatu, Alemayehu; Kebede, Derege; Fekadu, Abebaw

    2010-07-01

    Various infectious agents, such as Toxoplasma gondii, have been hypothesized to be potentially relevant etiological factors in the onset of some cases of schizophrenia. We conducted a randomized, double-blind, placebo-controlled treatment trial in an attempt to explore the hypothesis that the symptoms of schizophrenia may be related to infection of the central nervous system with toxoplasma gondii. Systematically selected patients with ongoing and at least moderately severe schizophrenia from Butajira, in rural Ethiopia, were randomly allocated to trimethoprim or placebo, which were added on to participants' regular antipsychotic treatments. Trial treatments were given for 6 months. The Positive and Negative Syndrome Scale (PANSS) was used to assess outcome. Ninety-one patients were included in the study, with 80 cases (87.9%) positive for T. gondii immunoglobulin G antibody. Seventy-nine subjects (87.0%) completed the trial. The mean age of subjects was 35.3 (SD = 8.0) years, with a mean duration of illness of 13.2 (SD = 6.7) years. Both treatment groups showed significant reduction in the overall PANSS score with no significant between-group difference. In this sample of patients with chronic schizophrenia, trimethoprim used as adjuvant treatment is not superior to placebo. However, it is not possible to draw firm conclusion regarding the etiological role of toxoplasmosis on schizophrenia based on this study because the timing and the postulated mechanisms through which toxoplasmosis produces schizophrenia are variable.

  5. The UK clinical research network--has it been a success for dermatology clinical trials?

    PubMed

    Thomas, Kim S; Koller, Karin; Foster, Katharine; Perdue, Jo; Charlesworth, Lisa; Chalmers, Joanne R

    2011-06-16

    Following the successful introduction of five topic-specific research networks in the UK, the Comprehensive Local Research Network (CLRN) was established in 2008 in order to provide a blanket level of support across the whole country regardless of the clinical discipline. The role of the CLRN was to facilitate recruitment into clinical trials, and to encourage greater engagement in research throughout the National Health Service (NHS). This report evaluates the impact of clinical research networks in supporting clinical trials in the UK, with particular reference to our experiences from two non-commercial dermatology trials. It covers our experience of engaging with the CLRN (and other research networks) using two non-commercial dermatology trials as case studies. We present the circumstances that led to our approach to the research networks for support, and the impact that this support had on the delivery of these trials. In both cases, recruitment was boosted considerably following the provision of additional support, although other factors such as the availability of experienced personnel, and the role of advertising and media coverage in promoting the trials were also important in translating this additional resource into increased recruitment. Recruitment into clinical trials is a complex task that can be influenced by many factors. A world-class clinical research infrastructure is now in place in England (with similar support available in Scotland and Wales), and it is the responsibility of the research community to ensure that this unique resource is used effectively and responsibly.

  6. The ethics of clinical trials

    PubMed Central

    Nardini, Cecilia

    2014-01-01

    Over the past decades, randomised controlled trials (RCTs) have prevailed over clinical judgement, case reports, and observational studies and became the gold evidential standard in medicine. Furthermore, during the same time frame, RCTs became a crucial part of the regulatory process whereby a new therapeutic can gain access to the drug market. Today, clinical trials are large and tightly regulated enterprises that have to comply with ethical requirements while maintaining high epistemic standards, a balance that becomes increasingly difficult as the research questions become more sophisticated. In this review, the author will discuss some of the most important ethical issues surrounding RCTs, with an eye to the most recent debates and the context of oncological research in particular. PMID:24482672

  7. Topical fluoride for caries prevention: executive summary of the updated clinical recommendations and supporting systematic review.

    PubMed

    Weyant, Robert J; Tracy, Sharon L; Anselmo, Theresa Tracy; Beltrán-Aguilar, Eugenio D; Donly, Kevin J; Frese, William A; Hujoel, Philippe P; Iafolla, Timothy; Kohn, William; Kumar, Jayanth; Levy, Steven M; Tinanoff, Norman; Wright, J Timothy; Zero, Domenick; Aravamudhan, Krishna; Frantsve-Hawley, Julie; Meyer, Daniel M

    2013-11-01

    A panel of experts convened by the American Dental Association (ADA) Council on Scientific Affairs presents evidence-based clinical recommendations regarding professionally applied and prescription-strength, home-use topical fluoride agents for caries prevention. These recommendations are an update of the 2006 ADA recommendations regarding professionally applied topical fluoride and were developed by using a new process that includes conducting a systematic review of primary studies. The authors conducted a search of MEDLINE and the Cochrane Library for clinical trials of professionally applied and prescription-strength topical fluoride agents--including mouthrinses, varnishes, gels, foams and pastes--with caries increment outcomes published in English through October 2012. The panel included 71 trials from 82 articles in its review and assessed the efficacy of various topical fluoride caries-preventive agents. The panel makes recommendations for further research. The panel recommends the following for people at risk of developing dental caries: 2.26 percent fluoride varnish or 1.23 percent fluoride (acidulated phosphate fluoride) gel, or a prescription-strength, home-use 0.05 percent fluoride gel or paste or 0.09 percent fluoride mouthrinse for patients 6 years or older. Only 2.26 percent fluoride varnish is recommended for children younger than 6 years. The strengths of the recommendations for the recommended products varied from "in favor" to "expert opinion for." As part of the evidence-based approach to care, these clinical recommendations should be integrated with the practitioner's professional judgment and the patient's needs and preferences.

  8. Comparative effectiveness of topical drugs in dermatologic priority diseases: geometry of randomized trial networks.

    PubMed

    Maruani, Annabel; Samimi, Mahtab; Lorette, Gérard; le Cleach, Laurence

    2015-01-01

    Among the 100 initial priority topics for comparative effectiveness research, three concern topical drugs in the following dermatologic diseases: psoriasis, chronic lower-extremity wounds (CLEWs), and acne vulgaris (AV). Our objective was to explore the geometry of the corresponding networks of randomized controlled trials (RCTs). We performed a review of RCTs on topical drugs in psoriasis, CLEWs, and AV. We searched MEDLINE, Embase, and CENTRAL for published trials from 2007 to 2012 and ClinicalTrials.gov for unpublished trials registered since 2011. RCTs comparing at least one topical treatment with any active or inactive comparator, regardless of RCT design and outcomes, were eligible. We produced network graphs (each node representing a treatment and links between nodes representing trials) and tested for co-occurrence (preference or avoidance of specific comparisons). We included 60 RCTs on psoriasis (14,255 patients) and 19 registered RCTs, 50 of CLEWs (5,916 patients) and 7 registered RCTs, and 90 of AV (22,984 patients) and 21 registered RCTs. Head-to-head comparisons were made in 78%, 32%, and 57% of published RCTs of these conditions, respectively. The co-occurrence test suggested that no specific head-to-head comparison was significantly preferred or avoided (P-value=0.53, 0.20, and 0.57, respectively). This study has limitations, the main being that the search period was restricted to 5 years. In conclusion, more comparative effectiveness trials are needed for CLEWs, for which head-to-head comparisons are fewer than those for psoriasis and AV.

  9. [Internet use in clinical trials].

    PubMed

    Refolo, P; Sacchini, D; Minacori, R; Spagnolo, A G

    2014-01-01

    Recruiting patients is a critical point of today's clinical research and, along the years, several solutions have been proposed, even if their efficacy seems to be doubtful. On the other hand, nowadays, Internet represents a great opportunity for improving clinical trial recruitments. Nevertheless, on-line recruitment services (e-recruitment) could ensure some advantages (such as facilitating interaction between supply and demand of clinical research, time and money savings/optimizations, data entry errors reduction), but also raise some issues (such as those related to sampling, information, consent, real identity of participants and risks for data breaches). The article debates on the difficulties to recruit patients for clinical research, in general, and e-recruitment particularly, discussing some ethical issues raised by internet enrolment.

  10. Statistical Controversies in Reporting of Clinical Trials: Part 2 of a 4-Part Series on Statistics for Clinical Trials.

    PubMed

    Pocock, Stuart J; McMurray, John J V; Collier, Tim J

    2015-12-15

    This paper tackles several statistical controversies that are commonly faced when reporting a major clinical trial. Topics covered include: multiplicity of data, interpreting secondary endpoints and composite endpoints, the value of covariate adjustment, the traumas of subgroup analysis, assessing individual benefits and risks, alternatives to analysis by intention to treat, interpreting surprise findings (good and bad), and the overall quality of clinical trial reports. All is put in the context of topical cardiology trial examples and is geared to help trialists steer a wise course in their statistical reporting, thereby giving readers a balanced account of trial findings.

  11. The Dynamo Clinical Trial

    NASA Astrophysics Data System (ADS)

    Ayres, Thomas R.

    2016-04-01

    The Dynamo Clinical Trial evaluates long-term stellar magnetic health through periodic X-ray examinations (by the Chandra Observatory). So far, there are only three subjects enrolled in the DTC: Alpha Centauri A (a solar-like G dwarf), Alpha Cen B (an early K dwarf, more active than the Sun), and Alpha Canis Majoris A (Procyon, a mid-F subgiant similar in activity to the Sun). Of these, Procyon is a new candidate, so it is too early to judge how it will fare. Of the other two, Alpha Cen B has responded well, with a steady magnetic heartbeat of about 8 years duration. The sickest of the bunch, Alpha Cen A, was in magnetic cardiac arrest during 2005-2010, but has begun responding to treatment in recent years, and seems to be successfully cycling again, perhaps achieving a new peak of magnetic health in the 2016 time frame. If this is the case, it has been 20 years since A's last healthful peak, significantly longer than the middle-aged Sun's 11-year magnetic heartbeat, but perhaps in line with Alpha Cen A's more senescent state (in terms of "relative evolutionary age," apparently an important driver of activity). (By the way, don't miss the exciting movie of the Alpha Cen stars' 20-year X-ray dance.)

  12. Clinical trials in cancer research.

    PubMed Central

    Gehan, E A

    1979-01-01

    This is a review paper which gives a discussion of various aspects of clinical trials in cancer research. Since the conduct of the first randomized controlled clinical trial in cancer patients in the mid-1950's, substantial progress has been made in the utilization of the clinical trial technique for the evaluation of therapeutic efficiacy. The important elements of a protocol are given with some discussion of items to be considered in designing a protocol. The types of clinical trial (phase I, II, III) are defined, and the place of each phase of study in the context of the search for new treatments is delineated. A comprehensive discussion is given of the elements in the comparative clinical trial (phase III), including objectives, consierations in planning (comparability of treatment groups stratification of patients, feasibility and size of study, and prospective versus retrospective studies). Brief descriptions are given of designs for comparative clinical trials and a trial in oat cell lung carcinoma is discussed in some detail. Finally, some comments and references are given concerning the analysis of clinical trials. PMID:232043

  13. Diphenhydramine as adjuvant therapy for acute migraine. An ED-based randomized clinical trial

    PubMed Central

    Friedman, Benjamin W; Cabral, Lisa; Adewunmi, Victoria; Solorzano, Clemencia; Esses, David; Bijur, Polly E; Gallagher, E John

    2015-01-01

    Background More than one million patients present to US emergency departments (ED) annually seeking care for acute migraine. Parenteral anti-histamines have long been used in combination with anti-dopaminergics such as metoclopramide to treat acute migraine in the ED. High quality data supporting this practice do not exist. We determined whether administration of diphenhydramine 50mg IV + metoclopramide 10mg IV resulted in greater rates of sustained headache relief than placebo+ metoclopramide 10mg IV. Methods This was a randomized, double-blind clinical trial comparing two active treatments for acute migraine in an ED. Eligible patients were adults younger than 65 years presenting with an acute moderate or severe headache meeting International Classification of Headache Disorders-2 migraine criteria. Patients were stratified based on presence or absence of allergic symptoms. The primary outcome was sustained headache relief, defined as achieving a headache level of mild or none within two hours of medication administration, and maintaining this level of relief without use of any additional headache medication for 48 hours. Secondary efficacy outcomes include mean improvement on a 0 to 10 verbal scale between baseline and one hour, the frequency with which subjects indicated they would want the same medication the next time they present to the ED with migraine, and the ED throughput time. Sample size calculation using a 2-sided alpha of 0.05, a beta of 0.20 and a 15% difference between study arms determined the need for 374 patients. An interim analysis was conducted when data were available for 200 subjects. Results 420 patients were approached for participation. 208 eligible patients consented to participate and were randomized. At the planned interim analysis, the data safety monitoring committee recommended that the study be halted for futility. Baseline characteristics were comparable between the groups. 14% (29/208) of the sample reported allergic symptoms

  14. Data monitoring committees for pragmatic clinical trials.

    PubMed

    Ellenberg, Susan S; Culbertson, Richard; Gillen, Daniel L; Goodman, Steven; Schrandt, Suzanne; Zirkle, Maryan

    2015-10-01

    In any clinical trial, it is essential to monitor the accumulating data to be sure that the trial continues to be safe for participants and that the trial is being conducted properly. Data monitoring committees, independent expert panels who undertake regular reviews of the data as the trial progresses, serve an important role in safeguarding the interests of research participants and ensuring trial integrity in many trials. Many pragmatic clinical trials, which aim to inform healthcare decisions by comparing alternate interventions in heterogeneous healthcare delivery settings, will warrant review by an independent data monitoring committee due to their potential impact on clinical practice. However, the very features that make a trial "pragmatic" may pose challenges in terms of which aspects of a trial to monitor and when it is appropriate for a data monitoring committee to intervene. Using the Pragmatic-Explanatory Continuum Indicator Summary tool that draws distinctions between pragmatic and explanatory clinical trials, we review characteristics of pragmatic clinical trials that may have implications for data monitoring committees and interim monitoring plans. These include broad eligibility criteria, a focus on subjective patient-centered outcomes, and in some cases a lack of standardized follow-up procedures across study sites. Additionally, protocol adherence is often purposefully not addressed in pragmatic trials in order to accurately represent the clinical practice setting and maintain practicability of implementation; there are differing viewpoints as to whether adherence should be assessed and acted upon by data monitoring committees in these trials. Some other issues not specifically related to the Pragmatic-Explanatory Continuum Indicator Summary criteria may also merit special consideration in pragmatic trials. Thresholds for early termination of a pragmatic clinical trial might be controversial. The distinguishing features of pragmatic clinical

  15. κ-opioid Receptor Gene as a Predictor of Response in a Cocaine Vaccine Clinical Trial

    PubMed Central

    Nielsen, D.A.; Hamon, S.C.; Kosten, T.R.

    2013-01-01

    Objectives We examined a pharmacogenetic association between a variant in the κ-opioid receptor (OPRK1) gene and the response to treatment with a cocaine vaccine tested in a recent clinical trial. This gene has a protective allele for opiate addiction that may act by inhibiting dopamine activation associated with reinforcement. Methods Sixty-nine DNA samples were obtained from 114 cocaine and opioid dependent subjects who were enrolled in a 16 week Phase IIb randomized double-blind placebo-controlled trial and who received five vaccinations over the first 12 weeks. We genotyped 66 of these subjects for the rs6473797 variant of the OPRK1 gene and we compared vaccine to placebo subjects in terms of cocaine-free urines over time. Results Using repeated measures analysis of variance, corrected for population structure, vaccine pharmacotherapy reduced cocaine positive urines significantly based on OPRK1 genotype. In subjects treated with the cocaine vaccine, those who were homozygous for the protective A allele of rs6473797 had the proportion of positive urines drop from 78% to 51% on vaccine (point-wise P < .0001, experiment-wise P <.005), while the positive urines of those individuals carrying the non-protective, risk G allele dropped from 82% to 77%. Strong interactions of treatment by SNP (single nucleotide polymorphism) reflected a lower baseline and significant reduction for placebo subjects with the risk G allele (P <0.00001). Conclusions This study indicates that a patient’s OPRK1 genotype could be used to identify a subset of individuals for which vaccine treatment may be an effective pharmacotherapy for cocaine dependence. PMID:23995774

  16. Clinical trial for evaluation of Ricinus communis and sodium hypochlorite as denture cleanser

    PubMed Central

    BADARÓ, Maurício Malheiros; SALLES, Marcela Moreira; LEITE, Vanessa Maria Fagundes; de ARRUDA, Carolina Noronha Ferraz; OLIVEIRA, Viviane de Cássia; do NASCIMENTO, Cássio; de SOUZA, Raphael Freitas; PARANHOS, Helena de Freitas de Oliveira; SILVA-LOVATO, Cláudia Helena

    2017-01-01

    Abstract The development of opportunistic infections due to poor denture hygiene conditions justified the search for effective hygiene protocols for controlling denture biofilm. Objective This study evaluated Ricinus communis and sodium hypochlorite solutions in terms of biofilm removal ability, remission of candidiasis, antimicrobial activity, and participant satisfaction. Material and Methods It was conducted a controlled clinical trial, randomized, double-blind, and crossover. Sixty-four denture wearers with (n=24) and without candidiasis (n=40) were instructed to brush (3 times/day) and immerse their dentures (20 min/day) in different storage solutions (S1 / S2: 0.25% / 0.5% sodium hypochlorite; S3: 10% R. communis; S4: Saline).The trial period for each solution was seven days and a washout period of seven days was used before starting the use of another solution. The variables were analyzed at baseline and after each trial period. The biofilm of inner surfaces of maxillary dentures was disclosed, photographed, and total and dyed areas were measured (Image Tool software). The percentage of biofilm was calculated. Remission of candidiasis was assessed by visual scale and score were attributed. Antimicrobial activity was assessed by the DNA-Checkerboard hybridization method. Patient satisfaction was measured using a questionnaire. Results S1 (4.41±7.98%) and S2 (2.93±5.23%) were more effective then S3 (6.95±10.93%) in biofilm remotion(P<0.0001). All solutions were different from the control (11.07±11.99%). S3 was the most effective solution in remission of candidiasis (50%), followed by S1 (46%). Concerning antimicrobial action, S1/S2 were similar and resulted in the lowest microorganism mean count (P=0.04), followed by S3. No significant differences were found with patient’s satisfaction. Conclusions 10% R. communis and 0.25% sodium hypochlorite were effective in biofilm removal, causing remission of candidiasis and reducing the formation of microbial

  17. Bayesian Clinical Trials in Action

    PubMed Central

    Lee, J. Jack; Chu, Caleb T.

    2012-01-01

    Although the frequentist paradigm has been the predominant approach to clinical trial design since the 1940s, it has several notable limitations. The alternative Bayesian paradigm has been greatly enhanced by advancements in computational algorithms and computer hardware. Compared to its frequentist counterpart, the Bayesian framework has several unique advantages, and its incorporation into clinical trial design is occurring more frequently. Using an extensive literature review to assess how Bayesian methods are used in clinical trials, we find them most commonly used for dose finding, efficacy monitoring, toxicity monitoring, diagnosis/decision making, and for studying pharmacokinetics/pharmacodynamics. The additional infrastructure required for implementing Bayesian methods in clinical trials may include specialized software programs to run the study design, simulation, and analysis, and Web-based applications, which are particularly useful for timely data entry and analysis. Trial success requires not only the development of proper tools but also timely and accurate execution of data entry, quality control, adaptive randomization, and Bayesian computation. The relative merit of the Bayesian and frequentist approaches continues to be the subject of debate in statistics. However, more evidence can be found showing the convergence of the two camps, at least at the practical level. Ultimately, better clinical trial methods lead to more efficient designs, lower sample sizes, more accurate conclusions, and better outcomes for patients enrolled in the trials. Bayesian methods offer attractive alternatives for better trials. More such trials should be designed and conducted to refine the approach and demonstrate its real benefit in action. PMID:22711340

  18. Bayesian clinical trials in action.

    PubMed

    Lee, J Jack; Chu, Caleb T

    2012-11-10

    Although the frequentist paradigm has been the predominant approach to clinical trial design since the 1940s, it has several notable limitations. Advancements in computational algorithms and computer hardware have greatly enhanced the alternative Bayesian paradigm. Compared with its frequentist counterpart, the Bayesian framework has several unique advantages, and its incorporation into clinical trial design is occurring more frequently. Using an extensive literature review to assess how Bayesian methods are used in clinical trials, we find them most commonly used for dose finding, efficacy monitoring, toxicity monitoring, diagnosis/decision making, and studying pharmacokinetics/pharmacodynamics. The additional infrastructure required for implementing Bayesian methods in clinical trials may include specialized software programs to run the study design, simulation and analysis, and web-based applications, all of which are particularly useful for timely data entry and analysis. Trial success requires not only the development of proper tools but also timely and accurate execution of data entry, quality control, adaptive randomization, and Bayesian computation. The relative merit of the Bayesian and frequentist approaches continues to be the subject of debate in statistics. However, more evidence can be found showing the convergence of the two camps, at least at the practical level. Ultimately, better clinical trial methods lead to more efficient designs, lower sample sizes, more accurate conclusions, and better outcomes for patients enrolled in the trials. Bayesian methods offer attractive alternatives for better trials. More Bayesian trials should be designed and conducted to refine the approach and demonstrate their real benefit in action.

  19. HLA-DR EXPRESSION AS A BIOMARKER OF INFLAMMATION FOR MULTICENTER CLINICAL TRIALS OF OCULAR SURFACE DISEASE

    PubMed Central

    Epstein, Seth P.; Gadaria-Rathod, Neha; Wei, Yi; Maguire, Maureen G.; Asbell, Penny A.

    2014-01-01

    There are currently no validated minimally invasive objective metrics for the classification and evaluation of ocular surface diseases and/or for evaluating treatment efficacy. We thus sought to establish a standardized methodology for determining the relative amount of the inflammatory biomarker HLA-DR on the ocular surface and to evaluate the precision, reliability and repeatability of its use for large multicenter clinical trials and translational research studies of ocular surface disease. Multiple studies were conducted to establish a Standard Operating Procedure (SOP) for utilizing HLA-DR expression as a minimally invasive, objective, ocular surface inflammatory biomarker. The established SOPs provide specific guidelines for HLA-DR collection and analysis, in order to incorporate it reliably into multicenter clinical trials and/or translational research. Duplicate cell samples from impression cytology (IC) samples of both normal and dry eye individuals were collected and split to assess repeatability (between the splits and between the duplicate samples). To determine storage capability, one duplicate was stained immediately and the other after 30 days cold storage. To demonstrate the feasibility of the use of the SOP for a multicenter clinical trial, clinicians out-of-state were trained to collect IC samples, and the samples shipped to our Biomarker Laboratory, logged, processed and analyzed. Demonstration of the ability to incorporate of IC into a randomized double masked clinical trial of dry eye disease (DED) was performed. In all cases, processing and analyses were performed by a masked independent observer. The validity/viability of the SOPs was established by demonstrating that: 1) sufficient numbers of cells can be collected via IC; 2) the precision/repeatability of the relative biomarker expression quantified in samples; 3) personnel at distant sites can be taught to collect, store and ship samples successfully; 4) samples can be stored for up to 30

  20. Interview "Problems" as Topics for Analysis

    ERIC Educational Resources Information Center

    Roulston, Kathryn

    2011-01-01

    In this article the author argues that interactional difficulties and questioning practices identified in the methodological literature on qualitative interviewing as "problems" provide topics of analysis. Methodological examinations of interview data drawing on conversation analysis also explicate how interview "problems" may be conceptualized in…

  1. Interview "Problems" as Topics for Analysis

    ERIC Educational Resources Information Center

    Roulston, Kathryn

    2011-01-01

    In this article the author argues that interactional difficulties and questioning practices identified in the methodological literature on qualitative interviewing as "problems" provide topics of analysis. Methodological examinations of interview data drawing on conversation analysis also explicate how interview "problems" may be conceptualized in…

  2. Constructing a trial as a personal lifestyle change project: participants' experiences in a clinical study for nicotine vaccination.

    PubMed

    Wolters, Anna; de Wert, Guido; van Schayck, Onno; Horstman, Klasien

    2014-03-01

    The purpose of this study was to gain insight into the experiences and dynamics of the involvement of research participants in a randomized clinical trial for nicotine vaccination. Participants received an experimental nicotine vaccine or a placebo, in addition to quit smoking medication and counseling. The longitudinal design of this qualitative study allowed us to follow people from their first visit to the trial location until the unblinding of their treatment with either verum or placebo vaccine. The empirical data consisted of 49 semi-structured, in-depth interviews, field notes and memos, and trial documents collected in the Netherlands between 2010 and 2012. Participants' expectations and experiences of the innovative nicotine vaccine were characterized by ambivalence: Although they complied with the research design, throughout the study they tinkered with discourses, objects, and activities to make them serve their individual goals. They made the concepts of nicotine vaccination and placebo treatment meaningful for quitting, reshaped the meaning of research tests and obligatory visits to serve their own personal goals, and introduced a new element into the trial by creating space to discuss problems that might endanger the quit attempt. In short, the participants constructed the clinical study for nicotine vaccination as their own personal lifestyle change project. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Antiphospholipid syndrome (Hughes syndrome): 10 clinical topics.

    PubMed

    Hughes, G R V

    2010-04-01

    This year in Galveston, Texas, Silvia Pierangeli hosts the 13th International Congress on Antiphospholipid Antibodies. Twenty-six years after the first antiphospholipid syndrome meeting, the number of interested colleagues has multiplied, and the subject has become more scientifically understood. So also has the clinical picture. In this short contribution, I will highlight a number of clinical observations which may, or may not, contribute to our understanding of antiphospholipid syndrome.

  4. Topical tazarotene: The BEST (balancing efficacy, speed, and tolerability) in acne trial.

    PubMed

    Shalita, Alan

    2004-10-01

    Results of clinical trials have shown that tazarotene cream used as monotherapy effectively reduces the number of both inflammatory and noninflammatory lesions in patients with acne vulgaris. The efficacy of tazarotene cream in clinical practice, however, has not been reported. To evaluate the benefits of tazarotene cream in everyday clinical practice, an uncontrolled observational study was conducted in a large population of patients with facial acne vulgaris; 243 investigators enrolled 1118 patients for treatment with once-daily tazarotene 0. 1% cream as monotherapy, or in combination with other agents, for up to 12 weeks. Tazarotene efficacy was well rated by both investigators and patients and had a rapid onset of action. Reduction in comedone counts was greatest when tazarotene 0.1% was used as first-line therapy. The incidence of adverse events (almost exclusively peeling, erythema, dryness, or burning) was low and typically declined with continued use of the medication. The combination of tazarotene 0.1% cream and clindamycin-benzoyl peroxide was the best tolerated of all the treatment regimens. Patients and investigators reported high levels of treatment satisfaction with topical tazarotene 0.1% cream.

  5. Clinical Trials and the Role of the Oncology Clinical Trials Nurse.

    PubMed

    Ness, Elizabeth A; Royce, Cheryl

    2017-03-01

    Clinical trials are paramount to improving human health. New trial designs and informed consent issues are emerging as a result of genomic profiling and the development of molecularly targeted agents. Many groups and individuals are responsible for ensuring the protection of research participants and the quality of the data produced. The specialty role of the clinical trials nurse (CTN) is critical to clinical trials. Oncology CTNs have competencies that can help guide their practice; however, not all oncology clinical trials are supervised by a nurse. Using the process of engagement, one organization has restructured oncology CTNs under a nurse-supervised model.

  6. [Pre-anesthetic medication with intranasal dexmedetomidine and oral midazolam as an anxiolytic. A clinical trial].

    PubMed

    Linares Segovia, B; García Cuevas, M A; Ramírez Casillas, I L; Guerrero Romero, J F; Botello Buenrostro, I; Monroy Torres, R; Ramírez Gómez, X S

    2014-10-01

    Dexmedetomidine is a pharmacological option for sedation in children. In this study, the efficacy of intranasal dexmedetomidine to reduce preoperative anxiety in pediatric patients is compared with that of oral midazolam. A prospective, randomized, double-blind, controlled trial was conducted on children 2-12 years of age, randomly assigned to one of the following two groups: group A received premedication with oral midazolam and intranasal placebo, group B received intranasal dexmedetomidine and oral placebo. Anxiety was assessed with the modified Yale scale, and a risk analysis and number needed to treat was performed. A total of 108 patients were included, 52 (48.1%) treated with dexmedetomidine, and 56 (51.9%) with midazolam. Anxiety was less frequent in the dexmedetomidine group at 60minutes (P=.001), induction (p=.04), and recovery (P=.0001). Risk analysis showed that dexmedetomidine reduced the risk of anxiety by 28% (RAR=0.28, 95% CI; 0.12 to 0.43) and to prevent one case of anxiety, four patients need to be treated with intranasal dexmedetomidine (NNT=4, 95% CI: 3-9).Changes in heart rate, mean arterial pressure, and oxygen saturation, were statistically significant in the dexmedetomidine group, with no clinical consequences. There were no cases of bradycardia, hypotension or oxygen desaturation. Intranasal dexmedetomidine premedication is more effective than oral midazolam to reduce preoperative anxiety in pediatric patients. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  7. Antimicrobial Peptides Under Clinical Trials.

    PubMed

    Greber, Katarzyna E; Dawgul, Małgorzata

    2017-01-01

    Today microbial drug resistance has become a serious problem not only within inpatient setting but also within outpatient setting. Repeated intake and unnecessary usage of antibiotics as well as the transfer of resistance genes are the most important factors that make the microorganisms resistant to conventional antibiotics. A large number of antimicrobials successfully used for prophylaxis and therapeutic purposes have now become ineffective [1, 2]. Therefore, new molecules are being studied to be used in the treatment of various diseases. Some of these molecules are structural compounds based on a combination of peptides, for example, naturally occurring endogenous peptide antibiotics and their synthetic analogues or molecules designed de novo using QSAR (quantitative structureproperty relationships)-based methods [3]. Trying to exploit numerous advantages of antimicrobial peptides such as high potency and selectivity, broad range of targets, potentially low toxicity and low accumulation in tissues, pharmaceutical industry aims to develop them as commercially available drugs and appropriate clinical trials are being conducted [4]. In this paper we define clinical trials steps and describe current status of several antimicrobial peptides under clinical development as well as briefly depict peptide drug formulation.

  8. Trial analytics--a tool for clinical trial management.

    PubMed

    Bose, Anindya; Das, Suman

    2012-01-01

    Prolonged timelines and large expenses associated with clinical trials have prompted a new focus on improving the operational efficiency of clinical trials by use of Clinical Trial Management Systems (CTMS) in order to improve managerial control in trial conduct. However, current CTMS systems are not able to meet the expectations due to various shortcomings like inability of timely reporting and trend visualization within/beyond an organization. To overcome these shortcomings of CTMS, clinical researchers can apply a business intelligence (BI) framework to create Clinical Research Intelligence (CLRI) for optimization of data collection and analytics. This paper proposes the usage of an innovative and collaborative visualization tool (CTA) as CTMS "add-on" to help overwhelm these deficiencies of traditional CTMS, with suitable examples.

  9. Patient-centeredness in the design of clinical trials.

    PubMed

    Mullins, C Daniel; Vandigo, Joseph; Zheng, Zhiyuan; Wicks, Paul

    2014-06-01

    Evidence from clinical trials should contribute to informed decision making and a learning health care system. People frequently, however, find participating in clinical trials meaningless or disempowering. Moreover, people often do not incorporate trial results directly into their decision making. The lack of patient centeredness in clinical trials may be partially addressed through trial design. For example, Bayesian adaptive trials designed to adjust in a prespecified manner to changes in clinical practice could motivate people and their health care providers to view clinical trials as more applicable to real-world clinical decisions. The way in which clinical trials are designed can transform the evidence generation process to be more patient centered, providing people with an incentive to participate or continue participating in clinical trials. To achieve the transformation to patient-centeredness in clinical trial decisions, however, there is a need for transparent and reliable methods and education of trial investigators and site personnel.

  10. Patient-centeredness in the design of clinical trials

    PubMed Central

    Mullins, C. Daniel; Vandigo, Joseph E.; Zheng, Jason; Wicks, Paul

    2014-01-01

    Evidence from clinical trials should contribute to informed decision making and a learning health care system. People frequently, however, find participating in clinical trials meaningless or disempowering. Moreover, people often do not incorporate trial results directly into their decision making. The lack of patient centeredness in clinical trials may be partially addressed through trial design. For example, Bayesian adaptive trials designed to adjust in a pre-specified manner to changes in clinical practice could motivate people and their health care providers to view clinical trials as more applicable to real-world clinical decisions. The way in which clinical trials are designed can transform the evidence generation process to be more patient centered, providing people with an incentive to participate or continue participating in clinical trials. In order to achieve the transformation to patient-centeredness in clinical trial decisions, however, there is a need for transparent and reliable methods and education of trial investigators and site personnel. PMID:24969009

  11. Clinical trials in neonatal sepsis.

    PubMed

    Oeser, Clarissa; Lutsar, Irja; Metsvaht, Tuuli; Turner, Mark A; Heath, Paul T; Sharland, Mike

    2013-12-01

    Antibiotic licensing studies remain a problem in neonates. The classical adult clinical syndrome-based licensing studies do not apply to neonates, where sepsis is the most common infection. The main obstacle to conducting neonatal antibiotic trials is a lack of consensus on the definition of neonatal sepsis itself and the selection of appropriate endpoints. This article describes the difficulties of the clinical and laboratory definitions of neonatal sepsis and reviews the varying designs of previous neonatal sepsis trials. The optimal design of future trials of new antibiotics will need to be based on pharmacokinetic/pharmacodynamic parameters, combined with adequately powered clinical studies to determine safety and efficacy.

  12. OARSI Clinical Trials Recommendations: Design and conduct of clinical trials of lifestyle diet and exercise interventions for osteoarthritis.

    PubMed

    Messier, S P; Callahan, L F; Golightly, Y M; Keefe, F J

    2015-05-01

    The objective was to develop a set of "best practices" for use as a primer for those interested in entering the clinical trials field for lifestyle diet and/or exercise interventions in osteoarthritis (OA), and as a set of recommendations for experienced clinical trials investigators. A subcommittee of the non-pharmacologic therapies committee of the OARSI Clinical Trials Working Group was selected by the Steering Committee to develop a set of recommended principles for non-pharmacologic diet/exercise OA randomized clinical trials. Topics were identified for inclusion by co-authors and reviewed by the subcommittee. Resources included authors' expert opinions, traditional search methods including MEDLINE (via PubMed), and previously published guidelines. Suggested steps and considerations for study methods (e.g., recruitment and enrollment of participants, study design, intervention and assessment methods) were recommended. The recommendations set forth in this paper provide a guide from which a research group can design a lifestyle diet/exercise randomized clinical trial in patients with OA.

  13. Informed Consent (Clinical Trials)

    MedlinePlus

    ... Credit: National Cancer Institute Informed consent is a process through which you learn details about the trial before deciding whether to take part. This includes learning about the trial’s purpose and possible risks and ...

  14. The Potential Role of Sensory Testing, Skin Biopsy, and Functional Brain Imaging as Biomarkers in Chronic Pain Clinical Trials: IMMPACT Considerations.

    PubMed

    Smith, Shannon M; Dworkin, Robert H; Turk, Dennis C; Baron, Ralf; Polydefkis, Michael; Tracey, Irene; Borsook, David; Edwards, Robert R; Harris, Richard E; Wager, Tor D; Arendt-Nielsen, Lars; Burke, Laurie B; Carr, Daniel B; Chappell, Amy; Farrar, John T; Freeman, Roy; Gilron, Ian; Goli, Veeraindar; Haeussler, Juergen; Jensen, Troels; Katz, Nathaniel P; Kent, Jeffrey; Kopecky, Ernest A; Lee, David A; Maixner, William; Markman, John D; McArthur, Justin C; McDermott, Michael P; Parvathenani, Lav; Raja, Srinivasa N; Rappaport, Bob A; Rice, Andrew S C; Rowbotham, Michael C; Tobias, Jeffrey K; Wasan, Ajay D; Witter, James

    2017-02-27

    Valid and reliable biomarkers can play an important role in clinical trials as indicators of biological or pathogenic processes or as a signal of treatment response. Currently, there are no biomarkers for pain qualified by the U.S. Food and Drug Administration or the European Medicines Agency for use in clinical trials. This article summarizes an Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials meeting in which 3 potential biomarkers were discussed for use in the development of analgesic treatments: 1) sensory testing, 2) skin punch biopsy, and 3) brain imaging. The empirical evidence supporting the use of these tests is described within the context of the 4 categories of biomarkers: 1) diagnostic, 2) prognostic, 3) predictive, and 4) pharmacodynamic. Although sensory testing, skin punch biopsy, and brain imaging are promising tools for pain in clinical trials, additional evidence is needed to further support and standardize these tests for use as biomarkers in pain clinical trials.

  15. The potential role of sensory testing, skin biopsy, and functional brain imaging as biomarkers in chronic pain clinical trials: IMMPACT considerations

    PubMed Central

    Smith, Shannon M.; Dworkin, Robert H.; Turk, Dennis C.; Baron, Ralf; Polydefkis, Michael; Tracey, Irene; Borsook, David; Edwards, Robert R.; Harris, Richard E.; Wager, Tor D.; Arendt-Nielsen, Lars; Burke, Laurie B.; Carr, Daniel B.; Chappell, Amy; Farrar, John T.; Freeman, Roy; Gilron, Ian; Goli, Veeraindar; Haeussler, Juergen; Jensen, Troels; Katz, Nathaniel P.; Kent, Jeffrey; Kopecky, Ernest A.; Lee, David A.; Maixner, William; Markman, John D.; McArthur, Justin C.; McDermott, Michael P.; Parvathenani, Lav; Raja, Srinivasa N.; Rappaport, Bob A.; Rice, Andrew S. C.; Rowbotham, Michael C.; Tobias, Jeffrey K.; Wasan, Ajay D.; Witter, James

    2017-01-01

    Valid and reliable biomarkers can play an important role in clinical trials as indicators of biological or pathogenic processes or as a signal of treatment response. Currently, there are no biomarkers for pain qualified by the US Food and Drug Administration or the European Medicines Agency for use in clinical trials. This article summarizes an Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) meeting in which 3 potential biomarkers were discussed for use in the development of analgesic treatments: (1) sensory testing, (2), skin punch biopsy, and (3) brain imaging. The empirical evidence supporting the use of these tests is described within the context of the 4 categories of biomarkers: (1) diagnostic, (2) prognostic, (3) predictive, and (4) pharmacodynamic. Although sensory testing, skin punch biopsy, and brain imaging are promising tools for pain in clinical trials, additional evidence is needed to further support and standardize these tests for use as biomarkers in pain clinical trials. PMID:28254585

  16. Experimental studies: randomized clinical trials.

    PubMed

    Gjorgov, A N

    1998-01-01

    There are two major approaches to medical investigations: observational studies and experimental trials. The classical application of the experimental design to studies of human populations is the randomized clinical trial of the efficacy of a new drug or treatment. A further application of the experimental studies is to the testing of hypotheses about the etiology of a disease, already tested and corroborated from various forms of observational studies. Ethical considerations and requirements for consent of the experimental subjects are of primary concern in the clinical trials, and those concerns set the first and final limits for implementing a trial. General moral principles in research with human and animal beings, defined by the "Nuremberg Code," deal with strict criteria for approval, endorsement and evaluation of a clinical trial.

  17. [New Royal Decree on clinical trials: main implications for emergency medicine physicians who do research].

    PubMed

    García Arenillas, Mar; Haj-Ali Saflo, Okba; Sáenz de Tejada, Marta

    2017-06-01

    The new European Union directives affecting clinical trials of medicines introduced important changes for Spain, leading to the publication of a Royal Decree regulating the conduct of clinical trials that went into effect in January 2016. The decree sets out the principles for complying with the EU directives, regulates the work of institutional review boards (IRBs) or ethics committees that review research proposals, introduces means to facilitate clinical research, and clarifies the role of the Spanish register of clinical trials, among other topics. This paper discusses the main changes that have been introduced, especially those intended to facilitate research, such as the new concepts of low intervention trial and noncommercial clinical research. These concepts may be particularly useful for clinical trials designed by emergency medicine physicians. We also comment on changes affecting vulnerable populations and the documents that must be presented to both the researchers' IRB and the Spanish Agency for Medicines and Health Care Products.

  18. Clinical Trials, a Healthier Future for All

    MedlinePlus

    ... Clinical Trials Clinical Trials, A Healthier Future for All Past Issues / Fall 2016 Table of Contents Did ... be harmed by, the treatment. Most, but not all, clinical trials in the U.S. are approved and ...

  19. HIV/AIDS Clinical Trials Fact Sheet

    MedlinePlus

    ... and effective in people. What is an HIV/AIDS clinical trial? HIV/AIDS clinical trials help researchers ... to HIV Can anyone participate in an HIV/AIDS clinical trial? It depends on the study. Some ...

  20. Clinical efficacy of oral and topical acyclovir in herpes simplex virus stromal necrotizing keratitis

    PubMed Central

    Dutt, Surabhi; Acharya, Manisha; Gour, Abha; Sapra, Neelam; Chauhan, Lokesh; Mathur, Umang

    2016-01-01

    Purpose: To evaluate the efficacy of systemic and topical antiviral therapy in the treatment of active herpes simplex virus (HSV) necrotizing stromal keratitis (NSK). Design: Prospective interventional case series. Methodology: Patients with a diagnosis of HSV NSK based on history and clinical findings were enrolled in the study. A standard protocol was used for microbiologic investigations. Ten weeks regime of systemic acyclovir and 2 weeks of topical acyclovir was given. Complete ophthalmic examination was performed at every visit. Outcome measures were a reduction in the area of infiltration and improvement in visual acuity. Results: Fifteen patients were enrolled in the study. The mean age of presentation was 51.53 years. The duration of symptoms at presentation ranged from 2 to 8 weeks. HSV1 DNA polymerase chain reaction was positive in 70% cases of those tested. Area of infiltration at trial entry and at the end of 2 weeks of antiviral treatment reduced significantly (P = 0.007). All patients showed a complete resolution of keratitis at the end of study. Conclusion: Topical and systemic acyclovir for treatment of NSK facilitates healing of ulceration. Topical steroids after initial antiviral therapy are safe and decreases inflammation and improve visual recovery. Early initiation of therapy has better outcomes as compared to late presentations. PMID:27221681

  1. HIV/AIDS Clinical Trials

    MedlinePlus

    ... Contact Us | En Español OFFERING INFORMATION ON HIV/AIDS TREATMENT, PREVENTION, AND RESEARCH Search Search Search Search Search Menu Home Guidelines Understanding HIV/AIDS Drugs Clinical Trials Apps Home Guidelines Understanding HIV/ ...

  2. Why are spousal caregivers more prevalent than nonspousal caregivers as study partners in AD dementia clinical trials?

    PubMed Central

    Cary, Mark S.; Rubright, Jonathan D.; Grill, Joshua D.; Karlawish, Jason

    2014-01-01

    Objectives Most Alzheimer’s disease (AD) caregivers are not spouses and yet most AD dementia trials enroll spousal study partners. This study examines the association between caregiver relationship to the patient and willingness to enroll in an AD clinical trial and how caregiver burden and research attitudes modify willingness. Design Interviews with 103 AD caregivers who met criteria for ability to serve as a study partner. Results 54% of caregivers were spouses or domestic partners and the remaining were adult children. Willingness to enroll a patient in a clinical trial was associated with being a spouse (OR = 2.53, p = 0.01), increasing age (OR = 1.39, p = 0.01), and increasing scores on the Research Attitudes Questionnaire (OR = 1.39, p < 0.001). No measures of caregiver burden or patient health were significant predictors of willingness. In multivariate models both research attitudes (OR = 1.37, p < 0.001) and being a spouse, as opposed to an adult child, (OR = 2.06, p = 0.048) were independently associated with willingness to participate. Conclusions Spousal caregivers had both a higher willingness to participate and a more positive attitude toward research. Caregiver burden had no association with willingness to participate. The strongest predictor of willingness was research attitudes. PMID:24805971

  3. Volunteering for clinical trials.

    PubMed

    Mirken, B

    1999-04-01

    HIV/AIDS researchers are finding it increasingly difficult to recruit volunteers for their studies, and are working on designing studies that are more broadly applicable and palatable to the volunteers. Studies offer both opportunities and risks for people who volunteer. This overview describes the basics of trial design and practice, with the purposes of each trial phase clearly described. Participation requires informed consent, and before entering a study patients should ask, among other things, what side effects they can expect, and who will manage their treatment.

  4. A multicenter, randomized, placebo-controlled, double-blind clinical trial of a novel formulation of 5% minoxidil topical foam versus placebo in the treatment of androgenetic alopecia in men.

    PubMed

    Olsen, Elise A; Whiting, David; Bergfeld, Wilma; Miller, Jeffrey; Hordinsky, Maria; Wanser, Rita; Zhang, Paul; Kohut, Bruce

    2007-11-01

    An alternative to currently marketed topical minoxidil solutions is desirable. To assess the efficacy and safety of a new 5% minoxidil topical formulation in a propylene glycol-free foam vehicle in men with androgenetic alopecia (AGA). This was a 16-week, double-blind, placebo-controlled trial of 5% minoxidil topical foam (MTF) in 352 men, 18 to 49 years old. At week 16, 143 subjects continued on an open-label phase to collect 52 weeks of safety information on 5% MTF. At week 16 compared with baseline, there was a statistically significant increase in (1) hair counts in the 5% MTF group versus placebo (P < .0001) and (2) subjective assessment of improved hair loss condition (P < .0001) in the 5% MTF group versus placebo. The 5% MTF was well tolerated over a 52-week period. There was no collection of efficacy data beyond 16 weeks. We believe that 5% MTF is a safe and effective treatment for men with AGA.

  5. [Clinical trials. Some general ethical questions].

    PubMed

    Melo, J A

    1999-01-01

    This article provides an overview of the main problems that ethics committees deal with when analysing clinical trials. Some characteristics of the different phases are discussed as well as some particular problems of the Portuguese law.

  6. Terminating a long-term clinical trial.

    PubMed

    Klimt, C R

    1981-05-01

    Long-term clinical trials often include more than one active treatment group. These may be discontinued independently if found to be ineffective or possibly harmful. Certain subgroups of patients may be discovered, in the course of a clinical trial, who do not respond satisfactorily and are, therefore, excluded during the course of a trial. Yet another kind of termination comes when we have a therapeutic breakthrough or when hope has to be abandoned for demonstrating beneficial effects for one, several, or all treatments included in a trial. Examples from the authors' experience are presented, as are successful and unsuccessful techniques in managing terminations of various types.

  7. [Sports cardiology : Overview of relevant clinical topics].

    PubMed

    Laszlo, R; Scharhag, J; Burgstahler, C; Striegel, H; Steinacker, J M

    2017-01-23

    Physical activity is nowadays an established therapeutic principle concerning primary and secondary prevention of cardiovascular diseases; therefore, in internal sports medicine various aspects go beyond basic cardiological knowledge and require special medical expertise (sports cardiology). Acute cardiac risk is increased during physical activity; therefore, physical activity should be individually phased under consideration of the whole clinical situation. Physical training results in a functional adaptation of the cardiovascular system. Moreover, a structural adaptation can also be observed in competitive athletes but a differentiation between athlete's heart and cardiomyopathy is sometimes challenging. Preparticipation screening verifiably reduces the incidence of sudden cardiac death in athletes. Respective recommendations for the required diagnostics have been published and statutory health insurances are increasingly more willing to bear the incurred costs. Statistically, doping is more frequent in performance-orientated leisure time sports than in competitive sports. Drugs which are relevant for doping have partially irreversible cardiac side effects.

  8. Topical herbal medicines for atopic eczema: a systematic review of randomized controlled trials.

    PubMed

    Thandar, Y; Gray, A; Botha, J; Mosam, A

    2017-02-01

    Despite the availability of medicines with proven efficacy, many patients use complementary or alternative medicines (CAMs) to manage atopic eczema (AE). Due to the lack of objective information on topical CAMs, this systematic review evaluates the current evidence for the efficacy and safety of topical herbal preparations in AE. Using Cochrane systematic review methodology, PubMed, the Cochrane Library, the Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL (via EBSCO), MEDLINE (via EBSCO), Proquest Health and Medical Complete, GREAT and CAM-QUEST were searched from inception until June 2014. Bibliographies of retrieved studies were hand searched for further relevant trials. All controlled clinical trials of topical herbal medicines for AE in humans of any age were included regardless of the control intervention or randomization. Only English-language publications were considered. Eight studies met the inclusion criteria. Seven investigated extracts of single plants and one an extract from multiple plants. Only two studies that showed a positive effect were considered to have a low risk of bias across all domains (those of liquorice gel and Hypericum perforatum). In these two, the test product was reported to be superior to placebo. Despite variations in diagnostic criteria and lack of validated tools for outcome assessments in one of these, the promising results may warrant continued research in better-designed studies. No meta-analysis was performed due to heterogeneity in all studies. There is currently insufficient evidence of efficacy for any topical herbal extract in AE. Many studies had methodological flaws and even those showing efficacy were single trials with small patient cohorts. © 2016 British Association of Dermatologists.

  9. Sample Size Estimation in Clinical Trial

    PubMed Central

    Sakpal, Tushar Vijay

    2010-01-01

    Every clinical trial should be planned. This plan should include the objective of trial, primary and secondary end-point, method of collecting data, sample to be included, sample size with scientific justification, method of handling data, statistical methods and assumptions. This plan is termed as clinical trial protocol. One of the key aspects of this protocol is sample size estimation. The aim of this article is to discuss how important sample size estimation is for a clinical trial, and also to understand the effects of sample size over- estimation or under-estimation on outcome of a trial. Also an attempt is made to understand importance of minimum sample to detect a clinically important difference. This article is also an attempt to provide inputs on different parameters that impact sample size and basic rules for these parameters with the help of some simple examples. PMID:21829786

  10. Characteristics of clinical trials registered in ClinicalTrials.gov, 2007-2010.

    PubMed

    Califf, Robert M; Zarin, Deborah A; Kramer, Judith M; Sherman, Rachel E; Aberle, Laura H; Tasneem, Asba

    2012-05-02

    Recent reports highlight gaps between guidelines-based treatment recommendations and evidence from clinical trials that supports those recommendations. Strengthened reporting requirements for studies registered with ClinicalTrials.gov enable a comprehensive evaluation of the national trials portfolio. To examine fundamental characteristics of interventional clinical trials registered in the ClinicalTrials.gov database. A data set comprising 96,346 clinical studies from ClinicalTrials.gov was downloaded on September 27, 2010, and entered into a relational database to analyze aggregate data. Interventional trials were identified and analyses were focused on 3 clinical specialties-cardiovascular, mental health, and oncology-that together encompass the largest number of disability-adjusted life-years lost in the United States. Characteristics of registered clinical trials as reported data elements in the trial registry; how those characteristics have changed over time; differences in characteristics as a function of clinical specialty; and factors associated with use of randomization, blinding, and data monitoring committees (DMCs). The number of registered interventional clinical trials increased from 28,881 (October 2004-September 2007) to 40,970 (October 2007-September 2010), and the number of missing data elements has generally declined. Most interventional trials registered between 2007 and 2010 were small, with 62% enrolling 100 or fewer participants. Many clinical trials were single-center (66%; 24,788/37,520) and funded by organizations other than industry or the National Institutes of Health (NIH) (47%; 17,592/37,520). Heterogeneity in the reported methods by clinical specialty; sponsor type; and the reported use of DMCs, randomization, and blinding was evident. For example, reported use of DMCs was less common in industry-sponsored vs NIH-sponsored trials (adjusted odds ratio [OR], 0.11; 95% CI, 0.09-0.14), earlier-phase vs phase 3 trials (adjusted OR, 0

  11. Compliance with mandatory reporting of clinical trial results on ClinicalTrials.gov: cross sectional study.

    PubMed

    Prayle, Andrew P; Hurley, Matthew N; Smyth, Alan R

    2012-01-03

    To examine compliance with mandatory reporting of summary clinical trial results (within one year of completion of trial) on ClinicalTrials.gov for studies that fall under the recent Food and Drug Administration Amendments Act (FDAAA) legislation. Registry based study of clinical trial summaries. ClinicalTrials.gov, searched on 19 January 2011, with cross referencing with Drugs@FDA to determine for which trials mandatory reporting was required within one year. Selection criteria Studies registered on ClinicalTrials.gov with US sites which completed between 1 January and 31 December 2009. Proportion of trials for which results had been reported. The ClinicalTrials.gov registry contained 83,579 entries for interventional trials, of which 5642 were completed within the timescale of interest. We identified trials as falling within the mandatory reporting rules if they were covered by the FDAAA (trials of a drug, device, or biological agent, which have at least one US site, and are of phase II or later) and if they investigated a drug that already had approval from the Food and Drug Administration. Of these, 163/738 (22%) had reported results within one year of completion of the trial compared with 76/727 (10%) trials that were not subject to mandatory reporting (95% confidence interval for the difference in proportions 7.8% to 15.5%; χ(2) test, P = 2.6 × 10(-9)). Later phase trials were more likely to report results (P = 4.4 × 10(-11)), as were industry funded trials (P = 2.2 × 10(-16)). Most trials subject to mandatory reporting did not report results within a year of completion.

  12. Malaria Diagnostics in Clinical Trials

    PubMed Central

    Murphy, Sean C.; Shott, Joseph P.; Parikh, Sunil; Etter, Paige; Prescott, William R.; Stewart, V. Ann

    2013-01-01

    Malaria diagnostics are widely used in epidemiologic studies to investigate natural history of disease and in drug and vaccine clinical trials to exclude participants or evaluate efficacy. The Malaria Laboratory Network (MLN), managed by the Office of HIV/AIDS Network Coordination, is an international working group with mutual interests in malaria disease and diagnosis and in human immunodeficiency virus/acquired immunodeficiency syndrome clinical trials. The MLN considered and studied the wide array of available malaria diagnostic tests for their suitability for screening trial participants and/or obtaining study endpoints for malaria clinical trials, including studies of HIV/malaria co-infection and other malaria natural history studies. The MLN provides recommendations on microscopy, rapid diagnostic tests, serologic tests, and molecular assays to guide selection of the most appropriate test(s) for specific research objectives. In addition, this report provides recommendations regarding quality management to ensure reproducibility across sites in clinical trials. Performance evaluation, quality control, and external quality assessment are critical processes that must be implemented in all clinical trials using malaria tests. PMID:24062484

  13. Malaria diagnostics in clinical trials.

    PubMed

    Murphy, Sean C; Shott, Joseph P; Parikh, Sunil; Etter, Paige; Prescott, William R; Stewart, V Ann

    2013-11-01

    Malaria diagnostics are widely used in epidemiologic studies to investigate natural history of disease and in drug and vaccine clinical trials to exclude participants or evaluate efficacy. The Malaria Laboratory Network (MLN), managed by the Office of HIV/AIDS Network Coordination, is an international working group with mutual interests in malaria disease and diagnosis and in human immunodeficiency virus/acquired immunodeficiency syndrome clinical trials. The MLN considered and studied the wide array of available malaria diagnostic tests for their suitability for screening trial participants and/or obtaining study endpoints for malaria clinical trials, including studies of HIV/malaria co-infection and other malaria natural history studies. The MLN provides recommendations on microscopy, rapid diagnostic tests, serologic tests, and molecular assays to guide selection of the most appropriate test(s) for specific research objectives. In addition, this report provides recommendations regarding quality management to ensure reproducibility across sites in clinical trials. Performance evaluation, quality control, and external quality assessment are critical processes that must be implemented in all clinical trials using malaria tests.

  14. Justifying clinical trials for porcine islet xenotransplantation.

    PubMed

    Ellis, Cara E; Korbutt, Gregory S

    2015-01-01

    The development of the Edmonton Protocol encouraged a great deal of optimism that a cell-based cure for type I diabetes could be achieved. However, donor organ shortages prevent islet transplantation from being a widespread solution as the supply cannot possibly equal the demand. Porcine islet xenotransplantation has the potential to address these shortages, and recent preclinical and clinical trials show promising scientific support. Consequently, it is important to consider whether the current science meets the ethical requirements for moving toward clinical trials. Despite the potential risks and the scientific unknowns that remain to be investigated, there is optimism regarding the xenotransplantation of some types of tissue, and enough evidence has been gathered to ethically justify clinical trials for the most safe and advanced area of research, porcine islet transplantation. Researchers must make a concerted effort to maintain a positive image for xenotransplantation, as a few well-publicized failed trials could irrevocably damage public perception of xenotransplantation. Because all of society carries the burden of risk, it is important that the public be involved in the decision to proceed. As new information from preclinical and clinical trials develops, policy decisions should be frequently updated. If at any point evidence shows that islet xenotransplantation is unsafe, then clinical trials will no longer be justified and they should be halted. However, as of now, the expected benefit of an unlimited supply of islets, combined with adequate informed consent, justifies clinical trials for islet xenotransplantation.

  15. Funding oncology clinical trials: are cooperative group trials sustainable?

    PubMed

    Seow, Hsien-Yeang; Whelan, Patrick; Levine, Mark N; Cowan, Kathryn; Lysakowski, Barbara; Kowaleski, Brenda; Snider, Anne; Xu, Rebecca Y; Arnold, Andrew

    2012-05-01

    Many oncology clinical trials departments (CTDs) are in serious fiscal deficit and their sustainability is in jeopardy. This study investigates whether the payment models used to fund industry versus cooperative group trials contribute to the fiscal deficit of a CTD. We examined the lifetime costs of all cooperative group and industry trials activated in the CTD of a cancer center between 2007 and 2011. A trial's lifetime is defined as being from the date the first patient was accrued until the last patient's actual or projected final follow-up visit. For each trial, we calculated the lifetime monthly net income, which was defined as monthly revenue minus monthly costs. Data sources included study protocols, trial budgets, and accrual data. Of the 97 trials analyzed, 64 (66%) were cooperative group trials. The pattern of lifetime net income for cooperative group trials has a positive peak during patient accrual followed by a negative trough during follow-up. In contrast, the pattern for industry trials resembled an "l" shape. The patterns reflect the differing payment models: upfront lump-sum payments (cooperative group) versus milestone payments (industry). The negative trough in the lifetime net income of a cooperative group trial occurs because follow-up costs are typically not funded or are underfunded. CTDs accrue more patients in new trials to offset that deficit. The CTD uses revenue from accrual to existing trials to cross-subsidize past trials in follow-up. As the number of patients on follow-up increases, the fiscal deficit grows larger each year, perpetuating the cycle.

  16. Unique topics and issues in rheumatology and clinical immunology.

    PubMed

    Selmi, Carlo

    2014-08-01

    Clinicians are facing unexpected issues in everyday practice, and these may become counterintuitive or challenging. Illustrative examples are provided by the hypersensitivity to universally used immunosuppressants such as corticosteroids or antibiotics such as beta-lactam. Secondly, additional issues are represented by the discovery of new pathogenetic mechanisms involved in rheumatoid and psoriatic arthritis or other chronic inflammatory diseases, genomic susceptibility to enigmatic diseases such as giant cell arteritis, or the shared role of specific mediators such as semaphorins. Third, the therapeutic armamentarium has dramatically changed over the past decade following the introduction of biotechnological drugs, and new mechanisms are being proposed to reduce adverse events or increase the drug effectiveness, particularly on cardiovascular comorbidities. Finally, rare diseases continue to represent difficult cases, as for Cogan's syndrome, with limited literature available for clinical recommendations. For these reason, the present issue of Clinical Reviews in Allergy and Immunology is timely and dedicated to these and other unique topics in clinical immunology and allergy. The aim of this issue is thus to help clinicians involved in internal medicine as well as allergists and clinical immunologists while discussing new pathways that will prove important in the near future.

  17. Tuberculosis vaccines in clinical trials

    PubMed Central

    Rowland, Rosalind; McShane, Helen

    2011-01-01

    Effective prophylactic and/or therapeutic vaccination is a key strategy for controlling the global TB epidemic. The partial effectiveness of the existing TB vaccine, bacille Calmette–Guérin (BCG), suggests effective vaccination is possible and highlights the need for an improved vaccination strategy. Clinical trials are evaluating both modifications to the existing BCG immunization methods and also novel TB vaccines, designed to replace or boost BCG. Candidate vaccines in clinical development include live mycobacterial vaccines designed to replace BCG, subunit vaccines designed to boost BCG and therapeutic vaccines designed as an adjunct to chemotherapy. There is a great need for validated animal models, identification of immunological biomarkers of protection and field sites with the capacity for large-scale efficacy testing in order to develop and license a novel TB vaccine or regimen. PMID:21604985

  18. Characteristics of pediatric cardiovascular clinical trials registered on ClinicalTrials.gov.

    PubMed

    Hill, Kevin D; Chiswell, Karen; Califf, Robert M; Pearson, Gail; Li, Jennifer S

    2014-06-01

    ClinicalTrials.gov is an National Institutes of Health-sponsored registry of federally and privately funded trials. We sought to determine fundamental characteristics of registered pediatric cardiovascular trials (PCVTs). A data set including 68,134 interventional clinical trials was downloaded from ClinicalTrials.gov and entered into a relational database. Aggregate data from PCVTs were compared with other trial specialties. Multivariable logistic regression was used to evaluate factors associated with improved trial quality metrics including blinding and randomization. Between July 1, 2005, and September 27, 2010, 5035 (7%) registered trials targeted pediatric populations, including 213 PCVTs (4.2%), 1,176 pediatric infectious disease trials (23%), 664 pediatric mental health trials (13%), and 346 pediatric hematology/oncology trials (7%). Median (interquartile range) PCVT enrollment was 65 subjects (36-186) and median study duration was 2.3 years (1.3-3.7). The most common PCVTs targeted acquired diseases including hypertension (n = 41, 14%), obesity (n = 26, 9%), pulmonary hypertension (n = 25, 9%), and dyslipidemia (n = 19, 7%). Important factors associated with improved quality metrics included National Institutes of Health as opposed to industry funding (OR, 1.9; P < .0001); trial location (trials with both US and foreign enrollment vs trials with US only or foreign only enrollment, P = .02) and trials restricted to younger children as opposed to trials including adolescents (OR, 1.4; P < .0001). PCVTs represent a small proportion of clinical trials relative to other pediatric subspecialties. Most PCVTs tend to parallel adult morbidities while there is a relative paucity of trials focused on congenital heart disease. These data may be useful to stakeholders in informing decisions regarding the conduct of PCVTs, and to provide insight into mechanisms to advance PCVT infrastructure. Copyright © 2014 Mosby, Inc. All rights reserved.

  19. Treatment of blepharitis: recent clinical trials.

    PubMed

    Pflugfelder, Stephen C; Karpecki, Paul M; Perez, Victor L

    2014-10-01

    Blepharitis is a chronic inflammatory disease of the eyelids that is frequently encountered in clinical practice. The etiology of the disorder is complex and not fully understood, but the general consensus is that bacteria and inflammation contribute to the pathology. Blepharitis can be classified into anterior blepharitis, involving the anterior lid margin and eyelashes, and posterior blepharitis, characterized by dysfunction of the meibomian glands. Long-term management of symptoms may include daily eyelid cleansing routines and the use of therapeutic agents that reduce infection and inflammation. A cure is not possible in most cases, and subjective symptoms may persist even when a clinical assessment of signs indicates that the condition has improved. There are no established guidelines regarding therapeutic regimens, but recent clinical trials have shown that antibiotics and topical corticosteroids can produce significant improvement in signs and symptoms of blepharitis. Fixed combinations of a topical antibiotic and a corticosteroid offer an effective and convenient treatment modality that addresses both infectious and inflammatory components of the disease. Further clinical trials are needed to determine optimal therapies for managing blepharitis. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Clinical Trials | Division of Cancer Prevention

    Cancer.gov

    Information about actively enrolling, ongoing, and completed clinical trials of cancer prevention, early detection, and supportive care, including phase I, II, and III agent and action trials and clinical trials management. |

  1. Smart Technology in Lung Disease Clinical Trials.

    PubMed

    Geller, Nancy L; Kim, Dong-Yun; Tian, Xin

    2016-01-01

    This article describes the use of smart technology by investigators and patients to facilitate lung disease clinical trials and make them less costly and more efficient. By "smart technology" we include various electronic media, such as computer databases, the Internet, and mobile devices. We first describe the use of electronic health records for identifying potential subjects and then discuss electronic informed consent. We give several examples of using the Internet and mobile technology in clinical trials. Interventions have been delivered via the World Wide Web or via mobile devices, and both have been used to collect outcome data. We discuss examples of new electronic devices that recently have been introduced to collect health data. While use of smart technology in clinical trials is an exciting development, comparison with similar interventions applied in a conventional manner is still in its infancy. We discuss advantages and disadvantages of using this omnipresent, powerful tool in clinical trials, as well as directions for future research.

  2. Clinical Trial of a Combination of Lynestrenol and Mestranol (Lyndiol) as an Oral Contraceptive Agent

    PubMed Central

    Rice-Wray, Edris; Becerra, Carmen; Esquivel, Julio; Maqueo, Manuel

    1966-01-01

    Contraception with lynestrenol-mestranol (Lyndiol) was studied in 332 Mexican women during a period of two and one-half years. Side effects were minimal or transient. No pregnancies occurred in those who took the medication according to instructions. The women were followed with yearly pelvic examinations and Papanicolaou smears, serial endometrial biopsies and extensive studies of blood, liver and glandular function. Complete ophthalmological studies were done on 30 patients. No clinical or laboratory evidence of harmful effects could be demonstrated. Return to ovulation (using pregnanediol excretion and endometrial biopsies as parameters) occurred in all of 22 women studied in the first three post-treatment cycles. Eight posttreatment pregnancies and the resulting offspring were normal. The first post-treatment cycle, as with other oral contraceptives, was unpredictable and tended to be prolonged. It varied in length from 22 to 60 days. ImagesFig. 3Fig. 4 PMID:5332557

  3. Clinical Trials - Participants

    MedlinePlus

    ... Watch: Addictive Behaviors : Carl Lejuez, Professor of Clinical Psychology at the University of Maryland, College Park, and Director of the Center for Addictions, Personality & Emotional Research, discusses translational research — studying the basic internal processes ...

  4. Optimizing biologically targeted clinical trials for neurofibromatosis

    PubMed Central

    Gutmann, David H; Blakeley, Jaishri O; Korf, Bruce R; Packer, Roger J

    2014-01-01

    Introduction The neurofibromatoses (neurofibromatosis type 1, NF1 and neurofibromatosis type 2, NF2) comprise the most common inherited conditions in which affected children and adults develop tumors of the central and peripheral nervous system. In this review, the authors discuss how the establishment of the Neurofibromatosis Clinical Trials Consortium (NFCTC) has positively impacted on the design and execution of treatment studies for individuals with NF1 and NF2. Areas covered Using an extensive PUBMED search in collaboration with select NFCTC members expert in distinct NF topics, the authors discuss the clinical features of NF1 and NF2, the molecular biology of the NF1 and NF2 genes, the development and application of clinically relevant Nf1 and Nf2 genetically engineered mouse models and the formation of the NFCTC to enable efficient clinical trial design and execution. Expert opinion The NFCTC has resulted in a more seamless integration of mouse preclinical and human clinical trials efforts. Leveraging emerging enabling resources, current research is focused on identifying subtypes of tumors in NF1 and NF2 to deliver the most active compounds to the patients most likely to respond to the targeted therapy. PMID:23425047

  5. Optimizing biologically targeted clinical trials for neurofibromatosis.

    PubMed

    Gutmann, David H; Blakeley, Jaishri O; Korf, Bruce R; Packer, Roger J

    2013-04-01

    The neurofibromatoses (neurofibromatosis type 1, NF1 and neurofibromatosis type 2, NF2) comprise the most common inherited conditions in which affected children and adults develop tumors of the central and peripheral nervous system. In this review, the authors discuss how the establishment of the Neurofibromatosis Clinical Trials Consortium (NFCTC) has positively impacted on the design and execution of treatment studies for individuals with NF1 and NF2. Using an extensive PUBMED search in collaboration with select NFCTC members expert in distinct NF topics, the authors discuss the clinical features of NF1 and NF2, the molecular biology of the NF1 and NF2 genes, the development and application of clinically relevant Nf1 and Nf2 genetically engineered mouse models and the formation of the NFCTC to enable efficient clinical trial design and execution. The NFCTC has resulted in a more seamless integration of mouse preclinical and human clinical trials efforts. Leveraging emerging enabling resources, current research is focused on identifying subtypes of tumors in NF1 and NF2 to deliver the most active compounds to the patients most likely to respond to the targeted therapy.

  6. Orienting to Topic in Clinical Discourse Elicitation of Everyday Conversation

    ERIC Educational Resources Information Center

    Fond, Marissa Joanne

    2013-01-01

    Talking topically, as it is understood intuitively and evoked metadiscursively, requires constructing an intersubjective orientation to talk that must be continually renewed. Analysis of interactants' ability to orient to topic emergence provides evidence of what is achieved in interaction, as well as why conversational coordination can lapse…

  7. Genomic Array as Compared to Karyotyping in Myelodysplastic Syndromes in a Prospective Clinical trial.

    PubMed

    Stevens-Kroef, Marian J; Olde Weghuis, Daniel; ElIdrissi-Zaynoun, Najat; van der Reijden, Bert; Cremers, Eline M P; Alhan, Canan; Westers, Theresia M; Visser-Wisselaar, Heleen A; Chitu, Dana A; Cunha, Sonia M; Vellenga, Edo; Klein, Saskia K; Wijermans, Pierre; de Greef, Georgine E; Schaafsma, M R; Muus, Petra; Ossenkoppele, Gert J; van de Loosdrecht, Arjan A; Jansen, Joop H

    2017-02-25

    Karyotyping is considered as the gold standard in the genetic subclassification of myelodysplastic syndrome (MDS). Oligo/SNP-based genomic array profiling is a high-resolution tool that also enables genome wide analysis. We compared karyotyping with oligo/SNP-based array profiling in 104 MDS patients from the HOVON-89 study. Oligo/SNP-array identified all cytogenetically defined genomic lesions, except for subclones in two cases and balanced translocations in three cases. On the other hand oligo/SNP-based genomic array profiling had a higher success rate, showing 55 abnormal cases, while an abnormal karyotype was found in only 35 patients. In 9 patients whose karyotyping was unsuccessful because of insufficient metaphases or failure, oligo/SNP-based array analysis was successful. Based on cytogenetic visible abnormalities as identified by oligo/SNP-based genomic array prognostic scores based on IPSS/-R were assigned. These prognostic scores were identical to the IPSS/-R scores as obtained with karyotyping in 95-96% of the patients. In addition to the detection of cytogenetically defined lesions, oligo/SNP-based genomic profiling identified focal copy number abnormalities or regions of copy neutral loss of heterozygosity that were out of the scope of karyotyping and fluorescence in situ hybridization. Of interest, in 26 patients we demonstrated such cytogenetic invisible abnormalities. These abnormalities often involved regions that are recurrently affected in hematological malignancies, and may therefore be of clinical relevance. Our findings indicate that oligo/SNP-based genomic array can be used to identify the vast majority of recurrent cytogenetic abnormalities in MDS. Furthermore, oligo/SNP-based array profiling yields additional genetic abnormalities that may be of clinical importance. This article is protected by copyright. All rights reserved.

  8. Topical glyceryl trinitrate as adjunctive treatment in Raynaud's disease.

    PubMed

    Franks, A G

    1982-01-09

    The effects of topical glyceryl trinitrate in Raynaud's disease were compared with those of placebo in a double-blind, crossover trial in 17 patients with bilateral Raynaud's disease and an associated collagen disease, who were receiving oral sympatholytic agents at the maximum levels they could tolerate. 1% glyceryl trinitrate ointment or a placebo of lanolin was applied to one hand only for 6 weeks, then patients changed to the other preparation for 6 weeks. The results were evaluated every 2 weeks. The frequency of attacks, severity of attacks, and size of ulcers in the treated hand were significantly lower when the patients were using glyceryl trinitrate ointment than when they were using placebo. The treatment of Raynaud's disease may be improved by using topical glyceryl trinitrate ointment as an adjunct to a basic regimen of oral sympatholytic agents. Glyceryl trinitrate ointment may obviate the need for more aggressive treatment, such as intraarterial reserpine, in selected patients.

  9. Structural Integration as an Adjunct to Outpatient Rehabilitation for Chronic Nonspecific Low Back Pain: A Randomized Pilot Clinical Trial

    PubMed Central

    Jacobson, Eric E.; Meleger, Alec L.; Bonato, Paolo; Wayne, Peter M.; Langevin, Helene M.; Kaptchuk, Ted J.; Davis, Roger B.

    2015-01-01

    Structural Integration (SI) is an alternative method of manipulation and movement education. To obtain preliminary data on feasibility, effectiveness, and adverse events (AE), 46 outpatients from Boston area with chronic nonspecific low back pain (CNSLBP) were randomized to parallel treatment groups of SI plus outpatient rehabilitation (OR) versus OR alone. Feasibility data were acceptable except for low compliance with OR and lengthy recruitment time. Intent-to-treat data on effectiveness were analyzed by Wilcoxon rank sum, n = 23 per group. Median reductions in VAS Pain, the primary outcome, of −26 mm in SI + OR versus 0 in OR alone were not significantly different (P = 0.075). Median reductions in RMDQ, the secondary outcome, of −2 points in SI + OR versus 0 in OR alone were significantly different (P = 0.007). Neither the proportions of participants with nor the seriousness of AE were significantly different. SI as an adjunct to OR for CNSLBP is not likely to provide additional reductions in pain but is likely to augment short term improvements in disability with a low additional burden of AE. A more definitive trial is feasible, but OR compliance and recruitment might be challenging. This trial is registered with ClinicalTrials.gov (NCT01322399). PMID:25945112

  10. Topical tranexamic acid as a promising treatment for melasma

    PubMed Central

    Ebrahimi, Bahareh; Naeini, Farahnaz Fatemi

    2014-01-01

    Background: In recent times, tranexamic acid (TA) is claimed to have whitening effects especially for ultraviolet-induced hyperpigmentation including melasma. The aim of our study was to evaluate the efficacy and safety of topical solution of TA and compare it with combined solution of hydroquinone and dexamethasone as the gold standard treatment of melasma in Iranian women. Materials and Methods: This was a double-blind split-face trial of 12 weeks which was conducted in Isfahan, Iran. Fifty Iranian melasma patients applied topical solution of 3% TA on one side of the face, and topical solution of 3% hydroquinone + 0.01% dexamethasone on the other side two times a day. The Melasma Area and Severity Index (MASI) and the side effects were evaluated at baseline and every 4 weeks before and after photographs to be compared by a dermatologist were taken. The patient satisfaction was documented at week 12. Results: A repeated measurement analysis was used to evaluate the changes in the MASI score before and after treatments. A significant decreasing trend was observed in the MASI score of both groups with no significant difference between them during the study (P < 0.05). No differences were seen in patients’ and investigator's satisfaction of melasma improvement between two groups (P < 0.05). However, the side effects of hydroquinone + dexamethasone were significantly prominent compared with TA (P = 0.01). Conclusion: This study's results introduce the topical TA as an effective and safe medication for the treatment of melasma. PMID:25422661

  11. Topical Turmeric Microemulgel in the Management of Plaque Psoriasis; A Clinical Evaluation

    PubMed Central

    Sarafian, Golnaz; Afshar, Minoo; Mansouri, Parvin; Asgarpanah, Jinous; Raoufinejad, Kosar; Rajabi, Mehdi

    2015-01-01

    Psoriasis is an autoimmune and recurrent chronic inflammatory skin disease. About 1-3% of the world wide populations are affected. The characteristic features are hyperprolifration of keratinocytes leading to redness, thickening and scaling of epidermis followed with itching and appearance of the lesions which in most cases bother the patients medically and psychologically. Psoriasis is symptomatically treated by the range of oral and topical medications, however, major side effects in some cases are associated with them. Based on several studies, Curcuma longa can inhibit several inflammatory enzymes mainly involved in the inflammatory process of Psoriasis. Therefore, we decided to target this well-known herbal agent with fantastic safety profile to be formulated as a novel topical microemulgel. The clinical and therapeutic benefit of this novel topical formulation was evaluated on 34 patients with mild to moderate plaque psoriasis in a randomized, prospective intra-individual, right–left comparative, placebo-controlled, double-blind clinical trial. The Dermatology Life Quality Index (DLQI) Questionnaire and Psoriasis area & severity index (PASI) score as well as photos before and after treatment was used to evaluate the outcomes. The results show that the clinical and quality of life parameters in treated lesions in comparison with untreated lesions have improved (P<0.05). The reported side effects were also recorded and were trivial. Based on our findings, the proposed microemulgel may well be considered as an alternative in some patients and most likely as an add-on therapeutic option for many patients suffering with plaque psoriasis. PMID:26330875

  12. An analysis of registered clinical trials in otolaryngology from 2007 to 2010: ClinicalTrials.gov.

    PubMed

    Witsell, David L; Schulz, Kristine A; Lee, Walter T; Chiswell, Karen

    2013-11-01

    To describe the conditions studied, interventions used, study characteristics, and funding sources of otolaryngology clinical trials from the ClinicalTrials.gov database; compare this otolaryngology cohort of interventional studies to clinical visits in a health care system; and assess agreement between clinical trials and clinical activity. Database analysis. Trial registration data downloaded from ClinicalTrials.gov and administrative data from the Duke University Medical Center from October 1, 2007 to September 27, 2010. Data extraction from ClinicalTrials.gov was done using MeSH and non-MeSH disease condition terms. Studies were subcategorized to create the following groupings for descriptive analysis: ear, nose, allergy, voice, sleep, head and neck cancer, thyroid, and throat. Duke Health System visits were queried by using selected ICD-9 codes for otolaryngology and non-otolaryngology providers. Visits were grouped similarly to ClinicalTrials.gov for further analysis. Chi-square tests were used to explore differences between groups. A total of 1115 of 40,970 registered interventional trials were assigned to otolaryngology. Head and neck cancer trials predominated. Study models most frequently incorporated parallel design (54.6%), 2 study groups (46.6%), and randomization (69.1%). Phase 2 or 3 studies constituted 46.4% of the cohort. Comparison of the ClinicalTrials.gov database with administrative health system visit data by disease condition showed discordance between national research activity and clinical visit volume for patients with otolaryngology complaints. Analysis of otolaryngology-related clinical research as listed in ClinicalTrials.gov can inform patients, physicians, and policy makers about research focus areas. The relative burden of otolaryngology-associated conditions in our tertiary health system exceeds research activity within the field.

  13. An Analysis of Registered Clinical Trials in Otolaryngology from 2007 to 2010: ClinicalTrials.gov

    PubMed Central

    Witsell, David L.; Schulz, Kristine A.; Lee, Walter T.; Chiswell, Karen

    2014-01-01

    Objective To describe the conditions studied, interventions used, study characteristics, and funding sources of otolaryngology clinical trials from the ClinicalTrials.gov database; compare this otolaryngology cohort of interventional studies to clinical visits in a health care system; and assess agreement between clinical trials and clinical activity. Study Design Database analysis. Setting Trial registration data downloaded from Clinical Trials.gov and administrative data from the Duke University Medical Center from October 1, 2007 to September 27, 2010. Methods Data extraction from ClinicalTrials.gov was done using MeSH and non-MeSH disease condition terms. Studies were subcategorized to create the following groupings for descriptive analysis: ear, nose, allergy, voice, sleep, head and neck cancer, thyroid, and throat. Duke Health System visits were queried by using selected ICD-9 codes for otolaryngology and non-otolaryngology providers. Visits were grouped similarly to ClinicalTrials.gov for further analysis. Chi-square tests were used to explore differences between groups. Results A total of 1115 of 40,970 registered interventional trials were assigned to otolaryngology. Head and neck cancer trials predominated. Study models most frequently incorporated parallel design (54.6%), 2 study groups (46.6%), and randomization (69.1%). Phase 2 or 3 studies constituted 46.4% of the cohort. Comparison of the ClinicalTrials.gov database with administrative health system visit data by disease condition showed discordance between national research activity and clinical visit volume for patients with otolaryngology complaints. Conclusions Analysis of otolaryngology-related clinical research as listed in ClinicalTrials.gov can inform patients, physicians, and policy makers about research focus areas. The relative burden of otolaryngology-associated conditions in our tertiary health system exceeds research activity within the field. PMID:24107478

  14. Medical coding in clinical trials.

    PubMed

    Babre, Deven

    2010-01-01

    Data generated in all clinical trial are recorded on the data collection instrument Case report Form / Electronic Case Report Form by investigators located at various sites in various countries. In multicentric clinical trials since different investigator or medically qualified experts are from different sites / centers recording the medical term(s) uniformly is a big challenge. Medical coders from clinical data management team process these terms and perform medical coding. Medical coding is performed to categorize the medical terms reported appropriately so that they can be analyzed/reviewed. This article describes process which is used for medical coding in clinical data management and two most commonly used medical dictionaries MedDRA and WHO-DDE in brief. It is expected to help medical coders to understand the process of medical coding in clinical data management. Few common issues which the medical coder faces while performing medical coding, are also highlighted.

  15. Current status and perspectives of interventional clinical trials for glioblastoma - analysis of ClinicalTrials.gov.

    PubMed

    Cihoric, Nikola; Tsikkinis, Alexandros; Minniti, Giuseppe; Lagerwaard, Frank J; Herrlinger, Ulrich; Mathier, Etienne; Soldatovic, Ivan; Jeremic, Branislav; Ghadjar, Pirus; Elicin, Olgun; Lössl, Kristina; Aebersold, Daniel M; Belka, Claus; Herrmann, Evelyn; Niyazi, Maximilian

    2017-01-03

    The records of 208.777 (100%) clinical trials registered at ClinicalTrials.gov were downloaded on the 19th of February 2016. Phase II and III trials including patients with glioblastoma were selected for further classification and analysis. Based on the disease settings, trials were classified into three groups: newly diagnosed glioblastoma, recurrent disease and trials with no differentiation according to disease setting. Furthermore, we categorized trials according to the experimental interventions, the primary sponsor, the source of financial support and trial design elements. Trends were evaluated using the autoregressive integrated moving average model. Two hundred sixteen (0.1%) trials were selected for further analysis. Academic centers (investigator initiated trials) were recorded as primary sponsors in 56.9% of trials, followed by industry 25.9%. Industry was the leading source of monetary support for the selected trials in 44.4%, followed by 25% of trials with primarily academic financial support. The number of newly initiated trials between 2005 and 2015 shows a positive trend, mainly through an increase in phase II trials, whereas phase III trials show a negative trend. The vast majority of trials evaluate forms of different systemic treatments (91.2%). In total, one hundred different molecular entities or biologicals were identified. Of those, 60% were involving drugs specifically designed for central nervous system malignancies. Trials that specifically address radiotherapy, surgery, imaging and other therapeutic or diagnostic methods appear to be rare. Current research in glioblastoma is mainly driven or sponsored by industry, academic medical oncologists and neuro-oncologists, with the majority of trials evaluating forms of systemic therapies. Few trials reach phase III. Imaging, radiation therapy and surgical procedures are underrepresented in current trials portfolios. Optimization in research portfolio for glioblastoma is needed.

  16. Orthopedic cellular therapy: An overview with focus on clinical trials

    PubMed Central

    Noh, Moon Jong; Lee, Kwan Hee

    2015-01-01

    In this editorial, the authors tried to evaluate the present state of cellular therapy in orthopedic field. The topics the authors try to cover include not only the clinical trials but the various research areas as well. Both the target diseases for cellular therapy and the target cells were reviewed. New methods to activate the cells were interesting to review. Most advanced clinical trials were also included because several of them have advanced to phase III clinical trials. In the orthopedic field, there are many diseases with a definite treatment gap at this time. Because cellular therapies can regenerate damaged tissues, there is a possibility for cellular therapies to become disease modifying drugs. It is not clear whether cellular therapies will become the standard of care in any of the orthopedic disorders, however the amount of research being performed and the number of clinical trials that are on-going make the authors believe that cellular therapies will become important treatment modalities within several years. PMID:26601056

  17. Clinical predictors of psychogenic nonepileptic seizures: a critically appraised topic.

    PubMed

    Hoerth, Matthew T; Wellik, Kay E; Demaerschalk, Bart M; Drazkowski, Joseph F; Noe, Katherine H; Sirven, Joseph I; Wingerchuk, Dean M

    2008-07-01

    Psychogenic nonepileptic seizures (PNES) are often disabling and usually associated with psychiatric disorders and reduced quality of life. Although often suspected based on historical and clinical features, the gold standard for diagnosis of PNES is video electroencephalography. Identification of clinical features that reliably distinguish PNES from ES would be valuable in acute care settings, for patients that have coexisting disorders, and those with multiple event types. To determine the diagnostic value of putative clinical symptoms or signs of PNES against the gold standard of video electroencephalography. We addressed the objective through development of a structured critically appraised topic that included a clinical scenario, structured question, search strategy, critical appraisal, results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the field of epileptology. There were wide variations in the rates of coexisting PNES and epilepsy and study methodology. Ictal stuttering and the "teddy bear" sign were associated with moderate specificity for PNES. However, the presence of pelvic thrusting or ictal eye closure did not accurately distinguish PNES from ES. The presence of either ictal stuttering or the teddy bear sign is moderately specific but poorly sensitive for PNES. Pelvic thrusting and ictal eye closure are not reliable indicators of PNES. Future studies should establish more precise and reliable definitions of clinical signs and evaluate combinations of such signs in a broad spectrum of patients with PNES and ES spell phenotypes that may be difficult to distinguish, such as spells of unresponsiveness with motor manifestations. Because PNES and ES may coexist, analysis of diagnostic accuracy of clinical features should be performed for individual spells.

  18. Allergen Immunotherapy Clinical Trial Outcomes and Design: Working Toward Harmonization of Methods and Principles.

    PubMed

    Nelson, Harold S; Calderon, Moises A; Bernstein, David I; Casale, Thomas B; Durham, Stephen R; Andersen, Jens S; Esch, Robert; Cox, Linda S; Nolte, Hendrik

    2017-03-01

    Progress has been made in the harmonization of efficacy and safety outcome measures for allergen immunotherapy (AIT) trials, but unresolved issues still remain. Furthermore, there are discrepancies in recommendations from professional medical societies and regulatory agencies regarding requirements for AIT trials. In this article, we reviewed published recommendations and current data from recent clinical trials, as well as the criteria applied by regulatory authorities for approval of AIT products, to provide updated considerations for conducting phase 3 AIT trials. Topics discussed include analysis of outcomes and trial designs for pediatric and asthma indications, as well as trial designs for perennial allergic rhinoconjunctivitis. In addition, the need for harmonization of safety reporting is emphasized. Considerations presented in this article may further effort to find common ground among professional medical societies and government agencies in developing future recommendations for AIT trial design.

  19. Clinical Trials in a Dish

    PubMed Central

    Strauss, David G.; Blinova, Ksenia

    2017-01-01

    Clinical trials ‘in a dish’ involve testing medical therapies for safety or effectiveness in the laboratory with human tissue. This has become possible owing to recent biotechnology advances including induced pluripotent stem cells, organs-on-a-chip, and whole-genome sequencing. We provide here an overview of the landscape and highlight steps the FDA is taking to advance the science of clinical trials in a dish and to support the development and validation of new regulatory paradigms to assess drug safety using these new technologies. PMID:27876286

  20. [Reading a clinical trial report].

    PubMed

    Bergmann, J F; Chassany, O

    2000-04-15

    To improve medical knowledge by reading clinical trial reports it is necessary to check for the respect of the methodological rules, and to analyze and criticize the results. A control group and a randomisation are always necessary. Double blind assessment, sample size calculation, intention to treat analysis, a unique primary end point are also important. The conclusions of the trial are valid only for the population included and the clinical signification of the results, depending on the control treatment, has to be evaluated. Respect of the reading rules is necessary to assess the reliability of the conclusions, in order to promote evidence-based practice.

  1. Delayed onset of ambulation in boys with Duchenne muscular dystrophy: Potential use as an endpoint in clinical trials.

    PubMed

    Gissy, Jacob J; Johnson, Teresa; Fox, Deborah J; Kumar, Anil; Ciafaloni, Emma; van Essen, Anthonie J; Peay, Holly L; Martin, Ann; Lucas, Ann; Finkel, Richard S

    2017-10-01

    Individuals with Duchenne muscular dystrophy (DMD) often exhibit delayed motor and cognitive development, including delayed onset of ambulation. Data on age when loss of independent ambulation occurs are well established for DMD; however, age at onset of walking has not been well described. We hypothesize that an effective medication given in early infancy would advance the age when walking is achieved so that it is closer to age-matched norms, and that this discrete event could serve as the primary outcome measure in a clinical trial. This study examined three data sets, Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet); Dutch Natural History Survey (DNHS); and Parent Project Muscular Dystrophy (PPMD). The distribution of onset of ambulation in DMD (mean ± SD) and median age, in months, at the onset of ambulation was 17.3 (±5.5) and 16.0 in MD STARnet, 21.8 (±7.1) and 20.0 in DNHS, and 16.1 (±4.4) and 15 in PPMD. Age of ambulation in these data sets were all significantly later (P <0.001) than the corresponding age for typically developing boys, 12.1 (±1.8). A hypothetical clinical trial study design and power analyses are presented based on these data. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. [International clinical trials: perspectives of clinical research coordinators].

    PubMed

    Aotani, Eriko

    2007-02-01

    There are several different task roles among the co-medicals who are involved in international clinical trials (ICTs). In this review article, several issues related with ICTs from the view point of clinical research coordinators (CRCs) will be discussed. The discussions include interview results from eight CRCs of four institutions who have been involved in ICTs, current status of education for co-medicals in the field of ICTs, and future perspectives of ICTs from the CRC's view point. The following topics are especially focused in the discussion. 1) It is necessary to establish the infra-structure for free discussion among the ICT team so that opinions of co-medicals as the operation managers of the participating institutions can be openly shared and importantly taken into account. 2) It is also important for co-medicals to conduct research studies to clarify the problems in the current ICT support systems. 3) Lastly, the significance of early involvement of CRCs into the ICT protocol development must be emphasized, because the quality of protocols will be better improved by the practical insight of CRCs, and consequently, the accomplishment of the ICT, such as the speed and the data quality, may be accelerated.

  3. Automated Text Messaging as an Adjunct to Cognitive Behavioral Therapy for Depression: A Clinical Trial.

    PubMed

    Aguilera, Adrian; Bruehlman-Senecal, Emma; Demasi, Orianna; Avila, Patricia

    2017-05-08

    Cognitive Behavioral Therapy (CBT) for depression is efficacious, but effectiveness is limited when implemented in low-income settings due to engagement difficulties including nonadherence with skill-building homework and early discontinuation of treatment. Automated messaging can be used in clinical settings to increase dosage of depression treatment and encourage sustained engagement with psychotherapy. The aim of this study was to test whether a text messaging adjunct (mood monitoring text messages, treatment-related text messages, and a clinician dashboard to display patient data) increases engagement and improves clinical outcomes in a group CBT treatment for depression. Specifically, we aim to assess whether the text messaging adjunct led to an increase in group therapy sessions attended, an increase in duration of therapy attended, and reductions in Patient Health Questionnaire-9 item (PHQ-9) symptoms compared with the control condition of standard group CBT in a sample of low-income Spanish speaking Latino patients. Patients in an outpatient behavioral health clinic were assigned to standard group CBT for depression (control condition; n=40) or the same treatment with the addition of a text messaging adjunct (n=45). The adjunct consisted of a daily mood monitoring message, a daily message reiterating the theme of that week's content, and medication and appointment reminders. Mood data and qualitative responses were sent to a Web-based platform (HealthySMS) for review by the therapist and displayed in session as a tool for teaching CBT skills. Intent-to-treat analyses on therapy attendance during 16 sessions of weekly therapy found that patients assigned to the text messaging adjunct stayed in therapy significantly longer (median of 13.5 weeks before dropping out) than patients assigned to the control condition (median of 3 weeks before dropping out; Wilcoxon-Mann-Whitney z=-2.21, P=.03). Patients assigned to the text messaging adjunct also generally

  4. Automated Text Messaging as an Adjunct to Cognitive Behavioral Therapy for Depression: A Clinical Trial

    PubMed Central

    Bruehlman-Senecal, Emma; Demasi, Orianna; Avila, Patricia

    2017-01-01

    Background Cognitive Behavioral Therapy (CBT) for depression is efficacious, but effectiveness is limited when implemented in low-income settings due to engagement difficulties including nonadherence with skill-building homework and early discontinuation of treatment. Automated messaging can be used in clinical settings to increase dosage of depression treatment and encourage sustained engagement with psychotherapy. Objectives The aim of this study was to test whether a text messaging adjunct (mood monitoring text messages, treatment-related text messages, and a clinician dashboard to display patient data) increases engagement and improves clinical outcomes in a group CBT treatment for depression. Specifically, we aim to assess whether the text messaging adjunct led to an increase in group therapy sessions attended, an increase in duration of therapy attended, and reductions in Patient Health Questionnaire-9 item (PHQ-9) symptoms compared with the control condition of standard group CBT in a sample of low-income Spanish speaking Latino patients. Methods Patients in an outpatient behavioral health clinic were assigned to standard group CBT for depression (control condition; n=40) or the same treatment with the addition of a text messaging adjunct (n=45). The adjunct consisted of a daily mood monitoring message, a daily message reiterating the theme of that week’s content, and medication and appointment reminders. Mood data and qualitative responses were sent to a Web-based platform (HealthySMS) for review by the therapist and displayed in session as a tool for teaching CBT skills. Results Intent-to-treat analyses on therapy attendance during 16 sessions of weekly therapy found that patients assigned to the text messaging adjunct stayed in therapy significantly longer (median of 13.5 weeks before dropping out) than patients assigned to the control condition (median of 3 weeks before dropping out; Wilcoxon-Mann-Whitney z=−2.21, P=.03). Patients assigned to the

  5. Terminating a long-term clinical trial.

    PubMed

    Klimt, C R; Canner, P L

    1979-05-01

    Long-term trials often include more than one active treatment group. These may be discontinued independently if found ineffective or possibly harmful. Certain subgroups of patients may be discovered, in the course of a clinical trial, who do not respond satisfactorily and are, therefore, excluded during the course of a trial. Yet anouther kind of termination comes when we have a therapeutic breakthrough or when hope has to be abandoned for demonstrating beneficial effects for one, several, or all treatments included in a trial. Examples from the authors' experience are presented, as are successful and unsuccessful techniques in managing terminations of various types.

  6. Dental hygiene work in a clinical trial.

    PubMed

    Luís, H S; Morgado, I; Assunção, V; Bernardo, M F; Leroux, B; Martin, M D; DeRouen, T A; Leitão, J

    2008-08-01

    Dental hygiene activities were developed as part of a randomized clinical trial designed to assess the safety of low-level mercury exposure from dental amalgam restorations. Along with dental-hygiene clinical work, a community programme was implemented after investigators noticed the poor oral hygiene habits of participants, and the need for urgent action to minimize oral health problems in the study population. Clinical and community activity goal was to promote oral health and prevent new disease. Community activities involved participants and their fellow students and were aimed at providing education on oral health in a school environment. Dental hygienists developed clinical work with prophylaxis, sealants application and topical fluoride and implemented the community programme with in-class sessions on oral health themes. Twice a month fluoride mouthrinses and bi-annual tooth brushing instructional activity took place. Participation at dental-hygiene activities, sealed teeth with no need of restoration and dental-plaque-index were measures used to evaluate success of the programme for the participants. Improvement in dental hygiene is shown by the decrease in dental plaque index scores (P < 0.0001); also sealants integrity is achieved in 86.3% of teeth. 888 (13.7%) teeth with sealants had to be restored or were lost. Children participated actively on dental hygiene activities. Teachers became aware of the problem and included oral-health in school curricula. Dental hygiene activities have shown to be helpful to promote dental hygiene, promote oral health and to provide school-age children with education on habits that will be important for their future good health.

  7. Examining longitudinal stimulant use and treatment attendance as parallel outcomes in two contingency management randomized clinical trials

    PubMed Central

    McPherson, Sterling; Brooks, Olivia; Barbosa-Leiker, Celestina; Lederhos, Crystal; Lamp, Amanda; Murphy, Sean; Layton, Matthew; Roll, John

    2015-01-01

    The primary aim of this study was to examine stimulant use and longitudinal treatment attendance in one ‘parallel outcomes’ model in order to determine how these two outcomes are related to one another during treatment, and to quantify how the intervention impacts these two on- and off-target outcomes differently. Data came from two multi-site randomized clinical trials (RCTs) of contingency management (CM) that targeted stimulant use. We used parallel multilevel modeling to examine the impact of multiple pre-specified covariates, including selected Addiction Severity Index (ASI) scores, age and sex, in addition to CM on concurrent attendance and stimulant use in two separate analyses, i.e., one per trial. In one trial, CM was positively associated with attending treatment throughout the trial (β = 0.060, p < 0.05). In the second trial, CM predicted negative urinalysis (−UA) over the 12-week treatment period (β = 0.069, p < 0.05). In both trials, there was a significant, positive relationship between attendance and −UA submission, but in the first trial a −UA at both baseline and over time was related to attendance over time (r = 0.117; r = 0.013, respectively) and in the second trial, a −UA submission at baseline was associated with increased attendance over time (r = 0.055). These findings indicate that stimulant use and treatment attendance over time are related but distinct outcomes that, when analyzed simultaneously, portray a more informative picture of their predictors and the separate trajectories of each. This ‘indirect reinforcement’ between two clinically meaningful on-target (directly reinforced behavior) and off-target (indirectly reinforced behavior) outcomes is in need of further examination in order to fully exploit the potential clinical benefits that could be realized in substance use disorder treatment trials. PMID:26456717

  8. Examining Longitudinal Stimulant Use and Treatment Attendance as Parallel Outcomes in Two Contingency Management Randomized Clinical Trials.

    PubMed

    McPherson, Sterling; Brooks, Olivia; Barbosa-Leiker, Celestina; Lederhos, Crystal; Lamp, Amanda; Murphy, Sean; Layton, Matthew; Roll, John

    2016-02-01

    The primary aim of this study was to examine stimulant use and longitudinal treatment attendance in one 'parallel outcomes' model in order to determine how these two outcomes are related to one another during treatment, and to quantify how the intervention impacts these two on- and off-target outcomes differently. Data came from two multi-site randomized clinical trials (RCTs) of contingency management (CM) that targeted stimulant use. We used parallel multilevel modeling to examine the impact of multiple pre-specified covariates, including selected Addiction Severity Index (ASI) scores, age and sex, in addition to CM on concurrent attendance and stimulant use in two separate analyses, i.e., one per trial. In one trial, CM was positively associated with attending treatment throughout the trial (β=0.060, p<0.05). In the second trial, CM predicted negative urinalysis ((-)UA) over the 12-week treatment period (β=0.069, p<0.05). In both trials, there was a significant, positive relationship between attendance and (-)UA submission, but in the first trial a (-)UA at both baseline and over time was related to attendance over time (r=0.117; r=0.013, respectively) and in the second trial, a (-)UA submission at baseline was associated with increased attendance over time (r=0.055). These findings indicate that stimulant use and treatment attendance over time are related but distinct outcomes that, when analyzed simultaneously, portray a more informative picture of their predictors and the separate trajectories of each. This 'indirect reinforcement' between two clinically meaningful on-target (directly reinforced behavior) and off-target (indirectly reinforced behavior) outcomes is in need of further examination in order to fully exploit the potential clinical benefits that could be realized in substance use disorder treatment trials.

  9. Clinical trial design in feedlots.

    PubMed

    Perino, L J; Apley, M D

    1998-07-01

    As mentioned at the outset, the ultimate test of a product or procedure must be under field conditions and is best obtained from controlled studies of field use. Economic justification for use is based on this information. Each producer places a different value on attributable benefits such as improved health or growth performance. These values also change with fluctuating market values of cattle and feed. This makes determining the cost-benefit ratio of any procedure or product a moving target. Addressing this issue requires the clinically relevant and statistically significant differences that practitioners should be able to generate if they follow the guidelines presented here. There already exists a number of unusable studies. We suggest that those interested in undertaking this challenge be uncompromising in their experimental design. To be reliable, studies must follow the recommendations outlined above. Without sound field trial design and execution which ensures that the information is reliable and statistical significance which ensures that the differences are real, clinical outcomes cannot be extrapolated to economic justification. Any other course leads to making less than optimal recommendations on product use because of a lack of clinically relevant information.

  10. Environmental Enrichment as a Therapy for Autism: A Clinical Trial Replication and Extension

    PubMed Central

    Woo, Cynthia C.; Donnelly, Joseph H.; Steinberg-Epstein, Robin; Leon, Michael

    2015-01-01

    Based on work done in animal models showing that autism-like symptoms are ameliorated following exposure to an enriched sensorimotor environment, we attempted to develop a comparable therapy for children with autism. In an initial randomized controlled trial, children with autism who received sensorimotor enrichment at home for six months had significant improvements in both their cognitive ability and the severity of their autism symptoms (Woo & Leon, 2013). We now report the outcomes of a similar randomized controlled trial in which children with autism, aged 3-6 years old, were randomly assigned to groups that received either daily sensorimotor enrichment, administered by their parents, along with standard care, or they received standard care alone. After six months, enriched children showed statistically significant gains in their IQ scores, a decline in their atypical sensory responses, and an improvement in their receptive language performance, compared to controls. Furthermore, after six months of enrichment therapy, 21% of the children who initially had been given an autism classification, using the Autism Diagnostic Observation Schedule, improved to the point that, although they remained on the autism spectrum, they no longer met the criteria for classic autism. None of the standard care controls reached an equivalent level of improvement. Finally, the outcome measures for children who received only a subset of sensory stimuli were similar to those receiving the full complement of enrichment exercises. Sensorimotor enrichment therapy therefore appears to be a cost-effective means of treating a range of symptoms for children with autism. PMID:26052790

  11. Achieving consensus for clinical trials

    PubMed Central

    Blakeley, Jaishri O.; Dombi, Eva; Fisher, Michael J.; Hanemann, C. Oliver; Walsh, Karin S.; Wolters, Pamela L.; Widemann, Brigitte C.

    2013-01-01

    The neurofibromatoses (NF)—including neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2), and schwannomatosis—are related tumor-suppressor syndromes characterized by a predisposition to multiple tumor types and other disease manifestations, which often result in functional disability, reduced quality of life, pain, and, in some cases, malignancy. With increasing knowledge of the biology and pathogenesis of NF, clinical trials with targeted agents directed at NF tumors have become available. Most clinical trials for patients with NF have used designs and endpoints similar to oncology trials. However, differences in the disease manifestations and natural history of NF (compared to cancers) require the development of new designs and endpoints to perform meaningful NF clinical trials. The Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration was established in 2011 at the Children's Tumor Foundation meeting to achieve consensus within the NF community about the design of future clinical trials, with a specific emphasis on endpoints. The REiNS Collaboration includes 7 working groups that focus on imaging of tumor response; functional, visual, patient-reported, and neurocognitive outcomes; whole-body MRI; and disease biomarkers. This supplement includes the first series of recommendations by the REiNS Collaboration. The hope is that these recommendations will be used by members of the group and by researchers outside of the REiNS International Collaboration to standardize the measurement of outcomes and thus improve clinical trials for patients with NF. Ultimately, we plan to engage industry partners and national regulatory agencies in this process to facilitate the approval of drugs for patients with NF. PMID:24249801

  12. Nonconsensual clinical trials: a foreseeable risk of offshoring under global corporatism.

    PubMed

    Spielman, Bethany

    2015-03-01

    This paper explores the connection of offshoring and outsourcing to nonconsensual global pharmaceutical trials in low-income countries. After discussing reasons why the topic of nonconsensual offshored clinical trials may be overlooked in bioethics literature, I suggest that when pharmaceutical corporations offshore clinical trials today, nonconsensual experiments are often foreseeable and not simply the result of aberrant ethical conduct by a few individuals. Offshoring of clinical trials is structured so that experiments can be presented as health care in a unique form of outsourcing from the host country to pharmaceutical corporations. Bioethicists' assessments of the risks and potential benefits of offshore corporate pharmaceutical trials should therefore systematically include not only the hoped for benefits and the risks of the experimental drug but also the risk that subjects will not have consented, as well as the broader international consequences of nonconsensual experimentation.

  13. Full-mouth disinfection as a therapeutic protocol for type-2 diabetic subjects with chronic periodontitis: twelve-month clinical outcomes: a randomized controlled clinical trial.

    PubMed

    Santos, Vanessa R; Lima, Jadson A; Miranda, Tamires S; Gonçalves, Tiago E D; Figueiredo, Luciene C; Faveri, Marcelo; Duarte, Poliana M

    2013-02-01

    The aim of this randomized controlled clinical trial was to evaluate the clinical effects of chlorhexidine (CHX) application in a full-mouth disinfection (FMD) protocol in poorly controlled type-2 diabetic subjects with generalized chronic periodontitis. Thirty-eight subjects were randomly assigned into FMD group (n=19): full-mouth scaling and root planing (FMSRP) within 24 h + local application of CHX gel + CHX rinses for 60 days or Control group (n = 19): FMSRP within 24 h + local application of placebo gel + placebo rinses for 60 days. Clinical parameters, glycated haemoglobin and fasting plasma glucose were assessed at baseline, 3, 6 and 12 months post-therapies. All clinical parameters improved significantly at 3, 6 and 12 months post-therapies for both groups (p < 0.05). There were no significant differences between groups for any clinical parameters, and glycemic condition at any time-point (p > 0.05). The treatments did not differ with respect to clinical parameters, including the primary outcome variable (i.e. changes in clinical attachment level in deep pockets), for up to 12 months post-treatments. © 2012 John Wiley & Sons A/S.

  14. Randomized Clinical Trials in Localized Anal Cancer.

    PubMed

    Smith, Clayton A; Kachnic, Lisa A

    2017-10-01

    Management of anal carcinoma began as abdominoperineal resection and has evolved to combined chemotherapy and radiation. Early randomized trials demonstrated superior clinical outcomes of combined modality therapy over radiotherapy alone. Subsequent trials investigated alterations in the standard backbone of radiotherapy concurrent with 5-fluorouracil and mitomycin C with intent to maintain clinical outcomes while reducing treatment-related morbidity. The addition of intensity-modulated radiotherapy to radiation planning and delivery has subsequently reduced acute toxicity and detrimental treatment breaks. Ongoing and future trials are aimed at reducing therapy in favorable patient populations to decrease morbidity while intensifying treatment in patients with negative prognostic factors. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Economic endpoints in clinical trials.

    PubMed

    Cook, John; Drummond, Michael; Heyse, Joseph F

    2004-04-01

    Healthcare decision makers are increasingly requesting information on the cost and cost-effectiveness of new medicines at the time of product launch. In order to provide this information, data on healthcare resource utilization and, in some cases, costs, may be collected in clinical trials. In this paper, we discuss some of the issues statisticians need to address when it is appropriate to include these economic endpoints in the trial. Several design issues are discussed, including the alternative types of and methods for collecting economic endpoint data, sample size and generalizability. Alternative approaches in the analysis of resource utilization, cost and cost-effectiveness are also presented. Finally, several of the analytic approaches are applied to actual data from a clinical trial.

  16. Randomised controlled trial of topical kanuka honey for the treatment of rosacea

    PubMed Central

    Braithwaite, Irene; Hunt, Anna; Riley, Judith; Fingleton, James; Kocks, Janwillem; Corin, Andrew; Helm, Colin; Sheahan, Davitt; Tofield, Christopher; Montgomery, Barney; Holliday, Mark; Weatherall, Mark; Beasley, Richard

    2015-01-01

    Objective To investigate the efficacy of topical 90% medical-grade kanuka honey and 10% glycerine (Honevo) as a treatment for rosacea. Design Randomised controlled trial with blinded assessment of primary outcome variable. Setting Outpatient primary healthcare population from 5 New Zealand sites. Participants 138 adults aged ≥16, with a diagnosis of rosacea, and a baseline blinded Investigator Global Assessment of Rosacea Severity Score (IGA-RSS) of ≥2. 69 participants were randomised to each treatment arm. 1 participant was excluded from the Honevo group, and 7 and 15 participants withdrew from the Honevo and control groups, respectively. Interventions Participants were randomly allocated 1:1 to Honevo or control cream (Cetomacrogol), applied twice daily for 8 weeks. Main outcome measures The primary outcome measure was the proportion of participants who had a ≥2 improvement in the 7-point IGA-RSS at week 8 compared to baseline. Secondary outcomes included change in IGA-RSS and subject-rated visual analogue score of change in severity (VAS-CS) on a 100 mm scale (0 mm ‘much worse’, 100 mm ‘much improved’) at weeks 2 and 8. Results 24/68 (34.3%) in the Honevo group and 12/69 (17.4%) in the control group had a ≥2 improvement in IGA-RSS at week 8 compared to baseline (relative risk 2.03; 95% CI 1.11 to 3.72, p=0.020). The change in IGA-RSS for Honevo compared to control at week 2 minus baseline was −1 (Hodges-Lehman estimate, 95% CI −1 to 0, p=0.03), and at week 8 minus baseline was −1 (Hodges-Lehman estimate, 95% CI −1 to 0, p=0.005). The VAS-CS at week 2 was 9.1 (95% CI 3.5 to 14.7), p=0.002, and at week 8 was 12.3 (95% CI 5.7 to 18.9)¸ p<0.001 for Honevo compared to control. Conclusions Honevo is an effective treatment for rosacea. Trial registration number This trial was registered in the Australian and New Zealand Clinical Trials Registry ACTRN12614000004662. PMID:26109117

  17. Clinical Trials in Your Community

    Cancer.gov

    The NCI Community Oncology Research Program (NCORP) is a national network of investigators, cancer care providers, academic institutions, and other organizations. NCORP conducts multi-site cancer clinical trials and studies in diverse populations in community-based healthcare systems across the United States and Puerto Rico.

  18. Predictors of local adverse effects caused by topical tretinoin cream 0·1% in the Veterans Affairs Topical Tretinoin Chemoprevention trial.

    PubMed

    Pomerantz, H; Weinstock, M A

    2014-09-01

    Topical tretinoin is commonly prescribed, but its frequent adverse effects are barriers to use. Predictors of resistance or susceptibility to retinoid irritation are not known. To identify baseline patient characteristics associated with adverse effects of topical tretinoin. This cohort study used data collected from 324 participants in the Veterans Affairs Topical Tretinoin Chemoprevention trial who were randomized to apply tretinoin cream on the face and ears. Univariate and multivariate logistic regression models were used to examine the associations between baseline characteristics and local adverse effects. One hundred and ninety-seven patients (61% of those randomized to tretinoin) reported local adverse effects within 6 months. Clinical signs of severe photodamage at baseline [odds ratio (OR) 0·15, 95% confidence interval (CI) 0·04-0·54] and history of acne (OR 0·46, 95% CI 0·27-0·77) were associated with a decreased risk of adverse effects to tretinoin. The use of other topical medications at enrolment (OR 1·88, 95% CI 1·15-3·08) predicted an increase in adverse effects. In this study population, the common indications of topical tretinoin treatment were associated with lower risks of adverse effects. The concurrent use of other topical medications may worsen irritation caused by tretinoin. © 2014 British Association of Dermatologists.

  19. Trials, tricks and transparency: how disclosure rules affect clinical knowledge.

    PubMed

    Dahm, Matthias; González, Paula; Porteiro, Nicolás

    2009-12-01

    Scandals of selective reporting of clinical trial results by pharmaceutical firms have underlined the need for more transparency in clinical trials. We provide a theoretical framework which reproduces incentives for selective reporting and yields three key implications concerning regulation. First, a compulsory clinical trial registry complemented through a voluntary clinical trial results database can implement full transparency (the existence of all trials as well as their results is known). Second, full transparency comes at a price. It has a deterrence effect on the incentives to conduct clinical trials, as it reduces the firms' gains from trials. Third, in principle, a voluntary clinical trial results database without a compulsory registry is a superior regulatory tool; but we provide some qualified support for additional compulsory registries when medical decision-makers cannot anticipate correctly the drug companies' decisions whether to conduct trials.

  20. Skin care education and individual counselling versus treatment as usual in healthcare workers with hand eczema: randomised clinical trial

    PubMed Central

    Jemec, Gregor B E; Diepgen, Thomas L; Gluud, Christian; Lindschou Hansen, Jane; Winkel, Per; Thomsen, Simon Francis; Agner, Tove

    2012-01-01

    Objective To evaluate the effect of a secondary prevention programme with education on skin care and individual counselling versus treatment as usual in healthcare workers with hand eczema. Design Randomised, observer blinded parallel group superiority clinical trial. Setting Three hospitals in Denmark. Participants 255 healthcare workers with self reported hand eczema within the past year randomised centrally and stratified by profession, severity of eczema, and hospital. 123 were allocated to the intervention group and 132 to the control group. Interventions Education in skin care and individual counselling based on patch and prick testing and assessment of work and domestic related exposures. The control was treatment as usual. Main outcome measures The primary outcome was clinical severity of disease at five month follow-up measured by scores on the hand eczema severity index. The secondary outcomes were scores on the dermatology life quality index, self evaluated severity of hand eczema, skin protective behaviours, and knowledge of hand eczema from onset to follow-up. Results Follow-up data were available for 247 of 255 participants (97%). At follow-up, the mean score on the hand eczema severity index was significantly lower (improved) in the intervention group than control group: difference of means, unadjusted −3.56 (95% confidence interval −4.92 to −2.14); adjusted −3.47 (−4.80 to −2.14), both P<0.001 for difference. The mean score on the dermatology life quality index was also significantly lower (improved) in the intervention group at follow-up: difference of means: unadjusted −0.78, non-parametric test P=0.003; adjusted −0.92, −1.48 to −0.37). Self evaluated severity and skin protective behaviour by hand washings and wearing of protective gloves were also statistically significantly better in the intervention group, whereas this was not the case for knowledge of hand eczema. Conclusion A secondary prevention programme for hand eczema

  1. Parents as Agents of Change (PAC) in pediatric weight management: The protocol for the PAC randomized clinical trial

    PubMed Central

    2012-01-01

    Background There is an urgent need to develop and evaluate weight management interventions to address childhood obesity. Recent research suggests that interventions designed for parents exclusively, which have been named parents as agents of change (PAC) approaches, have yielded positive outcomes for managing pediatric obesity. To date, no research has combined a PAC intervention approach with cognitive behavioural therapy (CBT) to examine whether these combined elements enhance intervention effectiveness. This paper describes the protocol our team is using to examine two PAC-based interventions for pediatric weight management. We hypothesize that children with obesity whose parents complete a CBT-based PAC intervention will achieve greater reductions in adiposity and improvements in cardiometabolic risk factors, lifestyle behaviours, and psychosocial outcomes than children whose parents complete a psycho-education-based PAC intervention (PEP). Methods/Design This study is a pragmatic, two-armed, parallel, single-blinded, superiority, randomized clinical trial. The primary objective is to examine the differential effects of a CBT-based PAC vs PEP-based PAC intervention on children’s BMI z-score (primary outcome). Secondary objectives are to assess intervention-mediated changes in cardiometabolic, lifestyle, and psychosocial variables in children and parents. Both interventions are similar in frequency of contact, session duration, group facilitation, lifestyle behaviour goals, and educational content. However, the interventions differ insofar as the CBT-based intervention incorporates theory-based concepts to help parents link their thoughts, feelings, and behaviours; these cognitive activities are enabled by group leaders who possess formal training in CBT. Mothers and fathers of children (8–12 years of age; BMI ≥85th percentile) are eligible to participate if they are proficient in English (written and spoken) and agree for at least one parent to attend

  2. Swiss regulations for controlling clinical trials.

    PubMed

    Zanini, G M

    1998-04-01

    Switzerland has recently issued regulations designed to control all trials with drugs in human subjects, namely the 'Regolamento dell'Ufficio Intercantonale per il controllo dei medicamenti in fase di studio clinico' (Intercantonal Regulations Controlling Drugs used in Clinical Trials), which have been operating since 1st January 1995. These new regulations are generally consistent with other international regulations and have introduced the concept of good clinical practice (GCP) into Switzerland. There are other regulations in Switzerland, such as Federal regulations on immunobiological products, special rules governing the administration of radiolabelled drugs to humans, drugs of abuse and medical devices. Any gap in the central regulations must be filled by cantonal regulations, where they exist. This is a comprehensive review of the regulations governing clinical trials in Switzerland, with special attention being devoted to trials with therapeutic compounds and to compatibility between Swiss and international procedures.

  3. Self-Monitoring as a Mediator of Weight Loss in the SMART Randomized Clinical Trial

    PubMed Central

    Turk, Melanie Warziski; Elci, Okan U.; Wang, Jing; Sereika, Susan M.; Ewing, Linda J.; Acharya, Sushama D.; Glanz, Karen; Burke, Lora E.

    2012-01-01

    Background Integral components of behavioral weight-loss treatment include self-monitoring of diet and physical activity along with feedback to participants regarding their behaviors. While providing feedback has been associated with weight loss, no studies have examined the impact of feedback frequency on weight loss, or the mediating role of self-monitoring adherence in this relationship. Purpose This study examined the effect of participant feedback frequency on weight loss and determined if this effect was mediated by adherence to self-monitoring in a behavioral weight-loss trial conducted in the United States. Method Participants (N=210) were randomly assigned to one of three self-monitoring methods with either no daily feedback messages or daily feedback messages: 1) paper diary (PD)- no daily feedback, 2) personal digital assistant (PDA)- no daily feedback, and 3) PDA- daily, tailored feedback messages (PDA+FB). The Sobel test via bootstrapping examined the direct effect of feedback frequency on weight loss and the indirect effect through self-monitoring adherence. Results Receiving daily feedback messages significantly increased participants’ self-monitoring adherence. A significant effect of feedback frequency on weight loss was noted; however, after adjusting for self-monitoring adherence, the effect of feedback frequency on weight loss was no longer significant. Feedback frequency had a significant indirect effect on weight loss through self-monitoring adherence. Conclusion Self-monitoring adherence mediated the effect of feedback frequency on weight loss. Increasing the frequency with which participants receive feedback could enhance self-monitoring adherence, a critical component of behavioral weight-loss treatment. PMID:22936524

  4. Exploring the viability of using online social media advertising as a recruitment method for smoking cessation clinical trials.

    PubMed

    Frandsen, Mai; Walters, Julia; Ferguson, Stuart G

    2014-02-01

    The aim of the present study was to explore the viability of using social media as a recruitment tool in a clinical research trial. Sociodemographic data and smoking characteristics were assessed in 266 participants recruited to investigate the effectiveness of a behavioral support program for smoking cessation. For analysis, participants were separated into 2 groups based on whether they were recruited either using traditional means (flyers, word of mouth, or newspaper advertisement; n = 125, 47.0%) or by advertisements in online social media (n = 138, 51.9%). Participants recruited via social media were significantly younger, but there were no differences in other socioeconomic variables or smoking characteristics compared with participants recruited via other traditional means. The findings of the present study suggest that using online social media is a viable recruitment method for smoking studies and compliments other more traditional recruitment methods.

  5. Gene therapy for mitochondrial diseases: Leber Hereditary Optic Neuropathy as the first candidate for a clinical trial.

    PubMed

    Cwerman-Thibault, Hélène; Augustin, Sébastien; Ellouze, Sami; Sahel, José-Alain; Corral-Debrinski, Marisol

    2014-03-01

    Mitochondrial disorders cannot be ignored anymore in most medical disciplines; indeed their minimum estimated prevalence is superior to 1 in 5000 births. Despite the progress made in the last 25 years on the identification of gene mutations causing mitochondrial pathologies, only slow progress was made towards their effective treatments. Ocular involvement is a frequent feature in mitochondrial diseases and corresponds to severe and irreversible visual handicap due to retinal neuron loss and optic atrophy. Interestingly, three clinical trials for Leber Congenital Amaurosis due to RPE65 mutations are ongoing since 2007. Overall, the feasibility and safety of ocular Adeno-Associated Virus delivery in adult and younger patients and consistent visual function improvements have been demonstrated. The success of gene-replacement therapy for RPE65 opens the way for the development of similar approaches for a broad range of eye disorders, including those with mitochondrial etiology such as Leber Hereditary Optic Neuropathy (LHON).

  6. The Dynamo Clinical Trial

    NASA Astrophysics Data System (ADS)

    Ayres, Thomas

    2016-07-01

    Poster concerning the coronal activity cycles of Alpha Centauri A and B, the nearest sun-like stars, as observed by several generations of X-ray observatories including ROSAT, XMM-Newton, and most recently Chandra.

  7. Clinical Trial Basics

    MedlinePlus

    ... the research team explain the details of the study. Translation or interpretive assistance can be provided for participants with limited English proficiency. The research team provides an informed ... about the study, such as its purpose, duration, required procedures, and ...

  8. Systematic review of interventional sickle cell trials registered in ClinicalTrials.gov.

    PubMed

    Lebensburger, Jeffrey D; Hilliard, Lee M; Pair, Lauren E; Oster, Robert; Howard, Thomas H; Cutter, Gary R

    2015-12-01

    The registry ClinicalTrials.gov was created to provide investigators and patients an accessible database of relevant clinical trials. To understand the state of sickle cell disease clinical trials, a comprehensive review of all 174 "closed," "interventional" sickle cell trials registered at ClinicalTrials.gov was completed in January 2015. The majority of registered sickle cell disease clinical trials listed an academic center as the primary sponsor and were an early phase trial. The primary outcome for sickle cell disease trials focused on pain (23%), bone marrow transplant (BMT) (13%), hydroxyurea (8%), iron overload (8%), and pulmonary hypertension (8%). A total of 52 trials were listed as terminated or withdrawn, including 25 (14% of all trials) terminated for failure to enroll participants. At the time of this review, only 19 trials uploaded results and 29 trials uploaded a manuscript in the ClinicalTrials.gov database. A systematic review of pubmed.gov revealed that only 35% of sickle cell studies completed prior to 2014 resulted in an identified manuscript. In comparison, of 80 thalassemia trials registered in ClinicalTrials.gov, four acknowledged failure to enroll participants as a reason for trial termination or withdrawal, and 48 trials (60%) completed prior to 2014 resulted in a currently identified manuscript. ClinicalTrials.gov can be an important database for investigators and patients with sickle cell disease to understand the current available research trials. To enhance the validity of the website, investigators must update their trial results and upload trial manuscripts into the database. This study, for the first time, quantifies outcomes of sickle cell disease trials and provides support to the belief that barriers exist to successful completion, publication, and dissemination of sickle cell trial results. © The Author(s) 2015.

  9. Clinical Effects of Topical Tacrolimus on Fox-Fordyce Disease

    PubMed Central

    Kaya Erdoğan, Hilal; Bulur, Işıl; Kaya, Zeliha

    2015-01-01

    Fox-Fordyce Disease (FFD) is a rare, chronic, pruritic, inflammatory disorder of apocrine glands. It is characterized by dome-shaped, firm, discrete, skin-colored, and monomorphic perifollicular papules. The most common sites of involvement are axillae and anogenital and periareolar regions which are rich in apocrine sweat glands. Treatment is difficult. Topical, intralesional steroids, topical tretinoin, adapalene, clindamycin, benzoyl peroxide, oral contraceptives, isotretinoin, phototherapy, electrocauterisation, excision-liposuction and curettage, and fractional carbon dioxide laser are among the treatment options. In the literature, there are articles reporting beneficial effects of pimecrolimus in FFD. Nevertheless, there have not been any reports about the use of tacrolimus in FFD. We report two patients diagnosed with FFD by clinical and histopathologic examination and discussed therapeutic effects of topical tacrolimus on FFD in the light of literature. PMID:26171257

  10. Clinical trials on AIDS start.

    PubMed

    A 6-month clinical trial in the Philippines sought to determine the efficacy of coconut oil and of "monolaurin," a coconut oil byproduct, in killing HIV by breaking down its coating. This research is based on the theory that medium-chain fatty acids, like monolaurin, can have this effect on certain viruses. The trial involves 12 women and 3 men in the early stage of HIV infection. 10 patients will take different doses of monolaurin, and 5 will consume coconut oil. It is hypothesized that the regimen will lead to higher CD4 counts and a lower viral load. The trial was almost abandoned because it received only lukewarm approval from the Health Secretary.

  11. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2007-11-01

    1-Octanol, 9vPnC-MnCc; Abiraterone acetate, Adalimumab, Adefovir dipivoxil, Alemtuzumab, Aliskiren fumarate, Aminolevulinic acid hexyl ester, Amlodipine besylate/atorvastatin calcium, Amrubicin hydrochloride, Anakinra, Aripiprazole, ARRY-520, AS-1404, Asimadoline, Atazanavir sulfate, AVE-0277, Azelnidipine; Bevacizumab, Bimatoprost, Boceprevir, Bortezomib, Bosentan, Botulinum toxin type B; Certolizumab pegol, Cetuximab, Clevudine, Contusugene ladenovec, CP-751871, Crofelemer, Cypher, CYT006-AngQb; Darbepoetin alfa, Desmopressin, Dexlansoprazole, DG-041; E-5555, Ecogramostim, Entecavir, Erlotinib hydrochloride, Escitalopram oxalate, Eszopiclone, Everolimus, Ezetimibe, Ezetimibe/simvastatin; Falecalcitriol, Fampridine, Fesoterodine fumarate, Fingolimod hydrochloride; Gefitinib, Ghrelin (human), GS-7904L, GV-1001; HT-1001; Insulin detemir, ISIS-112989, Istradefylline; Laquinimod sodium, Latanoprost/timolol maleate, Lenalidomide, Levobetaxolol hydrochloride, Liposomal doxorubicin, Liposomal morphine sulfate, Lubiprostone, Lumiracoxib, LY-518674; MEM-1003, Mesna disulfide, Mipomersen sodium, MM-093, Mycophenolic acid sodium salt; Naptumomab estafenatox, Natalizumab; Olmesartan medoxomil, Olmesartan medoxomil/hydrochlorothiazide; Paclitaxel nanoparticles, Paclitaxel poliglumex, Pasireotide, Pazufloxacin mesilate, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Peginterferon alfa-2b/ribavirin, Pegvisomant, Pemetrexed disodium, Pimagedine, Pimecrolimus, Pramlintide acetate, Prasterone, Pregabalin, Prulifloxacin; QAE-397; Rec-15/2615, RFB4(dsFv)-PE38, rhGAD65, Roflumilast, Romiplostim, Rosuvastatin calcium, Rotigotine, Rupatadine fumarate; Safinamide mesilate, SIR-Spheres, Sitagliptin phosphate, Sodium phenylacetate, Sodium phenylacetate/Sodium benzoate, Sorafenib, SSR-244738; Taribavirin hydrochloride, Taxus, Teduglutide, Tegaserod maleate, Telaprevir, Telbivudine, Tenofovir disoproxil fumarate, Tigecycline, Tiotropium bromide, Trabectedin, Travoprost

  12. Involving South Asian patients in clinical trials.

    PubMed

    Hussain-Gambles, M; Leese, B; Atkin, K; Brown, J; Mason, S; Tovey, P

    2004-10-01

    To investigate how South Asian patients conceptualise the notion of clinical trials and to identify key processes that impact on trial participation and the extent to which communication difficulties, perceptions of risk and attitudes to authority influence these decisions. Also to identify whether 'South Asian' patients are homogeneous in these issues, and which factors differ between different South Asian subgroups and finally how professionals regard the involvement of South Asian patients and their views on strategies to increase participation. A review of the literature on minority ethnic participation in clinical trials was followed by three qualitative interview studies. Interviews were taped and transcribed (and translated if required) and subjected to framework analysis. Face-to-face interviews were conducted with 25 health professionals; 60 South Asian lay people who had not taken part in a trial and 15 South Asian trial participants. Motivations for trial participation were identified as follows: to help society, to improve own health or that of family and friends, out of obligation to the doctor and to increase scientific knowledge. Deterrents were concerns about drug side-effects, busy lifestyles, language, previous bad experiences, mistrust and feelings of not belonging to British society. There was no evidence of antipathy amongst South Asians to the concept of clinical trials and, overall, the younger respondents were more knowledgeable than the older ones. Problems are more likely to be associated with service delivery. Lack of being approached was a common response. Lay-reported factors that might affect South Asian participation in clinical trials include age, language, social class, feeling of not belonging/mistrust, culture and religion. Awareness of clinical trials varied between each group. There are more similarities than differences in attitudes towards clinical trial participation between the South Asian and the general population

  13. Interpersonal psychotherapy versus treatment as usual for PTSD and depression among Sichuan earthquake survivors: a randomized clinical trial

    PubMed Central

    2014-01-01

    Background Without effective treatment, PTSD and depression can cause persistent disability in disaster-affected populations. Methods Our objective was to test the efficacy of Interpersonal Psychotherapy (IPT) delivered by trained local personnel compared with treatment as usual (TAU) for Posttraumatic Stress Disorder (PTSD) and Major Depressive Disorder (MDD) among adults affected by the Sichuan 2008 earthquake. A small randomized controlled trial of IPT + TAU versus TAU alone was delivered by local mental health personnel in Shifang, China. Between July 2011 and January 2012, 49 adults ≥ 18 years with PTSD, MDD or both were enrolled and randomized to 12 weekly sessions of IPT + TAU (27) or TAU (22) alone x 12 weeks. IPT was then offered to the TAU group. Unblinded follow up assessments were conducted at three and six months. IPT was a 12 session, weekly one hour treatment delivered by local personnel who were trained and supervised in IPT. TAU was continuation of prescribed psychotropic medication (if applicable) and crisis counseling, as needed. Main Outcome(s) and Measures (s): Clinician Administered PTSD Scale (CAPS) PTSD diagnosis; Structured Clinical Interview for DSM-IV (SCID) for MDD diagnosis. Secondary measures included PTSD/depression symptoms, interpersonal conflict/anger, social support, self-efficacy and functioning. Results Using an intent-to-treat analysis, 22 IPT + TAU and 19 TAU participants were compared at three months post-baseline. A significantly greater reduction of PTSD and MDD diagnoses was found in the IPT group (51.9%, 30.1%, respectively) versus the TAU group (3.4%, 3.4%, respectively). Despite the small sample, the estimates for time-by-condition analyses of target outcomes (2.37 for PTSD (p = .018) and 1.91 for MDD (p = .056)) indicate the improvement was better in the IPT + TAU condition versus the TAU group. Treatment gains were maintained at 6 months for the IPT group. A similar treatment response

  14. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-03-01

    ABT-869, Acadesine, Acetylsalicylic acid/omeprazole, Adefovir, Adefovir dipivoxil, AEG-35156, Agatolimod sodium, Albiglutide, Alemtuzumab, Alipogene tiparvovec, Alogliptin benzoate, AMG-386, Amrubicin hydrochloride, Apremilast, Aripiprazole, Asoprisnil, Atorvastatin/fenofibrate, AVN-944, Axitinib; Belinostat, Bevacizumab, BHT-3021, BI-2536, Biapenem, Bilastine, Biphasic insulin aspart, Blinatumomab, Bortezomib, Bosentan; Catumaxomab, CD-NP, Cediranib, Certolizumab pegol, Cetuximab, Choline fenofibrate, Ciclesonide, CK-1827452,Clevudine, Clofarabine, CSL-360, CYT-997; Dapagliflozin, Darinaparsin, Denosumab, Densiron 68, Desloratadine, Dulanermin; Edoxaban tosilate, Emtricitabine, Entecavir, Erlotinib hydrochloride, Everolimus, Exenatide, Ezetimibe, Ezetimibe/simvastatin; Fidaxomicintiacumiv, Fulvestrant; G-207, GCR-8015, Gefitinib, Ghrelin (human), Glufosfamide; HPV16L1E7CVLP; Ibutamoren mesilate, Imatinib mesylate, Insulin detemir, Insulin glargine, Iodine (I131) tositumomab, Istaroxime, ITMN-191, Ixabepilone; JZP-4, Lenalidomide; Levetiracetam, Linaclotide acetate, Liposomal cytarabine/daunorubicin, Liposomal doxorubicin, Liraglutide, LY-518674; Milatuzumab, MMR-V, Motesanib diphosphate, Mycophenolic acid sodium salt; Niacin/simvastatin; Obatoclax mesylate, Odanacatib; Paclitaxel nanoparticles, Paclitaxel-eluting stent, Pazufloxacin, PBT-2, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Peginterferon alfa-2b/ribavirin, Pemetrexed disodium, Perampanel, PfCP2.9, Pitavastatin calcium, Poly I:CLC, Pomalidomide, Pralatrexate, Pramlintide acetate, Prucalopride; rhGAD65, Roflumilast; RTS,S/AS02D; SCH-530348, Semagacestat, Sirolimus-eluting coronary stent, Sirolimus-Eluting Stent, SIR-Spheres, Sivelestat sodium hydrate, Sorafenib, Sunitinib malate; Tadalafil, Tafluprost, Tanespimycin, Teduglutide, Telaprevir, Telbivudine, Tenofovir disoproxil fumarate, Tiotropium bromide, TMC-435350, Tositumomab/iodine (I131) tositumomab, Travoprost/timolol, Triciribine

  15. Quantitative Imaging in Cancer Clinical Trials

    PubMed Central

    Yankeelov, Thomas E.; Mankoff, David A.; Schwartz, Lawrence H.; Lieberman, Frank S.; Buatti, John M.; Mountz, James M.; Erickson, Bradley J.; Fennessy, Fiona M.M.; Huang, Wei; Kalpathy-Cramer, Jayashree; Wahl, Richard L.; Linden, Hannah M.; Kinahan, Paul; Zhao, Binsheng; Hylton, Nola M.; Gillies, Robert J.; Clarke, Laurence; Nordstrom, Robert; Rubin, Daniel L.

    2015-01-01

    As anti-cancer therapies designed to target specific molecular pathways have been developed, it has become critical to develop methods to assess the response induced by such agents. While traditional, anatomic CT and MRI exams are useful in many settings, there is increasing evidence that these methods cannot answer the fundamental biological and physiological questions essential for assessment and, eventually, prediction of treatment response in the clinical trial setting, especially in the critical period soon after treatment is initiated. To optimally apply advances in quantitative imaging methods to trials of targeted cancer therapy, new infrastructure improvements are needed that incorporate these emerging techniques into the settings where they are most likely to have impact. In this review, we first elucidate the needs for therapeutic response assessment in the era of molecularly targeted therapy and describe how quantitative imaging can most effectively provide scientifically and clinically relevant data. We then describe the tools and methods required to apply quantitative imaging and provide concrete examples of work making these advances practically available for routine application in clinical trials. We conclude by proposing strategies to surmount barriers to wider incorporation of these quantitative imaging methods into clinical trials and, eventually, clinical practice. Our goal is to encourage and guide the oncology community to deploy standardized quantitative imaging techniques in clinical trials to further personalize care for cancer patients, and to provide a more efficient path for the development of improved targeted therapies. PMID:26773162

  16. Quantitative Imaging in Cancer Clinical Trials.

    PubMed

    Yankeelov, Thomas E; Mankoff, David A; Schwartz, Lawrence H; Lieberman, Frank S; Buatti, John M; Mountz, James M; Erickson, Bradley J; Fennessy, Fiona M M; Huang, Wei; Kalpathy-Cramer, Jayashree; Wahl, Richard L; Linden, Hannah M; Kinahan, Paul E; Zhao, Binsheng; Hylton, Nola M; Gillies, Robert J; Clarke, Laurence; Nordstrom, Robert; Rubin, Daniel L

    2016-01-15

    As anticancer therapies designed to target specific molecular pathways have been developed, it has become critical to develop methods to assess the response induced by such agents. Although traditional, anatomic CT, and MRI examinations are useful in many settings, increasing evidence suggests that these methods cannot answer the fundamental biologic and physiologic questions essential for assessment and, eventually, prediction of treatment response in the clinical trial setting, especially in the critical period soon after treatment is initiated. To optimally apply advances in quantitative imaging methods to trials of targeted cancer therapy, new infrastructure improvements are needed that incorporate these emerging techniques into the settings where they are most likely to have impact. In this review, we first elucidate the needs for therapeutic response assessment in the era of molecularly targeted therapy and describe how quantitative imaging can most effectively provide scientifically and clinically relevant data. We then describe the tools and methods required to apply quantitative imaging and provide concrete examples of work making these advances practically available for routine application in clinical trials. We conclude by proposing strategies to surmount barriers to wider incorporation of these quantitative imaging methods into clinical trials and, eventually, clinical practice. Our goal is to encourage and guide the oncology community to deploy standardized quantitative imaging techniques in clinical trials to further personalize care for cancer patients and to provide a more efficient path for the development of improved targeted therapies.

  17. Navarakizhi and pinda sweda as muscle-nourishing Ayurveda procedures in hemiplegia: double-blind randomized comparative pilot clinical trial.

    PubMed

    Guruprasad Aggithaya, Madhur; Narahari, Saravu R; Vijaya, Shanthakumari; Sushma, Kandathu Valappil; Kumar, Nadesa Panicker Anil; Prajeesh, Parameswaran

    2014-01-01

    Hemiplegia and the Ayurvedic description of ardhanga disease presents with comparable clinical features. This pilot trial compared two traditional procedure-based treatments: Navarakizhi, a massage of cooked navara rice in a medicated hot bolus, and pinda sweda, a similar massage made of a different type of rice. This article also describes the steps of a double-blind trial in Ayurveda, which was hitherto considered difficult to perform. Eighteen (18) patients suffering from hemiplegia with disease duration of 6 months to 2 years received treatment with navarakizhi or pinda sweda for 7 days. Both groups received the same Ayurvedic oral medications for 14 days. All steps of randomization and blinding of procedure-based therapy in Ayurveda are described. The physiotherapist evaluated muscle tone, muscle strength, tendon reflexes, range of movement, and balance of functional abilities at baseline, 7 days, and 14 days after starting therapy. Both patient and the assessing physiotherapist were blinded. Intraquartile range values showed better range in patients who received navarakizhi than those who received pinda sweda. A larger trial is needed to confirm the superiority of navarakizhi over the rice varieties in treating hemiplegia. This study demonstrates that double-blind randomized clinical trials are possible in Ayurvedic settings, ending the long-debated controversy in trial methodology involving procedure-based traditional medicines.

  18. RECENT CLINICAL TRIALS IN LUPUS NEPHRITIS

    PubMed Central

    Ward, Michael M.

    2014-01-01

    SYNOPSIS Recent clinical trials have provided evidence for the efficacy of low-dose intravenous cyclophosphamide and mycophenolate mofetil as induction treatment for patients with proliferative lupus nephritis in comparative trials with standard-dose intravenous cyclophosphamide. Trials of maintenance treatments have had more variable results, but suggest that mycophenolate mofetil may be similar to quarterly standard-dose intravenous cyclophosphamide and somewhat more efficacious than azathioprine. Differential responses to mycophenolate mofetil based on ethnicity suggest that it may be more effective in black and Hispanic patients. Rituximab was not efficacious as an adjunct to induction treatment with mycophenolate mofetil. PMID:25034160

  19. Quality of clinical trials: A moving target

    PubMed Central

    Bhatt, Arun

    2011-01-01

    Quality of clinical trials depends on data integrity and subject protection. Globalization, outsourcing and increasing complexicity of clinical trials have made the target of achieving global quality challenging. The quality, as judged by regulatory inspections of the investigator sites, sponsors/contract research organizations and Institutional Review Board, has been of concern to the US Food and Drug Administration, as there has been hardly any change in frequency and nature of common deficiencies. To meet the regulatory expectations, the sponsors need to improve quality by developing systems with specific standards for each clinical trial process. The quality systems include: personnel roles and responsibilities, training, policies and procedures, quality assurance and auditing, document management, record retention, and reporting and corrective and preventive action. With an objective to improve quality, the FDA has planned new inspection approaches such as risk-based inspections, surveillance inspections, real-time oversight, and audit of sponsor quality systems. The FDA has partnered with Duke University for Clinical Trials Transformation Initiative, which will conduct research projects on design principles, data quality and quantity including monitoring, study start-up, and adverse event reporting. These recent initiatives will go a long way in improving quality of clinical trials. PMID:22145122

  20. Nurse Practitioners' attitudes about cancer clinical trials and willingness to recommend research participation

    PubMed Central

    Ulrich, Connie M.; Zhou, Quiping; Ratcliffe, Sarah J.; Ye, Lichuan; Grady, Christine; Watkins-Bruner, Deborah

    2016-01-01

    Background Recruitment and retention of human participants in cancer clinical trials remains challenging for all investigators. Nurse Practitioners (NPs) are in a prime position to discuss, educate and refer patients to clinical trials as many NPs work in ethnically and geographically diverse primary care settings in the U.S., yet they remain an untapped resource. We examined NPs' general attitudes toward cancer clinical trial recommendations and assessed their willingness to recommend such trials. Methods We randomly surveyed 455 primary care NPs in the state of Pennsylvania during 2008 with an adjusted response rate of 55.3%. Descriptive statistics were used to characterize NPs' demographic and practice characteristics, and logistic regression was used to assess the relative influence of the various attitudes and beliefs on the likelihood that the NP would bring up clinical trials as a treatment option. Results NPs were more likely to bring up the topic of clinical trials with at least some patients if they were comfortable discussing treatment options with their cancer patients (OR = 4.29, p = 0.001), were comfortable discussing options of entering a clinical trial for treatment (OR = 3.54, p = 0.003), had adequate time during patients' visit to explain clinical trials (OR = 3.40, p = 0.008), and if they believed that patients in clinical trials were receiving the best medical treatment (OR = 3.34, p = 0.019). NPs who were comfortable discussing cancer clinical trials were almost 5 times more likely to think clinical trials were useful (OR = 4.70; 95% CI = 1.81–12.19; p = 0.001). Nearly three-quarters (72.6%) of the entire responder sample reported three or more ethical concerns associated with clinical trials, including issues of randomization, informed consent, and patient burden. Conclusions NPs are willing to recommend clinical trials but need more education about the benefits and burdens of clinical trials, the associated ethical concerns, and evidence

  1. Definition of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage as an outcome event in clinical trials and observational studies: proposal of a multidisciplinary research group.

    PubMed

    Vergouwen, Mervyn D I; Vermeulen, Marinus; van Gijn, Jan; Rinkel, Gabriel J E; Wijdicks, Eelco F; Muizelaar, J Paul; Mendelow, A David; Juvela, Seppo; Yonas, Howard; Terbrugge, Karel G; Macdonald, R Loch; Diringer, Michael N; Broderick, Joseph P; Dreier, Jens P; Roos, Yvo B W E M

    2010-10-01

    In clinical trials and observational studies there is considerable inconsistency in the use of definitions to describe delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage. A major cause for this inconsistency is the combining of radiographic evidence of vasospasm with clinical features of cerebral ischemia, although multiple factors may contribute to DCI. The second issue is the variability and overlap of terms used to describe each phenomenon. This makes comparisons among studies difficult. An international ad hoc panel of experts involved in subarachnoid hemorrhage research developed and proposed a definition of DCI to be used as an outcome measure in clinical trials and observational studies. We used a consensus-building approach. It is proposed that in observational studies and clinical trials aiming to investigate strategies to prevent DCI, the 2 main outcome measures should be: (1) cerebral infarction identified on CT or MRI or proven at autopsy, after exclusion of procedure-related infarctions; and (2) functional outcome. Secondary outcome measure should be clinical deterioration caused by DCI, after exclusion of other potential causes of clinical deterioration. Vasospasm on angiography or transcranial Doppler can also be used as an outcome measure to investigate proof of concept but should be interpreted in conjunction with DCI or functional outcome. The proposed measures reflect the most relevant morphological and clinical features of DCI without regard to pathogenesis to be used as an outcome measure in clinical trials and observational studies.

  2. Capillaroscopy as an Outcome Measure for Clinical Trials on the Peripheral Vasculopathy in SSc—Is It Useful?

    PubMed Central

    Cutolo, Maurizio; Sulli, Alberto; Pizzorni, Carmen; Smith, Vanessa

    2010-01-01

    Peripheral microvascular impairment in systemic sclerosis (SSc) may be easily detected and scored in a safe noninvasive way by nailfold videocapillaroscopy (NVC). The paper highlights clinical conditions related to SSc in which NVC may represent an outcome measure of therapeutical interventions, by elaborating on their already assessed relationship with the NVC patterns and eventually scores. The 3 important biological/clinical conditions are: the positivity for SSc-specific serum autoantibodies, the presence of SSc skin digital ulcers (DUs) and of pulmonary arterial hypertension (PAH) SSc associated. In conclusion, to the question if capillaroscopy (NVC) may represent in SSc an outcome measure for clinical trials on the peripheral vasculopathy, based on the growing evidence and our detailed studies, the answer is positive. Recent therapeutic trials in SSc are confirming this role, and the experience is growing rapidly. PMID:20827384

  3. Status of the pediatric clinical trials enterprise: an analysis of the US ClinicalTrials.gov registry.

    PubMed

    Pasquali, Sara K; Lam, Wendy K; Chiswell, Karen; Kemper, Alex R; Li, Jennifer S

    2012-11-01

    Clinical trials are the gold standard for generating evidence-based knowledge in medicine. Recent legislation requiring trials to be registered at ClinicalTrials.gov has enabled evaluation of the clinical trial enterprise as a whole, which was previously not possible. The purpose of this study was to create a snapshot of the pediatric clinical trial portfolio. All interventional trials registered at ClinicalTrials.gov from July 2005 to September 2010 were included. Pediatric (ie, enrolling patients aged 0-18 years) trial characteristics, therapeutic area, location, and funding were described. Secondary objectives included describing pediatric trials over time and comparison with nonpediatric trials. During this time, 5035 pediatric trials were registered compared with >10 times as many nonpediatric trials. Neonates/infants were eligible for enrollment in 46.6% of trials versus children (77.9%) and adolescents (45.2%). Nearly one-half of pediatric trials enrolled <100 subjects, and more pediatric trials versus nonpediatric trials evaluated preventive therapies. The proportion of pediatric trials evaluating a drug intervention declined over time, and there were fewer Phase 0 to II versus Phase III to IV trials. Infectious disease/vaccine studies (23%) were the most common, followed by psychiatric/mental health (13%) studies. Many trials enrolled patients outside the United States, and <15% of trials were sponsored by the National Institutes of Health or other US federal agencies. Analysis of the ClinicalTrials.gov data set allows description of the current scope of pediatric trials. These data may be useful to stakeholders in informing decisions regarding the conduct of trials in children and provide insight into mechanisms to advance pediatric trial infrastructure and methodology toward improving child health.

  4. 'Cloud computing' and clinical trials: report from an ECRIN workshop.

    PubMed

    Ohmann, Christian; Canham, Steve; Danielyan, Edgar; Robertshaw, Steve; Legré, Yannick; Clivio, Luca; Demotes, Jacques

    2015-07-29

    Growing use of cloud computing in clinical trials prompted the European Clinical Research Infrastructures Network, a European non-profit organisation established to support multinational clinical research, to organise a one-day workshop on the topic to clarify potential benefits and risks. The issues that arose in that workshop are summarised and include the following: the nature of cloud computing and the cloud computing industry; the risks in using cloud computing services now; the lack of explicit guidance on this subject, both generally and with reference to clinical trials; and some possible ways of reducing risks. There was particular interest in developing and using a European 'community cloud' specifically for academic clinical trial data. It was recognised that the day-long workshop was only the start of an ongoing process. Future discussion needs to include clarification of trial-specific regulatory requirements for cloud computing and involve representatives from the relevant regulatory bodies.

  5. Veterinary oncology clinical trials: design and implementation.

    PubMed

    Thamm, Douglas H; Vail, David M

    2015-08-01

    There has been a recent increase in interest among veterinarians and the larger biomedical community in the evaluation of novel cancer therapies in client-owned (pet) animals with spontaneous cancer. This includes novel drugs designed to be veterinary therapeutics, as well as agents for which data generated in animals with tumors may inform human clinical trial design and implementation. An understanding of the process involved in moving a therapeutic agent through the stages of clinical evaluation is critical to the successful implementation of clinical investigations, as well as interpretation of the veterinary oncology literature. This review outlines considerations in the design and conduct of the various phases of oncology clinical trials, along with recent adaptations/modifications of these basic designs that can enhance the generation of timely and meaningful clinical data. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. A clinical and mechanistic study of topical borneol-induced analgesia.

    PubMed

    Wang, Shu; Zhang, Dan; Hu, Jinsheng; Jia, Qi; Xu, Wei; Su, Deyuan; Song, Hualing; Xu, Zhichun; Cui, Jianmin; Zhou, Ming; Yang, Jian; Xiao, Jianru

    2017-04-10

    Bingpian is a time-honored herb in traditional Chinese medicine (TCM). It is an almost pure chemical with a chemical composition of (+)-borneol and has been historically used as a topical analgesic for millennia. However, the clinical efficacy of topical borneol lacks stringent evidence-based clinical studies and verifiable scientific mechanism. We examined the analgesic efficacy of topical borneol in a randomized, double-blind, placebo-controlled clinical study involving 122 patients with postoperative pain. Topical application of borneol led to significantly greater pain relief than placebo did. Using mouse models of pain, we identified the TRPM8 channel as a molecular target of borneol and showed that topical borneol-induced analgesia was almost exclusively mediated by TRPM8, and involved a downstream glutamatergic mechanism in the spinal cord. Investigation of the actions of topical borneol and menthol revealed mechanistic differences between borneol- and menthol-induced analgesia and indicated that borneol exhibits advantages over menthol as a topical analgesic. Our work demonstrates that borneol, which is currently approved by the US FDA to be used only as a flavoring substance or adjuvant in food, is an effective topical pain reliever in humans and reveals a key part of the molecular mechanism underlying its analgesic effect.

  7. Gatekeepers for pragmatic clinical trials.

    PubMed

    Whicher, Danielle M; Miller, Jennifer E; Dunham, Kelly M; Joffe, Steven

    2015-10-01

    To successfully implement a pragmatic clinical trial, investigators need access to numerous resources, including financial support, institutional infrastructure (e.g. clinics, facilities, staff), eligible patients, and patient data. Gatekeepers are people or entities who have the ability to allow or deny access to the resources required to support the conduct of clinical research. Based on this definition, gatekeepers relevant to the US clinical research enterprise include research sponsors, regulatory agencies, payers, health system and other organizational leadership, research team leadership, human research protections programs, advocacy and community groups, and clinicians. This article provides a framework to help guide gatekeepers' decision-making related to the use of resources for pragmatic clinical trials. Relevant ethical considerations for gatekeepers include (1) concern for the interests of individuals, groups, and communities affected by the gatekeepers' decisions, including protection from harm and maximization of benefits; (2) advancement of organizational mission and values; and (3) stewardship of financial, human, and other organizational resources. Separate from these ethical considerations, gatekeepers' actions will be guided by relevant federal, state, and local regulations. This framework also suggests that to further enhance the legitimacy of their decision-making, gatekeepers should adopt transparent processes that engage relevant stakeholders when feasible and appropriate. We apply this framework to the set of gatekeepers responsible for making decisions about resources necessary for pragmatic clinical trials in the United States, describing the relevance of the criteria in different situations and pointing out where conflicts among the criteria and relevant regulations may affect decision-making. Recognition of the complex set of considerations that should inform decision-making will guide gatekeepers in making justifiable choices regarding

  8. Clinical Trials in Head Injury

    PubMed Central

    NARAYAN, RAJ K.; MICHEL, MARY ELLEN; Ansell, Beth; Baethmann, Alex; Biegon, Anat; Bracken, Michael B.; Bullock, M. Ross; Choi, Sung C.; Clifton, Guy L.; Contant, Charles F.; Coplin, William M.; Dietrich, W. Dalton; Ghajar, Jamshid; Grady, Sean M.; Grossman, Robert G.; Hall, Edward D.; Heetderks, William; Hovda, David A.; Jallo, Jack; Katz, Russell L.; Knoller, Nachshon; Kochanek, Patrick M.; Maas, And