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Sample records for disorders efficacy safety

  1. Efficacy and Safety of Atomoxetine in Childhood Attention-Deficit/Hyperactivity Disorder with Comorbid Oppositional Defiant Disorder

    ERIC Educational Resources Information Center

    Kaplan, S.; Heiligenstein, J.; West, S.; Busner, J.; Harder, D.; Dittmann, R.; Casat, C.; Wernicke, J. F.

    2004-01-01

    Objective: To compare the safety and efficacy of atomoxetine, a selective inhibitor of the norepinephrine transporter, versus placebo in Attention-Deficit/Hyperactivity Disorder (ADHD) patients with comorbid Oppositional Defiant Disorder (ODD). Methods: A subset analysis of 98 children from two identical, multi-site, double-blind, randomized,…

  2. Efficacy and Safety of Lisdexamfetamine Dimesylate in Adolescents with Attention-Deficit/Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Findling, Robert L.; Childress, Ann C.; Cutler, Andrew J.; Gasior, Maria; Hamdani, Mohamed; Ferreira-Cornwell, M. Celeste; Squires, Liza

    2011-01-01

    Objective: To examine lisdexamfetamine dimesylate (LDX) efficacy and safety versus placebo in adolescents with attention-deficit/hyperactivity disorder (ADHD). Method: Adolescents (13 through 17) with at least moderately symptomatic ADHD (ADHD Rating Scale IV: Clinician Version [ADHD-RS-IV] score greater than or equal to 28) were randomized to…

  3. Efficacy and safety of the probiotic Saccharomyces boulardii for the prevention and therapy of gastrointestinal disorders

    PubMed Central

    Kelesidis, Theodoros

    2012-01-01

    Several clinical trials and experimental studies strongly suggest a place for Saccharomyces boulardii as a biotherapeutic agent for the prevention and treatment of several gastrointestinal diseases. S. boulardii mediates responses resembling the protective effects of the normal healthy gut flora. The multiple mechanisms of action of S. boulardii and its properties may explain its efficacy and beneficial effects in acute and chronic gastrointestinal diseases that have been confirmed by clinical trials. Caution should be taken in patients with risk factors for adverse events. This review discusses the evidence for efficacy and safety of S. boulardii as a probiotic for the prevention and therapy of gastrointestinal disorders in humans. PMID:22423260

  4. Efficacy and safety of herbal stimulants and sedatives in sleep disorders.

    PubMed

    Gyllenhaal, Charlotte; Merritt, Sharon L.; Peterson, Sara Davia; Block, Keith I.; Gochenour, Tom

    2000-06-01

    World-wide use of herbal medicines is increasing, following regulatory and manufacturing developments. Herbs are attractive alternative medications to many patients with sleep disorders, who may be averse to using conventional drugs. We review here the most common herbal stimulants and sedatives. Caffeine, in herbal teas, black tea, coffee, soft drinks and pharmaceuticals, is used widely to control sleepiness, but more research is needed on its use in sleep disorders. Ephedra, and its constituent ephedrine, are used in both stimulant and weight loss preparations, sometimes with caffeine; safety concerns have arisen with this practice. Yohimbe is another herb used in stimulant and body-building preparations which has safety concerns. Asian and Siberian ginseng have been traditionally used for fatigue, and have some supportive experimental evidence for this use. Herbal sedatives also have some evidence for efficacy; the observations that certain plant flavonoid compounds bind to benzodiazepine receptors adds interest to their use. Valerian and kava have received the most research attention; both have decreased sleep onset time and promoted deeper sleep in small studies, and kava also shows anxiolytic effects. German chamomile, lavender, hops, lemon balm and passionflower are reputed to be mild sedatives but need much more experimental examination.

  5. Efficacy and Safety of Atomoxetine in the Treatment of Children and Adolescents with Attention Deficit Hyperactivity Disorder

    PubMed Central

    Kohn, Michael R.; Tsang, Tracey W.; Clarke, Simon D.

    2012-01-01

    Several non-stimulant medications have been used in the treatment of attention deficit hyperactivity disorder (ADHD). Atomoxetine, was introduced in 2002. The safety and efficacy of atomoxetine in the treatment of ADHD for children, adolescents, and adults has been evaluated in over 4000 patients in randomized controlled studies and double blinded studies as well as in recent large longitudinal studies. This paper provides an updated summary of the literature on atomoxetine, particularly in relation to findings on the short- and long-term safety of atomoxetine in children and adolescents arising from recent large longitudinal cohort studies. Information is presented about the efficacy, safety, and tolerability of this medication. PMID:23641171

  6. Efficacy and Safety of Dexmethylphenidate Extended-Release Capsules in Children with Attention-Deficit/Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Greenhill, Laurence L.; Muniz, Rafael; Ball, Roberta R.; Levine, Alan; Pestreich, Linda; Jiang, Hai

    2006-01-01

    Objective: The efficacy and safety of dexmethylphenidate extended release (d-MPH-ER) was compared to placebo in pediatric patients with attention-deficit/hyperactivity disorder (ADHD). Method: This multicenter, randomized, double-blind, placebo-controlled, parallel-group, two-phase study included 97 patients (ages 6-17 years) with…

  7. Complementary and alternative medicine for autism spectrum disorders: rationale, safety and efficacy.

    PubMed

    Whitehouse, Andrew J O

    2013-09-01

    Complementary and alternative medicine is widely used for children with autism spectrum disorder, despite uncertainty regarding efficacy. This review describes complementary and alternative practices commonly used among this population, the rationale for the use of each practice, as well as the side-effect profile and evidence for efficacy. The existing evidence base indicates that melatonin can be recommended as a treatment for sleeping disturbances associated with autism spectrum disorder, while secretin can be rejected as an efficacious treatment for broader autistic symptoms. There is insufficient evidence to draw conclusions on the efficacy of modified diets, hyperbaric oxygen therapy, immune therapy, and vitamin and fatty acid supplementation. There is a clear need for methodologically rigorous studies to provide evidence-based guidance to families and clinicians regarding complementary and alternative practices for individuals with autism spectrum disorders. © 2013 The Author. Journal of Paediatrics and Child Health © 2013 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

  8. Efficacy and Safety Extrapolation Analyses for Atomoxetine in Young Children with Attention-Deficit/Hyperactivity Disorder

    PubMed Central

    Kratochvil, Christopher; Ghuman, Jaswinder; Camporeale, Angelo; Lipsius, Sarah; D'Souza, Deborah; Tanaka, Yoko

    2015-01-01

    Abstract Objectives: This extrapolation analysis qualitatively compared the efficacy and safety profile of atomoxetine from Lilly clinical trial data in 6–7-year-old patients with attention-deficit/hyperactivity disorder (ADHD) with that of published literature in 4–5-year-old patients with ADHD (two open-label [4–5-year-old patients] and one placebo-controlled study [5-year-old patients]). Methods: The main efficacy analyses included placebo-controlled Lilly data and the placebo-controlled external study (5-year-old patients) data. The primary efficacy variables used in these studies were the ADHD Rating Scale-IV Parent Version, Investigator Administered (ADHD-RS-IV-Parent:Inv) total score, or the Swanson, Nolan and Pelham (SNAP-IV) scale score. Safety analyses included treatment-emergent adverse events (TEAEs) and vital signs. Descriptive statistics (means, percentages) are presented. Results: Acute atomoxetine treatment improved core ADHD symptoms in both 6–7-year-old patients (n=565) and 5-year-old patients (n=37) (treatment effect: −10.16 and −7.42). In an analysis of placebo-controlled groups, the mean duration of exposure to atomoxetine was ∼7 weeks for 6–7-year-old patients and 9 weeks for 5-year-old patients. Decreased appetite was the most common TEAE in atomoxetine-treated patients. The TEAEs observed at a higher rate in 5-year-old versus 6–7-year-old patients were irritability (36.8% vs. 3.6%) and other mood-related events (6.9% each vs. <3.0%). Blood pressure and pulse increased in both 4–5-year-old patients and 6–7-year-old patients, whereas a weight increase was seen only in the 6–7-year-old patients. Conclusions: Although limited by the small sample size of the external studies, these analyses suggest that in 5-year-old patients with ADHD, atomoxetine may improve ADHD symptoms, but possibly to a lesser extent than in older children, with some adverse events occurring at a higher rate in 5-year-old patients. PMID:25265343

  9. Efficacy and Safety Extrapolation Analyses for Atomoxetine in Young Children with Attention-Deficit/Hyperactivity Disorder.

    PubMed

    Upadhyaya, Himanshu; Kratochvil, Christopher; Ghuman, Jaswinder; Camporeale, Angelo; Lipsius, Sarah; D'Souza, Deborah; Tanaka, Yoko

    2015-12-01

    This extrapolation analysis qualitatively compared the efficacy and safety profile of atomoxetine from Lilly clinical trial data in 6-7-year-old patients with attention-deficit/hyperactivity disorder (ADHD) with that of published literature in 4-5-year-old patients with ADHD (two open-label [4-5-year-old patients] and one placebo-controlled study [5-year-old patients]). The main efficacy analyses included placebo-controlled Lilly data and the placebo-controlled external study (5-year-old patients) data. The primary efficacy variables used in these studies were the ADHD Rating Scale-IV Parent Version, Investigator Administered (ADHD-RS-IV-Parent:Inv) total score, or the Swanson, Nolan and Pelham (SNAP-IV) scale score. Safety analyses included treatment-emergent adverse events (TEAEs) and vital signs. Descriptive statistics (means, percentages) are presented. Acute atomoxetine treatment improved core ADHD symptoms in both 6-7-year-old patients (n=565) and 5-year-old patients (n=37) (treatment effect: -10.16 and -7.42). In an analysis of placebo-controlled groups, the mean duration of exposure to atomoxetine was ∼ 7 weeks for 6-7-year-old patients and 9 weeks for 5-year-old patients. Decreased appetite was the most common TEAE in atomoxetine-treated patients. The TEAEs observed at a higher rate in 5-year-old versus 6-7-year-old patients were irritability (36.8% vs. 3.6%) and other mood-related events (6.9% each vs. <3.0%). Blood pressure and pulse increased in both 4-5-year-old patients and 6-7-year-old patients, whereas a weight increase was seen only in the 6-7-year-old patients. Although limited by the small sample size of the external studies, these analyses suggest that in 5-year-old patients with ADHD, atomoxetine may improve ADHD symptoms, but possibly to a lesser extent than in older children, with some adverse events occurring at a higher rate in 5-year-old patients.

  10. Efficacy and safety of atomoxetine hydrochloride in Korean adults with attention-deficit hyperactivity disorder.

    PubMed

    Lee, Soyoung Irene; Song, Dong-Ho; Shin, Dong Won; Kim, Ji Hoon; Lee, Young Sik; Hwang, Jun-Won; Park, Tae Won; Yook, Ki-Hwan; Lee, Jong Il; Bahn, Geon Ho; Hirata, Yuko; Goto, Taro; Takita, Yasushi; Takahashi, Michihiro; Lee, Sanghoon; Treuer, Tamás

    2014-12-01

    This article aims to assess the efficacy and safety of atomoxetine in Korean adults with attention-deficit hyperactivity disorder (ADHD). This post hoc double-blind, placebo-controlled study of atomoxetine (40-120 mg/day) over 10 weeks in adults with ADHD at 45 Japanese, Korean, and Taiwanese study sites focused on patient data from Korea (atomoxetine, n = 37; placebo, n = 37). Primary efficacy outcome was change in baseline-to-endpoint Conners' Adult ADHD Rating Scale-Investigator-rated: Screening Version (CAARS-Inv:SV) Total ADHD Symptoms score. Secondary efficacy outcomes included changes in Adult ADHD Quality of Life (AAQoL) total, Behavior Rating Inventory of Executive Function-Adult Version Self-Report (BRIEF-A:Self-Report), and Clinical Global Impression-ADHD-Severity (CGI-ADHD-S) scale scores. Atomoxetine-treated patients demonstrated a mean 18.9-point reduction in CAARS-Inv:SV total ADHD Symptoms score, compared with the 7.45-point reduction in placebo-treated patients (P ≤ 0.01). Significantly greater improvement was found for atomoxetine versus placebo in CGI-ADHD-S (P ≤ 0.01), BRIEF-A:Self-Report global executive composite (P ≤ 0.05), and metacognition index (P ≤ 0.01) executive function scores. Nausea, decreased appetite, and dry mouth were reported with significantly greater frequency by atomoxetine-treated patients, and only one placebo-treated patient discontinued because of adverse event. A 2.1-kg reduction in weight and a 7.5-beat/minute increase in pulse rate were observed in atomoxetine-treated patients. These data support a significant benefit of 80- to 120-mg once daily atomoxetine versus placebo for treatment of ADHD in adult Korean patients. A high placebo response rate was observed in this adult Korean sample; a higher discontinuation rate was also observed in atomoxetine-treated patients. These observations warrant further investigation. © 2014 Wiley Publishing Asia Pty Ltd.

  11. [Efficacy, tolerability and safety of paliperidone extended-release in the treatment of schizophrenia and schizoaffective disorder].

    PubMed

    Bellantuono, Cesario; Santone, Giovanni

    2012-01-01

    The paper represents a systematic review on the efficacy, tolerability and safety of paliperidone, an antipsychotic drug recently approved in Italy for the treatment of schizophrenia and of schizoaffective disorder. A comprehensive PubMed search using the term "paliperidone" was performed from January 1980 to February 2011. Papers reporting data on efficacy in the treatment of schizophrenia and of schizoaffective disorder were included, also if published as abstracts and all retrieved articles were manually searched for other references of interest. Paliperidone was found to be effective in short and long-term treatment of schizophrenia, as well as in the treatment of schizoaffective disorder. For both disorders, paliperidone showed to be effective in improving psychotic and affective symptoms. In the studies analyzed it was well tolerated and the most frequent reported adverse events were mild extrapyramidal symptoms and an increase in serum prolactin levels. Paliperidone has been shown to be an effective and safe medication for the treatment of schizophrenia and schizoaffective disorder. Further controlled clinical trials are needed to confirm this clinical profile in the long-term treatment, as well as for specific conditions such as schizophrenic patients with medical comorbidities.

  12. Natural Product-Derived Treatments for Attention-Deficit/Hyperactivity Disorder: Safety, Efficacy, and Therapeutic Potential of Combination Therapy

    PubMed Central

    Ahn, James; Ahn, Hyung Seok; Cheong, Jae Hoon; dela Peña, Ike

    2016-01-01

    Typical treatment plans for attention-deficit/hyperactivity disorder (ADHD) utilize nonpharmacological (behavioral/psychosocial) and/or pharmacological interventions. Limited accessibility to behavioral therapies and concerns over adverse effects of pharmacological treatments prompted research for alternative ADHD therapies such as natural product-derived treatments and nutritional supplements. In this study, we reviewed the herbal preparations and nutritional supplements evaluated in clinical studies as potential ADHD treatments and discussed their performance with regard to safety and efficacy in clinical trials. We also discussed some evidence suggesting that adjunct treatment of these agents (with another botanical agent or pharmacological ADHD treatments) may be a promising approach to treat ADHD. The analysis indicated mixed findings with regard to efficacy of natural product-derived ADHD interventions. Nevertheless, these treatments were considered as a “safer” approach than conventional ADHD medications. More comprehensive and appropriately controlled clinical studies are required to fully ascertain efficacy and safety of natural product-derived ADHD treatments. Studies that replicate encouraging findings on the efficacy of combining botanical agents and nutritional supplements with other natural product-derived therapies and widely used ADHD medications are also warranted. In conclusion, the risk-benefit balance of natural product-derived ADHD treatments should be carefully monitored when used as standalone treatment or when combined with other conventional ADHD treatments. PMID:26966583

  13. The efficacy and safety of alprazolam versus other benzodiazepines in the treatment of panic disorder.

    PubMed

    Moylan, Steven; Staples, John; Ward, Stephanie Alison; Rogerson, Jan; Stein, Dan J; Berk, Michael

    2011-10-01

    We performed a meta-analysis of all single- or double-blind, randomized controlled trials comparing alprazolam to another benzodiazepine in the treatment of adult patients meeting the Diagnostic and Statistical Manual of Mental Disorders, Third or Fourth Edition, criteria for panic disorder or agoraphobia with panic attacks. Eight studies met inclusion criteria, describing a total of at least 631 randomized patients. In the pooled results, there were no significant differences in efficacy between alprazolam and the comparator benzodiazepines on any of the prespecified outcomes: improvement in mean panic attack frequency (between-arm weighted mean difference of 0.6 panic attacks per week; 95% confidence interval [CI], -0.3 to 1.6), improvement in Hamilton Anxiety Rating Scale score (weighted mean difference of 0.8 points; 95% CI, -0.5 to 2.1), and proportion of patients free of panic attacks at the final evaluation (pooled relative risk, 1.1; 95% CI, 0.9-1.4). Statistical heterogeneity on prespecified outcomes was not eliminated by stratification on baseline anxiety level. The available evidence fails to demonstrate alprazolam as superior to other benzodiazepines for the treatment of panic disorder.

  14. Systematic review: Efficacy and safety of medical marijuana in selected neurologic disorders

    PubMed Central

    Koppel, Barbara S.; Brust, John C.M.; Fife, Terry; Bronstein, Jeff; Youssof, Sarah; Gronseth, Gary; Gloss, David

    2014-01-01

    Objective: To determine the efficacy of medical marijuana in several neurologic conditions. Methods: We performed a systematic review of medical marijuana (1948–November 2013) to address treatment of symptoms of multiple sclerosis (MS), epilepsy, and movement disorders. We graded the studies according to the American Academy of Neurology classification scheme for therapeutic articles. Results: Thirty-four studies met inclusion criteria; 8 were rated as Class I. Conclusions: The following were studied in patients with MS: (1) Spasticity: oral cannabis extract (OCE) is effective, and nabiximols and tetrahydrocannabinol (THC) are probably effective, for reducing patient-centered measures; it is possible both OCE and THC are effective for reducing both patient-centered and objective measures at 1 year. (2) Central pain or painful spasms (including spasticity-related pain, excluding neuropathic pain): OCE is effective; THC and nabiximols are probably effective. (3) Urinary dysfunction: nabiximols is probably effective for reducing bladder voids/day; THC and OCE are probably ineffective for reducing bladder complaints. (4) Tremor: THC and OCE are probably ineffective; nabiximols is possibly ineffective. (5) Other neurologic conditions: OCE is probably ineffective for treating levodopa-induced dyskinesias in patients with Parkinson disease. Oral cannabinoids are of unknown efficacy in non–chorea-related symptoms of Huntington disease, Tourette syndrome, cervical dystonia, and epilepsy. The risks and benefits of medical marijuana should be weighed carefully. Risk of serious adverse psychopathologic effects was nearly 1%. Comparative effectiveness of medical marijuana vs other therapies is unknown for these indications. PMID:24778283

  15. Efficacy and Safety of Amphetamine Extended-Release Oral Suspension in Children with Attention-Deficit/Hyperactivity Disorder.

    PubMed

    Childress, Ann C; Wigal, Sharon B; Brams, Matthew N; Turnbow, John M; Pincus, Yulia; Belden, Heidi W; Berry, Sally A

    2018-06-01

    To determine the efficacy and safety of amphetamine extended-release oral suspension (AMPH EROS) in the treatment of attention-deficit/hyperactivity disorder (ADHD) in a dose-optimized, randomized, double-blind, parallel-group study. Boys and girls aged 6 to 12 years diagnosed with ADHD were enrolled. During a 5-week, open-label, dose-optimization phase, patients began treatment with 2.5 or 5 mg/day of AMPH EROS; doses were titrated until an optimal dose (maximum 20 mg/day) was reached. During the double-blind phase, patients were randomized to receive treatment with either their optimized dose (10-20 mg/day) of AMPH EROS or placebo for 1 week. Efficacy was assessed in a laboratory classroom setting on the final day of double-blind treatment using the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale and Permanent Product Measure of Performance (PERMP) test. Safety was assessed measuring adverse events (AEs) and vital signs. The study was completed by 99 patients. The primary efficacy endpoint (change from predose SKAMP-Combined score at 4 hours postdose) and secondary endpoints (change from predose SKAMP-Combined scores at 1, 2, 6, 8, 10, 12, and 13 hours postdose) were statistically significantly improved with AMPH EROS treatment versus placebo at all time points. Onset of treatment effect was present by 1 hour postdosing, the first time point measured, and duration of efficacy lasted 13 hours postdosing. PERMP data mirrored the SKAMP-Combined score data. AEs (>5%) reported during dose optimization were decreased appetite, insomnia, affect lability, upper abdominal pain, mood swings, and headache. AMPH EROS was effective in reducing symptoms of ADHD and had a rapid onset and extended duration of effect. Reported AEs were consistent with those of other extended-release amphetamine products.

  16. Efficacy and Safety of Pediatric Prolonged-Release Melatonin for Insomnia in Children With Autism Spectrum Disorder.

    PubMed

    Gringras, Paul; Nir, Tali; Breddy, John; Frydman-Marom, Anat; Findling, Robert L

    2017-11-01

    To assess the efficacy and safety of novel pediatric-appropriate, prolonged-release melatonin minitablets (PedPRM) versus placebo for insomnia in children and adolescents with autism spectrum disorder (ASD), with or without attention-deficit/hyperactivity disorder (ADHD) comorbidity, and neurogenetic disorders (NGD). A total of 125 children and adolescents (2-17.5 years of age; 96.8% ASD, 3.2% Smith-Magenis syndrome [SMS]) whose sleep failed to improve on behavioral intervention alone were randomized (1:1 ratio), double-blind, to receive PedPRM (2 mg escalated to 5 mg) or placebo for 13 weeks. Sleep measures included the validated caregivers' Sleep and Nap Diary (SND) and Composite Sleep Disturbance Index (CSDI). The a priori primary endpoint was SND-reported total sleep time (TST) after 13 weeks of treatment. The study met the primary endpoint: after 13 weeks of double-blind treatment, participants slept on average 57.5 minutes longer at night with PedPRM compared to 9.14 minutes with placebo (adjusted mean treatment difference PedPRM-placebo -32.43 minutes; p = .034). Sleep latency (SL) decreased by 39.6 minutes on average with PedPRM and 12.5 minutes with placebo (adjusted mean treatment difference -25.30 minutes; p = .011) without causing earlier wakeup time. The rate of participants attaining clinically meaningful responses in TST and/or SL was significantly higher with PedPRM than with placebo (68.9% versus 39.3% respectively; p = .001) corresponding to a number needed to treat (NNT) of 3.38. Overall sleep disturbance (CSDI) tended to decrease. PedPRM was generally safe; somnolence was more commonly reported with PedPRM than placebo. PedPRM was efficacious and safe for treatment of insomnia in children and adolescents with ASD with/without ADHD and NGD. The acceptability of this pediatric formulation in a population who usually experience significant difficulties in swallowing was remarkably high. Clinical trial registration information-Efficacy and

  17. Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder.

    PubMed

    Moreno, Francisco A; Wiegand, Christopher B; Taitano, E Keolani; Delgado, Pedro L

    2006-11-01

    Anecdotal reports suggest that psychedelic agents may relieve symptoms of obsessive-compulsive disorder (OCD). This modified double-blind study investigated the safety, tolerability, and clinical effects of psilocybin, a potent 5-HT(1A) and 5-HT(2A/2C) agonist, in patients with OCD. Nine subjects with DSM-IV-defined OCD and no other current major psychiatric disorder participated in up to 4 single-dose exposures to psilocybin in doses ranging from sub-hallucinogenic to frankly hallucinogenic. Low (100 microg/kg), medium (200 microg/kg), and high (300 microg/kg) doses were assigned in that order, and a very low dose (25 microg/kg) was inserted randomly and in double-blind fashion at any time after the first dose. Testing days were separated by at least 1 week. Each session was conducted over an 8-hour period in a controlled environment in an outpatient clinic; subjects were then transferred to a psychiatric inpatient unit for overnight observation. The Yale-Brown Obsessive Compulsive Scale (YBOCS) and a visual analog scale measuring overall obsessive-compulsive symptom severity were administered at 0, 4, 8, and 24 hours post-ingestion. The Hallucinogen Rating Scale was administered at 8 hours, and vital signs were recorded at 0, 1, 4, 8, and 24 hours after ingestion. The study was conducted from November 2001 to November 2004. Nine subjects were administered a total of 29 psilocybin doses. One subject experienced transient hypertension without relation to anxiety or somatic symptoms, but no other significant adverse effects were observed. Marked decreases in OCD symptoms of variable degrees were observed in all subjects during 1 or more of the testing sessions (23%-100% decrease in YBOCS score). Repeated-measures analysis of variance for all YBOCS values revealed a significant main effect of time on Wilks lambda (F = 9.86, df = 3,3; p = .046), but no significant effect of dose (F = 2.25, df = 3,3; p = .261) or interaction of time and dose (F = 0.923, df = 9,45; p

  18. Efficacy and Safety of a Chewable Methylphenidate Extended-Release Tablet in Children with Attention-Deficit/Hyperactivity Disorder

    PubMed Central

    Childress, Ann; Berry, Sally A.; Belden, Heidi; Walters, Faith; Chappell, Phillip; Sherman, Nancy; Orazem, John; Palumbo, Donna

    2017-01-01

    Abstract Objective: This phase 3, laboratory classroom study assessed the efficacy and safety of methylphenidate hydrochloride extended-release chewable tablets (MPH ERCT) compared with placebo in children with attention-deficit/hyperactivity disorder (ADHD). Methods: Following a 6-week, open-label, dose-optimization period, children 6–12 years of age (n = 90) with ADHD were randomly assigned to double-blind MPH ERCT at the final optimized dose (20–60 mg/day) or placebo. After 1 week of double-blind treatment, efficacy was assessed predose and 0.75, 2, 4, 8, 10, 12, and 13 hours postdose in a laboratory classroom setting. The primary efficacy measure was the average of postdose Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale-Combined scores, analyzed using a mixed-model, repeated-measures analysis. Secondary efficacy measures included Permanent Product Measure of Performance (PERMP) total number of problems attempted and total number of problems correct. Safety assessments included adverse event (AE) monitoring and the Columbia-Suicide Severity Rating Scale (C-SSRS). Results: MPH ERCT treatment statistically significantly reduced the average of all postdose SKAMP-Combined scores versus placebo (least-squares mean difference [95% confidence interval], −7.0 [−10.9, −3.1]; p < 0.001). Statistically significant treatment differences in SKAMP-Combined scores were observed at 2 hours postdose through 8 hours postdose (p-values <0.001). Statistically significant differences between MPH ERCT and placebo in PERMP total number of problems attempted and total number of problems correct were observed at 0.75 hours postdose through 8 hours postdose (p-values ≤0.049). Common AEs in the open-label period (≥5%) were decreased appetite, upper abdominal pain, mood swings, irritability, insomnia, upper respiratory tract infection (URTI), dysgeusia, and headache; URTI was the only AE reported by >1 subject receiving MPH ERCT in the double

  19. The efficacy and safety of multiple doses of vortioxetine for generalized anxiety disorder: a meta-analysis.

    PubMed

    Fu, Jie; Peng, Lilei; Li, Xiaogang

    2016-01-01

    Vortioxetine is a novel antidepressant approved for the treatment of major depressive disorder by the US Food and Drug Administration in September 2013. This meta-analysis assessed the efficacy and safety of different doses of vortioxetine for generalized anxiety disorder of adults. PubMed, Cochrane Library, PsycINFO, and Clinical Trials databases were searched from 2000 through 2015. The abstracts of the annual meetings of the American Psychiatric Association and previous reviews were searched to identify additional studies. The search was limited to individual randomized controlled trials (RCTs), and there was no language restriction. Four RCTs met the selection criteria. These studies included 1,843 adult patients. Results were expressed as odds ratios (ORs) and 95% confidence intervals (CIs). The data were pooled with a random-effects or fixed-effects model. The results showed that multiple doses (2.5, 5, and 10 mg/d) of vortioxetine did not significantly improve the generalized anxiety disorder symptoms compared to placebo (OR=1.16, 95% CI=0.84-1.60, Z=0.89, P=0.38; OR=1.41, 95% CI=0.82-2.41, Z=1.25, P=0.21; OR=1.05, 95% CI=0.76-1.46, Z=0.32, P=0.75, respectively). We measured the efficacy of 2.5 mg/d vortioxetine compared to 10 mg/d, and no significant differences were observed. The common adverse effects included nausea and headache. With increased dose, nausea was found to be more frequent in the vortioxetine (5 and 10 mg/d) group (OR=2.99, 95% CI=1.31-6.84, Z=2.60, P=0.009; OR=2.80, 95% CI=1.85-4.25, Z=4.85, P<0.00001, respectively), but no significant differences were observed for headache. The results showed no significant improvement in the treatment of generalized anxiety disorder for vortioxetine compared to placebo, and nausea was more frequent with higher doses. So the current evidences do not support using vortioxetine for the treatment of generalized anxiety disorder. Few RCTs were included in our meta-analysis, and more studies are needed to

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

    ERIC Educational Resources Information Center

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

    2011-01-01

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

  1. Safety and Preliminary Efficacy of the Acetylcholinesterase Inhibitor Huperzine A as a Treatment for Cocaine Use Disorder

    PubMed Central

    Verrico, Christopher D.; Newton, Thomas F.; Mahoney, James J.; Thompson-Lake, Daisy G. Y.

    2016-01-01

    Background: Cholinergic transmission is altered by drugs of abuse and contributes to psychostimulant reinforcement. In particular, acetylcholinesterase inhibitors, like huperzine A, may be effective as treatments for cocaine use disorder. Methods: The current report describes results from a double-blind, placebo-controlled study in which participants (n=14–17/group) were randomized to huperzine A (0.4 or 0.8mg) or placebo. Participants received randomized infusions of cocaine (0 and 40mg, IV) on days 1 and 9. On day 10, participants received noncontingent, randomized infusions of cocaine (0 and 20mg, IV) before making 5 choices to receive additional infusions. Results: Huperzine A was safe and well-tolerated and compared with placebo, treatment with huperzine A did not cause significant changes in any cocaine pharmacokinetic parameters (all P>.05). Time-course and peak effects analyses show that treatment with 0.4mg of huperzine A significantly attenuated cocaine-induced increases of “Any Drug Effect,” “High,” “Stimulated,” “Willing to Pay,” and “Bad Effects” (all P>.05). Conclusions: The current study represents a significant contribution to the addiction field since it serves as the first published report on the safety and potential efficacy of huperzine A as a treatment for cocaine use disorder. PMID:26364275

  2. The efficacy and safety of aripiprazole for tic disorders in children and adolescents: A systematic review and meta-analysis.

    PubMed

    Wang, Shuai; Wei, Yan-Zhao; Yang, Jian-Hong; Zhou, Yu-Ming; Cheng, Yu-Hang; Yang, Chao; Zheng, Yi

    2017-08-01

    The aims are to evaluate the efficacy and safety of aripiprazole for tic disorders (TDs) in children and adolescents. We searched PubMed, Embase, PsychINFO, Cochrane database as well as Chinese databases of CNKI, VIP, CBM and Wanfang from the database inception to October 2016, and 17 full-text studies (N=1305) were included in our article. The meta-analysis of 10 studies (N=817) showed that there was no significant difference in the reduction of total YGTSS score between aripiprazole and other drugs, and meta-analysis of 7 studies (n=324) which used tic symptom control ≧30% as outcome measure showed that there was no significant difference between aripiprazole and other treatments. The most common AEs of aripiprazole were the drowsiness, nausea/vomiting and increased appetite, and meta analysis which used the TESS scale as the outcome measurement showed that there was a significant difference between aripiprazole and haloperidol. In conclusion, these data provide moderate quality evidence that aripiprazole could be an effective and safe treatment option for TDs, and results from further trials are urgently needed to extend this evidence base. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  3. Lisdexamfetamine: chemistry, pharmacodynamics, pharmacokinetics, and clinical efficacy, safety, and tolerability in the treatment of binge eating disorder.

    PubMed

    Ward, Kristen; Citrome, Leslie

    2018-02-01

    The indications for lisdexamfetamine (LDX), a central nervous system stimulant, were recently expanded to include treatment of moderate to severe binge eating disorder (BED). Areas covered: This review aims to describe the chemistry and pharmacology of LDX, as well as the clinical trials investigating the efficacy and safety of this medication for the management of BED. Expert opinion: LDX is the first medication with United States Food and Drug Administration approval for the treatment of BED. It is an inactive prodrug of d-amphetamine that extends the half-life of d-amphetamine to allow for once daily dosing. D-amphetamine acts primarily to increase the concentrations of synaptic dopamine and norepinephrine. Metabolism of LDX to d-amphetamine occurs when peptidases in red blood cells cleave the covalent bond between d-amphetamine and l-lysine. D-amphetamine is then further metabolized by CYP2D6. Excretion is primarily through renal mechanisms. In clinical trials, LDX demonstrated statistical and clinical superiority over placebo in reducing binge eating days per week at doses of 50 and 70 mg daily. Commonly reported side effects of LDX include dry mouth, insomnia, weight loss, and headache, and its use should be avoided in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart arrhythmia or coronary artery disease. As with all CNS stimulants, risk of abuse needs to be assessed prior to prescribing.

  4. A double-blind efficacy and safety study of duloxetine flexible dosing in children and adolescents with major depressive disorder.

    PubMed

    Atkinson, Sarah D; Prakash, Apurva; Zhang, Qi; Pangallo, Beth A; Bangs, Mark E; Emslie, Graham J; March, John S

    2014-05-01

    The purpose of this study was to evaluate the efficacy and safety of duloxetine flexible dose in children (7-11 years) and adolescents (12-17 years) with major depressive disorder (MDD). Patients (n=337) in this 36 week study (10 week acute and 26 week extension treatment) received duloxetine (60-120 mg once daily [QD], n=117), fluoxetine (20-40 mg QD, n=117), or placebo (n=103). Measures included: Children's Depression Rating Scale-Revised (CDRS-R), treatment-emergent adverse events (TEAEs), and Columbia-Suicide Severity Rating Scale (C-SSRS). Neither active drug (duloxetine or fluoxetine) separated significantly (p<0.05) from placebo on mean change from baseline to end-point (10 weeks) on the CDRS-R total score. There were no significant differences between the duloxetine or fluoxetine groups compared with placebo on serious AEs (SAEs), total TEAEs, or discontinuation for AE during acute treatment. There were no completed suicides or deaths, and no clinically significant electrocardiogram (ECG) abnormalities observed during the study. One fluoxetine and one duloxetine patient experienced alanine aminotransferase (ALT) three or more times the upper limit of normal, which resolved during the study. A total of 8 (7.1%) duloxetine patients, 7 (6.8%) placebo patients, and 9 (8.0%) fluoxetine patients had worsening of suicidal ideation from baseline during acute treatment. Of the patients with suicidal ideation at baseline, 15/19 (79%) duloxetine, 19/19 (100%) placebo, and 16/19 (84%) fluoxetine had improvement in suicidal ideation at end-point during acute treatment. One duloxetine and two fluoxetine patients had treatment-emergent suicidal behavior during the 36 week study. Trial results were inconclusive, as neither the investigational drug (duloxetine) nor the active control (fluoxetine) separated from placebo on the CDRS-R at 10 weeks. No new duloxetine safety signals were identified relative to those seen in adults. Clinical Trial Registry Number: NCT00849901.

  5. Venom immunotherapy in patients with clonal mast cell disorders: efficacy, safety, and practical considerations.

    PubMed

    Bonadonna, Patrizia; Gonzalez-de-Olano, David; Zanotti, Roberta; Riccio, Annamaria; De Ferrari, Laura; Lombardo, Carla; Rogkakou, Anthi; Escribano, Luis; Alvarez-Twose, Ivan; Matito, Almudena; Vega, Arantza; Passalacqua, Giovanni

    2013-01-01

    A preferential association between systemic mastocytosis (SM) and hymenoptera allergy (HVA) has been observed. Patients with both diseases are at risk for more severe reactions, and venom immunotherapy (VIT) may represent a life-saving treatment, but the use of VIT in such patients raised concerns about its safety. We evaluated a large population of patients with SM and HVA who received VIT. This prospective study was performed in Italy and Spain. A diagnosis of SM and HVA and a VIT prescription were made according to international recommendations. The patients were carefully followed up during VIT, with special attention to field stings. A total of 84 patients (70 men, 14 women; mean age 52.1 years) were included, 81% with grade IV reaction, 91% with indolent SM. No difference was seen between the Italian and Spanish patients. There were 10 adverse reactions during the induction phase: 3 with the conventional induction and 7 with the rush-modified induction, none resulted in epinephrine administration and/or hospitalization. Fifty patients had one or more field re-sting (95 episodes), none during induction. The time elapsed from starting VIT and first re-sting was 2 months to 7 years, and the number of re-stings per patient was 1-6. Of the 50 patients who were re-stung, 43 (86%) resulted in being fully protected. Seven patients had reactions, and the maintenance dose was safely increased to 200 mcg. The maintenance dose interval was not different between patients with and those without reactions at re-stings. VIT is well tolerated, safe, and effective in patients with SM. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  6. A double-blind efficacy and safety study of duloxetine fixed doses in children and adolescents with major depressive disorder.

    PubMed

    Emslie, Graham J; Prakash, Apurva; Zhang, Qi; Pangallo, Beth A; Bangs, Mark E; March, John S

    2014-05-01

    The purpose of this study was to evaluate the efficacy and safety of duloxetine fixed dose in the treatment of children (7-11 years) and adolescents (12-17 years) with major depressive disorder (MDD). Patients (n=463) in this 36 week study (10 week acute and 26 week extension treatment) received duloxetine 60 mg QD (n=108), duloxetine 30 mg QD (n=116), fluoxetine 20 mg QD (n=117, active control), or placebo (n=122). Measures included: Children's Depression Rating Scale-Revised (CDRS-R), treatment-emergent adverse events (TEAEs), and Columbia-Suicide Severity Rating Scale (C-SSRS). Neither active drug (duloxetine or fluoxetine) separated significantly (p<0.05) from placebo on mean change from baseline to end-point (10 weeks) on the CDRS-R total score. Total TEAEs and discontinuation for AEs were significantly (p<0.05) higher only for the duloxetine 60 mg group versus the placebo group during acute treatment. No clinically significant electrocardiogram (ECG) or laboratory abnormalities were observed, and no completed suicides or deaths occurred during the study. A total of 7 (6.7%) duloxetine 60 mg, 6 (5.2%) duloxetine 30 mg, 9 (8.0%) fluoxetine, and 11 (9.4%) placebo patients had worsening of suicidal ideation from baseline during acute treatment. Of the patients with suicidal ideation at baseline, 13/16 (81%) duloxetine 60 mg, 16/17 (94%) duloxetine 30 mg, 11/16 (69%) fluoxetine, and 13/15 (87%) placebo had improvement in suicidal ideation at end-point during acute treatment. One fluoxetine, one placebo, and six duloxetine patients had treatment-emergent suicidal behavior during the 36 week study. Trial results were inconclusive, as neither the investigational drug (duloxetine) nor the active control (fluoxetine) separated from placebo on the CDRS-R at 10 weeks. No new duloxetine safety signals were identified relative to those seen in adults. Clinical Trial Registry Number ( www.ClinicalTrials.gov ): NCT00849693.

  7. A Double-Blind Efficacy and Safety Study of Duloxetine Fixed Doses in Children and Adolescents with Major Depressive Disorder

    PubMed Central

    Emslie, Graham J.; Zhang, Qi; Pangallo, Beth A.; Bangs, Mark E.; March, John S.

    2014-01-01

    Abstract Objective: The purpose of this study was to evaluate the efficacy and safety of duloxetine fixed dose in the treatment of children (7–11 years) and adolescents (12–17 years) with major depressive disorder (MDD). Methods: Patients (n=463) in this 36 week study (10 week acute and 26 week extension treatment) received duloxetine 60 mg QD (n=108), duloxetine 30 mg QD (n=116), fluoxetine 20 mg QD (n=117, active control), or placebo (n=122). Measures included: Children's Depression Rating Scale-Revised (CDRS-R), treatment-emergent adverse events (TEAEs), and Columbia-Suicide Severity Rating Scale (C-SSRS). Results: Neither active drug (duloxetine or fluoxetine) separated significantly (p<0.05) from placebo on mean change from baseline to end-point (10 weeks) on the CDRS-R total score. Total TEAEs and discontinuation for AEs were significantly (p<0.05) higher only for the duloxetine 60 mg group versus the placebo group during acute treatment. No clinically significant electrocardiogram (ECG) or laboratory abnormalities were observed, and no completed suicides or deaths occurred during the study. A total of 7 (6.7%) duloxetine 60 mg, 6 (5.2%) duloxetine 30 mg, 9 (8.0%) fluoxetine, and 11 (9.4%) placebo patients had worsening of suicidal ideation from baseline during acute treatment. Of the patients with suicidal ideation at baseline, 13/16 (81%) duloxetine 60 mg, 16/17 (94%) duloxetine 30 mg, 11/16 (69%) fluoxetine, and 13/15 (87%) placebo had improvement in suicidal ideation at end-point during acute treatment. One fluoxetine, one placebo, and six duloxetine patients had treatment-emergent suicidal behavior during the 36 week study. Conclusions: Trial results were inconclusive, as neither the investigational drug (duloxetine) nor the active control (fluoxetine) separated from placebo on the CDRS-R at 10 weeks. No new duloxetine safety signals were identified relative to those seen in adults. Clinical Trial Registry Number (www

  8. Efficacy and safety of i.v. sodium benzoate in urea cycle disorders: a multicentre retrospective study.

    PubMed

    Husson, Marie-Caroline; Schiff, Manuel; Fouilhoux, Alain; Cano, Aline; Dobbelaere, Dries; Brassier, Anais; Mention, Karine; Arnoux, Jean-Baptiste; Feillet, François; Chabrol, Brigitte; Guffon, Nathalie; Elie, Caroline; de Lonlay, Pascale

    2016-09-23

    The efficacy and safety of intra-venous (i.v.) sodium benzoate for treating acute episodes of hyperammonemia in urea cycle enzyme disorders (UCD) is well known. However, published data do not provide a clear picture of the benefits and risks of this drug. We report a retrospective multicentre study on the use of i.v. sodium benzoate in patients treated for UCD between 2000 and 2010 in the 6 French reference centres for metabolic diseases. Sixty-one patients with UCDs - 22 ornithine transcarbamylase (20 confirmed, 2 suspected), 18 arginino-succinate synthetase, 15 carbamoyl phosphate synthetase, 3 arginosuccinate lyase, 1 arginase deficiency, 1 N-acetylglutamate synthetase, 1 HHH syndrome - required i.v. sodium benzoate over the course of 95 acute episodes (NH3 > 100 μmol/L or high-risk situations, i.e., gastroenteritis, surgery). Forty out of 61 patients experienced only one episode of decompensation (neonatal coma, 68.6 %). The most frequent cause of late decompensation was infection (55.5 %). A loading dose of i.v. sodium benzoate (median 250 mg/kg over 2 h) was administered for 41/95 acute episodes. The median maintenance dose was 246.1 mg/kg/day, administered via peripheral venous infusion in all cases except one via a central line. The total median duration of i.v. sodium benzoate treatment per episode was 2 days (0-13 days). The median durations of hospitalization in intensive care and metabolic units were 4 days (0-17 days) and 10 days (0-70 days), respectively. Eight patients died during the neonatal coma (n = 6) or surgery (n = 2). The median plasma ammonium level before treatment was 245.5 μmol/L (20.0-2274.0 μmol/L); it decreased to 40.0 μmol/L in patients who were alive (13.0-181.0 μmol/L) at the end of treatment with i.v. sodium benzoate. A decrease in ammonium level to ≤ 100 μmol/L was obtained in 92.8 % of episodes (64/69 of the episodes recorded for the 53 surviving patients). Five patients required another

  9. Efficacy of "seeking safety" in a Dutch population of traumatized substance-use disorder outpatients: study protocol of a randomized controlled trial.

    PubMed

    Kok, Tim; de Haan, Hein A; van der Meer, Margreet; Najavits, Lisa M; DeJong, Cor A J

    2013-06-04

    Traumatic experiences and, more specifically, posttraumatic stress disorder (PTSD) are highly prevalent among substance use disorder (SUD) patients. This comorbidity is associated with worse treatment outcomes in substance use treatment programs and more crisis interventions. International guidelines advise an integrated approach to the treatment of trauma related problems and SUD. Seeking Safety is an integrated treatment program that was developed in the United States. The aim of the current study is to test the efficacy of this program in the Netherlands in an outpatient SUD population. A randomized controlled trial (RCT) will be used to test the efficacy of Seeking Safety compared to Cognitive Behavioral Therapy (CBT) in a population of SUD outpatients. Each treatment will consist of 12 group sessions. The primary outcome measure will be substance use severity. Secondary outcome measures are PTSD and trauma symptoms, coping skills, functioning, and cognitions. Questionnaires will be administered at the start of treatment, at the end of treatment (three months after the start of treatment) and at follow-up (six months after the start of treatment). This study protocol presents a RCT in which the efficacy of an integrated treatment for comorbid PTSD and SUD, Seeking Safety, is evaluated in a SUD outpatient population compared to CBT. It is expected that the intervention group will show significantly more improvement in substance use severity compared to the control group at end-of-treatment and at follow-up. Furthermore, a lower drop-out rate is expected for the intervention group. If the intervention proves to be effective, it can be implemented. A cost-effectiveness analysis will be conducted to evaluate the two treatments. The protocol for this study is registered with the Netherlands Trial Register with number NTR3084 and approved by the local medical ethical committee (METC\\11270.haa).

  10. Efficacy and Safety of Vilazodone in Patients With Generalized Anxiety Disorder: A Randomized, Double-Blind, Placebo-Controlled, Flexible-Dose Trial.

    PubMed

    Durgam, Suresh; Gommoll, Carl; Forero, Giovanna; Nunez, Rene; Tang, Xiongwen; Mathews, Maju; Sheehan, David V

    2016-12-01

    To evaluate the efficacy, safety, and tolerability of vilazodone as an acute treatment for generalized anxiety disorder (GAD). Vilazodone is a selective serotonin reuptake inhibitor and 5-HT1A receptor partial agonist approved for the treatment of major depressive disorder in adults. This was a randomized, placebo-controlled, parallel-group, multicenter, flexible-dose study conducted from May 2013-March 2014. Adult patients (18-70 years, inclusive) who met DSM-IV-TR criteria for GAD were randomized (1:1) to placebo or vilazodone 20-40 mg/d for 8 weeks of double-blind treatment. Primary and secondary efficacy parameters were change from baseline to week 8 in the Hamilton Anxiety Rating Scale (HARS) total score and in the Sheehan Disability Scale (SDS) total score, respectively, analyzed using a mixed-effects model for repeated measures approach on a modified intent-to-treat population. Safety outcomes were summarized descriptively. Efficacy analyses were based on 400 patients (placebo = 200, vilazodone = 200); 76% completed the study (placebo = 81%, vilazodone = 71%). The least squares mean difference (95% CI) in total score change from baseline to week 8 was statistically significant for vilazodone versus placebo on the HARS (-2.20 [-3.72 to -0.68]; P = .0048) and on the SDS (-1.89 [-3.52 to -0.26]; P = .0236). Treatment-emergent adverse events reported in ≥ 5% of vilazodone patients and at least twice the rate of placebo were nausea, diarrhea, dizziness, fatigue, delayed ejaculation, and erectile dysfunction. Statistically significant differences in favor of vilazodone 20-40 mg/d versus placebo were seen on all measures of anxiety and functional impairment in patients with GAD. Vilazodone was generally well tolerated, and no new safety concerns were noted. ClinicalTrials.gov identifier: NCT01844115. © Copyright 2016 Physicians Postgraduate Press, Inc.

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

    PubMed

    Breech, Lesley L; Braverman, Paula K

    2010-08-09

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

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

    PubMed Central

    Breech, Lesley L; Braverman, Paula K

    2010-01-01

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

  13. Efficacy and safety of sublingual ramelteon as an adjunctive therapy in the maintenance treatment of bipolar I disorder in adults: A phase 3, randomized controlled trial.

    PubMed

    Mahableshwarkar, Atul R; Calabrese, Joseph R; Macek, Thomas A; Budur, Kumar; Adefuye, Adedeji; Dong, Xinxin; Hanson, Elizabeth; Sachs, Gary S

    2017-10-15

    The optimal long-term management strategy for bipolar I disorder patients is not yet established. Evidence supports the rationale for circadian rhythm regulation to prevent mood episode relapse in bipolar patients. This study evaluated the efficacy and safety of a new sublingual formulation of the melatonin receptor agonist ramelteon (ramelteon SL) as adjunctive therapy in the maintenance treatment of bipolar I patients. In a double-blinded trial in the United States and Latin America, adult bipolar I disorder patients stable for ≥ 8 weeks before baseline and with a mood episode 8 weeks to 9 months before screening, were randomized to once-daily ramelteon SL 0.1mg (n = 164), 0.4mg (n = 160), or 0.8mg (n = 154), or placebo (n = 164), in addition to their existing treatment. The primary endpoint was time from randomization to relapse of symptoms. The prespecified futility criterion in a planned, unblinded, independent interim analysis was the failure of all ramelteon SL doses to achieve a conditional power ≥ 30% compared with placebo. No significant differences between any dose of ramelteon SL and placebo were observed. The study was terminated after meeting the futility criteria. Ramelteon SL was well tolerated, with a safety profile consistent with that for oral ramelteon. A low rate of relapse events precluded detection of any statistically significant difference between groups. The study failed to demonstrate the efficacy of ramelteon SL as adjunctive maintenance therapy for bipolar disorder. Interim analyses for futility in clinical studies are valuable in preventing unnecessary exposure of subjects to interventions. Copyright © 2017. Published by Elsevier B.V.

  14. Dopamine serotonin stabilizer RP5063: A randomized, double-blind, placebo-controlled multicenter trial of safety and efficacy in exacerbation of schizophrenia or schizoaffective disorder.

    PubMed

    Cantillon, Marc; Prakash, Arul; Alexander, Ajay; Ings, Robert; Sweitzer, Dennis; Bhat, Laxminarayan

    2017-11-01

    The study objectives were to evaluate the efficacy, safety, tolerability, and pharmacokinetics of RP5063 versus placebo. The study was conducted in adults with acute exacerbation of schizophrenia or schizoaffective disorder. This 28-day, multicenter, placebo-controlled, double-blind study randomized 234 subjects to RP5063 15, 30, or 50mg; aripiprazole; or placebo (3:3:3:1:2) once daily. The aripiprazole arm was included solely to show assay sensitivity and was not powered to show efficacy. The primary endpoint was change from baseline to Day 28/EOT (End-of-Treatment) in Positive and Negative Syndrome Scale (PANSS) total score; secondary endpoints included PANSS subscales, improvement ≥1 point on the Clinical Global Impressions-Severity (CGI-S), depression and cognition scales. The primary analysis of PANSS Total showed improvement by a mean (SE) of -20.23 (2.65), -15.42 (2.04), and -19.21 (2.39) in the RP5063 15, 30, and 50mg arms, versus -11.41 (3.45) in the placebo arm. The difference between treatment and placebo reached statistical significance for the 15mg (p=0.021) and 50mg (p=0.016) arms. Improvement with RP5063 was also seen for multiple secondary efficacy outcomes. Discontinuation for any reason was much lower for RP5063 (14%, 25%, 12%) versus placebo (26%) and aripiprazole (35%). The most common treatment-emergent adverse events (TEAE) in the RP5063 groups were insomnia and agitation. There were no significant changes in body weight, electrocardiogram, or incidence of orthostatic hypotension; there was a decrease in blood glucose, lipid profiles, and prolactin levels. In conclusion, the novel dopamine serotonin stabilizer, RP5063 is an efficacious and well-tolerated treatment for acute exacerbation of schizophrenia or schizoaffective disorder. Copyright © 2017. Published by Elsevier B.V.

  15. Efficacy and safety of escitalopram versus citalopram in major depressive disorder: a 6-week, multicenter, randomized, double-blind, flexible-dose study.

    PubMed

    Ou, Jian-Jun; Xun, Guang-Lei; Wu, Ren-Rong; Li, Le-Hua; Fang, Mao-Sheng; Zhang, Hong-Geng; Xie, Shi-Ping; Shi, Jian-Guo; Du, Bo; Yuan, Xue-Qin; Zhao, Jing-Ping

    2011-02-01

    S-citalopram (escitalopram) is the very active moiety of citalopram. It has been shown in many studies to be an effective and safe antidepressant for treating major depressive disorder (MDD). The aim of our study was to compare the efficacy and safety of escitalopram vs citalopram in Chinese MDD patients. In the double-blind study, 240 MDD patients were randomly assigned to treatment for 6 weeks either with escitalopram (10-20 mg/d) or citalopram (20-40 mg/d). The primary efficacy measurement was the change of 17-item Hamilton Depression Rating Scale (HAMD-17) total score from baseline to the end of study. The secondary efficacy measurements were response and remission rates. The adverse events (AEs) were recorded by the investigator. Two hundred and three (85%) patients completed the trial. The average dose was 13.9 mg/d in the escitalopram group and 27.6 mg/d in the citalopram group. No significant differences were found between the two groups in the change in HAMD-17 total score, response, and remission rate. These results were similar in severe MDD patients. No significant differences were found between the two groups in AEs. No serious AEs were observed in this study. The study suggests that escitalopram 10-20 mg/d are as effective and safe as citalopram 20-40 mg/d in the short-term treatment for Chinese MDD patients.

  16. Safety, Tolerability, and Efficacy of Quetiapine in Youth with Schizophrenia or Bipolar I Disorder: A 26-Week, Open-Label, Continuation Study

    PubMed Central

    Pathak, Sanjeev; Earley, Willie R.; Liu, Sherry; DelBello, Melissa

    2013-01-01

    Abstract Objective The purpose of this study was to describe the safety, tolerability, and efficacy of quetiapine monotherapy continued for up to 26-weeks in youth with schizophrenia or bipolar I disorder. Methods Medically healthy boys and girls with a baseline Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV-TR) diagnosis of schizophrenia (ages 13–17 years) or a manic episode of bipolar I disorder (ages 10–17 years) who participated in one of two acute, double-blind, placebo-controlled studies of immediate-release quetiapine were potentially eligible to enroll in a 26-week, open-label study. During the open-label study, quetiapine was flexibly dosed at 400–800 mg/day, with options to reduce dosing to 200 mg/day based on tolerability. Safety and tolerability outcomes assessed from open-label baseline to week 26 included adverse events (AEs), metabolic/laboratory parameters, extrapyramidal symptoms, suicidality, and vital signs. Results Of 381 patients enrolled in the open-label study (n=176, schizophrenia; n=205, bipolar disorder diagnosis), 237 patients (62.2%) completed the 26-week study period (71.0%, schizophrenia; 54.6%, bipolar disorder). The most common AEs reported during the study included somnolence, headache, sedation, weight increase, and vomiting. A total of 14.9% of patients experienced a shift to potentially clinically significant low levels of high-density lipoprotein cholesterol and 10.2% of patients experienced a shift to potentially clinically significant high triglyceride levels. Weight gain ≥7% was reported in 35.6% of patients between open-label baseline and final visit. After adjustment for normal growth, 18.3% of study participants experienced clinically significant weight gain (i.e., increase in body mass index ≥0.5 standard deviations from baseline). Conclusions In this 26-week study, quetiapine flexibly dosed at 400–800 mg/day, with options to reduce dosing based on tolerability, was generally safe

  17. Comparative efficacy and safety of Crocus sativus L. for treating mild to moderate major depressive disorder in adults: a meta-analysis of randomized controlled trials.

    PubMed

    Yang, Xiangying; Chen, Xiaolu; Fu, Yixiao; Luo, Qinghua; Du, Lian; Qiu, Haitang; Qiu, Tian; Zhang, Li; Meng, Huaqing

    2018-01-01

    To investigate the efficacy and safety of saffron in the treatment of major depressive disorder (MDD) in comparison to placebo and synthetic antidepressants. We conducted a systematic search in several electronic databases as well as manual search in bibliographies of relevant studies. We included randomized controlled trials that investigated the efficacy and safety of saffron for treating MDD in adults in comparison to either placebo or synthetic antidepressants. Primary outcome was change in scores on depressive symptoms from baseline. Secondary outcomes included remission rate, response rate, and drop-out rate for all reasons. We chose a random-effects model in order to obtain more conservative results. Standardized mean differences (SMDs) and odds ratios (ORs) with 95% confidence intervals (CIs) were estimated as the overall effect index by inverse variance models. Seven studies were included in this meta-analysis. Overall quality of these included studies was moderate. As for the primary outcome, saffron showed more improvements in depression symptoms when compared with placebo, with an SMD of -1.22 (95% CI -1.94, -0.49, P =0.001). Meanwhile, saffron was as effective as synthetic antidepressants, with an SMD of 0.16 (95% CI -0.25, 0.57, P =0.44). Moderate heterogeneity existed in our analysis. Through subgroup analyses, we found that treatment dosage and duration, types of synthetic antidepressants administered in the comparison group, and outcome measures could explain most of the variance. No differences were found in remission rate, response rate, or drop-out rate. Saffron was effective in the treatment of MDD and had comparable efficacy to synthetic antidepressants. Saffron was also a safe drug without serious adverse events reported.

  18. Internet-Delivered Psychological Treatments for Mood and Anxiety Disorders: A Systematic Review of Their Efficacy, Safety, and Cost-Effectiveness

    PubMed Central

    Arnberg, Filip K.; Linton, Steven J.; Hultcrantz, Monica; Heintz, Emelie; Jonsson, Ulf

    2014-01-01

    Background Greater access to evidence-based psychological treatments is needed. This review aimed to evaluate whether internet-delivered psychological treatments for mood and anxiety disorders are efficacious, noninferior to established treatments, safe, and cost-effective for children, adolescents and adults. Methods We searched the literature for studies published until March 2013. Randomized controlled trials (RCTs) were considered for the assessment of short-term efficacy and safety and were pooled in meta-analyses. Other designs were also considered for long-term effect and cost-effectiveness. Comparisons against established treatments were evaluated for noninferiority. Two reviewers independently assessed the relevant studies for risk of bias. The quality of the evidence was graded using an international grading system. Results A total of 52 relevant RCTs were identified whereof 12 were excluded due to high risk of bias. Five cost-effectiveness studies were identified and three were excluded due to high risk of bias. The included trials mainly evaluated internet-delivered cognitive behavioral therapy (I-CBT) against a waiting list in adult volunteers and 88% were conducted in Sweden or Australia. One trial involved children. For adults, the quality of evidence was graded as moderate for the short-term efficacy of I-CBT vs. waiting list for mild/moderate depression (d = 0.83; 95% CI 0.59, 1.07) and social phobia (d = 0.85; 95% CI 0.66, 1.05), and moderate for no efficacy of internet-delivered attention bias modification vs. sham treatment for social phobia (d = −0.04; 95% CI −0.24, 0.35). The quality of evidence was graded as low/very low for other disorders, interventions, children/adolescents, noninferiority, adverse events, and cost-effectiveness. Conclusions I-CBT is a viable treatment option for adults with depression and some anxiety disorders who request this treatment modality. Important questions remain before broad implementation can

  19. Efficacy and Safety of On-Demand Use of 2 Treatments Designed for Different Etiologies of Female Sexual Interest/Arousal Disorder: 3 Randomized Clinical Trials.

    PubMed

    Tuiten, Adriaan; van Rooij, Kim; Bloemers, Jos; Eisenegger, Christoph; van Honk, Jack; Kessels, Rob; Kingsberg, Sheryl; Derogatis, Leonard R; de Leede, Leo; Gerritsen, Jeroen; Koppeschaar, Hans P F; Olivier, Berend; Everaerd, Walter; Frijlink, Henderik W; Höhle, Daniël; de Lange, Robert P J; Böcker, Koen B E; Pfaus, James G

    2018-02-01

    In women, low sexual desire and/or sexual arousal can lead to sexual dissatisfaction and emotional distress, collectively defined as female sexual interest/arousal disorder (FSIAD). Few pharmaceutical treatment options are currently available. To investigate the efficacy and safety of 2 novel on-demand pharmacologic treatments that have been designed to treat 2 FSIAD subgroups (women with low sensitivity for sexual cues and women with dysfunctional over-activation of sexual inhibition) using a personalized medicine approach using an allocation formula based on genetic, hormonal, and psychological variables developed to predict drug efficacy in the subgroups. 497 women (21-70 years old) with FSIAD were randomized to 1 of 12 8-week treatment regimens in 3 double-blinded, randomized, placebo-controlled, dose-finding studies conducted at 16 research sites in the United States. Efficacy and safety of the following on-demand treatments was tested: placebo, testosterone (T; 0.5 mg), sildenafil (S; 50 mg), buspirone (B; 10 mg) and combination therapies (T 0.25 mg + S 25 mg, T 0.25 mg + S 50 mg, T 0.5 mg + S 25 mg, T 0.5 mg + S 50 mg, and T 0.25 mg + B 5 mg, T 0.25 mg + B 10 mg, T 0.5 mg + B 5 mg, T 0.5 mg + B 10 mg). The primary efficacy measure was the change in satisfying sexual events (SSEs) from the 4-week baseline to the 4-week average of the 8-week active treatment period after medication intake. For the primary end points, the combination treatments were compared with placebo and the respective monotherapies on this measure. In women with low sensitivity for sexual cues, 0.5 mg T + 50 mg S increased the number of SSEs from baseline compared with placebo (difference in change [Δ] = 1.70, 95% CI = 0.57-2.84, P = .004) and monotherapies (S: Δ = 1.95, 95% CI = 0.44-3.45, P = .012; T: Δ = 1.69, 95% CI = 0.58-2.80, P = .003). In women with overactive inhibition, 0.5 mg T + 10 mg B increased the number of SSEs from baseline compared with placebo (

  20. Efficacy and Safety of SSRIs, SNRIs, and Placebo in Common Psychiatric Disorders: A Comprehensive Meta-Analysis in Children and Adolescents

    PubMed Central

    Locher, Cosima; Koechlin, Helen; Zion, Sean R; Werner, Christoph; Pine, Daniel S.; Kirsch, Irving; Kessler, Ronald C.; Kossowsky, Joe

    2017-01-01

    Importance Depressive disorders (DD), anxiety disorders (AD), obsessive-compulsive disorder (OCD), and posttraumatic stress disorder (PTSD) are common mental disorders in children and adolescents. Objective To examine the relative efficacy and safety of SSRIs, SNRIs and placebo for the treatment of DD, AD, OCD, and PTSD in children and adolescents. Data Sources PubMed, Embase, PsycINFO, Web of Science, and Cochrane through August 2016. Study Selection Published and unpublished randomized, double-blind, placebo-controlled studies of SSRIs or SNRIs in youths diagnosed with DD, AD, OCD, or PTSD were included. Trials using other antidepressants (e.g. tricyclic antidepressants, MAOIs) were excluded. Data Extraction and Synthesis Effect sizes, (ES) calculated as standardized mean differences (Hedges’g) and Risk Ratios (RR) for adverse events, were assessed in a random-effects model. Main Outcome(s) and Measure(s) Primary outcomes, as defined by authors on pre- and post-intervention data, mean change data, and side effect data, were extracted independently by multiple observers following PRISMA guidelines. Results We deemed 36 studies eligible, including 6778 participants; 17 studies for DD, 10 for AD, 8 for OCD and one for PTSD., SSRIs and SNRIs were significantly more effective compared to placebo, yielding a small effect size (g=0.32, p<.001). AD (g=0.56, p<.001) showed significantly larger between-group ES than DD (g=0.20, p<.001). This difference was driven primarily by the placebo response: patients with DD exhibited significantly larger placebo responses (g=1.57, p<.001) compared to those with AD (g=1.03, p<.001). Of note is the relatively large effect size for SSRIs for anxiety disorders g=0.71, p<.001. Compared to placebo, patients taking an antidepressant reported significantly more treatment emergent adverse events (RR=1.07, p=.001 or RR=1.49, p<.001, depending on the reporting method), serious adverse events (RR=1.76, p<.001) and study discontinuation due to

  1. Narrative review of the safety and efficacy of marijuana for the treatment of commonly state-approved medical and psychiatric disorders.

    PubMed

    Belendiuk, Katherine A; Baldini, Lisa L; Bonn-Miller, Marcel O

    2015-04-21

    The present investigation aimed to provide an objective narrative review of the existing literature pertaining to the benefits and harms of marijuana use for the treatment of the most common medical and psychological conditions for which it has been allowed at the state level. Common medical conditions for which marijuana is allowed (i.e., those conditions shared by at least 80 percent of medical marijuana states) were identified as: Alzheimer's disease, amyotrophic lateral sclerosis, cachexia/wasting syndrome, cancer, Crohn's disease, epilepsy and seizures, glaucoma, hepatitis C virus, human immunodeficiency virus/acquired immunodeficiency syndrome, multiple sclerosis and muscle spasticity, severe and chronic pain, and severe nausea. Post-traumatic stress disorder was also included in the review, as it is the sole psychological disorder for which medical marijuana has been allowed. Studies for this narrative review were included based on a literature search in PsycINFO, MEDLINE, and Google Scholar. Findings indicate that, for the majority of these conditions, there is insufficient evidence to support the recommendation of medical marijuana at this time. A significant amount of rigorous research is needed to definitively ascertain the potential implications of marijuana for these conditions. It is important for such work to not only examine the effects of smoked marijuana preparations, but also to compare its safety, tolerability, and efficacy in relation to existing pharmacological treatments.

  2. Efficacy and safety of flexibly dosed brexpiprazole for the adjunctive treatment of major depressive disorder: a randomized, active-referenced, placebo-controlled study.

    PubMed

    Hobart, Mary; Skuban, Aleksandar; Zhang, Peter; Josiassen, Mette Krog; Hefting, Nanco; Augustine, Carole; Brewer, Claudette; Sanchez, Raymond; McQuade, Robert D

    2018-04-01

    To assess the efficacy, safety, and tolerability of brexpiprazole as adjunctive treatment in adults with major depressive disorder (MDD) and an inadequate response to prior antidepressant treatment (ADT). Patients with a current major depressive episode after prior treatment with 1-3 ADTs entered an 8- or 10-week prospective treatment phase in which they received double-blind placebo adjunct to open-label ADT. Inadequate responders were randomized (2:2:1) to brexpiprazole 2-3 mg/day, placebo, or quetiapine extended-release (XR) 150-300 mg/day, adjunct to the same ADT, for 6 weeks. The primary efficacy endpoint was the change from baseline (randomization) to week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. The key secondary efficacy endpoint was the change in Sheehan Disability Scale (SDS) mean score. Adjunctive brexpiprazole showed a greater improvement in MADRS total score than adjunctive placebo (least squares mean difference [95% confidence interval] = -1.48 [-2.56, -0.39]; p = .0078), whereas adjunctive quetiapine XR did not separate from placebo (-0.30 [-1.63, 1.04]; p = .66). Adjunctive brexpiprazole failed to separate from placebo on the SDS mean score (-0.23 [-0.52, 0.07]; p = .13), but did improve functioning on two of the three SDS items (family life and social life). The most frequent treatment-emergent adverse events in patients receiving brexpiprazole were akathisia (6.1%), somnolence (5.6%), and headache (5.6%). Adjunctive brexpiprazole 2-3 mg/day improved symptoms of depression compared with adjunctive placebo in patients with MDD and an inadequate response to ADTs, and was well tolerated with no unexpected side effects.

  3. Efficacy and safety of brand-risperidone versus similar-risperidone in elderly patients with neuropsychiatric disorders: A retrospective study

    PubMed Central

    Folquitto, Jefferson Cunha; de Barros, Sérgio Barbosa; Pinto Junior, Jony Arrais; Bottino, Cássio M.C.

    2010-01-01

    To compare the efficacy and tolerability of brand-risperidone against similar-risperidone in elderly outpatients. Method The medical files of 16 elderly outpatients from the IPq-HCFMUSP treated with two formulations of risperidone (brand and similar) between July/1999 and February/2000 were reviewed. Two independent raters, using the Clinical Global Impression scale, evaluated the efficacy of the treatment with risperidone and the frequency of adverse effects. Results Comparing October/1999 to November/1999, Rater 1 observed a trend (p=0.059) and Rater 2 found a statistically significant difference, in favor of the brand-risperidone group (p=0.014). Comparing October/1999 to February/2000, Rater 1 observed no statistically significant difference (p=0.190), but the Rater 2 found a statistically significant difference in favor of the brand-risperidone group (p=0.029). Comparing November/1999 to February/2000, both raters found no statistically significant differences between both risperidone formulations. Regarding adverse effects, a statistically significant difference (p=0.046) was found in favor of the patients treated with brand-risperidone. Conclusions The risperidone-reference, compared to similar-risperidone, showed a trend toward greater efficacy and tolerability. PMID:29213664

  4. Double-blind, placebo-controlled study of the efficacy and safety of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder.

    PubMed

    Adler, Lenard A; Goodman, David W; Kollins, Scott H; Weisler, Richard H; Krishnan, Suma; Zhang, Yuxin; Biederman, Joseph

    2008-09-01

    To evaluate the efficacy and safety of 30, 50, and 70 mg/day lisdexamfetamine dimesylate compared with placebo in adults with attention-deficit/hyperactivity disorder (ADHD). Following a 7- to 28-day washout, 420 adults aged 18 to 55 years with moderate to severe ADHD (DSM-IV-TR criteria) were treated with 30, 50, or 70 mg/day lisdexamfetamine or placebo, respectively, for 4 weeks (N = 119, 117, 122, and 62, respectively). The 50- and 70- mg/day groups underwent forced-dose titration. The primary efficacy measure was the clinician-determined ADHD Rating Scale (ADHD-RS) total score. The study was conducted from May 2006 to November 2006. Treatment groups were well matched at baseline, including in ADHD-RS scores. At endpoint, changes in ADHD-RS scores were significantly greater for each lisdexamfetamine dose than for placebo (placebo = -8.2, 30 mg/day lisdexamfetamine = -16.2, 50 mg/day lisdexamfetamine = -17.4, 70 mg/day lisdexamfetamine = -18.6; all p < .0001 vs. placebo), with no differences between doses. Significant differences relative to placebo were observed in each lisdexamfetamine group, beginning at week 1 and for each week throughout. The percentage of subjects who improved (Clinical Global Impressions-Improvement scale rating < or = 2) was significantly greater for each lisdexamfetamine dose than for placebo at each week and at endpoint (placebo = 29%, 30 mg/day lisdexamfetamine = 57%, 50 mg/day lisdexamfetamine = 62%, 70 mg/day lisdexamfetamine = 61%; all p < .01). Adverse events were generally mild and included dry mouth, decreased appetite, and insomnia. All 3 lisdexamfetamine doses were significantly more effective than placebo in the treatment of adults with ADHD, with improvements noted within 1 week. Lisdexamfetamine was generally well tolerated by these patients. Copyright 2008 Physicians Postgraduate Press, Inc.

  5. Acetylcholinesterase inhibitors and memantine in bipolar disorder: A systematic review and best evidence synthesis of the efficacy and safety for multiple disease dimensions.

    PubMed

    Veronese, Nicola; Solmi, Marco; Luchini, Claudio; Lu, Ru-Band; Stubbs, Brendon; Zaninotto, Leonardo; Correll, Christoph U

    2016-06-01

    Acetylcholinesterase inhibitors (AceI) and memantine might prove useful in bipolar disorder (BD) given their neuroprotective and pro-cognitive effects, as highlighted by several case reports. We aimed to systematically review the efficacy and safety of AceI and memantine across multiple outcome dimensions in BD. Systematic PubMed and SCOPUS search until 04/17/2015 without language restrictions. Included were randomized controlled trials (RCTs), open label studies and case series of AceI or memantine in BD patients reporting quantitative data on depression, mania, psychotic symptoms, global functioning, or cognitive performance. We summarized results using a best-evidence based synthesis. Out of 214 hits, 12 studies (RCTs=5, other designs=7, total n=422) were included. Donepezil (studies=5; treated=102 vs. placebo=21): there was strong evidence for no effect on mania and psychotic symptoms; low evidence indicating no effect on depression. Galantamine (studies=3; treated=21 vs. controls=20) (placebo=10, healthy subjects=10): there was strong evidence for no effect on mania; moderate evidence for no effect on depression; low evidence for no effect on global functioning. Memantine (studies=4; treated=152 vs. placebo=88): there was conflicting evidence regarding efficacy for mania, depression and global functioning. Paucity of RCTs; small sample size studies; heterogeneous design, outcome and patient characteristics. There is limited but converging evidence of no effect of AceI in BD, and conflicting evidence about memantine in BD. Too few studies of mostly medium/low quality and lacking sufficient numbers of patients in specific mood states, especially mania, contributed data, focusing solely on short-term/medium-term treatment, necessitating additional high-quality research to yield more definite results. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. An open-label extension long-term study of the safety and efficacy of aripiprazole for irritability in children and adolescents with autistic disorder in Japan.

    PubMed

    Ichikawa, Hironobu; Hiratani, Michio; Yasuhara, Akihiro; Tsujii, Noa; Oshimo, Takashi; Ono, Hiroaki; Tadori, Yoshihiro

    2018-02-01

    The purpose of this study was to evaluate the long-term safety and efficacy of aripiprazole in treating irritability in pediatric patients (6-17 years) with autistic disorder (AD) in Japan. In this open-label extension study, patients who had completed a previous randomized, double-blind, placebo-controlled 8-week study were enrolled and were flexibly dosed with aripiprazole (1-15 mg/day) until the new indication of irritability in pediatric autism spectrum disorder was approved in Japan. Seventy (81%) out of 86 enrolled patients completed week-48 assessments. The mean duration of treatment was 694.9 days. The mean daily dose of aripiprazole over the treatment period was 7.2 mg and the mean of the final dose was 8.5 mg. The most common treatment-emergent adverse events (TEAE; ≥20%) included nasopharyngitis, somnolence, influenza, and increased weight. The majority of these TEAE were mild or moderate in severity, and there were no deaths, and no clinically relevant findings in laboratory values except prolactin decrease, vital signs, height, or ECG parameters. At week 48 (observed case), the mean change from baseline in the Irritability subscale score for the Aberrant Behavior Checklist Japanese Version was -6.3 in prior placebo patients and -2.6 in prior aripiprazole patients. Aripiprazole was generally safe, well tolerated, and effective in the long-term treatment of irritability associated with AD in Japanese pediatric patients. © 2017 The Authors. Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.

  7. Safety, Tolerability and Efficacy of Drugs for Treating Behavioural Insomnia in Children with Attention-Deficit/Hyperactivity Disorder: A Systematic Review with Methodological Quality Assessment.

    PubMed

    Anand, Shweta; Tong, Henry; Besag, Frank M C; Chan, Esther W; Cortese, Samuele; Wong, Ian C K

    2017-06-01

    A large proportion of paediatric patients with attention-deficit/hyperactivity disorder (ADHD) have associated sleep problems which not only affect the child's wellbeing but also impact family functioning. Management of sleep problems is consequently an important aspect of overall ADHD management in paediatric patients. Although some drugs are being used off-label for the management of paediatric insomnia, there is scant clinical evidence supporting their use. Our aim was to identify and assess the quality of published studies reporting the safety, tolerability and efficacy of drugs used for treating behavioural insomnia in children with ADHD. After an initial screen to determine which drugs were most commonly used, we conducted a systematic review of English-language publications from searches of PubMed, EMBASE, PsycINFO and two trial register databases to February 2017, using keywords 'clonidine', 'melatonin', 'zolpidem', 'eszopiclone', 'L-theanine', 'guanfacine', 'ADHD', 'sleep disorder' and 'children'. For quality assessment of included studies, we used the CONSORT checklist for randomised control trials (RCTs) and the Downs and Black checklist for non-RCTs. Twelve studies were included. Two case series for clonidine, two RCTs and four observational studies for melatonin and one RCT each for zolpidem, eszopiclone, L-theanine and guanfacine. Of the 12 included studies, only one on eszopiclone scored excellent for quality. The quality of the rest of the studies varied from moderate to low. For clonidine, melatonin and L-theanine, improvements in sleep-onset latency and total sleep duration were reported; however, zolpidem, eszopiclone and guanfacine failed to show any improvement when compared with placebo. Clonidine, melatonin, L-theanine, eszopiclone and guanfacine were well tolerated with mild to moderate adverse events; zolpidem was associated with neuropsychiatric adverse effects. There is generally poor evidence for prescribing drugs for behavioural

  8. Assessment of safety and efficacy of lamotrigine over the course of 1-year observation in Japanese patients with bipolar disorder: post-marketing surveillance study report

    PubMed Central

    Terao, Takeshi; Ishida, Atsuko; Kimura, Toshifumi; Yoshida, Mitsuhiro; Hara, Terufumi

    2017-01-01

    Background A post-marketing surveillance (PMS) study was conducted with a 1-year observation period to assess the safety and efficacy of lamotrigine in routine clinical practice in patients with bipolar disorder (BD). Patients and methods Central enrollment method was used to recruit patients diagnosed with BD who were being treated for the first time with lamotrigine to prevent the recurrence/relapse of BD mood episodes. Adverse drug reactions (ADRs) and recurrence/relapse were assessed. Improvement of mania and depression was also assessed using the Hamilton’s Rating Scale for Depression (HAM-D) and the Young Mania Rating Scale (YMRS) at treatment initiation, 4–6 months post treatment initiation, and 10–12 months post treatment initiation. Results A total of 237/989 patients (24.0%) reported ADRs, most commonly rash (9.1%), and the incidence of serious ADRs was 3.3% (33/989 patients). Skin disorders occurred in 130 patients (13.1%), mostly within 8 weeks post treatment. A total of 237/703 patients (33.7%) experienced recurrence/relapse of mood episodes. The 25th percentile of the time to recurrence/relapse of mood episodes was 105 days. Remission of depression symptoms (HAM-D ≤7) occurred in 147/697 patients (21.1%) at treatment initiation, rising to 361 patients (67.4%) at 10–12 months post treatment. Remission of manic symptoms (YMRS ≤13) occurred in 615/676 patients (91.0%) at treatment initiation, rising to 500 patients (97.3%) at 10–12 months post treatment. Conclusion The results of this PMS study suggest that lamotrigine is a well-tolerated and effective drug for preventing recurrence/relapse of BD in clinical practice. PMID:28652744

  9. A randomized controlled trial investigating the safety and efficacy of aripiprazole in the long-term maintenance treatment of pediatric patients with irritability associated with autistic disorder.

    PubMed

    Findling, Robert L; Mankoski, Raymond; Timko, Karen; Lears, Katherine; McCartney, Theresa; McQuade, Robert D; Eudicone, James M; Amatniek, Joan; Marcus, Ronald N; Sheehan, John J

    2014-01-01

    To evaluate the efficacy and safety of aripiprazole versus placebo in preventing relapse of irritability symptoms associated with autistic disorder in pediatric patients. This multicenter, double-blind, randomized, placebo-controlled, relapse-prevention trial enrolled patients (6-17 years) who met the current Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DMS-IV-TR) criteria for autistic disorder and who also had serious behavioral problems (ie, tantrums, aggression, self-injurious behavior, or a combination of these behavioral problems) between March 2011 and June 2012. In phase 1, single-blind aripiprazole was flexibly dosed (2-15 mg/d) for 13-26 weeks. Patients with a stable response (≥ 25% decrease in Aberrant Behavior Checklist-irritability subscale score and a rating of "much improved" or "very much improved" on the Clinical Global Impressions-Improvement scale) for 12 consecutive weeks were randomized into phase 2 to continue aripiprazole or switch to placebo. Treatment was continued until relapse or up to 16 weeks. The primary end point was time from randomization to relapse. Eighty-five patients were randomized in phase 2. The difference in time to relapse between aripiprazole and placebo was not statistically significant (P = .097). Kaplan-Meier relapse rates at week 16 were 35% for aripiprazole and 52% for placebo (hazard ratio [HR] = 0.57; number needed to treat [NNT] = 6). The most common adverse events during phase 1 were weight increase (25.2%), somnolence (14.8%), and vomiting (14.2%); and, during phase 2 (aripiprazole vs placebo), they were upper respiratory tract infection (10.3% vs 2.3%), constipation (5.1% vs 0%), and movement disorder (5.1% vs 0%). In this study, there was no statistically significant difference between aripiprazole and placebo in time to relapse during maintenance therapy. However, the HR and NNT suggest some patients will benefit from maintenance treatment. Patients receiving

  10. Safety and efficacy of oral DMSA therapy for children with autism spectrum disorders: Part A - Medical results

    PubMed Central

    Adams, James B; Baral, Matthew; Geis, Elizabeth; Mitchell, Jessica; Ingram, Julie; Hensley, Andrea; Zappia, Irene; Newmark, Sanford; Gehn, Eva; Rubin, Robert A; Mitchell, Ken; Bradstreet, Jeff; El-Dahr, Jane

    2009-01-01

    Background This study investigated the effect of oral dimercapto succinic acid (DMSA) therapy for children with autism spectrum disorders ages 3-8 years. Methods Phase 1 involved 65 children who received one round of DMSA (3 days). Participants who had high urinary excretion of toxic metals were selected to continue on to phase 2. In phase 2, 49 participants were randomly assigned in a double-blind design to receive an additional 6 rounds of either DMSA or placebo. Results DMSA greatly increased the excretion of lead, substantially increased excretion of tin and bismuth, and somewhat increased the excretion of thallium, mercury, antimony, and tungsten. There was some increase in urinary excretion of essential minerals, especially potassium and chromium. The Phase 1 single round of DMSA led to a dramatic normalization of RBC glutathione in almost all cases, and greatly improved abnormal platelet counts, suggesting a significant decrease in inflammation. Conclusion Overall, DMSA therapy seems to be reasonably safe, effective in removing several toxic metals (especially lead), dramatically effective in normalizing RBC glutathione, and effective in normalizing platelet counts. Only 1 round (3 days) was sufficient to improve glutathione and platelets. Additional rounds increased excretion of toxic metals. PMID:19852789

  11. Efficacy, Safety and Tolerability of Augmentative rTMS in Treatment of Major Depressive Disorder (MDD): A Prospective Cohort Study in Croatia.

    PubMed

    Filipcic, Igor; Milovac, Zeljko; Sucic, Strahimir; Gajsak, Tomislav; Filipcic, Ivona Simunovic; Ivezic, Ena; Aljinovic, Vjekoslav; Orgulan, Ivana; Penic, Sandra Zecevic; Bajic, Zarko

    2017-03-01

    An increasing body of research suggest that repetitive Transcranial Magnetic Stimulation (rTMS) is effective and safe treatment option for patients with major depressive disorder (MDD). The Psychiatric Hospital "Sveti Ivan" has the first TMS laboratory with rTMS and deep TMS (dTMS) in Croatia. The objective of this study was to assess the efficacy, safety and tolerability of augmentative rTMS treatment vs standard treatment in Croatian patients with major depressive disorder (MDD). Total of 93 MDD patients were enrolled; 41 of them were treated by augmentative rTMS and 52 were treated by standard (psychopharmacotherapy and psychotherapy) therapy only. We delivered rTMS to the left dorsolateral prefrontal cortex at 120% motor threshold (10 Hz, 4-second train duration), 3000 pulses per session using a figure-eight coil, minimum of 20 sessions during four weeks. Our key outcome was the change in Hamilton Depression Scale (HAM-D17) result from baseline to 4 th week. Our secondary outcomes were changes in Hamilton Anxiety (HAM-A) and WHOQOL-BREF scales. After four weeks the changes of HAM-D17 and HAM-A results were significantly different between the group of patients treated by augmentative rTMS (48% and 53% decrease, respectively) and the group of patients treated by the standard therapy alone (24% and 30% decrease) (P=0.004, P=0.007). Absolute benefit increase defined as the difference between rates of remission (HAM-D17 ≤7) in rTMS and control group was 33% (P=0.001). Number of patients needed to treat with rTMS in order to achieve remission in one patient was NNT=3. In a group of patients treated with augmentative rTMS 21/41 (51%), and in control group 17/52 (33%) were responders (P=0.071). It seems that augmentative treatment with rTMS is more effective on depression and anxiety symptoms than standard therapy in MDD with equal safety and tolerability. Randomized, controlled studies are required to verify this finding.

  12. Comparative efficacy and safety of methylphenidate and atomoxetine for attention-deficit hyperactivity disorder in children and adolescents: Meta-analysis based on head-to-head trials.

    PubMed

    Liu, Qiang; Zhang, Hong; Fang, Qingqing; Qin, Lili

    2017-11-01

    Comparative efficacy and safety are important issues for appropriate drug selection for attention-deficit hyperactivity disorder (ADHD) treatment. Therefore we conducted a meta-analysis, where we compared atomoxetine (ATX) and methylphenidate (MPH) for ADHD treatment in children and adolescents. Literature retrieval was conducted in relevant databases from their inception to April 2016 to select head-to-head trials that compared ATX and MPH in children and adolescents. Outcomes like response rate, ADHD Rating Scale (ADHD-RS) score, and adverse events were compared between ATX and MPH treatments. The standardized mean difference (SMD) and risk ratio (RR) with their corresponding 95% confidence intervals (CIs) were used as the effect size for continuous data or dichotomous data, respectively. Eleven eligible randomized-controlled trials were included, and two of them were double-blind, while the remaining were open-label. Compared to ATX, MPH showed a higher response rate (RR = 1.14, 95% CI [1. 09, 1.20]), decreased inattention (SMD = -0.13, 95% CI [-0.25, -0.01]) and lower risk of adverse events (drowsiness: RR = 0.17, 95% CI [0.11, 0.26; nausea: RR = 0.49; 95% CI [0.29, 0.85; vomiting: RR = 0.41, 95% CI [0.27, 0.63]). However, MPH presented a higher risk of insomnia than ATX (RR = 2.27, 95% CI [1.63, 3.15], p < .01). Results of the meta-analysis add additional evidence of the effectiveness of both ATX and MPH and suggest that MPH should be a first treatment option in most patients with ADHD.

  13. Intranasal oxytocin in the treatment of autism spectrum disorders: a review of literature and early safety and efficacy data in youth.

    PubMed

    Anagnostou, Evdokia; Soorya, Latha; Brian, Jessica; Dupuis, Annie; Mankad, Deepali; Smile, Sharon; Jacob, Suma

    2014-09-11

    There is a paucity of treatments targeting core symptom domains in Autism Spectrum Disorder (ASD). Several animal models and research in typically developing volunteers suggests that manipulation of the oxytocin system may have therapeutic potential for the treatment of social deficits. We review the literature for oxytocin and ASD and report on early dosing, safety and efficacy data of multi-dose oxytocin on aspects of social cognition/function, as well as repetitive behaviors and co-occurring anxiety within ASD. Fifteen children and adolescents with verbal IQs≥70 were diagnosed with ASD using the ADOS and the ADI-R. They participated in a modified maximum tolerated dose study of intranasal oxytocin (Syntocinon). Data were modeled using repeated measures regression analysis controlling for week, dose, age, and sex. Among 4 doses tested, the highest dose evaluated, 0.4 IU/kg/dose, was found to be well tolerated. No serious or severe adverse events were reported and adverse events reported/observed were mild to moderate. Over 12 weeks of treatment, several measures of social cognition/function, repetitive behaviors and anxiety showed sensitivity to change with some measures suggesting maintenance of effect 3 months past discontinuation of intranasal oxytocin. This pilot study suggests that daily administration of intranasal oxytocin at 0.4 IU/kg/dose in children and adolescents with ASD is safe and has therapeutic potential. Larger studies are warranted. This article is part of a Special Issue entitled Oxytocin and Social Behav. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Safety and potential efficacy of gemfibrozil as a supportive treatment for children with late infantile neuronal ceroid lipofuscinosis and other lipid storage disorders.

    PubMed

    Kim, Kyeongsoon; Kleinman, Hynda K; Lee, Hahn-Jun; Pahan, Kalipada

    2017-06-17

    Neuronal Ceroid Lipofuscinosis (NCL), also known as Batten disease, is a group of genetically distinct lysosomal disorders that mainly affect the central nervous system, resulting in progressive motor and cognitive decline primarily in children. Multiple distinct genes involved in the metabolism of lipids have been identified to date with various mutations in this family of diseases. There is no cure for these diseases but some new therapeutic approaches have been tested that offer more hope than the standard palliative care. Many of the therapeutic advances require invasive procedures but some progress in slowing the disease has been found and more options can be expected in the future. We also review the literature on children with disease/conditions other than NCL for the non-invasive use, safety, and tolerability of a lipid-lowering drug, gemfibrozil, as a potential treatment for NCLs. Gemfibrozil has shown efficacy in an animal model of NCL known as CLN2 (late infantile classic juvenile) and has been shown to be safe for lowering lipids in children. Among the 200 non-NCL children found in the published literature who were treated with gemfibrozil for NCL-related problems, only 3 experienced adverse events, including 2 with muscle pain and 1 with localized linear IgA bullous dermatitis. We conclude that gemfibrozil is safe for long-term use in children, causes minimal adverse events, is well tolerated, and may delay the progression of NCLs. Gemfibrozil may potentially be an alternative to more invasive therapeutic approaches currently under investigation and has the potential to be used in combination with other therapeutic approaches.

  15. [Safety and efficacy of oral escitalopram as continuation treatment of intravenous citalopram, in patients with major depressive disorder--the navigade switch study].

    PubMed

    Schmitt, L; Arbus, C; Tonnoir, B

    2006-01-01

    patients' depression. The CGI-I and PGE scores were significantly correlated indicating good agreement between investigator and patient in rating the degree of improvement. At the end of the study, 67% of patients were classified as responders (decrease of MADRS score from baseline > or = 50%), and the majority of them were considered remitters (final MADRS score < or = 12). Overall, the switch from intravenous citalopram to oral escitalopram was well tolerated in the study population. In all, 57 patients (33%) reported at least one adverse event (AE) during the study (21 patients in the 10 mg group and 36 patients in the 20 mg group); of these, 7 patients (4%) withdrew from the study. The most frequently reported AEs were suggestive of residual symptoms of depression (anxiety, 9%; insomnia, 5% of patients). In conclusion, in this study oral escitalopram (10 mg or 20 mg) was well tolerated as continuation treatment after switching from intravenous citalopram (20 mg or 40 mg). From the efficacy and safety data of this study, it can be concluded that the switch from citalopram iv to oral escitalopram (10 and 20 mg/day) is effective in decreasing depressive symptoms, and could be safely proposed in patients with major depressive disorder.

  16. Safety and Efficacy of Microinvasive Glaucoma Surgery

    PubMed Central

    Chen, David Z.

    2017-01-01

    Microinvasive glaucoma surgery (MIGS) is emerging as a new therapeutic option for glaucoma patients who wish to reduce their medication burden and avoid the postoperative complications of conventional glaucoma filtration surgery. These devices differ in terms of their efficacy and safety profile. Schlemm's canal devices have the most favorable safety profile at the compromise of modest efficacy, while subconjunctival and suprachoroidal devices are potentially more effective at lowering the intraocular pressure at the expense of a higher rate of complications. This review consolidates the latest evidence on the efficacy and safety of the MIGS devices in clinical use and provides an overview on upcoming devices which would likely also become viable treatment options in the near future. These clinical data would assist a glaucoma surgeon in selecting the most appropriate MIGS device for each patient based on the glaucoma severity and patient expectations. PMID:28512578

  17. The Safety and Efficacy of Low-Dose Naltrexone in the Management of Chronic Pain and Inflammation in Multiple Sclerosis, Fibromyalgia, Crohn's Disease, and Other Chronic Pain Disorders.

    PubMed

    Patten, Denise K; Schultz, Bob G; Berlau, Daniel J

    2018-03-01

    Chronic inflammatory diseases are complex to treat and have an impact on a large number of patients. Due to the difficulty of treating these diseases and the great impact on quality of life, patients often seek off-label, complimentary, or alternative medicines to gain relief from symptoms. Low-dose naltrexone has been used off-label for treatment of pain and inflammation in multiple sclerosis, Crohn's disease, fibromyalgia, and other diseases. Naltrexone is a mu-opioid receptor antagonist indicated by the U.S. Food and Drug Administration for opioid and alcohol dependence. It is hypothesized that lower than standard doses of naltrexone inhibit cellular proliferation of T and B cells and block Toll-like receptor 4, resulting in an analgesic and antiinflammatory effect. It is the purpose of this review to examine the evidence of the safety, tolerability, and efficacy of low-dose naltrexone for use in chronic pain and inflammatory conditions. Currently, evidence supports the safety and tolerability of low-dose naltrexone in multiple sclerosis, fibromyalgia, and Crohn's disease. Fewer studies support the efficacy of low-dose naltrexone, with most of these focusing on subjective measures such as quality of life or self-reported pain. These studies do demonstrate that low-dose naltrexone has subjective benefits over placebo, but evidence for more objective measures is limited. However, further randomized controlled trials are needed to determine the efficacy of low-dose naltrexone due to insufficient evidence supporting its use in these disease states. This review provides practitioners with the extent of low-dose naltrexone evidence so that they can be cognizant of situations where it may not be the most appropriate therapy. © 2018 Pharmacotherapy Publications, Inc.

  18. Safety and Efficacy of Bupropion Extended Release in Treating a Community Sample of Hispanic and African American Adults With Major Depressive Disorder: An Open-Label Study

    PubMed Central

    Gross, Paul K.; Nourse, Rosemary; Wasser, Thomas E.; Bukenya, Deo

    2007-01-01

    Objectives: Many publications and federal agencies call for more trials and research on the effectiveness of medications and treatment needs in diverse patient populations with psychiatric disorders. This study investigates the effectiveness of bupropion extended release (XL) on a community sample of men and women of either Hispanic or African American heritage with major depressive disorder (MDD). Method: Twenty-six patients of Hispanic or African American descent with MDD as diagnosed by means of the Structured Clinical Interview for DSM-IV Axis I Disorders were required to have a score of 20 or greater on the Hamilton Rating Scale for Depression (17-item) (HAM-D-17) at baseline and prior to randomization. Patients were also required to have a score of 4 or greater on the Clinical Global Impressions-Severity of Illness scale (CGI-S) at baseline and prior to initiation of treatment. Patients were treated openly for an optimum of 9 weeks. Bupropion XL was initiated at 150 mg daily and then increased to 300 mg daily after 1 week and 450 mg daily 4 weeks later if judged clinically necessary by the investigator. Tools utilized for repeated-measures methodology indicating efficacy were the HAM-D-17, CGI-S, Clinical Global Impressions-Improvement scale (CGI-I), Change in Sexual Functioning Questionnaire (CSFQ), and the 18-item Motivation and Energy Inventory. The study was conducted from February 9, 2005, to March 23, 2006. Results: Efficacy was demonstrated on the HAM-D-17, CGI-S, CGI-I, and CSFQ (p < .05). Mean times ranged from 50% symptom reduction in about 2 weeks to 90% symptom reduction in less than 2 months. Dry mouth, transient stomach discomfort, and headache were the most commonly reported side effects. Conclusions: Data from this 10-week open-label study suggest bupropion XL is an effective and well tolerated treatment for depressive symptoms in the moderately to markedly ill Hispanic and African American community. PMID:17607332

  19. Safety and Efficacy of Neonatal Vaccination

    PubMed Central

    Demirjian, Alicia; Levy, Ofer

    2009-01-01

    Newborns have an immature immune system that renders them at high risk for infection while simultaneously reducing responses to most vaccines, thereby posing challenges in protecting this vulnerable population. Nevertheless, certain vaccines, such as Bacillus Calmette Guérin (BCG) and Hepatitis B vaccine (HBV), do demonstrate safety and some efficacy at birth, providing proof of principal that certain antigen-adjuvant combinations are able to elicit protective neonatal responses. Moreover, birth is a major point of healthcare contact globally meaning that effective neonatal vaccines achieve high population penetration. Given the potentially significant benefit of vaccinating at birth, availability of a broader range of more effective neonatal vaccines is an unmet medical need and a public health priority. This review focuses on safety and efficacy of neonatal vaccination in humans as well as recent research employing novel approaches to enhance the efficacy of neonatal vaccination. PMID:19089811

  20. Systematic review: efficacy and safety of medical marijuana in selected neurologic disorders: report of the Guideline Development Subcommittee of the American Academy of Neurology.

    PubMed

    Koppel, Barbara S; Brust, John C M; Fife, Terry; Bronstein, Jeff; Youssof, Sarah; Gronseth, Gary; Gloss, David

    2014-04-29

    To determine the efficacy of medical marijuana in several neurologic conditions. We performed a systematic review of medical marijuana (1948-November 2013) to address treatment of symptoms of multiple sclerosis (MS), epilepsy, and movement disorders. We graded the studies according to the American Academy of Neurology classification scheme for therapeutic articles. Thirty-four studies met inclusion criteria; 8 were rated as Class I. The following were studied in patients with MS: (1) Spasticity: oral cannabis extract (OCE) is effective, and nabiximols and tetrahydrocannabinol (THC) are probably effective, for reducing patient-centered measures; it is possible both OCE and THC are effective for reducing both patient-centered and objective measures at 1 year. (2) Central pain or painful spasms (including spasticity-related pain, excluding neuropathic pain): OCE is effective; THC and nabiximols are probably effective. (3) Urinary dysfunction: nabiximols is probably effective for reducing bladder voids/day; THC and OCE are probably ineffective for reducing bladder complaints. (4) Tremor: THC and OCE are probably ineffective; nabiximols is possibly ineffective. (5) Other neurologic conditions: OCE is probably ineffective for treating levodopa-induced dyskinesias in patients with Parkinson disease. Oral cannabinoids are of unknown efficacy in non-chorea-related symptoms of Huntington disease, Tourette syndrome, cervical dystonia, and epilepsy. The risks and benefits of medical marijuana should be weighed carefully. Risk of serious adverse psychopathologic effects was nearly 1%. Comparative effectiveness of medical marijuana vs other therapies is unknown for these indications.

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

    PubMed

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

    2010-10-01

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

  2. A randomized, double-blinded, placebo-controlled study to evaluate the efficacy and safety of venlafaxine extended release and a long-term extension study for patients with major depressive disorder in Japan.

    PubMed

    Higuchi, Teruhiko; Kamijima, Kunitoshi; Nakagome, Kazuyuki; Itamura, Rio; Asami, Yuko; Kuribayashi, Kazuhiko; Imaeda, Takayuki

    2016-01-01

    The aim of this study was to assess antidepressant efficacy and safety of venlafaxine extended release in Japanese patients with major depressive disorder (MDD). We carried out a double-blinded, placebo-controlled, randomized study using fixed (75 mg/day) and flexible (75-225 mg/day, most patients attained to 225 mg/day) doses, followed by the long-term, open-labeled, extension study. Outpatients aged at least 20 years diagnosed with MDD were included. The primary efficacy measure was change from baseline in the Hamilton Rating Scale for Depression (HAM-D17) score at week 8; secondary efficacy measures included the Montgomery-Åsberg Depression Rating Scale, the Quick Inventory of Depressive Symptomatology self-report version, HAM-D6, and Clinical Global Impression scales in the double-blinded study. Overall, 538 patients were randomized; significant differences were observed in the primary efficacy variable in the fixed-dose group (-10.76; P=0.031), but not in the flexible-dose (-10.37; P=0.106) group compared with placebo (-9.25). However, the flexible-dose group showed significant efficacy in several secondary measures. Treatment-related adverse events in the treatment period were 51.7 and 67.8% in the fixed-dose and flexible-dose groups, respectively, versus 38.8% with placebo. Throughout the study period, no Japanese-specific adverse events were observed. Thus, venlafaxine extended release was efficacious and safe for MDD treatment in Japan.

  3. A randomized, double-blinded, placebo-controlled study to evaluate the efficacy and safety of venlafaxine extended release and a long-term extension study for patients with major depressive disorder in Japan

    PubMed Central

    Higuchi, Teruhiko; Kamijima, Kunitoshi; Nakagome, Kazuyuki; Asami, Yuko; Kuribayashi, Kazuhiko; Imaeda, Takayuki

    2016-01-01

    The aim of this study was to assess antidepressant efficacy and safety of venlafaxine extended release in Japanese patients with major depressive disorder (MDD). We carried out a double-blinded, placebo-controlled, randomized study using fixed (75 mg/day) and flexible (75–225 mg/day, most patients attained to 225 mg/day) doses, followed by the long-term, open-labeled, extension study. Outpatients aged at least 20 years diagnosed with MDD were included. The primary efficacy measure was change from baseline in the Hamilton Rating Scale for Depression (HAM-D17) score at week 8; secondary efficacy measures included the Montgomery–Åsberg Depression Rating Scale, the Quick Inventory of Depressive Symptomatology self-report version, HAM-D6, and Clinical Global Impression scales in the double-blinded study. Overall, 538 patients were randomized; significant differences were observed in the primary efficacy variable in the fixed-dose group (−10.76; P=0.031), but not in the flexible-dose (−10.37; P=0.106) group compared with placebo (−9.25). However, the flexible-dose group showed significant efficacy in several secondary measures. Treatment-related adverse events in the treatment period were 51.7 and 67.8% in the fixed-dose and flexible-dose groups, respectively, versus 38.8% with placebo. Throughout the study period, no Japanese-specific adverse events were observed. Thus, venlafaxine extended release was efficacious and safe for MDD treatment in Japan. PMID:26513202

  4. Efficacy and safety of olanzapine/fluoxetine combination vs fluoxetine monotherapy following successful combination therapy of treatment-resistant major depressive disorder.

    PubMed

    Brunner, Elizabeth; Tohen, Mauricio; Osuntokun, Olawale; Landry, John; Thase, Michael E

    2014-10-01

    This study assessed prevention of relapse in patients with treatment-resistant depression (TRD) taking olanzapine/fluoxetine combination (OFC). Patients with major depressive disorder (MDD) who failed to satisfactorily respond to ≥ 2 different antidepressants for ≥ 6 weeks within the current MDD episode were acutely treated for 6-8 weeks, followed by stabilization (12 weeks) on OFC. Those who remained stable were randomized to OFC or fluoxetine for up to 27 weeks. Time-to-relapse was the primary efficacy outcome defined as 50% increase in Montgomery-Åsberg Depression Rating Scale score with Clinical Global Impressions-Severity of Depression score of ≥ 4; hospitalization for depression or suicidality; or discontinuation for lack of efficacy or worsening of depression or suicidality. A total of 444 patients were randomized 1:1 to OFC (N=221) or fluoxetine (N=223). Time-to-relapse was significantly longer in OFC-treated patients compared with fluoxetine-treated patients (p<0.001). Treatment-emergent weight gain and some mean and categorical fasting metabolic changes were significantly greater in OFC-treated patients. Clinically significant weight gain (≥ 7%) was observed in 55.7% of patients who remained on OFC throughout the study, including the relapse-prevention phase (up to 47 weeks). There were no significant differences between patients treated with OFC and fluoxetine in extrapyramidal symptoms or serious adverse events. We believe this is the first controlled relapse-prevention study in subjects with TRD that supports continued use of a second-generation antipsychotic beyond stabilization. A thorough assessment of benefits and risks (in particular metabolic changes) associated with continuing treatment with OFC or fluoxetine must be done based on individual patient needs.

  5. Efficacy and Safety of Olanzapine/Fluoxetine Combination vs Fluoxetine Monotherapy Following Successful Combination Therapy of Treatment-Resistant Major Depressive Disorder

    PubMed Central

    Brunner, Elizabeth; Tohen, Mauricio; Osuntokun, Olawale; Landry, John; Thase, Michael E

    2014-01-01

    This study assessed prevention of relapse in patients with treatment-resistant depression (TRD) taking olanzapine/fluoxetine combination (OFC). Patients with major depressive disorder (MDD) who failed to satisfactorily respond to ⩾2 different antidepressants for ⩾6 weeks within the current MDD episode were acutely treated for 6–8 weeks, followed by stabilization (12 weeks) on OFC. Those who remained stable were randomized to OFC or fluoxetine for up to 27 weeks. Time-to-relapse was the primary efficacy outcome defined as 50% increase in Montgomery-Åsberg Depression Rating Scale score with Clinical Global Impressions−Severity of Depression score of ⩾4; hospitalization for depression or suicidality; or discontinuation for lack of efficacy or worsening of depression or suicidality. A total of 444 patients were randomized 1:1 to OFC (N=221) or fluoxetine (N=223). Time-to-relapse was significantly longer in OFC-treated patients compared with fluoxetine-treated patients (p<0.001). Treatment-emergent weight gain and some mean and categorical fasting metabolic changes were significantly greater in OFC-treated patients. Clinically significant weight gain (⩾7%) was observed in 55.7% of patients who remained on OFC throughout the study, including the relapse-prevention phase (up to 47 weeks). There were no significant differences between patients treated with OFC and fluoxetine in extrapyramidal symptoms or serious adverse events. We believe this is the first controlled relapse-prevention study in subjects with TRD that supports continued use of a second-generation antipsychotic beyond stabilization. A thorough assessment of benefits and risks (in particular metabolic changes) associated with continuing treatment with OFC or fluoxetine must be done based on individual patient needs. PMID:24801768

  6. Comparative efficacy, acceptability, and safety of medicinal, cognitive-behavioral therapy, and placebo treatments for acute major depressive disorder in children and adolescents: a multiple-treatments meta-analysis.

    PubMed

    Ma, Dongfeng; Zhang, Zhijun; Zhang, Xiangrong; Li, Lingjiang

    2014-06-01

    New generation antidepressant therapies, including serotonin-norepinephrine reuptake inhibitor (SNRIs) and selective serotonin reuptake inhibitors (SSRIs) were introduced in the late 1980s; however, few comprehensive studies compared the benefits and risks of various contemporary treatments for major depressive disorder (MDD) in pediatric patients. Multiple-treatments meta-analysis (MTM) was conducted to assess efficacy, acceptability, and safety of contemporary interventions in children and adolescents with MDD. Cochrane Library, AMED, CINAHL, EMBASE, LiLACS, MEDLINE, PSYCINFO, PSYNDEX, and Journal of Medicine and Pharmacy databases were searched for randomized controlled trials (RCTs) comparing medicinal interventions (citalopram, escitalopram, fluoxetine, mirtazapine, paroxetine, sertraline, venlafaxine), cognitive behavioral therapy (CBT), combined fluoxetine with CBT, and placebo treatment for acute MDD from January 1988 to March 2013. Treatment success, dropout rate, and suicidal ideation/attempt outcomes were measured. Bayesian methods were used to conduct a MTM including age and funding subgroups. A total of 21 RCTs (4969 participants) were identified. Combined fluoxetine/CBT exhibited the highest efficacy, with fluoxetine alone superior to CBT, paroxetine, sertraline, citalopram, escitalopram, and placebo treatment. Sertraline, paroxetine, escitalopram, and venlafaxine showed superior acceptability to fluoxetine and combined fluoxetine/CBT. Combined fluoxetine/CBT combination was less safe, though CBT was safer than fluoxetine alone. Combined fluoxetine/CBT, fluoxetine, and mirtazapine exhibited the highest efficacy; sertraline, escitalopram, venlafaxine, and paroxetine were the best tolerated; and mirtazapine and venlafaxine were the safest. Sertraline and mirtazapine exhibited optimally balanced efficacy, acceptability, and safety for first-line acute treatment of child and adolescent MDD.

  7. Women's perceptions of contraceptive efficacy and safety.

    PubMed

    Kakaiya, Roshni; Lopez, Lia L; Nelson, Anita L

    2017-01-01

    Adoption of contraceptive implants and intrauterine devices has been less than might be expected given their superior efficacy and convenience. The purpose of this study was to assess knowledge and beliefs held by women, which may influence their contraceptive choices and theirongoing utilization of contraceptive methods. English speaking, nonpregnant, reproductive-age women, who were not surgically sterilized, were individually interviewed to obtain limited demographic characteristics and to assess their knowledge about the efficacy of various contraceptive methods in typical use and about the relative safety of oral contraceptives. A convenience sample of 500 women aged 18-45 years, with education levels that ranged from middle school to postdoctoral level was interviewed. The efficacy in typical use of both combined oral contraceptives and male condoms was correctly estimated by 2.2%; over two-thirds of women significantly over estimated the efficacy of each of those methods in typical use. Oral contraceptives were thought to be at least as hazardous to a woman's health as pregnancy by 56% of women. The majority of reproductive aged women surveyed substantially overestimated the efficacy of the two most popular contraceptive methods, often saying that they were 99% effective. Women with higher education levels were most likely to overestimate efficacy of oral contraceptives. Women of all ages and education levels significantly overestimated the health hazards of oral contraceptives compared to pregnancy. Overestimation of effectiveness of these methods of contraception, may contribute to lower adoption of implants and intrauterine devices. When individualizing patient counselling, misperceptions must be identified and addressed with women of all educational backgrounds. Not applicable.

  8. Comparable efficacy and safety of 8 weeks treatment with agomelatine 25-50mg or fluoxetine 20-40mg in Asian out-patients with major depressive disorder.

    PubMed

    Shu, L; Sulaiman, A H; Huang, Y S; Fones Soon Leng, C; Crutel, V Strijckmans; Kim, Y S

    2014-04-01

    This randomized, double-blind study evaluates the efficacy and tolerability of agomelatine, using fluoxetine as an active comparator, in Asian patients suffering from moderate to severe major depressive disorder (MDD). Patients were randomly assigned to receive either agomelatine (25-50mg/day, n=314) or fluoxetine (20-40mg/day, n=314) during an 8-week treatment period. The main outcome measure was the change in Hamilton Depression Rating Scale 17 items (HAM-D17) scores. Secondary efficacy criteria included scores on Clinical Global Impression Severity of illness (CGI-S) and Improvement of illness (CGI-I), patient sleeping improvement using the self-rating Leeds Sleep Evaluation Questionnaire (LSEQ) and anxiety using the Hamilton Anxiety Rating Scale (HAM-A) scores. Tolerability and safety evaluations were based on emergent adverse events. Agomelatine and fluoxetine exert a comparable antidepressant efficacy in the Asian population. Mean changes over 8 weeks were clinically relevant and similar in both groups (-14.8±7.3 and -15.0±8.1 on HAM-D17 scale in agomelatine and fluoxetine groups, respectively). The between-group difference reached statistical significance on non-inferiority test (p=0.015). Clinically relevant decreases in CGI-S and CGI-I scores were observed over the treatment period in both groups. The two treatments were equally effective on the symptoms of both anxiety and sleep. The good tolerability profile and safety of both doses of agomelatine was confirmed in the Asian population. Agomelatine and fluoxetine are equally effective in the treatment of MDD-associated symptoms in Asian depressed patients. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Randomized, double-blind, placebo-controlled 8-week trial of the efficacy, safety, and tolerability of 5, 10, and 20 mg/day vortioxetine in adults with major depressive disorder.

    PubMed

    Nishimura, Akira; Aritomi, Yutaka; Sasai, Kiyofumi; Kitagawa, Tadayuki; Mahableshwarkar, Atul R

    2018-02-01

    This study assessed the efficacy and safety of vortioxetine in adults with major depressive disorder. In this double-blind, placebo-controlled study, 600 patients with major depressive disorder were randomly assigned (1:1:1:1) to receive vortioxetine 5, 10, or 20 mg, or placebo once daily for 8 weeks. The primary end-point was change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) total score at week 8, evaluated by the last-observation-carried-forward method. Secondary end-points included response (≥ 50% decrease in the MADRS total score from baseline) and remission (MADRS total score ≤ 10), Clinical Global Impression Scale-Improvement, and change from baseline in Sheehan Disability Scale. Adverse events were summarized. Vortioxetine failed to show significant differences from placebo in the primary end-point. Nominally significant improvements over placebo were observed for vortioxetine doses of 10 and 20 mg when the primary end-point was evaluated using the mixed model for repeated measures as the secondary analysis, and 10 mg in secondary measures of response and patient functioning. Vortioxetine was well tolerated. Nausea, constipation, dry mouth, dizziness, and insomnia each occurred at a >twofold higher rate than placebo. Discontinuation symptom scores were comparable between all groups after 1 and 2 weeks following withdrawal of the study drug. While vortioxetine failed to meet significance versus placebo in the primary efficacy analysis, there was evidence of efficacy for the 10- and 20-mg doses in secondary analyses. Vortioxetine was safe and well tolerated. Additional studies appear warranted. © 2017 The Authors. Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.

  10. Efficacy and safety of second-generation antipsychotics in children and adolescents with psychotic and bipolar spectrum disorders: comprehensive review of prospective head-to-head and placebo-controlled comparisons.

    PubMed

    Fraguas, David; Correll, Christoph U; Merchán-Naranjo, Jessica; Rapado-Castro, Marta; Parellada, Mara; Moreno, Carmen; Arango, Celso

    2011-08-01

    To review data on efficacy and safety of second-generation antipsychotics (SGAs) in children and adolescents with psychotic and bipolar spectrum disorders. Medline/PubMed/Google Scholar search for studies comparing efficacy and/or tolerability: (i) between two or more SGAs; (ii) between SGAs and placebo; and (iii) between at least one SGA and one first-generation antipsychotic (FGA). The review focused on three major side-effect clusters: 1. body weight, body mass index, and cardiometabolic parameters, 2. prolactin levels, and 3. neuromotor side effects. In total, 34 studies with 2719 children and adolescents were included. Studies lasted between 3 weeks and 12 months, with most studies (79.4%) lasting 3 months or less. Nine studies (n=788) were conducted in patients with schizophrenia, 6 (n=719) in subjects with bipolar disorder, and 19 (n=1212) in a mixed population. Data on efficacy showed that, except for clozapine being superior for refractory schizophrenia, there were no significant differences between SGAs. By contrast, safety assessments showed relevant differences between SGAs. Mean weight gain ranged from 3.8 kg to 16.2 kg in patients treated with olanzapine (n=353), from 0.9 kg to 9.5 kg in subjects receiving clozapine (n=97), from 1.9 kg to 7.2 kg in those on risperidone (n=571), from 2.3 kg to 6.1 kg among patients taking quetiapine (n=133), and from 0 kg to 4.4 kg in those treated with aripiprazole (n=451). Prolactin levels increased the most in subjects on risperidone (mean change ranging from 8.3 ng/mL to 49.6 ng/mL), followed by olanzapine (-1.5 ng/mL to +13.7 ng/mL). Treatment with aripiprazole was associated with decreased prolactin levels, while clozapine and quetiapine were found to be mostly neutral. With respect to neuromotor side effects, SGAs were associated with less parkinsonism and akathisia than FGAs. Most of the studies comparing neuromotor side effects between SGAs found no significant differences. SGAs do not behave as a homogeneous

  11. Rationale and design of the PLACID study: a randomised trial comparing the efficacy and safety of inhaled loxapine versus IM aripiprazole in acutely agitated patients with schizophrenia or bipolar disorder.

    PubMed

    San, L; Estrada, G; Oudovenko, N; Vieta, E

    2017-04-04

    The management of acute agitation manifesting in patients with schizophrenia or bipolar disorder requires swift pharmacological intervention to provide rapid symptomatic relief and prevent escalation to aggression and violence. Antipsychotic medications are widely used in this setting and the availability of an inhaled formulation with deep lung absorption of the antipsychotic loxapine has the potential to deliver a faster onset of therapeutic effect than the available intramuscular formulations of antipsychotics. The efficacy of inhaled loxapine and the alternative antipsychotic aripiprazole delivered via intramuscular (IM) injection will be compared in the Phase IIIb PLACID study. Adults (18-65 years) with a confirmed diagnosis of schizophrenia or bipolar I disorder presenting with acute agitation will be randomly assigned to open-label treatment in a 1:1 ratio. Clinical evaluation will be conducted by raters blinded to treatment assignment. The primary efficacy endpoint is time to response (defined as a Clinical Global Impression of Improvement [CGI-I] score of 1 [very much improved] or 2 [much improved]). Secondary endpoints will include the percentage of responders at different time points after dosing; the proportion of patients who receive 1 or 2 doses of study drug; time to second dose; time to rescue medication; satisfaction with study drug (evaluated using Item 14 of the Treatment Satisfaction Questionnaire for Medication); and safety and tolerability. Approximately 360 patients will be recruited with an interim analysis conducted once 180 patients have completed the study to decide whether to stop for futility or continue with or without an increase in the sample size up to additional 288 patients. The PLACID trial will assess the efficacy and safety of inhaled loxapine with deep lung absorption compared with the IM antipsychotic, aripiprazole, in acutely agitated patients with schizophrenia or bipolar disorder. In the event that the median time to

  12. [Liposomal-amphotericin B efficacy and safety].

    PubMed

    Hamada, Yukihiro; Komatsu, Toshiaki; Seto, Yoshinori; Matsubara, Hajime; Kume, Hikaru; Sunakawa, Keisuke; Yago, Kazuo

    2010-03-01

    Liposomal amphotericin B (L-AMB), a lipid-based amphotericin B formulation, has been used in Japan since June 2006 to treat fungal infection. In the 3 years since L-AMB was launched, few reports have been made on its status. To ensure its appropriate use, we restrospectively reviewed its efficacy and safety in treating fungal infections. 25 subjects with fungal infection treated with L-AMB from April 2007 until February 2008. Of those, 16 showed clinical improvement. Elevated serum creatinine occurred in 1 and decreased serum potassium in 6. We found a positive relationship between the serum potassium decrease and L-AMB dose. Logistic regression analysis of this relationship showed that serum potassium tended to fall on day 5 to 6 of L-AMB administration. While L-AMB appears highly effective in fungal infection, it requires serum potassium monitoring to ensure patient safety.

  13. Review of the Efficacy and Safety of Antidepressants in Youth Depression

    ERIC Educational Resources Information Center

    Cheung, Amy H.; Emslie, Graham J.; Mayes, Taryn L.

    2005-01-01

    Background: Depression in children and adolescents is a cause of substantial morbidity and mortality in this population. It is a common disorder that affects 2% of children and up to 6% of adolescents. Although antidepressants are used frequently for the treatment of this disorder, there has been recent controversy about the efficacy and safety of…

  14. Safety self-efficacy and safety performance: potential antecedents and the moderation effect of standardization.

    PubMed

    Katz-Navon, Tal; Naveh, Eitan; Stern, Zvi

    2007-01-01

    The purpose of this paper is to suggest a new safety self-efficacy construct and to explore its antecedents and interaction with standardization to influence in-patient safety. The paper used a survey of 161 nurses using a self-administered questionnaire over a 14-day period in two large Israeli general hospitals. Nurses answered questions relating to four safety self-efficacy antecedents: enactive mastery experiences; managers as safety role models; verbal persuasion; and safety priority, that relate to the perceived level of standardization and safety self-efficacy. Confirmatory factor analysis was used to assess the scale's construct validity. Regression models were used to test hypotheses regarding the antecedents and influence of safety self-efficacy. Results indicate that: managers as safety role models; distributing safety information; and priority given to safety, contributed to safety self-efficacy. Additionally, standardization moderated the effects of safety self-efficacy and patient safety such that safety self-efficacy was positively associated with patient safety when standardization was low rather than high. Hospital managers should be aware of individual motivations as safety self-efficacy when evaluating the potential influence of standardization on patient safety. Theoretically, the study introduces a new safety self-efficacy concept, and captures its antecedents and influence on safety performance. Also, the study suggests safety self-efficacy as a boundary condition for the influence of standardization on safety performance. Implementing standardization in healthcare is problematic because not all processes can be standardized. In this case, self-efficacy plays an important role in securing patient safety. Hence, safety self-efficacy may serve as a "substitute-for-standardization," by promoting staff behaviors that affect patient safety.

  15. [Efficacy and safety of a herbal drug containing hawthorn berries and D-camphor in hypotension and orthostatic circulatory disorders/results of a retrospective epidemiologic cohort study].

    PubMed

    Hempel, Bernd; Kroll, Michael; Schneider, Berthold

    2005-01-01

    Korodin Herz-Kreislauf-Tropfen, a herbal drug containing D-camphor (CAS 76-22-2; 2.5 %) and a liquid extract of fresh hawthorn berries (97.3%), has been used since many years for the treatment of orthostatic hypotension. The combination as well as its constituents were tested in clinical trials against placebo with healthy volunteers and patients using tilt-tests. The objective of this study was to investigate efficacy and safety of the drug under the conditions of medical practice in comparison to other drugs admitted for this indication. The study was performed as an epidemiological retrospective cohort study in 46 medical practices in Germany. In the practices the files were reviewed for patients who were treated between 1st January 2000 and 31st December 2002 for orthostatic hypotension. Included in the study were all patients who were treated either with the test drug or a control drug containing etilefrine, oxilofrine, midodrine, norfenefrine or dihydroergotamine and who met the inclusion criteria. The data of the files were coded, transferred to case report forms and augmented by the physician's statements about symptoms and success. Effect criteria were the improvement of symptoms and change of blood pressure during treatment. The correctness of the data was controlled using anonymous copies of the files. A total of 490 patients (399 in the test-group and 91 in the control group) between 11 and 102 years were included in the study. To correct heterogeneities in baseline conditions, treatment results were adjusted by regression and stratification to equal baseline conditions using the propensity score. The adjusted odds ratio for improvement was 5.6, the adjusted mean increase of the systolic blood pressure the 2-fold compared to the control group. The difference was highly significant and did not depend on age or initial blood pressure. In the test group two adverse events were observed which had no relation to the medication; in the control group one

  16. Eslicarbazepine acetate: an update on efficacy and safety in epilepsy.

    PubMed

    Verrotti, Alberto; Loiacono, Giulia; Rossi, Alessandra; Zaccara, Gaetano

    2014-01-01

    Epilepsy is a common neurological disorder. Despite a broad range of commonly used antiepileptic drugs, approximately 30% of patients with epilepsy have drug resistance or encounter significant adverse effects. Eslicarbazepine acetate is a new central nervous system-active compound with anticonvulsant activity whose mechanism of action is by blocking the voltage-gated sodium channel. Eslicarbazepine acetate was approved by the European Medicines Agency and launched onto the European market in 2009 for adjunctive treatment in adult subjects of partial-onset seizures, with or without secondary generalization. This article provides an overview on the recent studies on eslicarbazepine acetate in the treatment of drug-resistant partial epilepsy. Efficacy and safety of this drug for partial-onset seizures were assessed in four randomized clinical trials with responder rates ranged between 17% and 43%. Adverse events were usually mild to moderate in intensity and the most common were dizziness, somnolence, nausea, diplopia, headache, vomiting, abnormal coordination, blurred vision, vertigo and fatigue. Eslicarbazepine acetate is not recommended below 18 years, but a published phase II trial had the main goal to evaluate the pharmacokinetics, efficacy and safety of this drug in pediatric population. Eslicarbazepine acetate appears to be a safe and effective drug with a linear pharmacokinetics, very low potential for drug-drug interactions and therefore it can offer a valid alternative to current antiepileptic drugs. Additionally, it is undergoing investigation for monotherapy in subjects with partial epilepsy, and other neurological and psychiatric disorders. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. [Human papillomavirus vaccine. Efficacy and safety].

    PubMed

    Bruni, Laia; Serrano, Beatriz; Bosch, Xavier; Castellsagué, Xavier

    2015-05-01

    Human papillomavirus (HPV) related disease remains a major cause of morbidity and mortality worldwide. Prophylactic vaccines have been recognized as the most effective intervention to control for HPV-related diseases. This article reviews the major phaseii/iii trials of the bivalent (HPVs16/18), quadrivalent (HPVs6/11/16/18), and the recently approved 9-valent vaccine (HPVs6/11/16/18/31/33/45/52/58). Large trials have been conducted showing the safety, immunogenicity and high efficacy of the bivalent and quadrivalent vaccines in the prevention of pre-invasive lesions and infection, especially when administered at young ages before exposure to HPV. Trials of the 9-valent vaccine have also demonstrated the safety, immunogenicity and efficacy of the vaccine in the prevention of infection and disease associated with the vaccine types, and its potential to substantially increase the overall prevention of HPV-related diseases. Post-licensure country reports have shown the recent and early impact of these vaccines at population level after the implementation of established HPV vaccination programs, including decreases in the prevalence of vaccine HPV types, the incidence of genital warts, and the incidence of high-grade cervical abnormalities. If widely implemented, current HPV vaccines may drastically reduce the incidence of cervical cancer and other HPV-related cancers and diseases. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  18. Safety and efficacy of drugs in pregnancy.

    PubMed

    Knoppert, David

    2011-01-01

    Although most drugs are used to treat chronic or pregnancy-induced conditions during pregnancy and lactation, very few are studied in pregnant or breastfeeding women. The information we have on drugs taken during pregnancy and lactation is usually obtained after market approval through published case reports or case series and from pregnancy exposure or retrospective birth defect registries. Furthermore, generic drugs approved for use in this vulnerable population may be approved based on results from a male trial population. This disregards the changes that can occur during pregnancy which can affect the pharmacokinetics of drugs. In an effort to improve the information provided to prescribers, in 2008 the United States Food and Drug Administration proposed a change in product labelling where information from pregnancy exposure registries would be required. As of 2009, European Medicines Agency requires additional statements on use during pregnancy within drug labelling information. In Canada, it is anticipated that the efficacy and safety of drugs in pregnancy will be included under the Drug Safety and Effectiveness Network initiative, and that this will offer a unified approach for such assessments. Pregmedic, a non-profit organization for the advancement of safe and effective use of drugs in pregnancy, has presented a number of proposals and draft guidelines to Health Canada on the inclusion of pregnant women in pharmacokinetic studies and the establishment of registries for women who take drugs during pregnancy. Pregmedic advocates for ensuring that drugs indicated for women are studied in women.

  19. Comparison of the Efficacy and Safety of Aripiprazole Versus Bupropion Augmentation in Patients With Major Depressive Disorder Unresponsive to Selective Serotonin Reuptake Inhibitors: A Randomized, Prospective, Open-Label Study.

    PubMed

    Cheon, Eun-Jin; Lee, Kwang-Hun; Park, Young-Woo; Lee, Jong-Hun; Koo, Bon-Hoon; Lee, Seung-Jae; Sung, Hyung-Mo

    2017-04-01

    The purpose of this study was to compare the efficacy and safety of aripiprazole versus bupropion augmentation in patients with major depressive disorder (MDD) unresponsive to selective serotonin reuptake inhibitors (SSRIs). This is the first randomized, prospective, open-label, direct comparison study between aripiprazole and bupropion augmentation. Participants had at least moderately severe depressive symptoms after 4 weeks or more of SSRI treatment. A total of 103 patients were randomized to either aripiprazole (n = 56) or bupropion (n = 47) augmentation for 6 weeks. Concomitant use of psychotropic agents was prohibited. Montgomery Asberg Depression Rating Scale, 17-item Hamilton Depression Rating scale, Iowa Fatigue Scale, Drug-Induced Extrapyramidal Symptoms Scale, Psychotropic-Related Sexual Dysfunction Questionnaire scores were obtained at baseline and after 1, 2, 4, and 6 weeks of treatment. Overall, both treatments significantly improved depressive symptoms without causing serious adverse events. There were no significant differences in the Montgomery Asberg Depression Rating Scale, 17-item Hamilton Depression Rating scale, and Iowa Fatigue Scale scores, and response rates. However, significant differences in remission rates between the 2 groups were evident at week 6 (55.4% vs 34.0%, respectively; P = 0.031), favoring aripiprazole over bupropion. There were no significant differences in adverse sexual events, extrapyramidal symptoms, or akathisia between the 2 groups. The present study suggests that aripiprazole augmentation is at least comparable to bupropion augmentation in combination with SSRI in terms of efficacy and tolerability in patients with MDD. Both aripiprazole and bupropion could help reduce sexual dysfunction and fatigue in patients with MDD. Aripiprazole and bupropion may offer effective and safe augmentation strategies in patients with MDD who are unresponsive to SSRIs. Double-blinded trials are warranted to confirm the present findings.

  20. [The results of Russian multicenter open-label observational study of the efficacy and safety of мelaxen (melatonin) for the treatment of disordered sleep in patients with chronic cerebral ischemia].

    PubMed

    Poluéktov, M G; Levin, Ia I; Boĭko, A N; Skoromets, A A; Bel'skaia, G N; Gustov, A V; Doronin, B M; Poverennova, I E; Spirin, N N; Iakupov, E Z

    2012-01-01

    The results of the multicenter open-label observational study of the efficacy and safety of the Melaxen (melatonin) for the treatment of disordered sleep in patients with chronic cerebral ischemia are presented. 2062 patients were studied with the use of subjective psychometric scales: subjective sleep characteristics scale, sleep apnea screening questionnaire, Epworth sleepiness scale, hospital anxiety and depression scale. Mean age of patients was 55.7±9.0 years, there were 74.1% females and 25.9% males. Melaxen was given in dosage of 3 mg. before sleep for 24 days. The use of Melaxen leads to the increase of subjective sleep quality by the subjective sleep characteristics scale from 19.7±3.1 points to и 22.7±3.4 points on day 14 and 22.7±3.4 on day 24 (differences are significant at p<0.0001). There was the decrease of the relative number of patients with frequent night awakenings, prolonged sleep latency, short night sleep, poor quality of morning awakening and multiple bothering dreams. Authors conclude that the use of Melaxen in dosage of 3 mg before sleep is effective and safe insomnia treatment in patients with chronic cerebral ischemia.

  1. [Efficacy and safety of a combined oral contraceptive containing drospirenone 3 mg and ethinylestradiol 20 µg in the treatment of premenstrual dysphoric disorder: a randomized, double blind placebo-controlled study].

    PubMed

    Fu, Yi; Mi, Weifeng; Li, Lingzhi; Zhang, Hongyan; Wang, Jia; Cheng, Wenjun; Sun, Lizhou; Li, Lingjiang; Xie, Shiping; Zhang, Jinbei

    2014-07-01

    To compare the efficacy and safety of a new low-dose oral contraceptive pill (YAZ) containing drospirenone 3 mg and ethinylestradiol 20 µg with placebo in reducing symptoms of premenstrual dysphoric disorder (PMDD). This multicenter, double- blind, randomized clinical trial consisted of 2 run- in and 3 treatment cycles (84 days) with daily symptom charting; 187 women with symptoms of PMDD were randomized to either placebo group (n = 94) or YAZ group (n = 93), and assessed with daily record of severity of problems scale (DRSP) and clinical global impressions scale (CGI) before, during and after the treatments. Hormones were administered for 24 days, followed by 4 days of inactive pills. Compared with baseline level of DRSP, both groups got improvement after treatment; the YAZ group (median -28.7, range: -82.5 to 2.3) had greater improvement than that in the placebo group (median -23.7, range: -86.0 to 11.8), while there was not significant difference (P > 0.05). The main adverse effects of YAZ included intermenstrual bleeding [13% (12/93) versus 3% (3/94)], menorrhagia [9% (8/93) versus 1% (1/94)], nausea [5% (5/93) versus 4% (4/94)] and skin rash [4% (4/93) versus 2% (2/94)]. YAZ could improve symptoms of PMDD better than placebo, while without statistic significance in this study. The most common adverse effects are intermenstrual bleeding, menorrhagia, nausea and rash.

  2. Efficacy and safety of mipomersen sodium (Kynamro).

    PubMed

    Hovingh, Kees; Besseling, Joost; Kastelein, John

    2013-07-01

    Mipomersen is a first-in-class drug indicated as an adjunct to lipid-lowering medications and diet to reduce low-density lipoprotein-cholesterol (LDL-C), apolipoprotein B (apoB), total cholesterol (TC) and non-high density lipoprotein-cholesterol (non-HDL-C) in patients with homozygous familial hypercholesterolemia (HoFH). This article summarizes the efficacy and safety profile of mipomersen based on literature, public materials available from the Endocrinologic and Metabolic Drugs Advisory Committee meeting (FDA) in review of the New Drug Application (NDA 203568) and the recent product label. Patients suffering from HoFH are characterized by elevated levels of LDL-C and are, therefore, at severely increased risk for cardiovascular disease (CVD). Currently available lipid-lowering therapies (LLT), such as statins, have been shown to lower LDL-C levels and CVD risk. However, in patients suffering from HoFH, additional therapy is urgently needed to further decrease LDL-C levels and CVD risk. Mipomersen (Kynamro) has recently been approved by the FDA as a novel LLT modality in patients with HoFH. Mipomersen has been show to result in highly relevant absolute LDL-C reductions in HoFH patients, and given the undisputed causal relationship between LDL-C levels and CVD risk, this additional LDL-C lowering is expected to result in a robust CVD risk reduction.

  3. Efficacy, Safety, and Tolerability of an Extended-Release Orally Disintegrating Methylphenidate Tablet in Children 6-12 Years of Age with Attention-Deficit/Hyperactivity Disorder in the Laboratory Classroom Setting.

    PubMed

    Childress, Ann C; Kollins, Scott H; Cutler, Andrew J; Marraffino, Andrea; Sikes, Carolyn R

    2017-02-01

    Methylphenidate extended-release orally disintegrating tablets (MPH XR-ODTs) represent a new technology for MPH delivery. ODTs disintegrate in the mouth without water and provide a pharmacokinetic profile that is consistent with once-daily dosing. This study sought to determine the efficacy, safety, and tolerability of this novel MPH XR-ODT formulation in school-age children with attention-deficit/hyperactivity disorder (ADHD) in a laboratory classroom setting. Children aged 6-12 years with ADHD (n = 87) were enrolled in this randomized, multicenter, double-blind, placebo-controlled, parallel, laboratory classroom study. The MPH XR-ODT dose was titrated to an optimized dose during a 4-week open-label period and maintained on that dose for 1 week. Participants (n = 85) were then randomized to receive their optimized dose of MPH XR-ODT or placebo once daily for 1 week (double blind), culminating in a laboratory classroom testing day. Efficacy was evaluated using the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Attention, Deportment, and Combined scores along with Permanent Product Measure of Performance (PERMP; Attempted and Correct) assessments. Onset and duration of drug action were also evaluated as key secondary endpoints. Safety assessments included adverse events (AEs), physical examinations, electrocardiograms (ECGs), and the Columbia Suicide Severity Rating Scale (C-SSRS). The average SKAMP-Combined score on the classroom study day was significantly better for the MPH XR-ODT group (n = 43) than for the placebo group (n = 39; p < 0.0001). The effect was evident at 1 hour and lasted through 12 hours postdose. The average SKAMP-Attention, SKAMP-Deportment, PERMP-A, and PERMP-C scores were indicative of significantly greater ADHD symptom control for the MPH XR-ODT group. The most common AEs reported were decreased appetite, upper abdominal pain, headache, insomnia, upper respiratory tract infection, affect lability, irritability, cough

  4. A Double-Blind, Placebo-Controlled, Phase II Study to Determine the Efficacy, Safety, Tolerability and Pharmacokinetics of a Controlled Release (CR) Formulation of Mazindol in Adults with DSM-5 Attention-Deficit/Hyperactivity Disorder (ADHD).

    PubMed

    Wigal, Tim L; Newcorn, Jeffrey H; Handal, Nelson; Wigal, Sharon B; Mulligan, Ioulietta; Schmith, Virginia; Konofal, Eric

    2018-03-01

    Mazindol is under investigation for the treatment of attention-deficit/hyperactivity disorder (ADHD) because of its alertness-enhancing properties. A novel controlled-release (CR) formulation of mazindol was developed to allow once-daily dosing. The aim of this study was to evaluate the efficacy of mazindol CR in adults with ADHD. We conducted a randomized, double-blind, placebo-controlled 6-week trial. Subjects diagnosed with ADHD using the Mini-International Neuropsychiatric Structured Interview (MINI) and with an ADHD Rating Scale, Diagnostic and Statistical Manual of Mental Disorders 5th Edition (ADHD-RS-DSM5) score ≥ 28 were randomized to receive placebo or 1-3 mg/day of mazindol for 6 weeks. The primary endpoint was the reduction from baseline in the ADHD-RS-DSM5 score on Day 42. Secondary endpoints were response rates defined by change in ADHD-RS-DSM5 (≥ 30 or ≥ 50% reduction) and dichotomized Clinical Global Impression-Improvement (CGI-I) score (1 or 2). An exploratory endpoint of functional impairment, as measured by the Target Impairment Scale, examined individualized deficits in specific settings. Safety, tolerability, and pharmacokinetics were assessed. Eighty-five participants were randomized (n = 43 active, 42 placebo); 75 completed. Weekly ADHD-RS-DSM5 measurements after mazindol differed from placebo beginning at Day 7, with a least squares mean difference (active-placebo) of - 13.2 at Day 42 and an effect size of 1.09. For the 30% or more reduction in ADHD-RS-DSM5 (minimal response), a significant difference (active-placebo) was seen starting at Day 7 and continuing to Day 42. For the CGI-I (1 or 2) and for the 50% or more reduction in ADHD-RS-DSM5 (measures of excellent response), the differences began at Day 14 and continued to Day 42. Functional impairment was significantly different in the proportion achieving at least a 50% reduction in target impairment score (42.9% mazindol vs 11.9% placebo) by Day 42. Dry mouth

  5. Safety and efficacy of sildenafil citrate in treating erectile dysfunction in patients with combat-related post-traumatic stress disorder: a double-blind, randomized and placebo-controlled study.

    PubMed

    Safarinejad, Mohammad Reza; Kolahi, Ali Asgar; Ghaedi, Gholamhossein

    2009-08-01

    To evaluate the safety and efficacy of sildenafil citrate for treating erectile dysfunction (ED) in patients with combat-related post-traumatic stress disorder (PTSD). In all, 266 combat-exposed war veterans with ED (aged 37-59 years) were recruited. They met the Diagnostic and Statistical Manual of Mental Disorders-IV criteria for PTSD according to the Structured Clinical Interview for Patients, Investigator Version. The patients were also evaluated with the Clinician-Administered PTSD Scale, both to establish the diagnosis of PTSD and to measure symptom severity. Only patients with psychogenic ED were included in the study. Patients with comorbid conditions (diabetes mellitus, hypercholesterolaemia, hypertension, Peyronie's disease) and smokers of more than five cigarettes daily were excluded. The patients were randomly divided into a group of 133 who received 100 mg of on-demand sildenafil 0.75-2 h before sexual stimulation, and 133 who received placebo. Patients were asked to use > or =16 doses or attempts at home. The efficacy of the treatments was assessed every four attempts during treatment, and at the end of the study, using responses to the 15-question International Index of Erectile Function (IIEF), Sexual Encounter Profile diary questions 2 and 3, Erectile Dysfunction Inventory of Treatment Satisfaction questionnaire, patients' event logs of sexual activity, and a Global Assessment Question about erections. Sildenafil did not produce significantly and substantially greater improvement than placebo in each of the primary and secondary outcome measures (P = 0.08). A normal EF domain score (> or =26) at endpoint was reported by 13 (9.8%), and 11 (8.3%) of patients on the sildenafil and placebo regimens, respectively (P = 0.09). Patients treated with sildenafil had no statistically significantly greater improvement in the five sexual function domains of the IIEF questionnaire than those treated with placebo (P = 0.08). The incidences of treatment

  6. Assessment of the efficacy and safety of eslicarbazepine acetate in acute mania and prevention of recurrence: experience from multicentre, double-blind, randomised phase II clinical studies in patients with bipolar disorder I.

    PubMed

    Grunze, Heinz; Kotlik, Eduardo; Costa, Raquel; Nunes, Teresa; Falcão, Amílcar; Almeida, Luis; Soares-da-Silva, Patrício

    2015-03-15

    Eslicarbazepine acetate (ESL) is an anticonvulsant approved as an adjunctive therapy in adults with partial-onset seizures. To evaluate the efficacy, safety and tolerability of ESL in the treatment of acute mania and prevention of recurrence in bipolar disorder I. Two 3-week multicentre, double-blind, randomised, placebo-controlled studies in acute mania (study BIA-2093-203: dose titrated by response, ESL 600-1800mg or 800-2400mg, once-daily; study BIA-2093-204: fixed doses of 600, 1200 and 1800mg, once-daily) were followed by a recurrence prevention study consisting of a 2-week open-label period (900mg, once-daily) continued by a double-blind, parallel-group, fixed dose (300, 900 and 1800mg, once-daily) period for a minimum of 6 months. The primary endpoint was changed from baseline until the end of the 3-week treatment period in Young Mania Rating Scale (YMRS) in studies BIA-2093-203 and BIA-2093-204, and the proportion of patients showing no worsening according to the Clinical Global Impressions - Bipolar Version (CGI-BP) over Part II in study BIA-2093-205. In study BIA-2093-203 (n=160, ITT), neither dose group was statistically different from placebo in the primary endpoint, though the ESL 800-2400mg showed a greater reduction in YMRS score (p=0.0523). CGI-BP score changes for mania and overall bipolar illness indicate a significant improvement in patient symptomatology for the ESL 800-2400mg group (from preceding and worst phase) and for ESL 600-1800mg group (from worst phase only) when compared to placebo. Study BIA-2093-204 (n=38) results were inconclusive due to premature termination caused by recruitment difficulties. In study BIA-2093-205 (n=85, ITT), at least 50% of patients showed no worsening in all treatment groups (p=0.250). ESL adverse events were mostly of mild and moderate intensities and consistent with previously reported observations for ESL. ESL treatment was not significantly different from placebo in manic patients in the primary outcome

  7. Efficacy and Safety of Immediate-Release Methylphenidate Treatment for Preschoolers with ADHD

    ERIC Educational Resources Information Center

    Greenhill, Laurence; Kollins, Scott; Abikoff, Howard; McCracken, James; Riddle, Mark; Swanson, James; McGough, James; Wigal, Sharon; Wigal, Tim; Vitiello, Benedetto; Skrobala, Anne; Posner, Kelly; Ghuman, Jaswinder; Cunningham, Charles; Davies, Mark; Chuang, Shirley; Cooper, Tom

    2006-01-01

    Objective: The Preschool ADHD Treatment Study (PATS) was a NIMH-funded, six-center, randomized, controlled trial to determine the efficacy and safety of immediate-release methylphenidate (MPH-IR), given t.i.d. to children ages 3 to 5.5 years with attention-deficit/hyperactivity disorder (ADHD). Method: The 8-phase, 70-week PATS protocol included…

  8. A translational approach to evaluate the efficacy and safety of the novel AMPA receptor positive allosteric modulator org 26576 in adult attention-deficit/hyperactivity disorder.

    PubMed

    Adler, Lenard A; Kroon, René A; Stein, Mark; Shahid, Mohammed; Tarazi, Frank I; Szegedi, Armin; Schipper, Jacques; Cazorla, Pilar

    2012-12-01

    It has been posited that glutamate dysregulation contributes to the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). Modulation of glutamate neurotransmission may provide alternative therapeutic options. The novel 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propanoic acid receptor positive allosteric modulator Org 26576 was investigated with a translational approach including preclinical and clinical testing. Neonatal rat 6-hydroxydopamine lesion-induced hyperactivity was used as preclinical model. Seventy-eight ADHD adults entered a multicenter, double-blind, placebo-controlled, two-period crossover trial. After 1 week placebo lead-in, 67 subjects were randomized into one of four treatment sequences: sequence A (n = 15) Org 26576 (100 mg b.i.d.) for 3 weeks, followed by a 2-week placebo crossover and 3 weeks placebo; sequence B (n = 16) 5 weeks placebo followed by 3 weeks Org 26576 (100 mg b.i.d.); sequence C (n = 18) Org 26576 flexible dose (100-300 mg b.i.d.) for 3 weeks, then 5 weeks placebo; sequence D (n = 18) 5 weeks placebo followed by 3 weeks Org 26576 (100-300 mg b.i.d.). The Adult ADHD Investigator Symptom Rating Scale was used to assess changes in ADHD symptomatology. Org 26576 (1, 3, 10 mg/kg intraperitoneal) produced dose-dependent inhibition of locomotor hyperactivity in 6-hydroxydopamine-lesioned rats. Org 26576 (100 mg b.i.d.) was superior to placebo in treating symptoms of adult ADHD subjects. The primary Adult ADHD Investigator Symptom Rating Scale results were supported by some secondary analyses. However, Org 26576 (100-300 mg b.i.d.) did not confirm these results. Most frequently reported adverse events were nausea, dizziness, and headache. These preclinical and clinical findings suggest that Org 25676 may have utility in the treatment of ADHD. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  9. Safety and Efficacy of Solitaire Stent Thrombectomy

    PubMed Central

    Campbell, Bruce C.V.; Hill, Michael D.; Rubiera, Marta; Menon, Bijoy K.; Demchuk, Andrew; Donnan, Geoffrey A.; Roy, Daniel; Thornton, John; Dorado, Laura; Bonafe, Alain; Levy, Elad I.; Diener, Hans-Christoph; Hernández-Pérez, María; Pereira, Vitor Mendes; Blasco, Jordi; Quesada, Helena; Rempel, Jeremy; Jahan, Reza; Davis, Stephen M.; Stouch, Bruce C.; Mitchell, Peter J.; Jovin, Tudor G.; Saver, Jeffrey L.

    2016-01-01

    Background and Purpose— Recent positive randomized trials of endovascular therapy for ischemic stroke used predominantly stent retrievers. We pooled data to investigate the efficacy and safety of stent thrombectomy using the Solitaire device in anterior circulation ischemic stroke. Methods— Patient-level data were pooled from trials in which the Solitaire was the only or the predominant device used in a prespecified meta-analysis (SEER Collaboration): Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment (SWIFT PRIME), Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE), Extending the Time for Thrombolysis in Emergency Neurological Deficits—Intra-Arterial (EXTEND-IA), and Randomized Trial of Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke Due to Anterior Circulation Large Vessel Occlusion Presenting Within Eight Hours of Symptom Onset (REVASCAT). The primary outcome was ordinal analysis of modified Rankin Score at 90 days. The primary analysis included all patients in the 4 trials with 2 sensitivity analyses: (1) excluding patients in whom Solitaire was not the first device used and (2) including the 3 Solitaire-only trials (excluding ESCAPE). Secondary outcomes included functional independence (modified Rankin Score 0–2), symptomatic intracerebral hemorrhage, and mortality. Results— The primary analysis included 787 patients: 401 randomized to endovascular thrombectomy and 386 to standard care, and 82.6% received intravenous thrombolysis. The common odds ratio for modified Rankin Score improvement was 2.7 (2.0–3.5) with no heterogeneity in effect by age, sex, baseline stroke severity, extent of computed tomography changes, site of occlusion, or pretreatment with alteplase. The number needed to treat to reduce disability was 2.5 and for an extra patient to achieve independent

  10. Effect of Bolus Viscosity on the Safety and Efficacy of Swallowing and the Kinematics of the Swallow Response in Patients with Oropharyngeal Dysphagia: White Paper by the European Society for Swallowing Disorders (ESSD).

    PubMed

    Newman, Roger; Vilardell, Natàlia; Clavé, Pere; Speyer, Renée

    2016-04-01

    Fluid thickening is a well-established management strategy for oropharyngeal dysphagia (OD). However, the effects of thickening agents on the physiology of impaired swallow responses are not fully understood, and there is no agreement on the degree of bolus thickening. To review the literature and to produce a white paper of the European Society for Swallowing Disorders (ESSD) describing the evidence in the literature on the effect that bolus modification has upon the physiology, efficacy and safety of swallowing in adults with OD. A systematic search was performed using the electronic Pubmed and Embase databases. Articles in English available up to July 2015 were considered. The inclusion criteria swallowing studies on adults over 18 years of age; healthy people or patients with oropharyngeal dysphagia; bolus modification; effects of bolus modification on swallow safety (penetration/aspiration) and efficacy; and/or physiology and original articles written in English. The exclusion criteria consisted of oesophageal dysphagia and conference abstracts or presentations. The quality of the selected papers and the level of research evidence were assessed by standard quality assessments. At the end of the selection process, 33 articles were considered. The quality of all included studies was assessed using systematic, reproducible, and quantitative tools (Kmet and NHMRC) concluding that all the selected articles reached a valid level of evidence. The literature search gathered data from various sources, ranging from double-blind randomised control trials to systematic reviews focused on changes occurring in swallowing physiology caused by thickened fluids. Main results suggest that increasing bolus viscosity (a) results in increased safety of swallowing, (b) also results in increased amounts of oral and/or pharyngeal residue which may result in post-swallow airway invasion, (c) impacts the physiology with increased lingual pressure patterns, no major changes in impaired

  11. Efficacy and safety of lubiprostone in patients with chronic constipation.

    PubMed

    Barish, Charles F; Drossman, Douglas; Johanson, John F; Ueno, Ryuji

    2010-04-01

    The aim of this study is to assess the efficacy and safety of lubiprostone in adults with chronic constipation. This multicenter, parallel-group trial enrolled 237 patients with chronic constipation and randomized them to 4 weeks of double-blind treatment with oral lubiprostone 24 mcg or placebo twice daily. The primary efficacy endpoint was the number of spontaneous bowel movements (SBMs) after 1 week of treatment. Secondary evaluations included SBMs at weeks 2, 3, and 4; percentage of patients with a SBM within 24 h of first study dose; stool consistency; degree of straining; constipation severity; abdominal bloating and discomfort; global treatment effectiveness; and safety assessments. Lubiprostone-treated patients experienced greater mean numbers of SBMs at week 1 compared with placebo (5.89 versus 3.99, P = 0.0001), with significantly greater percentages having SBMs within 24 h of the first dose (61.3% versus 31.4%, P < 0.0001). At each assessment, SBM frequency and percentages of full responders (> or =4 SBM per week) were significantly greater among lubiprostone-treated patients compared with placebo (P < or = 0.0171). Lubiprostone-treated patients reported significant improvements in stool consistency, straining, and constipation severity at all weeks, and in abdominal bloating at week 1. Patient assessments of treatment effectiveness were significantly greater with lubiprostone compared with placebo at all weeks (P < 0.0004). Gastrointestinal-related disorders were the most common adverse events in both treatment groups. In patients with chronic constipation, lubiprostone produced a bowel movement in the majority of individuals within 24 h of initial dosing, with sustained improvement in frequency as well as other constipation symptoms over 4 weeks of treatment.

  12. An 8-Week Randomized, Double-Blind Trial Comparing Efficacy, Safety, and Tolerability of 3 Vilazodone Dose-Initiation Strategies Following Switch From SSRIs and SNRIs in Major Depressive Disorder

    PubMed Central

    Rele, Shilpa; Millet, Robert; Kim, Sungman; Paik, Jong-Woo; Kim, Seonghwan; Masand, Prakash S.

    2015-01-01

    Introduction: Vilazodone, a selective and potent 5-HT1A partial agonist and 5-HT reuptake inhibitor, has been approved for treatment of major depressive disorder (MDD) in adults. The primary objective of the study was to compare the efficacy and tolerability of switching to 3 different doses of vilazodone from an equivalent dose range of generic selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) in adult subjects with MDD. Method: This was an 8-week, randomized, double-blind, parallel-group, 3-arm trial to compare vilazodone 10 mg/d, 20 mg/d, and 40 mg/d as starting doses. Data were collected from December 2012 to December 2013. There was no washout phase, prior medications were stopped at the baseline visit, and vilazodone was started the next day in adults with MDD (DSM-IV criteria). The 10-mg/d and 20-mg/d dose was increased to 40 mg/d by week 3 and week 1, respectively, and the 40-mg/d initiation dose continued unchanged. The primary efficacy measure was change in Montgomery-Asberg Depression Rating Scale (MADRS) score between the 3 dose groups. The secondary efficacy measures were changes in Clinical Global Impressions–Severity (CGI-S), CGI-Improvement (CGI-I), and Hamilton Anxiety Rating Scale (HARS) scores. Safety measures were obtained by spontaneously reported adverse events, vital signs recording, and laboratory tests. Multivariate tests were used for statistical analysis. Results: Seventy subjects were randomized, and 60 subjects completed the study (n = 20 in each group). Overall, there was a significant reduction in MADRS score from baseline (26.08 ± 1.1) to week 8 (9.86 ± 1.2) in the entire sample (P < .001). Similarly, there was a significant improvement in CGI-S (P < .001), CGI-I (P < .001) and HDRS (P < .001) scores from baseline to the end of the trial. There were no significant differences between the 3 vilazodone dose-initiation groups in changes in MADRS scores (P = .95) or changes in CGI

  13. Safety and efficacy of quetiapine in bipolar depression.

    PubMed

    Bogart, Gregory T; Chavez, Benjamin

    2009-11-01

    To review the clinical data investigating the efficacy and safety of quetiapine in bipolar depression. Searches of MEDLINE and PubMed (1977-July 2009) were conducted using the key words quetiapine and bipolar depression. The references of literature found were cross-referenced. The pharmaceutical company that produces quetiapine was contacted to obtain the posters for the EMBOLDEN I and EMBOLDEN II trials. Only double-blind, placebo-controlled trials were included for review, as well as any subanalyses of the literature that matched this criterion. There was a total of 5 double-blind, placebo-controlled trials and 5 subanalyses reviewed. The results of these data demonstrated quetiapine's efficacy in the treatment of depressive phases of bipolar disorder, including statistically significant improvement in the Montgomery-Asberg Depression Rating Scale (MADRS). In the trials reviewed in this article, the change in MADRS scores ranged from -15.4 to -16.94 within the quetiapine groups, and from -10.26 to -11.93 in the placebo groups. There were also statistically significant improvements in the Hamilton Anxiety Rating Scale, the Short Form of the Quality of Life Enjoyment and Satisfaction Questionnaire, the Pittsburgh Sleep Quality Index, and the Sheehan Disability Scale. All of these trials had a duration of 8 weeks and therefore cannot be applied to the long-term use of quetiapine in bipolar depression. The most common adverse events were sedation, somnolence, and dry mouth. The overall dropout rates for the trials reviewed ranged from 24% to 47%. Based on the literature reviewed here, quetiapine appears to be a safe and efficacious short-term treatment option for bipolar depression. Patients with bipolar type I showed greater improvement on the MADRS than those with bipolar type II. Patients with a rapid-cycling disease course showed an improvement in depressive symptoms, regardless of bipolar type.

  14. Real-Life Efficacy, Immunogenicity and Safety of Biosimilar Infliximab.

    PubMed

    Vegh, Zsuzsanna; Kurti, Zsuzsanna; Lakatos, Peter L

    2017-01-01

    Recently, the use of biosimilar infliximab (IFX) in the treatment of inflammatory bowel diseases has become widespread in some European and non-European countries. Data on the efficacy, safety and immunogenicity from real-life cohorts are accumulating. The first reports showed similar outcomes in the induction and maintenance of remission, mucosal healing, safety and immunogenicity profile to the originator IFX. In the present review, we aimed to summarize the existing knowledge on the efficacy, safety and immunogenicity profile of biosimilar IFX reported from real-life cohorts. © 2017 S. Karger AG, Basel.

  15. Efficacy and safety of methotrexate in alopecia areata*

    PubMed Central

    Hammerschmidt, Mariana; Mulinari Brenner, Fabiane

    2014-01-01

    BACKGROUND Alopecia areata is a chronic disorder of the hair follicles and nails, of unknown etiology, with clear autoimmune components and genetic factors. Several therapeutic options have been suggested; however, no treatment is able to modify the disease course. Methotrexate is an immunosuppressant used in various dermatoses and recently introduced as a therapeutic option for alopecia areata. OBJECTIVES To evaluate the efficacy and safety of methotrexate in alopecia areata. METHODS In a retrospective, non-controlled study, we evaluated 31 patients with alopecia areata in current or prior treatment with methotrexate to assess the therapeutic response according to sex, age, pattern of alopecia areata, disease duration, cumulative dose of methotrexate, use of systemic corticosteroids or other treatments, and drug safety. RESULTS Regrowth greater than 50% was observed in 67.7% of patients, with the best responses observed in those with <5 years of disease progression (79%), age over 40 years (73.3%), male patients (72.8%), cumulative dose of methotrexate 1000-1500 mg, and multifocal alopecia areata (93%). Among patients receiving systemic corticosteroids in combination with methotrexate, 77.3% had greater than 50% regrowth, compared with 44.4% in those who used methotrexate alone. The therapeutic dose ranged from 10-25 mg/week. No patient had serious adverse effects. Relapse was observed in 33.3% of patients with more than 50% regrowth. CONCLUSION Methotrexate appears to be a promising and safe medication for the treatment of severe alopecia areata when used alone or in combination with corticosteroids. PMID:25184911

  16. Biologics in pediatric psoriasis - efficacy and safety.

    PubMed

    Dogra, Sunil; Mahajan, Rahul

    2018-01-01

    Childhood psoriasis is a special situation that is a management challenge for the treating dermatologist. As is the situation with traditional systemic agents, which are commonly used in managing severe psoriasis in children, the biologics are being increasingly used in the recalcitrant disease despite limited data on long term safety. Areas covered: We performed an extensive literature search to collect evidence-based data on the use of biologics in pediatric psoriasis. The relevant literature published from 2000 to September 2017 was obtained from PubMed, using the MeSH words 'biologics', 'biologic response modifiers' and 'treatment of pediatric/childhood psoriasis'. All clinical trials, randomized double-blind or single-blind controlled trials, open-label studies, retrospective studies, reviews, case reports and letters concerning the use of biologics in pediatric psoriasis were screened. Articles covering the use of biologics in pediatric psoriasis were screened and reference lists in the selected articles were scrutinized to identify other relevant articles that had not been found in the initial search. Articles without relevant information about biologics in general (e.g. its mechanism of action, pharmacokinetics and adverse effects) and its use in psoriasis in particular were excluded. We screened 427 articles and finally selected 41 relevant articles. Expert opinion: The available literature on the use of biologics such as anti-tumor necrosis factor (TNF)-α agents, and anti-IL-12/23 agents like ustekinumab suggests that these are effective and safe in managing severe pediatric psoriasis although there is an urgent need to generate more safety data. Dermatologists must be careful about the potential adverse effects of the biologics before administering them to children with psoriasis. It is likely that with rapidly evolving scenario of biologics in psoriasis, these will prove to be very useful molecules particularly in managing severe and recalcitrant

  17. Safety and efficacy of shilajit (mumie, moomiyo).

    PubMed

    Stohs, Sidney J

    2014-04-01

    Shilajit (mumie; moomiyo, mummiyo) has been used for a wide variety of illnesses and conditions for many years. However, relatively few well-controlled human studies have been conducted on the effects of shiliajit, although a growing number of studies have been published in recent years involving animal and in vitro systems. The safety of shilajit is well documented based on animal and human studies. Various research studies indicate that shilajit exhibits antioxidant, anti-inflammatory, adaptogenic, immunomodulatory, and anti-dyslipidemic properties. Animal and human studies indicate that shilajit enhances spermatogenesis. Furthermore, animal and human data support its use as a 'revitalizer', enhancing physical performance and relieving fatigue with enhanced production of ATP. Key constituents in shilajit responsible for these effects appear to be dibenzo-α-pyrones and fulvic acid and their derivatives. Various mechanistic studies provide support for the above observed effects. Additional well-controlled human and animal studies involving the use of standardized products are needed. Copyright © 2013 John Wiley & Sons, Ltd.

  18. New treatment options for chronic constipation: Mechanisms, efficacy and safety

    PubMed Central

    Camilleri, Michael

    2011-01-01

    The present review has several objectives, the first of which is to review the pharmacology and selectivity of serotonergic agents to contrast the older serotonergic agents (which were withdrawn because of cardiac or vascular adverse effects) with the newer generation serotonin receptor subtype 4 agonists. Second, the chloride ion secretagogues that act through the guanylate cyclase C receptor are appraised and their pharmacology is compared with the approved medication, lubiprostone. Third, the efficacy and safety of the application of bile acid modulation to treat constipation are addressed. The long-term studies of surgically induced excess bile acid delivery to the colon are reviewed to ascertain the safety of this therapeutic approach. Finally, the new drugs for opiate-induced constipation are introduced. Assuming these drugs are approved, practitioners will have a choice; however, patient responsiveness will be based on trial and error. Nevertheless, the spectrum of mechanisms and demonstrated efficacy and safety augur well for satisfactory treatment outcomes. PMID:22114755

  19. Hospital disinfection: efficacy and safety issues.

    PubMed

    Dettenkofer, Markus; Block, Colin

    2005-08-01

    To review recent publications relevant to hospital disinfection (and cleaning) including the reprocessing of medical instruments. The key question as to whether the use of disinfectants on environmental surfaces rather than cleaning with detergents only reduces nosocomial infection rates still awaits conclusive studies. New disinfectants, mainly peroxygen compounds, show good sporicidal properties and will probably replace more problematical substances such as chlorine-releasing agents. The safe reprocessing of medical devices requires a well-coordinated approach, starting with proper cleaning. New methods and substances show promising activity for preventing the transmission of prions. Different aspects of virus inactivation have been studied, and the transmissibility, e.g. of norovirus, shows the need for sound data on how different disinfectant classes perform. Biofilms or other forms of surface-adherent organisms pose an extraordinary challenge to decontamination. Although resistance to biocides is generally not judged to be as critical as antibiotic resistance, scientific data support the need for proper use, i.e. the avoidance of widespread application, especially in low concentrations and in consumer products. Chemical disinfection of heat-sensitive instruments and targeted disinfection of environmental surfaces are established components of hospital infection control. To avoid danger to staff, patients and the environment, prudent use as well as established safety precautions are required. New technologies and products should be evaluated with sound methods. As emerging resistant pathogens will challenge healthcare facilities in the future even more than at present, there is a need for well-designed studies addressing the role of disinfection in hospital infection control.

  20. Efficacy of Cognitive-Behavioral Therapy for Comorbid Panic Disorder with Agoraphobia and Generalized Anxiety Disorder

    ERIC Educational Resources Information Center

    Labrecque, Joane; Marchand, Andre; Dugas, Michel J.; Letarte, Andree

    2007-01-01

    The goal of this study was to evaluate the efficacy of cognitive-behavioral therapy for comorbid panic disorder with agoraphobia (PDA) and generalized anxiety disorder (GAD) by combining treatment strategies for both disorders. A single-case, multiple-baseline design across participants was used. Three participants with primary PDA and secondary…

  1. Efficacy and safety of novel antipsychotics: a critical review.

    PubMed

    Balestrieri, Matteo; Vampini, Claudio; Bellantuono, Cesario

    2000-10-01

    Efficacy and safety of novel antipsychotic (AP) drugs (amisulpride, olanzapine, quetiapine, ziprasidone and zotepine) have been reviewed. Data on their antipsychotic efficacy and side effects profile have been evaluated only on the basis of controlled trials so far published. Overall, all these drugs have shown an antipsychotic efficacy on positive symptoms of schizophrenia similar to that of the conventional AP drugs. On negative symptoms, all novel AP drugs, except quetiapine and ziprasidone, demonstrated a better efficacy than haloperidol. Long-term efficacy of these AP drugs in the maintenance treatment of schizophrenia needs to be explored by further, better-designed, epidemiological studies. The safety profile shows that the novel AP drugs are generally well-tolerated and induce significantly less acute extrapyramidal side effects in comparison with haloperidol. Some methodological flaws in the experimental design of the clinical trials analysed are discussed. Although these novel AP drugs have potential clinical advantages, a number of relevant questions still remain to be addressed, in order to establish the impact of these drugs in the overall treatment of schizophrenia. Copyright 2000 John Wiley & Sons, Ltd.

  2. Efficacy and safety of garenoxacin tablets on bacterial pneumonia: postmarketing surveillance in Japan.

    PubMed

    Izumikawa, Koichi; Watanabe, Akira; Miyashita, Naoyuki; Ishida, Tadashi; Hosono, Hiroaki; Kushimoto, Satoru; Kohno, Shigeru

    2014-09-01

    We performed a postmarketing surveillance study to determine the efficacy and safety of the oral quinolone antibacterial agent, garenoxacin (Geninax(®) Tablets 200 mg), against bacterial pneumonia. Between October 2009 and March 2011, patients with community-acquired pneumonia visited 174 facilities in Japan; we collected survey forms from 739 patients of these patients who were suspected with bacterial pneumonia on the basis of factors, e.g., the presence of purulent sputum or suspected presence of bacterial pathogens in clinical specimens. We examined the safety in 730 patients and the efficacy in 535 patients. The efficacy rate of garenoxacin for bacterial pneumonia was 92.8% (479/516 patients). The eradication rates for Streptococcus pneumoniae and Haemophilus influenzae, the major pathogens of bacterial pneumonia, were 98.5% (65/66 strains) and 100% (65/65 strains), respectively. The incidence of adverse drug reactions (including abnormal laboratory tests) was 7.9% (58/730 patients). Among the main adverse drug reactions, abnormal laboratory tests were observed in 2.1% patients (15/730), hepatobiliary disorders were observed in 1.8% patients (13/730), and skin and subcutaneous tissue disorders were observed in 1.6% patients (12/730). In conclusion, garenoxacin showed an efficacy rate of greater than 90% for bacterial pneumonia and is considered to be useful in daily practice. Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  3. Determining animal drug combinations based on efficacy and safety.

    PubMed

    Kratzer, D D; Geng, S

    1986-08-01

    A procedure for deriving drug combinations for animal health is used to derive an optimal combination of 200 mg of novobiocin and 650,000 IU of penicillin for nonlactating cow mastitis treatment. The procedure starts with an estimated second order polynomial response surface equation. That surface is translated into a probability surface with contours called isoprobs. The isoprobs show drug amounts that have equal probability to produce maximal efficacy. Safety factors are incorporated into the probability surface via a noncentrality parameter that causes the isoprobs to expand as safety decreases, resulting in lower amounts of drug being used.

  4. Efficacy for Psychopathology and Body Weight and Safety of Topiramate-Antipsychotic Cotreatment in Patients With Schizophrenia Spectrum Disorders: Results From a Meta-Analysis of Randomized Controlled Trials.

    PubMed

    Correll, Christoph U; Maayan, Lawrence; Kane, John; Hert, Marc De; Cohen, Dan

    2016-06-01

    To meta-analyze the efficacy and tolerability of topiramate-antipsychotic cotreatment in schizophrenia. PubMed/MEDLINE database were searched until September 5, 2015, using the keywords topiramate AND antipsych* OR neurolept* OR specific antipsychotic names. Randomized controlled trials (RCTs) of topiramate-antipsychotic cotreatment versus placebo and ongoing antipsychotic treatment in patients with schizophrenia spectrum disorders were included. Two evaluators extracted data. Standardized mean difference (SMD), weighted mean difference (WMD), and risk ratio (RR) ± 95% CIs were calculated. In 8 RCTs, lasting a mean ± SD of 13.6 ± 4.9 weeks, 439 patients were randomized to topiramate (100-400 mg/d) versus placebo (trials = 7) or ongoing antipsychotic treatment (trial = 1). Topiramate outperformed the comparator regarding total psychopathology (trials = 6, n = 269, SMD = -0.57 [95% CI, -1.01 to -0.14], P = .01), positive symptoms (trials = 4, n = 190, SMD = -0.56 [95% CI, -1.0 to -0.11], P = .01), negative symptoms (trials = 4, n = 190, SMD = -0.62 [95% CI, -1.13 to -0.10], P = .02) general psychopathology (trials = 3, n = 179, SMD = -0.69 [95% CI, -1.27 to -0.11], P = .02), body weight (trials = 7, n = 327, WMD = -3.14 kg [95% CI, -5.55 to -0.73], P = .01), and body mass index (BMI) (trials = 4, n = 198, WMD = -1.80 [95% CI, -2.77 to -0.84], P = .0003). Topiramate's efficacy for total psychopathology and weight reduction effects were not mediated/moderated by trial duration, topiramate dose, sex, age, inpatient status, baseline Positive and Negative Syndrome Scale, or baseline BMI. Conversely, clozapine-topiramate cotreatment moderated greater efficacy, but less weight loss, compared to topiramate-nonclozapine antipsychotic combinations. All-cause discontinuation was similar between topiramate and control groups (trials = 7, RR = 1.24 [95% CI, 0.76 to 2.02], P = .39). Topiramate trended only toward more paresthesia than placebo (trials = 4, RR = 2.03 [95 % CI, 0

  5. Safety of pharmacotherapy options for bulimia nervosa and binge eating disorder.

    PubMed

    Bello, Nicholas T; Yeomans, Bryn L

    2018-01-01

    Eating disorders represent a set of psychiatric illnesses with lifelong complications and high relapse rates. Individuals with eating disorders are often stigmatized and clinicians have a limited set of treatments options. Pharmacotherapy has the potential to improve long term compliance and patient commitment to treatment for eating disorders. Areas covered: This review will examine the efficacy and safety profile of the FDA-approved medications for the treatment of bulimia nervosa (BN) and binge eating disorder (BED). This will include the evaluation of fluoxetine for BN, and lisdexamfetamine for BED. Safety information will be review from randomized control trials (RCT), open label trials, and case reports. Expert opinion: Fluoxetine for BN and lisdexamfetamine for BED are relatively safe and well-tolerated. Despite these properties, these two medications represent a limited arsenal for the pharmacological treatment of eating disorders. Thus, more research-based strategies are needed to develop safe, effective, and more targeted therapies for eating disorders.

  6. EFFICACY OF PROPRANOLOL ON SCHIZOPHRENIC THOUGHT DISORDER

    PubMed Central

    Sethi, B. B.; Dube, Sanjay

    1981-01-01

    SUMMARY 15 schizophrenic patients were treated with dl-propranolol in a 4 week open study. Dosage was gradually increased over a period of 17 days to 1920 mg/day. Improvements were rated on Thought Disorder Scores (A & B) of the MBPRS and GPRS subscale for schizophrenia. Majority of the patients showed a 50% improvement in terms of their residual scores by the 4th week of treatment and the side effects experienced were minimal. PMID:22064778

  7. Efficacy and Safety of Roflumilast in Korean Patients with COPD

    PubMed Central

    Lee, Jae Seung; Hong, Yoon Ki; Park, Tae Sun; Lee, Sei Won; Oh, Yeon-Mok

    2016-01-01

    Purpose Roflumilast is the only oral phosphodiesterase 4 inhibitor approved to treat chronic obstructive pulmonary disease (COPD) patients [post-bronchodilator forced expiratory volume in 1 second (FEV1) <50% predicted] with chronic bronchitis and a history of frequent exacerbations. This study evaluated the efficacy and safety of roflumilast in Korean patients with COPD and compared the efficacy based on the severity of airflow limitation. Materials and Methods A post-hoc subgroup analysis was performed in Korean COPD patients participating in JADE, a 12-week, double-blinded, placebo-controlled, parallel-group, phase III trial in Asia. The primary efficacy endpoint was the mean [least-squares mean adjusted for covariates (LSMean)] change in post-bronchodilator FEV1 from baseline to each post-randomization visit. Safety endpoints included adverse events (AEs) and changes in laboratory values, vital signs, and electrocardiograms. Results A total of 260 Korean COPD patients were recruited, of which 207 were randomized to roflumilast (n=102) or placebo (n=105) treatment. After 12 weeks, LSMean post-bronchodilator FEV1 increased by 43 mL for patients receiving roflumilast and decreased by 60 mL for those taking placebo. Adverse events were more common in the roflumilast group than in the placebo group; however, the types and frequency of AEs were comparable to those reported in previous studies. Conclusion Roflumilast significantly improved lung function with a tolerable safety profile in Korean COPD patients irrespective of the severity of airflow limitation. PMID:27189287

  8. Testosterone Replacement Therapy: Long-Term Safety and Efficacy

    PubMed Central

    Corona, Giovanni; Sforza, Alessandra

    2017-01-01

    Recent position statements and guidelines have raised the distinction between a true and false, age-related hypogonadism (HG) or late-onset hypogonadism (LOH). The former is the consequence of congenital or acquired “organic” damage of the brain centers or of the testis. The latter is mainly secondary to age-related comorbidities and does not require testosterone (T) therapy (TTh). In addition, concerns related to cardiovascular (CV) safety have further increased the scepticism related to TTh. In this paper, we reviewed the available evidence supporting the efficacy of TTh in non-organic HG and its long term safety. A large amount of evidence has documented that sexual symptoms are the most specific correlates of T deficiency. TTh is able to improve all aspects of sexual function independent of the pathogenetic origin of the disease supporting the scientific demonstration that LOH does exist according to an “ex-juvantibus” criterion. Although the presence of metabolic derangements could mitigate the efficacy of TTh on erectile dysfunction, the positive effect of TTh on body composition and insulin sensitivity might counterbalance the lower efficacy. CV safety concerns related to TTh are essentially based on a limited number of observational and randomized controlled trials which present important methodological flaws. When HG is properly diagnosed and TTh correctly performed no CV and prostate risk have been documented. PMID:28497912

  9. Testosterone Replacement Therapy: Long-Term Safety and Efficacy.

    PubMed

    Corona, Giovanni; Sforza, Alessandra; Maggi, Mario

    2017-08-01

    Recent position statements and guidelines have raised the distinction between a true and false, age-related hypogonadism (HG) or late-onset hypogonadism (LOH). The former is the consequence of congenital or acquired "organic" damage of the brain centers or of the testis. The latter is mainly secondary to age-related comorbidities and does not require testosterone (T) therapy (TTh). In addition, concerns related to cardiovascular (CV) safety have further increased the scepticism related to TTh. In this paper, we reviewed the available evidence supporting the efficacy of TTh in non-organic HG and its long term safety. A large amount of evidence has documented that sexual symptoms are the most specific correlates of T deficiency. TTh is able to improve all aspects of sexual function independent of the pathogenetic origin of the disease supporting the scientific demonstration that LOH does exist according to an "ex-juvantibus" criterion. Although the presence of metabolic derangements could mitigate the efficacy of TTh on erectile dysfunction, the positive effect of TTh on body composition and insulin sensitivity might counterbalance the lower efficacy. CV safety concerns related to TTh are essentially based on a limited number of observational and randomized controlled trials which present important methodological flaws. When HG is properly diagnosed and TTh correctly performed no CV and prostate risk have been documented. Copyright © 2017 Korean Society for Sexual Medicine and Andrology.

  10. Intervention Efficacy and Intensity for Children with Speech Sound Disorder

    ERIC Educational Resources Information Center

    Allen, Melissa M.

    2013-01-01

    Purpose: Clinicians do not have an evidence base they can use to recommend optimum intervention intensity for preschool children who present with speech sound disorder (SSD). This study examined the effect of dose frequency on phonological performance and the efficacy of the multiple oppositions approach. Method: Fifty-four preschool children with…

  11. Efficacy and safety of febuxostat in elderly female patients.

    PubMed

    Mizuno, Tomohiro; Hayashi, Takahiro; Hikosaka, Sayo; Shimabukuro, Yuka; Murase, Maho; Takahashi, Kazuo; Hayashi, Hiroki; Yuzawa, Yukio; Nagamatsu, Tadashi; Yamada, Shigeki

    2014-01-01

    Maintenance of low serum urate levels is important for the management of gout. Achieving the recommended serum urate levels of less than 6.0 mg/dL is difficult in elderly (65 years of age or older) patients with renal impairment. Xanthine oxidase inhibitors allopurinol and febuxostat are used for this purpose. Although febuxostat had been shown to be efficacious in elderly patients, its safety and efficacy in elderly female patients with hyperuricemia remain unclear. The aim of this study was to assess the efficacy and safety of febuxostat in elderly female patients. We studied a retrospective cohort study. The study included elderly Japanese patients (65 years of age or older) who were treated with febuxostat at Fujita Health University Hospital from January 2012 to December 2013. The treatment goal was defined as achievement of serum urate levels of 6.0 mg/dL or lower within 16 weeks; this was the primary endpoint in the present study. Adverse events of febuxostat were defined as more than twofold increases in Common Terminology Criteria for adverse events scores from baseline. We evaluated 82 patients treated with febuxostat during the observation period and classified them into male (n=53) and female (n=29) groups. The mean time to achievement of the treatment goal was significantly shorter in the female group (53 days) than in the male group (71 days). There were no significant differences in adverse events between the 2 groups. Our findings suggest that the efficacy of febuxostat in elderly female patients is superior to that in elderly male patients and that the safety is equivalent.

  12. Efficacy and safety of febuxostat in elderly female patients

    PubMed Central

    Mizuno, Tomohiro; Hayashi, Takahiro; Hikosaka, Sayo; Shimabukuro, Yuka; Murase, Maho; Takahashi, Kazuo; Hayashi, Hiroki; Yuzawa, Yukio; Nagamatsu, Tadashi; Yamada, Shigeki

    2014-01-01

    Background Maintenance of low serum urate levels is important for the management of gout. Achieving the recommended serum urate levels of less than 6.0 mg/dL is difficult in elderly (65 years of age or older) patients with renal impairment. Xanthine oxidase inhibitors allopurinol and febuxostat are used for this purpose. Although febuxostat had been shown to be efficacious in elderly patients, its safety and efficacy in elderly female patients with hyperuricemia remain unclear. Objective The aim of this study was to assess the efficacy and safety of febuxostat in elderly female patients. Methods We studied a retrospective cohort study. The study included elderly Japanese patients (65 years of age or older) who were treated with febuxostat at Fujita Health University Hospital from January 2012 to December 2013. The treatment goal was defined as achievement of serum urate levels of 6.0 mg/dL or lower within 16 weeks; this was the primary endpoint in the present study. Adverse events of febuxostat were defined as more than twofold increases in Common Terminology Criteria for adverse events scores from baseline. Results We evaluated 82 patients treated with febuxostat during the observation period and classified them into male (n=53) and female (n=29) groups. The mean time to achievement of the treatment goal was significantly shorter in the female group (53 days) than in the male group (71 days). There were no significant differences in adverse events between the 2 groups. Conclusion Our findings suggest that the efficacy of febuxostat in elderly female patients is superior to that in elderly male patients and that the safety is equivalent. PMID:25214776

  13. Analgesic Efficacy and Safety of Hydromorphone in Chinchillas (Chinchilla lanigera).

    PubMed

    Evenson, Emily A; Mans, Christoph

    2018-05-01

    Limited information is available regarding the efficacy of opioid analgesics in chinchillas. Here we sought to evaluate the analgesic efficacy and safety of hydromorphone in chinchillas. In a randomized, controlled, blind, complete crossover design, hydromorphone was administered at 0.5, 1, and 2 mg/kg SC to 16 chinchillas. Analgesic efficacy was determined by measuring hindlimb withdrawal latencies after a thermal noxious stimulus (Hargreaves method) at 0, 1, 2, 4, and 8 h after drug administration. Changes in daily food intake and fecal output after hydromorphone administration were recorded. At 2 mg/kg SC, but not at lower dosages, hydromorphone increased withdrawal latencies for less than 4 h. Food intake was reduced after all 3 dosages, and fecal output decreased in the 1- and 2-mg/kg groups. The decreases in these parameters were dose-dependent, with the greatest reduction measured over the first 24 h. Our current results indicate that hydromorphone at 2 mg/kg SC is an effective, short-acting analgesic drug in chinchillas that transiently reduces food intake and fecal output. Further studies are needed to evaluate the safety of hydromorphone in animals undergoing surgical procedures and general anesthesia and to determine whether lower doses provide analgesia in different nociceptive models.

  14. Efficacy and Safety of Lacosamide in Painful Diabetic Neuropathy

    PubMed Central

    Ziegler, Dan; Hidvégi, Tibor; Gurieva, Irina; Bongardt, Sabine; Freynhagen, Rainer; Sen, David; Sommerville, Kenneth

    2010-01-01

    OBJECTIVE To evaluate efficacy and safety of lacosamide compared with placebo in painful diabetic polyneuropathy. RESEARCH DESIGN AND METHODS Diabetic patients with at least moderate neuropathic pain were randomized to placebo or lacosamide 400 (in a slow or standard titration) or 600 mg/day over 6-week titration and 12-week maintenance periods. Primary efficacy criterion was intra-individual change in average daily Numeric Pain Rating Scale score from baseline to the last 4 weeks. RESULTS For the primary end point, pain reduction was numerically but not statistically greater with lacosamide compared with placebo (400 mg/day, P = 0.12; 600 mg/day, P = 0.18). Both doses were significantly more effective compared with placebo over the titration (P = 0.03, P = 0.006), maintenance (P = 0.01, P = 0.005), and entire treatment periods (P = 0.03, P = 0.02). Safety profiles between titration schemes were similar. CONCLUSIONS Lacosamide reduced neuropathic pain and was well tolerated in diabetic patients, but the primary efficacy criterion was not met, possibly due to an increased placebo response over the last 4 weeks. PMID:20067958

  15. Efficacy and Safety of Antiintegrin Antibody for Inflammatory Bowel Disease

    PubMed Central

    Lin, Lianjie; Liu, Xiang; Wang, Dongxu; Zheng, Changqing

    2015-01-01

    Abstract We sought to evaluate the safety and efficacy of available biologics that inhibit T-cell migration by blocking α4β7 integrins in inflammatory bowel diseases. The aim of this study is to evaluate whether Crohn disease (CD) patients receiving either vedolizumab or natalizumab have any different effect in CD Activity Index (CDAI). Using Medline, Excerpta Medica dataBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar until October 31, 2013, we identified 10 studies examining the safety and efficacy of specific integrin inhibitors—vedolizumab, which targets an epitope comprising the α4β7 heterodimer; natalizumab, which recognizes the α4 integrin subunit; etrolizumab, which is specific for the β7 subunit—in the treatment of CD and ulcerative colitis (UC). CD patients receiving either vedolizumab or natalizumab demonstrated a modest increase in remission rate, when compared with that of the placebo group. Further, although both treatments reduced the CDAI slightly, the observed clinical response was less robust than that of the remission rate. UC patients treated with vedolizumab and natalizumab were found to show more prominent increases in both remission and clinical response, compared with placebo, than patients with CD. Etrolizumab, however, was not found to significantly affect either response or remission rates in UC patients. Biologics targeting integrins show promise as therapeutics in the treatment of inflammatory bowel disease in patients who are either nonresponsive or intolerant to traditional approaches, though further research is necessary to optimize treatment efficacies. PMID:25761174

  16. Methylphenidate dose optimization for ADHD treatment: review of safety, efficacy, and clinical necessity

    PubMed Central

    Huss, Michael; Duhan, Praveen; Gandhi, Preetam; Chen, Chien-Wei; Spannhuth, Carsten; Kumar, Vinod

    2017-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is a chronic psychiatric disorder characterized by hyperactivity and/or inattention and is often associated with a substantial impact on psychosocial functioning. Methylphenidate (MPH), a central nervous system stimulant, is commonly used for pharmacological treatment of adults and children with ADHD. Current practice guidelines recommend optimizing MPH dosage to individual patient needs; however, the clinical benefits of individual dose optimization compared with fixed-dose regimens remain unclear. Here we review the available literature on MPH dose optimization from clinical trials and real-world experience on ADHD management. In addition, we report safety and efficacy data from the largest MPH modified-release long-acting Phase III clinical trial conducted to examine benefits of dose optimization in adults with ADHD. Overall, MPH is an effective ADHD treatment with a good safety profile; data suggest that dose optimization may enhance the safety and efficacy of treatment. Further research is required to establish the extent to which short-term clinical benefits of MPH dose optimization translate into improved long-term outcomes for patients with ADHD. PMID:28740389

  17. Methylphenidate dose optimization for ADHD treatment: review of safety, efficacy, and clinical necessity.

    PubMed

    Huss, Michael; Duhan, Praveen; Gandhi, Preetam; Chen, Chien-Wei; Spannhuth, Carsten; Kumar, Vinod

    2017-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is a chronic psychiatric disorder characterized by hyperactivity and/or inattention and is often associated with a substantial impact on psychosocial functioning. Methylphenidate (MPH), a central nervous system stimulant, is commonly used for pharmacological treatment of adults and children with ADHD. Current practice guidelines recommend optimizing MPH dosage to individual patient needs; however, the clinical benefits of individual dose optimization compared with fixed-dose regimens remain unclear. Here we review the available literature on MPH dose optimization from clinical trials and real-world experience on ADHD management. In addition, we report safety and efficacy data from the largest MPH modified-release long-acting Phase III clinical trial conducted to examine benefits of dose optimization in adults with ADHD. Overall, MPH is an effective ADHD treatment with a good safety profile; data suggest that dose optimization may enhance the safety and efficacy of treatment. Further research is required to establish the extent to which short-term clinical benefits of MPH dose optimization translate into improved long-term outcomes for patients with ADHD.

  18. Efficacy of radiation safety glasses in interventional radiology.

    PubMed

    van Rooijen, Bart D; de Haan, Michiel W; Das, Marco; Arnoldussen, Carsten W K P; de Graaf, R; van Zwam, Wim H; Backes, Walter H; Jeukens, Cécile R L P N

    2014-10-01

    This study was designed to evaluate the reduction of the eye lens dose when wearing protective eyewear in interventional radiology and to identify conditions that optimize the efficacy of radiation safety glasses. The dose reduction provided by different models of radiation safety glasses was measured on an anthropomorphic phantom head. The influence of the orientation of the phantom head on the dose reduction was studied in detail. The dose reduction in interventional radiological practice was assessed by dose measurements on radiologists wearing either leaded or no glasses or using a ceiling suspended screen. The different models of radiation safety glasses provided a dose reduction in the range of a factor of 7.9-10.0 for frontal exposure of the phantom. The dose reduction was strongly reduced when the head is turned to the side relative to the irradiated volume. The eye closest to the tube was better protected due to side shielding and eyewear curvature. In clinical practice, the mean dose reduction was a factor of 2.1. Using a ceiling suspended lead glass shield resulted in a mean dose reduction of a factor of 5.7. The efficacy of radiation protection glasses depends on the orientation of the operator's head relative to the irradiated volume. Glasses can offer good protection to the eye under clinically relevant conditions. However, the performance in clinical practice in our study was lower than expected. This is likely related to nonoptimized room geometry and training of the staff as well as measurement methodology.

  19. Efficacy and safety of remifentanil for analgesia in cesarean delivery

    PubMed Central

    Zhou, Xuan; Jin, Lian-jin; Hu, Chun-yang; Chen, Meng; Li, Ying; Zhang, Yue-shun

    2017-01-01

    Abstract Background: This study aimed to assess the efficacy and safety of remifentanil as a general anesthetic during cesarean delivery. Material and Methods: Fifty women with singleton pregnancies undergoing cesarean delivery were randomly divided into intervention and control groups, each group containing 25 subjects. Participants in the intervention group received remifentanil (infused at 2 μg/kg/h), whereas subjects in the control group were given dexmedetomidine (infused at 0.4 μg/kg/h). Outcome measurements included mean arterial blood pressure (MAP), heart rate (HR), bispectral index (BIS), Apgar scores at 1 and 5 minutes, and the pH, PCO2, PO2, and base excess (BE) of umbilical venous and arterial blood. Results: Forty-four participants completed the study. Patients in the intervention group did not experience greater effect and safety than those in the control group (P > .05), although MAP and BIS values decreased significantly immediately before laryngoscopy (P < .05). In addition, BIS values were reduced significantly at the time of skin incision, at uterine incision, and immediately after fetal delivery when compared with baseline values in both groups (P < .01). Conclusion: This study concluded that remifentanil and dexmedetomidine exhibited similar efficacy and safety during general anesthesia for cesarean delivery. PMID:29310326

  20. Immunogenicity of therapeutics: a matter of efficacy and safety.

    PubMed

    Nechansky, Andreas; Kircheis, Ralf

    2010-11-01

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

  1. Preschool ADHD: exploring uncertainties in diagnostic validity and utility, and treatment efficacy and safety.

    PubMed

    Sonuga-Barke, Edmund J S; Daley, David; Thompson, Margaret; Swanson, Jim

    2003-07-01

    The current scientific and clinical status of preschool attention deficit hyperactivity disorder and its management is reviewed. Recent clinical and neuropsychological research supporting the utility of the construct will be presented along with a critical analysis of diagnostic issues. The published literature on treatment efficacy (both pharmacological and nonpharmacological) will be reviewed with a special focus on the issue of the safety and side effects of psycho-stimulants. The need for early identification and preventative intervention is indicated but caution should be employed in the use of psychostimulants with this age group.

  2. EX-PRESS Glaucoma Filtration Device: efficacy, safety, and predictability

    PubMed Central

    Chan, Jessica E; Netland, Peter A

    2015-01-01

    Trabeculectomy has been the traditional primary surgical therapy for open-angle glaucoma. While trabeculectomy is effective in lowering intraocular pressure, complications associated with the procedure have motivated the development of alternative techniques and devices, including the EX-PRESS Glaucoma Filtration Device. This review describes the efficacy, safety, complication rates, and potential advantages and disadvantages of the EX-PRESS Glaucoma Filtration Device. EX-PRESS implantation is technically simpler compared with that of trabeculectomy, with fewer surgical steps. Vision recovery has been more rapid after EX-PRESS implantation compared with trabeculectomy. Intraocular pressure variation is lower during the early postoperative period, indicating a more predictable procedure. While efficacy of the EX-PRESS implant has been comparable to trabeculectomy, postoperative complications appear less common after EX-PRESS implantation compared with trabeculectomy. The EX-PRESS Glaucoma Filtration Device appears to be safe and effective in the surgical management of open-angle glaucoma. PMID:26366105

  3. Safety and efficacy of venom immunotherapy: a real life study

    PubMed Central

    Kołaczek, Agnieszka; Skorupa, Dawid; Antczak-Marczak, Monika; Kuna, Piotr

    2017-01-01

    Introduction Venom immunotherapy (VIT) is recommended as the first-line treatment for patients allergic to Hymenoptera venom. Aim To analyze the safety and efficacy of VIT in a real life setting. Material and methods One hundred and eighty patients undergoing VIT were studied to evaluate the safety, efficacy, incidence and nature of symptoms after field stings and adverse reactions to VIT. Results Significantly more patients were allergic to wasp than bee venom (146 vs. 34, p < 0.0001). Early and late side effects were more common during the maintenance (48 patients, 26.7%) than during the induction of VIT (32 patients, 17.8%), were more frequent in patients allergic to bees, and were not associated with angiotensin convertase inhibitors (ACEi) or β-adrenergic antagonists use. Systemic reactions were observed in 4 individuals on wasp VIT (2.7%) and in 6 patients allergic to bees (17.65%). The VIT was efficacious as most patients reported no reactions (50%) or reported only mild local reactions (43.75%) to field stings. The decrease in sIgE at completion of VIT correlated with the dose of vaccine received (r = 0.53, p = 0.004). Beekeeping (RR = 29.54, p < 0.0001) and female sex (RR = 1.27, p = 0.033) were associated with a higher risk of venom allergy. Conclusions Venom immunotherapy is highly efficacious and safe as most of the adverse events during the induction and maintenance phase are mild and local. Side effects of VIT are more common in subjects on bee VIT. Beekeeping and female sex are associated with a higher risk of allergy to Hymenoptera venom. PMID:28507496

  4. Safety and efficacy of venom immunotherapy: a real life study.

    PubMed

    Kołaczek, Agnieszka; Skorupa, Dawid; Antczak-Marczak, Monika; Kuna, Piotr; Kupczyk, Maciej

    2017-04-01

    Venom immunotherapy (VIT) is recommended as the first-line treatment for patients allergic to Hymenoptera venom. To analyze the safety and efficacy of VIT in a real life setting. One hundred and eighty patients undergoing VIT were studied to evaluate the safety, efficacy, incidence and nature of symptoms after field stings and adverse reactions to VIT. Significantly more patients were allergic to wasp than bee venom (146 vs. 34, p < 0.0001). Early and late side effects were more common during the maintenance (48 patients, 26.7%) than during the induction of VIT (32 patients, 17.8%), were more frequent in patients allergic to bees, and were not associated with angiotensin convertase inhibitors (ACEi) or β-adrenergic antagonists use. Systemic reactions were observed in 4 individuals on wasp VIT (2.7%) and in 6 patients allergic to bees (17.65%). The VIT was efficacious as most patients reported no reactions (50%) or reported only mild local reactions (43.75%) to field stings. The decrease in sIgE at completion of VIT correlated with the dose of vaccine received ( r = 0.53, p = 0.004). Beekeeping (RR = 29.54, p < 0.0001) and female sex (RR = 1.27, p = 0.033) were associated with a higher risk of venom allergy. Venom immunotherapy is highly efficacious and safe as most of the adverse events during the induction and maintenance phase are mild and local. Side effects of VIT are more common in subjects on bee VIT. Beekeeping and female sex are associated with a higher risk of allergy to Hymenoptera venom.

  5. Safety and efficacy of epicutaneous immunotherapy for food allergy.

    PubMed

    Wang, Julie; Sampson, Hugh A

    2018-06-01

    Food allergy is increasingly common in children, affecting about 4%-8%. The mainstays of management remain allergen avoidance and emergency preparedness to treat allergic reactions with emergency medications. Unfortunately, these approaches are unsatisfactory for many patients and their families as the restrictions, constant vigilance, and unpredictable severity of allergic reactions negatively impact quality of life. In recent decades, there has been significant interest in developing treatments for food allergy that lead to desensitization to increase thresholds for triggering allergic reactions and decrease the risk of reacting to allergen-contaminated food products. Epicutaneous immunotherapy (EPIT) is a novel therapy that is currently under investigation, delivering allergen via repeated applications to the skin and targeting antigen-presenting cells in the superficial skin layers. Murine models have demonstrated that allergen uptake is an active process by skin dendritic cells with subsequent migration to draining lymph nodes. Allergen exposure to the non-vascularized epidermis limits systemic absorption, contributing to the high-safety profile. Results from murine experiments showed that EPIT has comparable efficacy as subcutaneous immunotherapy in terms of challenge outcomes, airway hyper-responsiveness, and immunologic parameters. Several clinical trials of EPIT have recently been completed or are ongoing. Results support the high safety and tolerability of this approach. Efficacy data suggest that the change in threshold eliciting dose following 1 year of therapy is less than that seen compared to high-dose (2-4 g peanut protein) oral immunotherapy, but more prolonged treatment with EPIT appears to lead to increasing desensitization. Additional data from larger-scale studies should provide a more robust assessment of safety and efficacy of EPIT. © 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  6. Efficacy and Safety of Probiotics and Synbiotics in Liver Transplantation.

    PubMed

    Jorgenson, Margaret R; Descourouez, Jillian L; Siodlak, Magdalena; Tjugum, Shelby; Rice, John P; Fernandez, Luis A

    2018-05-26

    This article summarizes available literature regarding the utilization of probiotic and synbiotics in liver transplant (LTX) recipients, reviewing efficacy in both decreasing infectious complications and immunomodulation, as well as exploring safety concerns. Data suggest that the use of probiotics containing Lactobacillus species, either alone or in combination with prebiotics (referred to as synbiotics), may be effective in reducing infectious complications after LTX, a major contributor to graft loss, hospital length of stay, and mortality. Literature evaluating the use of probiotics to induce tolerance, reduce rejection, and prevent damage associated with ischemic reperfusion injury is limited to animal models, but compelling, as it suggests the use of probiotics may augment deleterious immune-mediated processes in this population. While the benefits of probiotics should be weighed against potential risks, these concerns are largely theoretically in the LTX recipient, with the majority of evidence extrapolated from case reports in other immunosuppressed populations. Based on available literature, it may be prudent to avoid products containing Saccharomyces sp, as these were not used in the efficacy studies, and the majority of the adverse event reporting stems from the use of products containing this organism. Further evaluation of the safety and efficacy of probiotic therapy is warranted. Studies specifically designed to elucidate the optimal product and initiation scenario and delineate safety in this population are needed to allow expanded use of this inexpensive, relatively non-toxic, and potentially beneficial therapeutic option after LTX. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  7. Failed efficacy of ziprasidone in the treatment of post-traumatic stress disorder.

    PubMed

    Ramaswamy, Sriram; Driscoll, David; Smith, Lynette M; Bhatia, Subhash C; Petty, Frederick

    2016-04-15

    Post-traumatic stress disorder (PTSD) is a chronic anxiety disorder that is often difficult to treat. Patients suffering from PTSD often fail to respond to antidepressants and may have a high incidence of positive symptoms of psychosis, though antipsychotic medications have been minimally studied in this population. The aim of this study was to assess the impact of the atypical antipsychotic ziprasidone (Geodon) on PTSD symptom clusters, as well as comorbid major depressive disorder. To our knowledge, this is the first completed randomized controlled trial investigating the potential efficacy and tolerability of ziprasidone in patients with chronic PTSD. We conducted a 9-week prospective, randomized, double-blind, placebo-controlled trial of ziprasidone in 30 patients diagnosed with PTSD and comorbid depression. After screening and randomization, patients completed nine weekly study visits at which treatment safety and efficacy were evaluated. Primary measures of efficacy included total and subscale scores from the Clinician-Administered PTSD Scale (CAPS), while the Hamilton Rating Scale for Depression (HAM-D), Hamilton Anxiety Scale (HAM-A), Clinical Global Impression (CGI), and Treatment Outcome PTSD Scale (TOP-8) were implemented as secondary efficacy measures. We observed no significant effect of treatment on reduction of PTSD or depression symptoms from pre- to post-treatment. Our findings suggest that ziprasidone treatment may not significantly improve symptoms of PTSD or comorbid depression, though further study is needed.

  8. Efficacy and Safety of Remifentanil as an Alternative Labor Analgesic

    PubMed Central

    Devabhakthuni, Sandeep

    2013-01-01

    The objective of this review was to evaluate the clinical efficacy and safety of remifentanil in the management of labor pain. Although neuraxial analgesia is the best option during labor, alternative analgesic options are needed for patients with contraindications. Using a systematic literature search, clinical outcomes of remifentanil for labor pain have been summarized. Also, comparisons of remifentanil to other options including meperidine, epidural analgesia, fentanyl, and nitrous oxide are provided. Based on the literature review, remifentanil is associated with high overall maternal satisfaction and favorable side-effect profile. However, due to the low reporting of adverse events, large, randomized controlled trials are needed to evaluate maternal and neonatal safety adequately and determine the optimal dosing needed to provide effective analgesia. While remifentanil is a feasible alternative for patients who cannot or do not want to receive epidural analgesia, administration should be monitored closely for potential adverse effects. PMID:24665213

  9. [Safety and efficacy of ketamine for pain relief].

    PubMed

    Niesters, Marieke; Dahan, Albert; van Kleef, Maarten

    2016-01-01

    Intravenous ketamine treatment is frequently used for the management of chronic pain, especially in those patients who do not benefit from other therapies. In this commentary we discuss the efficacy of ketamine for relief of chronic pain and ketamine's safety profile. A review of the literature indicates that only a few studies show that intravenous ketamine has analgesic effects that persist beyond the infusion period, an effect that occurs in about two-thirds of patients. Ketamine has multiple safety issues, ranging from psychotomimetic and schizotypal symptoms, sympathetic stimulation, tachycardia and hypertension, and damage to the liver and the urogenital tract. Damage to the urogenital tract seems to be restricted to individuals who chronically abuse ketamine. We indicate the need for large randomized trials in which ketamine is compared with an 'active' placebo.

  10. Diabetes and gout: efficacy and safety of febuxostat and allopurinol.

    PubMed

    Becker, M A; MacDonald, P A; Hunt, B J; Jackson, R L

    2013-11-01

    Assess influences of demographics and co-morbidities of gout patients with or without diabetes on safety and efficacy of urate-lowering agents. Post-hoc analysis of 312 diabetic and 1957 non-diabetic gout patients [baseline serum urate levels (sUA) ≥8.0 mg/dl] enrolled in a 6-month randomized controlled trial comparing urate-lowering efficacy (ULE) and safety of daily xanthine oxidase inhibitors (XOIs) febuxostat (40 mg or 80 mg) and allopurinol (200 mg or 300 mg). We compared baseline demographic, gout and co-morbid characteristics, ULE, and safety of XOI treatment in diabetic and non-diabetic gout patients. ULE was measured by the proportion of diabetic and non-diabetic patients in each treatment group achieving final visit sUA < 6.0 mg/dl. Safety was monitored throughout the trial. Diabetic gout patients were older, more frequently female, and had longer gout duration. Co-morbidities were more frequent among diabetic patients: cardiovascular disease; impaired renal function; hyperlipidemia; and obesity (body mass index >30 kg/m²) (p < 0.001 for all comparisons). Febuxostat 80 mg ULE exceeded that of febuxostat 40 mg or allopurinol (p < 0.050) at all levels of renal function, achieving sUA goal range in the majority of diabetic and non-diabetic patients. Diabetics and non-diabetics reported self-limiting diarrhoea and URIs as the most common adverse events. Despite higher co-morbidity rates in diabetic patients, febuxostat and allopurinol were safe in both groups at the doses tested. Febuxostat 80 mg achieved sUA <6.0 mg/dl more often than febuxostat 40 mg or allopurinol at commonly prescribed doses. © 2013 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

  11. Diabetes and gout: efficacy and safety of febuxostat and allopurinol

    PubMed Central

    Becker, M A; MacDonald, P A; Hunt, B J; Jackson, R L

    2013-01-01

    Aim Assess influences of demographics and co-morbidities of gout patients with or without diabetes on safety and efficacy of urate-lowering agents. Methods Post-hoc analysis of 312 diabetic and 1957 non-diabetic gout patients [baseline serum urate levels (sUA) ≥8.0 mg/dl] enrolled in a 6-month randomized controlled trial comparing urate-lowering efficacy (ULE) and safety of daily xanthine oxidase inhibitors (XOIs) febuxostat (40 mg or 80 mg) and allopurinol (200 mg or 300 mg). We compared baseline demographic, gout and co-morbid characteristics, ULE, and safety of XOI treatment in diabetic and non-diabetic gout patients. ULE was measured by the proportion of diabetic and non-diabetic patients in each treatment group achieving final visit sUA < 6.0 mg/dl. Safety was monitored throughout the trial. Results Diabetic gout patients were older, more frequently female, and had longer gout duration. Co-morbidities were more frequent among diabetic patients: cardiovascular disease; impaired renal function; hyperlipidemia; and obesity (body mass index >30 kg/m2) (p < 0.001 for all comparisons). Febuxostat 80 mg ULE exceeded that of febuxostat 40 mg or allopurinol (p < 0.050) at all levels of renal function, achieving sUA goal range in the majority of diabetic and non-diabetic patients. Diabetics and non-diabetics reported self-limiting diarrhoea and URIs as the most common adverse events. Conclusions Despite higher co-morbidity rates in diabetic patients, febuxostat and allopurinol were safe in both groups at the doses tested. Febuxostat 80 mg achieved sUA <6.0 mg/dl more often than febuxostat 40 mg or allopurinol at commonly prescribed doses. PMID:23683134

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-12-07

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

  14. Linagliptin: farmacology, efficacy and safety in type 2 diabetes treatment

    PubMed Central

    2013-01-01

    Type 2 diabetes mellitus (T2DM) has a high prevalence and incidence around the world. The complex pathophysiology mechanism is among the barriers for diabetes treatment. Type 2 diabetes patients have dysfunction in incretin hormones (as glucagon-like peptide-1 or GLP-1, and glucose-dependent insulinotropic polypeptide or GIP). By inhibiting the dipeptidyl peptidase-4 (DPP-4) enzyme, it is possible to slow the inactivation of GLP-1 and GIP, promoting blood glucose level reduction in a glucose-dependent manner. Linagliptin is a highly specific and potent inhibitor of DPP-4 that is currently indicated for the treatment of type 2 diabetes. Clinical studies with linagliptin demonstrated efficacy in reducing glycated hemoglobin (HbA1c) levels in type 2 diabetes patients, while maintaining a placebo-like safety and tolerability profile. Linagliptin has an interesting pharmacokinetic profile in terms of its predominantly non-renal elimination and the main implication of this characteristic is that no dose adjustment is necessary in patients with renal disease. Also, no dose adjustment is required in patients with hepatic insufficiency, as well in elderly or obese patients. This article will review the pharmacokinetic profile, efficacy data and safety aspects of linagliptin in type 2 diabetes patients. PMID:23697612

  15. Animal models for microbicide safety and efficacy testing.

    PubMed

    Veazey, Ronald S

    2013-07-01

    Early studies have cast doubt on the utility of animal models for predicting success or failure of HIV-prevention strategies, but results of multiple human phase 3 microbicide trials, and interrogations into the discrepancies between human and animal model trials, indicate that animal models were, and are, predictive of safety and efficacy of microbicide candidates. Recent studies have shown that topically applied vaginal gels, and oral prophylaxis using single or combination antiretrovirals are indeed effective in preventing sexual HIV transmission in humans, and all of these successes were predicted in animal models. Further, prior discrepancies between animal and human results are finally being deciphered as inadequacies in study design in the model, or quite often, noncompliance in human trials, the latter being increasingly recognized as a major problem in human microbicide trials. Successful microbicide studies in humans have validated results in animal models, and several ongoing studies are further investigating questions of tissue distribution, duration of efficacy, and continued safety with repeated application of these, and other promising microbicide candidates in both murine and nonhuman primate models. Now that we finally have positive correlations with prevention strategies and protection from HIV transmission, we can retrospectively validate animal models for their ability to predict these results, and more importantly, prospectively use these models to select and advance even safer, more effective, and importantly, more durable microbicide candidates into human trials.

  16. Efficacy and Safety of Human Retinal Progenitor Cells

    PubMed Central

    Semo, Ma'ayan; Haamedi, Nasrin; Stevanato, Lara; Carter, David; Brooke, Gary; Young, Michael; Coffey, Peter; Sinden, John; Patel, Sara; Vugler, Anthony

    2016-01-01

    Purpose We assessed the long-term efficacy and safety of human retinal progenitor cells (hRPC) using established rodent models. Methods Efficacy of hRPC was tested initially in Royal College of Surgeons (RCS) dystrophic rats immunosuppressed with cyclosporine/dexamethasone. Due to adverse effects of dexamethasone, this drug was omitted from a subsequent dose-ranging study, where different hRPC doses were tested for their ability to preserve visual function (measured by optokinetic head tracking) and retinal structure in RCS rats at 3 to 6 months after grafting. Safety of hRPC was assessed by subretinal transplantation into wild type (WT) rats and NIH-III nude mice, with analysis at 3 to 6 and 9 months after grafting, respectively. Results The optimal dose of hRPC for preserving visual function/retinal structure in dystrophic rats was 50,000 to 100,000 cells. Human retinal progenitor cells integrated/survived in dystrophic and WT rat retina up to 6 months after grafting and expressed nestin, vimentin, GFAP, and βIII tubulin. Vision and retinal structure remained normal in WT rats injected with hRPC and there was no evidence of tumors. A comparison between dexamethasone-treated and untreated dystrophic rats at 3 months after grafting revealed an unexpected reduction in the baseline visual acuity of dexamethasone-treated animals. Conclusions Human retinal progenitor cells appear safe and efficacious in the preclinical models used here. Translational Relevance Human retinal progenitor cells could be deployed during early stages of retinal degeneration or in regions of intact retina, without adverse effects on visual function. The ability of dexamethasone to reduce baseline visual acuity in RCS dystrophic rats has important implications for the interpretation of preclinical and clinical cell transplant studies. PMID:27486556

  17. Long-term safety and efficacy of etanercept in the treatment of ankylosing spondylitis

    PubMed Central

    Senabre-Gallego, José Miguel; Santos-Ramírez, Carlos; Santos-Soler, Gregorio; Salas-Heredia, Esteban; Sánchez-Barrioluengo, Mabel; Barber, Xavier; Rosas, José

    2013-01-01

    To date, anti-tumor necrosis factor alfa (anti-TNF-α) therapy is the only alternative to nonsteroidal anti-inflammatory drugs for the treatment of ankylosing spondylitis. Etanercept is a soluble TNF receptor, with a mode of action and pharmacokinetics different to those of antibodies and distinctive efficacy and safety. Etanercept has demonstrated efficacy in the treatment of ankylosing spondylitis, with or without radiographic sacroiliitis, and other manifestations of the disease, including peripheral arthritis, enthesitis, and psoriasis. Etanercept is not efficacious in inflammatory bowel disease, and its efficacy in the treatment of uveitis appears to be lower than that of other anti-TNF drugs. Studies of etanercept confirmed regression of bone edema on magnetic resonance imaging of the spine and sacroiliac joint, but failed to reduce radiographic progression, as do the other anti-TNF drugs. It seems that a proportion of patients remain in disease remission when the etanercept dose is reduced or administration intervals are extended. Etanercept is generally well tolerated with an acceptable safety profile in the treatment of ankylosing spondylitis. The most common adverse effect of etanercept treatment is injection site reactions, which are generally self-limiting. Reactivation of tuberculosis, reactivation of hepatitis B virus infection, congestive heart failure, demyelinating neurologic disorders, hematologic disorders like aplastic anemia and pancytopenia, vasculitis, immunogenicity, and exacerbation or induction of psoriasis are class effects of all the anti-TNF drugs, and have been seen in patients with ankylosing spondylitis. However, etanercept is less likely to induce reactivation of tuberculosis than the other anti-TNF drugs and it has been suggested that etanercept might be less immunogenic, especially in ankylosing spondylitis. Acute uveitis, Crohn’s disease, and sarcoidosis are other adverse events that have been rarely associated with etanercept

  18. Clinical efficacy and safety of a new 1000-mg suspension versus twice-daily 500-mg tablets of MPFF in patients with symptomatic chronic venous disorders: a randomized controlled trial.

    PubMed

    Carpentier, Patrick; van Bellen, Bonno; Karetova, Debora; Hanafiah, Harunarashid; Enriquez-Vega, Elizabeth; Kirienko, Alexander; Dzupina, Andrej; Sabovic, Miso; Reina Gutierrez, Lourdes; Subwongcharoen, Somboom; Tüzün, Hasan; Maggioli, Arnaud

    2017-10-01

    Chronic venous disorders (CVD) is estimated to affect 30% to 50% of women and 10% to 30% of men. The most widely prescribed treatment for CVD worldwide is micronized purified flavonoid fraction 500 mg (MPFF). The aim of this clinical trial was to develop a new once daily 1000-mg oral suspension of MPFF. In an international, randomized, double-blind, parallel-group study, symptomatic individuals classified CEAP C0s to C4s were randomized in either treatment arm and treated for 8 weeks. Lower limb symptoms (discomfort, pain and heaviness) were assessed using Visual Analog Scales (VAS), and quality of life (QoL) was measured with the CIVIQ-20 Questionnaire. A total of 1139 patients were included in the study. Both MPFF treatment regimens were well tolerated and associated with a significant reduction in lower limb symptoms. A non-inferiority of MPFF 1000-mg oral suspension once daily compared to MPFF 500-mg tablet twice daily (P<0.0001) was found for lower limb discomfort (-3.33 cm for MPFF 1000 mg and -3.37 cm for MPFF 500 mg), leg pain (-3.27 cm for MPFF 1000 mg and -3.31 cm for MPFF 500 mg) and leg heaviness (-3.41 cm for MPFF 1000 mg and -3.46 cm for MPFF 500 mg). The patients' QoL was improved by about 20 points on the CIVIQ scale in both groups (19.33 points for MPFF 1000 mg and 20.28 points for MPFF 500 mg). MPFF 1000-mg oral suspension and MPFF 500-mg tablets treatments were associated with similar reductions in lower limb symptoms and QoL improvement. The new once daily MPFF1000-mg oral suspension has a similar safety profile to two tablets of MPFF 500 mg, with the advantage of one daily intake, potentially associated with improved patient adherence and easier CVD management.

  19. Safety and efficacy of ezetimibe: A meta-analysis.

    PubMed

    Savarese, Gianluigi; De Ferrari, Gaetano M; Rosano, Giuseppe M C; Perrone-Filardi, Pasquale

    2015-12-15

    The addition of ezetimibe to statin therapy has been widely demonstrated to significantly reduce low-density lipoprotein cholesterol levels. However, the efficacy of ezetimibe in reducing CV events and its safety has been less investigated. The aim of the current meta-analysis was to report efficacy and safety of ezetimibe from randomized clinical trials. Randomized clinical trials with a follow-up of at least 24 weeks, enrolling more than 200 patients, comparing ezetimibe versus placebo or ezetimibe plus another hypolipidemic agent versus the same hypolipidemic drug alone and reporting at least one event among all-cause and CV mortality, myocardial infarction (MI), stroke and new onset of cancer were included in the analysis. 7 trials enrolling 31,048 patients (median follow-up 34.1 ± 26.3 months; 70% women; mean age 61 ± 8 years) were included in the analysis. Compared to control therapy, ezetimibe significantly reduced the risk of MI by 13.5% (RR: 0.865, 95% CI: 0.801 to 0.934, p<0.001) and the risk of any stroke by 16.0% (RR: 0.840, 95% CI: 0.744 to 0.949, p=0.005), without any effect on all-cause and CV mortality (RR: 1.003, 95% CI: 0.954 to 1.055, p=0.908; RR: 0.958, 95% CI: 0.879 to 1.044, p=0.330; respectively) and risk of new cancer (RR: 1.040, 95% CI: 0.965 to 1.120, p=0.303). Ezetimibe significantly reduces the risk of MI and stroke without any effect on all-cause and CV mortality and risk of cancer. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Bitter melon (Momordica charantia): a review of efficacy and safety.

    PubMed

    Basch, Ethan; Gabardi, Steven; Ulbricht, Catherine

    2003-02-15

    The pharmacology, clinical efficacy, adverse effects, drug interactions, and place in therapy of bitter melon are described. Bitter melon (Momordica charantia) is an alternative therapy that has primarily been used for lowering blood glucose levels in patients with diabetes mellitus. Components of bitter melon extract appear to have structural similarities to animal insulin. Antiviral and antineoplastic activities have also been reported in vitro. Four clinical trials found bitter melon juice, fruit, and dried powder to have a moderate hypoglycemic effect. These studies were small and were not randomized or double-blind, however. Reported adverse effects of bitter melon include hypoglycemic coma and convulsions in children, reduced fertility in mice, a favism-like syndrome, increases in gamma-glutamyltransferase and alkaline phosphatase levels in animals, and headaches. Bitter melon may have additive effects when taken with other glucose-lowering agents. Adequately powered, randomized, placebo-controlled trials are needed to properly assess safety and efficacy before bitter melon can be routinely recommended. Bitter melon may have hypoglycemic effects, but data are not sufficient to recommend its use in the absence of careful supervision and monitoring.

  1. Safety and efficacy of overnight orthokeratology in myopic children.

    PubMed

    Mika, Renée; Morgan, Bruce; Cron, Michael; Lotoczky, Josh; Pole, John

    2007-05-01

    This prospective case series was conducted to describe the safety and efficacy of orthokeratology with the Emerald Contact Lens for Overnight Orthokeratology (Oprifocon A; Euclid Systems Corporation, Herndon, Virginia) among young myopes. Twenty subjects (ages 10 to 16) were enrolled in the 6-month pilot study. Subjects were fit empirically with overnight orthokeratology lenses and evaluated at 1 day, 1 week, 1 month, 2 months, 3 months, and 6 months. Sixteen subjects completed the study. The mean baseline spherical equivalent refraction (SER) was -2.06 diopters (D) (+/-0.75). The mean SER at 6 months was -0.16 D (+/-0.38). The mean baseline uncorrected acuity was 0.78 (+/-0.28) logarithmic minimum angle of resolution (logMAR) equivalent (20/100 Snellen). The mean logMAR equivalent at 6 months was -0.03 +/- 0.12 (<20/20 Snellen). On average, 40% of eyes showed some type of corneal staining between the 1-week and 6-month visits. No serious adverse events occurred during the study. In contrast to previously published studies that reported maximum results at 2 weeks, subjects reached maximum reduction in myopia at the 1-week visit and, on average, obtained a 92.2% reduction in spherical equivalent refractive error at 6 months. This pilot study lends to a growing body of evidence that short-term correction of mild to moderate myopia with overnight orthokeratology is safe and efficacious in children and adolescents.

  2. Efficacy and safety of methimazole ointment for patients with hyperthyroidism.

    PubMed

    Wu, Xi; Liu, Hong; Zhu, Xixing; Shen, Jun; Shi, Yongquan; Liu, Zhimin; Gu, Mingjun; Song, Zhimin

    2013-11-01

    Oral methimazole has been widely used to treat hyperthyroidism, but its usage is restricted by its adverse systemic effects. The aim of this study was to investigate the efficacy and safety of methimazole ointment for the treatment of hyperthyroidism. One hundred forty-four subjects with hyperthyroidism were initially enrolled. These patients were initially divided into two groups and given the following treatments for 12 weeks: patients in group A received 5% methimazole ointment applied to the skin around the thyroid and an oral placebo; and patients in group B received methimazole tablets and placebo ointment. One hundred thirty-one subjects were included in the final analysis. Therapeutic efficacy was assessed via the levels of free triiodothyronine and thyroxine in the serum and by biweekly monitoring of the symptoms of thyrotoxicosis. Adverse effects were recorded. Fifty-nine (89.40%) patients in group A and 57 (87.69%) patients in group B were euthyroid and experienced alleviation of thyrotoxicosis symptoms (complete control; p>0.05). The median times required to achieve complete control for the patients in the two groups were 6.5 weeks and 6.4 weeks for groups A and B, respectively (p>0.05). Systemic adverse effects (e.g., rash, liver dysfunction, leucopenia, etc.) were significantly less common in group A (1.5%) than in group B (12.3%; p<0.05). This study showed that methimazole ointment has a clinical efficacy similar to that of oral tablets, but methimazole ointment caused fewer systemic adverse effects in patients with hyperthyroidism. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Microwave ablation of pancreatic head cancer: safety and efficacy.

    PubMed

    Carrafiello, Gianpaolo; Ierardi, Anna Maria; Fontana, Federico; Petrillo, Mario; Floridi, Chiara; Lucchina, Natalie; Cuffari, Salvatore; Dionigi, Gianlorenzo; Rotondo, Antonio; Fugazzola, Carlo

    2013-10-01

    To evaluate the safety and efficacy of percutaneous microwave (MW) ablation treatment in locally advanced, nonresectable, nonmetastatic pancreatic head cancer. Ten patients with pancreatic head cancer treated with percutaneous (n = 5) or laparotomic (n = 5) MW ablation were retrospectively reviewed. The MW generator used (45 W at 915 MHz) was connected by coaxial cable to 14-gauge straight MW antennas with a 3.7- or 2-cm radiating section. One or two antennae were used, with an ablation time of 10 minutes. Ultrasonographic (US) and combined US/cone-beam computed tomographic (CT) guidance were used in five patients each. Follow-up was performed by CT after 1, 3, 6, and, when possible, 12 months. Tumor response was assessed per Response Evaluation Criteria In Solid Tumors (version 1.1) and Choi criteria. The feasibility, safety, and major and minor complications associated with quality of life (QOL) were recorded prospectively. The procedure was feasible in all patients (100%). One late major complication was observed in one patient, and no visceral injury was detected. No patient had further surgery, and all minor complications resolved during the hospital stay. An improvement in QOL was observed in all patients despite a tendency to return to preoperative levels in the months following the procedure, without the influence of minor complications. No repeat treatment was performed. Despite the small number of patients, the present results can be considered encouraging, showing that MW ablation is a feasible approach in the palliative treatment of pancreatic tumors. © SIR, 2013.

  4. Teaching Safety Responding to Children with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Rossi, Margaret R.; Vladescu, Jason C.; Reeve, Kenneth F.; Gross, Amy C.

    2017-01-01

    Children have been taught to demonstrate a safety response when they encounter a dangerous stimulus using behavioral skills training (BST). However, little research has evaluated the usefulness of BST to teach safety skills to children with autism spectrum disorder (ASD). In the current study, we evaluated BST to establish a generalized repertoire…

  5. Longterm Safety and Efficacy of Subcutaneous Abatacept in Patients with Rheumatoid Arthritis: 5-year Results from a Phase IIIb Trial.

    PubMed

    Genovese, Mark C; Pacheco-Tena, César; Covarrubias, Arturo; Leon, Gustavo; Mysler, Eduardo; Keiserman, Mauro; Valente, Robert M; Nash, Peter; Simon-Campos, J Abraham; Box, Jane; Legerton, Clarence W; Nasonov, Evgeny; Durez, Patrick; Elegbe, Ayanbola; Wong, Robert; Li, Xiaohui; Banerjee, Subhashis; Alten, Rieke

    2018-04-15

    To assess 5-year safety, tolerability, and efficacy of subcutaneous (SC) abatacept (ABA) in methotrexate (MTX)-refractory patients with rheumatoid arthritis (RA). The Abatacept Comparison of sub[QU]cutaneous versus intravenous in Inadequate Responders to methotrexatE (ACQUIRE) phase IIIb, randomized, double-dummy, multinational trial compared efficacy and safety of SC and intravenous (IV) ABA in patients with RA. In the initial 6-month double-blind (DB) period, patients received IV or SC ABA, plus MTX, and in the subsequent open-label longterm extension (LTE) period, all patients received SC ABA (125 mg/wk). The final 5-year safety, tolerability, and efficacy analyses are reported. Of 1385 patients who completed the DB period, 1372 entered LTE and 945 (68.8%) completed ≥ 5 years of treatment. During LTE, 97 (7.1%) patients discontinued treatment because of an adverse event (AE). Incidence rate (IR; event/100 patient-yrs of exposure; based on LTE data, 95% CI) for AE of interest were the following: serious AE 7.73 (6.96-8.58), infection 38.60 (36.24-41.12), serious infection 1.68 (1.35-2.07), malignancies 1.09 (0.84-1.42), and autoimmune disorders 1.33 (1.05-1.69), and were stable over time. No association between immunogenicity and either worsening of ABA safety or loss of efficacy was noted. Efficacy in the LTE was consistent with the DB period and was maintained to the end of the study. These 5-year data establish that SC ABA (125 mg/wk) has a consistent safety profile and durable efficacy for longterm treatment of patients with RA who had an inadequate response to MTX.

  6. Efficacy and safety of levetiracetam for outpatient alcohol detoxification.

    PubMed

    Müller, C A; Schäfer, M; Schneider, S; Heimann, H M; Hinzpeter, A; Volkmar, K; Förg, A; Heinz, A; Hein, J

    2010-07-01

    Anticonvulsant drugs are increasingly being used for alcohol detoxification in in- and outpatient settings. The aim of this study was to examine the efficacy, medical safety and mid-term outcome of levetiracetam, a drug with no marked liver toxicity, for outpatient alcohol detoxification. This was an open-label observational study. After screening eligibility for outpatient alcohol detoxification, patients were seen daily for 5 days and received levetiracetam in a flexible dosage regime between 500 and 4 000 mg/d for a maximum of 7 days. Diazepam was used as a rescue medication. The severity of alcohol withdrawal was evaluated daily using the ALCOHOL WITHDRAWAL SYNDROME SCALE (AWSS). Mid-term treatment outcome was assessed at a 6-month follow-up. A total number of 131 consecutively admitted alcohol-dependent patients received an outpatient detoxification treatment, 122 (93.1%) completed the programme successfully. The mean initial dose of levetiracetam was 1 850 mg/d. Alcohol withdrawal syndrome as indicated by the AWSS score decreased clearly over 5 days. Overall, the medication was well tolerated. There was no treatment discontinuations due to side effects of levetiracetam. No serious medical complications, especially seizures or deliria, were observed during the detoxification. At the 6-month follow-up, 57 patients (43.5%) were still abstinent. Patients with previous detoxifications had a significant higher risk for relapse (HR=1.88; p=0.016; CI 95%: 1.12-3.14) than patients without previous treatments. The findings of this study provide some evidence that levetiracetam is an efficacious and safe treatment option for outpatient alcohol detoxification. Further randomised, controlled trials including mid- and long-term follow-ups are needed to confirm these findings. Copyright Georg Thieme Verlag KG Stuttgart New York.

  7. Safety and efficacy of peramivir for influenza treatment

    PubMed Central

    Hata, Atsuko; Akashi-Ueda, Ryoko; Takamatsu, Kazufumi; Matsumura, Takuro

    2014-01-01

    Objective This report presents a review of the efficacy and safety of peramivir, a neuraminidase inhibitor that was granted Emergency Use Authorization by the US Food and Drug Administration (FDA) from October 23, 2009 to June 23, 2010 during the 2009 H1N1 pandemic. Methods Literature was accessed via PubMed (January 2000–April 2014) using several search terms: peramivir; BCX-1812; RWJ 270201; H1N1, influenza; antivirals; and neuraminidase inhibitors. The peramivir manufacturers, Shionogi and Co Ltd and BioCryst Pharmaceuticals, were contacted to obtain unpublished data and information presented at recent scientific meetings. Information was obtained from the Centers for Disease Control and Prevention (CDC) and from US FDA websites. English-language and Japanese-language reports in the literature were reviewed and selected based on relevance, along with information from the CDC, US FDA, and the drug manufacturers. Results We obtained eleven clinical trial reports of intravenous peramivir, two of which described comparisons with oseltamivir. Seven of nine other recently reported published studies was a dose–response study. Clinical reports of critically ill patients and pediatric patients infected with pandemic H1N1 described that early treatment significantly decreased mortality. Peramivir administered at 300 mg once daily in adult patients with influenza significantly reduces the time to alleviation of symptoms or fever compared to placebo. It is likely to be as effective as other neuraminidase inhibitors. Conclusion Although peramivir shows efficacy for the treatment of seasonal and pH1N1 influenza, it has not received US FDA approval. Peramivir is used safely and efficiently in hospitalized adult and pediatric patients with suspected or laboratory-confirmed influenza. Peramivir might be a beneficial alternative antiviral treatment for many patients, including those unable to receive inhaled or oral neuraminidase inhibitors, or those requiring nonintravenous

  8. Endoscopic spray cryotherapy for esophageal cancer: safety and efficacy

    PubMed Central

    Greenwald, Bruce D.; Dumot, John A.; Abrams, Julian A.; Lightdale, Charles J.; David, Donald S.; Nishioka, Norman S.; Yachimski, Patrick; Johnston, Mark H.; Shaheen, Nicholas J.; Zfass, Alvin M.; Smith, Jenny O.; Gill, Kanwar Rupinder S.; Burdick, J. Steven; Mallat, Damien; Wolfsen, Herbert C.

    2011-01-01

    Background Few options exist for patients with localized esophageal cancer ineligible for conventional therapies. Endoscopic spray cryotherapy with low-pressure liquid nitrogen has demonstrated efficacy in this setting in early studies. Objective To assess the safety and efficacy of cryotherapy in esophageal carcinoma. Design Multicenter, retrospective cohort study. Setting Ten academic and community medical centers between 2006 and 2009. Patients Subjects with esophageal carcinoma in whom conventional therapy failed and those who refused or were ineligible for conventional therapy. Interventions Cryotherapy with follow-up biopsies. Treatment was complete when tumor eradication was confirmed by biopsy or when treatment was halted because of tumor progression, patient preference, or comorbid condition. Main Outcome Measurements Complete eradication of luminal cancer and adverse events. Results Seventy-nine subjects (median age 76 years, 81% male, 94% with adenocarcinoma) were treated. Tumor stage included T1-60, T2-16, and T3/4-3. Mean tumor length was 4.0 cm (range 1–15 cm). Previous treatment including endoscopic resection, photodynamic therapy, esophagectomy, chemotherapy, and radiation therapy failed in 53 subjects (67%). Forty-nine completed treatment. Complete response of intraluminal disease was seen in 31 of 49 subjects (61.2%), including 18 of 24 (75%) with mucosal cancer. Mean (standard deviation) length of follow-up after treatment was 10.6 (8.4) months overall and 11.5 (2.8) months for T1 disease. No serious adverse events were reported. Benign stricture developed in 10 (13%), with esophageal narrowing from previous endoscopic resection, radiotherapy, or photodynamic therapy noted in 9 of 10 subjects. Limitations Retrospective study design, short follow-up. Conclusions Spray cryotherapy is safe and well tolerated for esophageal cancer. Short-term results suggest that it is effective in those who could not receive conventional treatment, especially for

  9. Endoscopic spray cryotherapy for esophageal cancer: safety and efficacy.

    PubMed

    Greenwald, Bruce D; Dumot, John A; Abrams, Julian A; Lightdale, Charles J; David, Donald S; Nishioka, Norman S; Yachimski, Patrick; Johnston, Mark H; Shaheen, Nicholas J; Zfass, Alvin M; Smith, Jenny O; Gill, Kanwar Rupinder S; Burdick, J Steven; Mallat, Damien; Wolfsen, Herbert C

    2010-04-01

    Few options exist for patients with localized esophageal cancer ineligible for conventional therapies. Endoscopic spray cryotherapy with low-pressure liquid nitrogen has demonstrated efficacy in this setting in early studies. To assess the safety and efficacy of cryotherapy in esophageal carcinoma. Multicenter, retrospective cohort study. Ten academic and community medical centers between 2006 and 2009. Subjects with esophageal carcinoma in whom conventional therapy failed and those who refused or were ineligible for conventional therapy. Cryotherapy with follow-up biopsies. Treatment was complete when tumor eradication was confirmed by biopsy or when treatment was halted because of tumor progression, patient preference, or comorbid condition. Complete eradication of luminal cancer and adverse events. Seventy-nine subjects (median age 76 years, 81% male, 94% with adenocarcinoma) were treated. Tumor stage included T1-60, T2-16, and T3/4-3. Mean tumor length was 4.0 cm (range 1-15 cm). Previous treatment including endoscopic resection, photodynamic therapy, esophagectomy, chemotherapy, and radiation therapy failed in 53 subjects (67%). Forty-nine completed treatment. Complete response of intraluminal disease was seen in 31 of 49 subjects (61.2%), including 18 of 24 (75%) with mucosal cancer. Mean (standard deviation) length of follow-up after treatment was 10.6 (8.4) months overall and 11.5 (2.8) months for T1 disease. No serious adverse events were reported. Benign stricture developed in 10 (13%), with esophageal narrowing from previous endoscopic resection, radiotherapy, or photodynamic therapy noted in 9 of 10 subjects. Retrospective study design, short follow-up. Spray cryotherapy is safe and well tolerated for esophageal cancer. Short-term results suggest that it is effective in those who could not receive conventional treatment, especially for those with mucosal cancer. Copyright 2010 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All

  10. Analgesic Efficacy and Safety of Buprenorphine in Chinchillas (Chinchilla lanigera).

    PubMed

    Fox, Lana; Mans, Christoph

    2018-05-01

    Buprenorphine is routinely used in chinchillas at reported doses of 0.01 to 0.1 mg/kg IM or SC. However, these dose recommendations are based on anecdotal reports or extrapolation from studies in other species. Therefore, the purpose of this study was to evaluate the analgesic efficacy and safety of subcutaneously administered buprenorphine in chinchillas. Using a randomized, blind, controlled, complete crossover design, we evaluated buprenorphine at a single dose of 0.05, 0.1 or 0.2 mg/kg SC (experiment A) and 0.2 mg/kg SC (experiment B). Analgesic efficacy was determined by measuring limb withdrawal latencies in response to a thermal noxious stimulus (Hargreaves method) at 0, 3, 6, 12, and 24 h (experiment A) and at 0, 1, 2, 4, and 8 h (experiment B). In a third experiment, food intake and fecal output were monitored after repeated administration of buprenorphine (0.2 mg/kg SC every 6 h for 3 doses). Buprenorphine at 0.2 mg/kg SC, but not at 0.05 or 0.1 mg/kg SC, significantly increased limb withdrawal latencies for less than 4 h. Self-limiting reduction in food intake and fecal output occurred after administration at the 0.2-mg/kg dose in animals undergoing algesiometry. In chinchillas not undergoing algesiometry, the administration of 3 doses at 0.2 mg/kg SC every 6 h did not reduce food intake but significantly decreased fecal output for the first 24 h. Additional studies are needed to evaluate buprenorphine in different algesiometry models and to establish its pharmacokinetic profile in chinchillas.

  11. [Preliminary investigation on the safety and efficacy of Trabectome].

    PubMed

    Huang, Ping; Wang, Huaizhou; Wu, Huijuan; Sun, Yanran; Wang, Minshu; Cui, Ying; Qiu, Weiqiang; Yang, Yiquan; Ren, Zeqin; Zhang, Chun; Wang, Ningli

    2015-02-01

    To evaluate the safety and efficacy of ab interno trabeculectomy (Trabectome) surgery in Chinese open angle glaucoma patients. Prospective non-comparative case series study. A total of 41 cases (34 primary open angle glaucoma patients, 3 developmental glaucoma patients and 4 pigmentary glaucoma patients) were included in the study. All the cases underwent Trabectome, including 9 cases combined with phacoemulsification cataract extraction. Major outcomes include intraocular pressure (IOP), number of glaucoma medications, secondary glaucoma surgery and postoperative complications. Criteria for successful operation were defined as IOP ≤ 21 mmHg (1 mmHg = 0.133 kPa), at least 20% IOP reduction in any two consecutive visits after 3 months with or without IOP-lowering drugs and no additional glaucoma surgery. IOP and number of glaucoma medications were compared to baseline using Wilcoxon signed-rank test with Bonferroni correction. Kaplan-Meier analysis was performed to analyze the success rate of surgery. In the all 41 patients, 21 cases (51.2%) were followed up for up to 12 months. IOP was reduced from (22.5 ± 8.1) mmHg to (17.6 ± 6.4) mmHg (P = 0.02), meanwhile number of glaucoma medications was reduced from 2.0 ± 0.9 to 1.2 ± 0.9 (P = 0.02) at 12 months. The success rate at one year was 85% and 4 cases required additional glaucoma surgery. Trabectome has many advantages, such as shorter surgery time, simple post-operative care, less intraoperative and postoperative complications and clear IOP-lowering effect. But it slong-term efficacy is still need a large sample, long-term follow-up to verify.

  12. Efficacy and Safety of Dual Antiplatelet Therapy After Complex PCI.

    PubMed

    Giustino, Gennaro; Chieffo, Alaide; Palmerini, Tullio; Valgimigli, Marco; Feres, Fausto; Abizaid, Alexandre; Costa, Ricardo A; Hong, Myeong-Ki; Kim, Byeong-Keuk; Jang, Yangsoo; Kim, Hyo-Soo; Park, Kyung Woo; Gilard, Martine; Morice, Marie-Claude; Sawaya, Fadi; Sardella, Gennaro; Genereux, Philippe; Redfors, Bjorn; Leon, Martin B; Bhatt, Deepak L; Stone, Gregg W; Colombo, Antonio

    2016-10-25

    Optimal upfront dual antiplatelet therapy (DAPT) duration after complex percutaneous coronary intervention (PCI) with drug-eluting stents (DES) remains unclear. This study investigated the efficacy and safety of long-term (≥12 months) versus short-term (3 or 6 months) DAPT with aspirin and clopidogrel according to PCI complexity. The authors pooled patient-level data from 6 randomized controlled trials investigating DAPT durations after PCI. Complex PCI was defined as having at least 1 of the following features: 3 vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation with 2 stents implanted, total stent length >60 mm, or chronic total occlusion. The primary efficacy endpoint was major adverse cardiac events (MACE), defined as the composite of cardiac death, myocardial infarction, or stent thrombosis. The primary safety endpoint was major bleeding. Intention-to-treat was the primary analytic approach. Of 9,577 patients included in the pooled dataset for whom procedural variables were available, 1,680 (17.5%) underwent complex PCI. Overall, 85% of patients received new-generation DES. At a median follow-up time of 392 days (interquartile range: 366 to 710 days), patients who underwent complex PCI had a higher risk of MACE (adjusted hazard ratio [HR]: 1.98; 95% confidence interval [CI]: 1.50 to 2.60; p < 0.0001). Compared with short-term DAPT, long-term DAPT yielded significant reductions in MACE in the complex PCI group (adjusted HR: 0.56; 95% CI: 0.35 to 0.89) versus the noncomplex PCI group (adjusted HR: 1.01; 95% CI: 0.75 to 1.35; p interaction  = 0.01). The magnitude of the benefit with long-term DAPT was progressively greater per increase in procedural complexity. Long-term DAPT was associated with increased risk for major bleeding, which was similar between groups (p interaction  = 0.96). Results were consistent by per-treatment landmark analysis. Alongside other established clinical risk factors, procedural complexity is an

  13. Clinical safety and efficacy of probiotic administration following burn injury.

    PubMed

    Mayes, Theresa; Gottschlich, Michele M; James, Laura E; Allgeier, Chris; Weitz, Julie; Kagan, Richard J

    2015-01-01

    Provision of probiotics has been limited postburn by questionable potential for bacterial translocation and risk of infection in an immune-compromised population. The purpose of this study was to evaluate the safety of probiotic administration in acutely burned, pediatric patients. Subjects were randomized to receive probiotic (n = 10) vs placebo (n = 10) twice daily. The investigational product was initiated within 10 days of burn, and daily supplementation continued until wound closure. Nursing staff was provided education regarding optimal procedures to minimize potential for study product cross contamination. Clinical outcomes (infection, antibiotic, antifungal, and operative days, tolerance, and mortality) were recorded. Length of stay was modified for burn size. Student's t-test, χ test, and nonparametric Wilcoxon's rank-sum test were used for comparative analysis. No differences were noted (probiotic; placebo) for age (7.1 ± 2.2; 6.9 ± 1.7), burn size (38.0 ± 5.9; 45.5 ± 4.45), full thickness (24.6 ± 5.6; 32.1 ± 5.4), postburn day admit (0.8 ± 0.4; 1.1 ± 0.4), or inhalation injury (10%; 20%). Infection days, antibiotic use, constipation, and emesis were similar between groups. Trends toward increased antifungal and laxative use as well as diarrhea incidence were evident in the controls (P < .30). Flatulence was statistically higher with probiotics. The control group trended toward higher requirement for excision/graft procedure. Medical length of stay was not significantly different between groups; however, time required to complete wound healing was shortened with probiotics. This study documents safety and provides preliminary efficacy data relative to probiotic supplementation postburn.

  14. Efficacy and safety of a polyherbal formulation in hemorrhoids

    PubMed Central

    Tripathi, Raakhi K.; Bolegave, Somesh S.; Shetty, Parvan A.; Uchil, Dinesh A.; Rege, Nirmala N.; Chawda, Mukesh B.; Rege, Sameer A.

    2015-01-01

    Background: The medical management of hemorrhoids should include an integrated approach. This integrated approach can be achieved by polyherbal formulations containing anti-inflammatory, styptics, analgesics, and laxative effect which reduce inflammation, pain, and bleeding, and increase gastro-intestinal motility and soften stools. One such polyherbal kit is “Arshkeyt™, a 7 day kit,” which consists of oral tablets and powder along with topical cream. Objective: Efficacy and safety of Arshkeyt™, a 7 day kit, a marketed polyherbal formulation was evaluated in comparison with conventional therapy practiced in surgery outpatient departments. Materials and Methods: Patients (n = 90) with hemorrhoids were randomly allocated to receive either Arshkeyt™ or standard therapy (combination of oral Isabgul powder and 2% lidocaine gel) for 14 days. Assessment on the basis of rectal symptoms and proctoscopic examination was done on day 0, 7, and 14 to derive a “composite score” which ranged from 0 to 25 by a blinded evaluator. The primary endpoint was number of patients achieving composite score 0 at the end of therapy (day 14). Inter-group analysis was done using Chi-square test. Results: On day 14, the composite score of 0 was achieved in 15 patients of Arshkeyt™ group versus 6 patients receiving standard therapy. The symptoms and signs which showed significant improvement in Arshkeyt™ group compared to standard treatment group were the tenesmus (visual analog score) score (P = 0.047), anal sphincter spasm (P = 0.0495) and a decrease in the grade of hemorrhoids (P = 0.0205) on day 14. Arshkeyt™ was also more beneficial in case of bleeding hemorrhoids as compared to nonbleeding hemorrhoids (P < 0.05). The incidence of adverse drug reactions in both groups was comparable and no patient required any treatment for the same. Conclusion: “Arshkeyt™, a 7 day kit,” was effective in the treatment of hemorrhoids and had a good safety profile. PMID:26834421

  15. The Efficacy, Safety and Applications of Medical Hypnosis.

    PubMed

    Häuser, Winfried; Hagl, Maria; Schmierer, Albrecht; Hansen, Ernil

    2016-04-29

    The efficacy and safety of hypnotic techniques in somatic medicine, known as medical hypnosis, have not been supported to date by adequate scientific evidence. We systematically reviewed meta-analyses of randomized controlled trials (RCTs) of medical hypnosis. Relevant publications (January 2005 to June 2015) were sought in the Cochrane databases CDSR and DARE, and in PubMed. Meta-analyses involving at least 400 patients were included in the present analysis. Their methodological quality was assessed with AMSTAR (A Measurement Tool to Assess Systematic Reviews). An additional search was carried out in the CENTRAL and PubMed databases for RCTs of waking suggestion (therapeutic suggestion without formal trance induction) in somatic medicine. Out of the 391 publications retrieved, five were reports of metaanalyses that met our inclusion criteria. One of these meta-analyses was of high methodological quality; three were of moderate quality, and one was of poor quality. Hypnosis was superior to controls with respect to the reduction of pain and emotional stress during medical interventions (34 RCTs, 2597 patients) as well as the reduction of irritable bowel symptoms (8 RCTs, 464 patients). Two meta-analyses revealed no differences between hypnosis and control treatment with respect to the side effects and safety of treatment. The effect size of hypnosis on emotional stress during medical interventions was low in one meta-analysis, moderate in one, and high in one. The effect size on pain during medical interventions was low. Five RCTs indicated that waking suggestion is effective in medical procedures. Medical hypnosis is a safe and effective complementary technique for use in medical procedures and in the treatment of irritable bowel syndrome. Waking suggestions can be a component of effective doctor-patient communication in routine clinical situations.

  16. The efficacy of neurofeedback in the management of children with attention deficit/hyperactivity disorder

    PubMed Central

    Baydala, Lola; Wikman, Erik

    2001-01-01

    Attention deficit/hyperactivity disorder (ADHD) is a behavioural disorder characterized by an inappropriate level of inattention with or without impulsivity or overactivity. The estimated prevalence of ADHD is 7% to 10% in boys and 3% in girls aged four to 11 years. The higher prevalence in boys is believed to be the result of a referral bias because boys with ADHD are more disruptive and aggressive, and, therefore, more likely to be referred to specialty clinics. ADHD is caused by a combination of biological – often genetically determined neurochemical disturbances – and environmental disadvantages that are associated with learning difficulties, behavioural problems and social rejection. The identification and treatment of children with ADHD are essential in preventing or at least minimizing the serious complications associated with this disorder. Stimulant medications are the most effective means of symptomatic control of ADHD symptoms, and the safety and efficacy of these medications is well established in the literature. Despite the known efficacy of stimulant medications, alternatives are often sought by parents of children with ADHD. A number of alternative and controversial treatments for ADHD are available, including dietary management, nutritional supplementation, vision therapy, hypnotherapy, guided imagery, relaxation training and electroencephalogram (EEG) neurofeedback. Published well controlled scientific studies either to support or refute the effectiveness of EEG neurofeedback for children with ADHD are not available. At the present time, EEG neurofeedback needs to be considered as an experimental treatment, the validity of which has not yet been determined. PMID:20107553

  17. Efficacy of print advertising for a bipolar disorder study.

    PubMed

    Roy, Sumeet; Patel, Shilpa; Sheehan, Kathy Harnett; Janavs, Juris; Sheehan, David

    2008-01-01

    Using quality and quantity of responses, this study evaluated the efficacy of advertising in print media for a bipolar disorder clinical trial. We analyzed the corresponding quantity of calls generated and the cost per patient yield at each of the standard study milestones, spending on print advertising. Quality of calls was based on the attrition rates at each of the study stages. Five hundred and twenty-six calls were received over a 28-month period (February 2004 to June 2006). The largest number of calls were received early in the week (Monday, 25.6%; Tuesday, 23.5%; Wednesday, 18.8%), corresponding with increased advertisements toward the end of the previous week. From the total calls received, 17.14% were eligible for a screening visit, 10.28% were randomized, 9.14% were evaluable, and 7% completed the 8-week study. Sixty percent of the subjects who attended the screening visit were randomized and 68.5% of the randomized subjects completed the study. The yield from phone calls responding to print advertising for a bipolar disorder study was 7%, costing $1,330 per evaluable subject and $1,725 per completed subject. These figures may be useful benchmarks in recruitment planning and budgeting for participants in clinical trials on bipolar disorder.

  18. Rotavirus vaccines: safety, efficacy and public health impact.

    PubMed

    Gray, J

    2011-09-01

    Rotaviruses are the cause of acute gastroenteritis, and disease is widespread amongst infants and young children throughout the world. Also, rotavirus is associated with significant mortality in developing countries with more than 500 000 children dying each year as a result of the severe dehydration associated with rotavirus disease. Efforts have been ongoing for more than 30 years to develop a safe and effective rotavirus vaccine. Currently, two vaccines, RotaRix and RotaTeq, have been licensed for use in many countries throughout the world following comprehensive safety and efficiency trials. Monitoring their effectiveness after licensure has confirmed that their incorporation into early childhood vaccination schedules can significantly prevent severe rotavirus diarrhoea, which would have resulted in hospitalizations, emergency room visits or increased diarrhoea-related mortality. Although the efficacy of both vaccines is lower at approximately 40-59% in developing countries, their use could significantly reduce the mortality associated with rotavirus disease that is concentrated in these countries. © 2011 The Association for the Publication of the Journal of Internal Medicine.

  19. Dietary strategies for improving iron status: balancing safety and efficacy

    PubMed Central

    Mendoza, Yery A.; Pereira, Dora; Cerami, Carla; Wegmuller, Rita; Constable, Anne; Spieldenner, Jörg

    2017-01-01

    In light of evidence that high-dose iron supplements lead to a range of adverse events in low-income settings, the safety and efficacy of lower doses of iron provided through biological or industrial fortification of foodstuffs is reviewed. First, strategies for point-of-manufacture chemical fortification are compared with biofortification achieved through plant breeding. Recent insights into the mechanisms of human iron absorption and regulation, the mechanisms by which iron can promote malaria and bacterial infections, and the role of iron in modifying the gut microbiota are summarized. There is strong evidence that supplemental iron given in nonphysiological amounts can increase the risk of bacterial and protozoal infections (especially malaria), but the use of lower quantities of iron provided within a food matrix, ie, fortified food, should be safer in most cases and represents a more logical strategy for a sustained reduction of the risk of deficiency by providing the best balance of risk and benefits. Further research into iron compounds that would minimize the availability of unabsorbed iron to the gut microbiota is warranted. PMID:27974599

  20. Efficacy and safety of a transdermal contraceptive system.

    PubMed

    Smallwood, G H; Meador, M L; Lenihan, J P; Shangold, G A; Fisher, A C; Creasy, G W

    2001-11-01

    To evaluate the efficacy, cycle control, compliance, and safety of a transdermal contraceptive system that delivers norelgestromin 150 microg and ethinyl estradiol 20 microg daily. In this open-label, 73-center study, 1672 healthy, ovulatory, sexually active women received ORTHO EVRA/EVRA for six (n = 1171) or 13 cycles (n = 501). The treatment regimen for each cycle was three consecutive 7-day patches (21 days) followed by 1 patch-free week. The overall and method-failure probabilities of pregnancy through 13 cycles were 0.7% and 0.4%, respectively. The incidence of breakthrough bleeding was low throughout the study. Perfect compliance (21 consecutive days of dosing, followed by a 7-day drug-free interval; no patch could be worn for more than 7 days) was achieved in 90% of subject cycles; only 1.9% of patches detached completely. Adverse events were typical of hormonal contraception, and most were mild-to-moderate in severity and not treatment limiting. The most common adverse events resulting in discontinuation were application site reactions (1.9%), nausea (1.8%), emotional lability (1.5%), headache (1.1%), and breast discomfort (1.0%). The transdermal contraceptive patch provides effective contraception and cycle control, and is well tolerated. The weekly change schedule for the contraceptive patch is associated with excellent compliance and wearability characteristics.

  1. Safety and efficacy of LigaSure usage in pancreaticoduodenectomy.

    PubMed

    Eng, Oliver S; Goswami, Julie; Moore, Dirk; Chen, Chunxia; Brumbaugh, Jennifer; Gannon, Christopher J; August, David A; Carpizo, Darren R

    2013-10-01

    Over recent years, use of the LigaSure™ vessel sealing device has increased in major abdominal surgery to include pancreaticoduodenectomy (PD). LigaSure™ use during PD has expanded to include all steps of the procedure, including the division of the uncinate margin. This introduces the potential for thermal major vascular injury or margin positivity. The aim of the present study was to evaluate the safety and efficacy of LigaSure™ usage in PD in comparison to established dissection techniques. One hundred and forty-eight patients who underwent PD from 2007 to 2012 at Robert Wood Johnson University Hospital were identified from a retrospective database. Two groups were recognized: those in which the LigaSure™ device was used (N = 114), and in those it was not (N = 34). Peri-operative outcomes were compared. Vascular intra-operative complications directly caused by thermal injury from LigaSure™ use occurred in 1.8% of patients. Overall vascular intra-operative complications, uncinate margin positivity, blood loss, length of stay, and complication severity were not significantly different between groups. The mean operative time was 77 min less (P < 0.010) in the LigaSure™ group. Savings per case where the LigaSure™ was used amounted to $1776.73. LigaSure™ usage during PD is safe and effective. It is associated with decreased operative times, which may decrease operative costs in PD. © 2013 International Hepato-Pancreato-Biliary Association.

  2. Safety and efficacy of LigaSure usage in pancreaticoduodenectomy

    PubMed Central

    Eng, Oliver S; Goswami, Julie; Moore, Dirk; Chen, Chunxia; Brumbaugh, Jennifer; Gannon, Christopher J; August, David A; Carpizo, Darren R

    2013-01-01

    Background Over recent years, use of the LigaSure™ vessel sealing device has increased in major abdominal surgery to include pancreaticoduodenectomy (PD). LigaSure™ use during PD has expanded to include all steps of the procedure, including the division of the uncinate margin. This introduces the potential for thermal major vascular injury or margin positivity. The aim of the present study was to evaluate the safety and efficacy of LigaSure™ usage in PD in comparison to established dissection techniques. Methods One hundred and forty-eight patients who underwent PD from 2007 to 2012 at Robert Wood Johnson University Hospital were identified from a retrospective database. Two groups were recognized: those in which the LigaSure™ device was used (N = 114), and in those it was not (N = 34). Peri-operative outcomes were compared. Results Vascular intra-operative complications directly caused by thermal injury from LigaSure™ use occurred in 1.8% of patients. Overall vascular intra-operative complications, uncinate margin positivity, blood loss, length of stay, and complication severity were not significantly different between groups. The mean operative time was 77 min less (P < 0.010) in the LigaSure™ group. Savings per case where the LigaSure™ was used amounted to $1776.73. Conclusion LigaSure™ usage during PD is safe and effective. It is associated with decreased operative times, which may decrease operative costs in PD. PMID:23782268

  3. [Therapeutic efficacy and safety of repetitive Transcranial Magnetic Stimulation in depressions of the elderly: a review].

    PubMed

    Jalenques, I; Legrand, G; Vaille-Perret, E; Tourtauchaux, R; Galland, F

    2010-06-01

    During the past 15 years, therapeutic effects of repetitive Transcranial Magnetic Stimulation (rTMS) have been studied in psychiatric diseases, particularly in the treatment of depressive disorders. There are more and more data suggesting its efficacy in the treatment of depression in older patients. Thus, the authors found it useful to conduct an up-to-date review of studies that examined the efficacy and safety of rTMS to treat depressive disorders in the aged. After an exhaustive consultation of databases (Medline/PubMed and the Avery-George-Holtzheimer Database of rTMS Depression Studies), supplemented by a manual research, the authors retained studies evaluating the therapeutic efficacy of rTMS on depressive disorders in the aged. Fifteen studies were retained. Four open studies using high frequency rTMS, applied to the left dorsolateral prefrontal cortex (DLPFC), demonstrated a decrease in the mean Hamilton Depression Rating Scale (HDRS) scores; however, only a quarter of the aged patients studied experienced a significant remission of depression. Five parallel arm double-blind versus placebo studies concluded in contradicting results: two studies confirmed a significantly greater efficacy of rTMS compared to placebo, whereas three studies did not; but the sham procedure (positioning coil at 90 degrees from the scalp) was disputable in most studies. One study concluded in therapeutic efficacy by inhibiting the right DLPFC. Three controlled parallel arm studies compared rTMS and electroconvulsive-therapy (ECT); one study concluded in greater efficacy of ECT at end of treatment, but the number of ECT treatments depended on the patients' response, whereas a 15-day course of rTMS was systematically administered; additionally HDRS scores were similar in two groups of patients (rTMS and ECT) at 6 months. Lastly, three studies focused on aged patients with cerebrovascular disease. They showed the efficacy of rTMS, although older age and smaller frontal gray mater

  4. Investigating Change in Adolescent Self-Efficacy of Food Safety through Educational Interventions

    ERIC Educational Resources Information Center

    Beavers, Amy S.; Murphy, Lindsay; Richards, Jennifer K.

    2015-01-01

    A successfully targeted intervention can influence food safety knowledge, attitudes, and behaviors, as well as encourage participants to recognize their own responsibility for safe food handling. This acknowledgement of an individual's responsibility and capacity to address food safety can be understood as self-efficacy of food safety (SEFS). This…

  5. Management of atopic dermatitis: safety and efficacy of phototherapy

    PubMed Central

    Patrizi, Annalisa; Raone, Beatrice; Ravaioli, Giulia Maria

    2015-01-01

    Atopic dermatitis (AD) is a common chronic inflammatory skin disease that can affect all age groups. It is characterized by a relapsing course and a dramatic impact on quality of life for patients. Environmental interventions together with topical devices represent the mainstay of treatment for AD, in particular emollients, corticosteroids, and calcineurin inhibitors. Systemic treatments are reserved for severe cases. Phototherapy represents a valid second-line intervention in those cases where non-pharmacological and topical measures have failed. Different forms of light therapy are available, and have showed varying degrees of beneficial effect against AD: natural sunlight, narrowband (NB)-UVB, broadband (BB)-UVB, UVA, UVA1, cold-light UVA1, UVA and UVB (UVAB), full-spectrum light (including UVA, infrared and visible light), saltwater bath plus UVB (balneophototherapy), Goeckerman therapy (coal tar plus UVB radiation), psoralen plus UVA (PUVA), and other forms of phototherapy. In particular, UVA1 and NB-UVB have gained importance in recent years. This review illustrates the main trials comparing the efficacy and safety of the different forms of phototherapy. No sufficiently large randomized controlled studies have been performed as yet, and no light modality has been defined as superior to all. Parameters and dosing protocols may vary, although clinicians mainly refer to the indications included in the American Academy of Dermatology psoriasis guidelines devised by Menter et al in 2010. The efficacy of phototherapy (considering all forms) in AD has been established in adults and children, as well as for acute (UVA1) and chronic (NB-UVB) cases. Its use is suggested with strength of recommendation B and level of evidence II. Home phototherapy can also be performed; this technique is recommended with strength C and level of evidence III. Phototherapy is generally considered to be safe and well tolerated, with a low but established percentage of short-term and long

  6. Expanded Safety and Efficacy Data for a New Method of Performing Electroconvulsive Therapy

    PubMed Central

    Sahlem, Gregory L.; Short, E. Baron; Kerns, Suzanne; Snipes, Jon; DeVries, William; Fox, James B.; Burns, Carol; Schmidt, Matthew; Nahas, Ziad H.; George, Mark S.; Sackeim, Harold A.

    2016-01-01

    Objective Electroconvulsive therapy (ECT) is the most rapid and effective antidepressant treatment but with concerns about cognitive adverse effects. A new form of ECT, focal electrically administered seizure therapy (FEAST), was designed to increase the focality of stimulation and better match stimulus parameters with neurophysiology. We recently reported on the safety and feasibility of FEAST in a cohort (n = 17) of depressed patients. We now report on the safety, feasibility, preliminary efficacy, and cognitive effects of FEAST in a new cohort. Methods Open-label FEAST was administered to 20 depressed adults (6 men; 3 with bipolar disorder; age 49.1 ± 10.6 years). Clinical and cognitive assessments were obtained at baseline and end of course. Time to orientation recovery was assessed at each treatment. Nonresponders switched to conventional ECT. Results Participants tolerated the treatment well with no dropouts. Five patients (25%) transitioned from FEAST to conventional ECT due to inadequate response. After FEAST (mean, 9.3 ± 3.5 sessions; range, 4–14), there was a 58.1% ± 36.0% improvement in Hamilton Rating Scale for Depression scores compared with that in the baseline (P < 0.0001); 13 (65%) of 20 patients met response criteria, and 11 (55%) of 20 met remission criteria. Patients achieved reorientation (4 of 5 items) in 4.4 ± 3.0 minutes (median, 4.5 minutes), timed from eyes opening. There was no deterioration in neuropsychological measures. Conclusions These findings provide further support for the safety and efficacy of FEAST. The remission and response rates were in the range found using conventional ECT, and the time to reorientation may be quicker. However, without a randomized comparison group, conclusions are tentative. PMID:27379790

  7. Efficacy and safety of acupuncture for dizziness and vertigo in emergency department: a pilot cohort study.

    PubMed

    Chiu, Chih-Wen; Lee, Tsung-Chieh; Hsu, Po-Chi; Chen, Chia-Yun; Chang, Shun-Chang; Chiang, John Y; Lo, Lun-Chien

    2015-06-09

    Dizziness and vertigo account for roughly 4% of chief symptoms in the emergency department (ED). Pharmacological therapy is often applied for these symptoms, such as vestibular suppressants, anti-emetics and benzodiazepines. However, every medication is accompanied with unavoidable side-effects. There are several research articles providing evidence of acupuncture treating dizziness and vertigo but few studies of acupuncture as an emergent intervention in ED. We performed a pilot cohort study to evaluate the efficacy and safety of acupuncture in treating patients with dizziness and vertigo in ED. A total of 60 participants, recruited in ED, were divided into acupuncture and control group. Life-threatening conditions or central nervous system disorders were excluded to ensure participants' safety. The clinical effect of treating dizziness and vertigo was evaluated by performing statistical analyses on data collected from questionnaires of Dizziness Handicap Inventory (DHI), Visual Analog Scale (VAS) of dizziness and vertigo, and heart rate variability (HRV). The variation of VAS demonstrated a significant decrease (p-value: 0.001 and p-value: 0.037) between two groups after two different durations: 30 mins and 7 days. The variation of DHI showed no significant difference after 7 days. HRV revealed a significant increase in high frequency (HF) in the acupuncture group. No adverse event was reported in this study. Acupuncture demonstrates a significant immediate effect in reducing discomforts and VAS of both dizziness and vertigo. This study provides clinical evidence on the efficacy and safety of acupuncture to treat dizziness and vertigo in the emergency department. ClinicalTrials.gov ID: NCT02358239 . Registered 5 February 2015.

  8. Vitrectomy for floaters: prospective efficacy analyses and retrospective safety profile.

    PubMed

    Sebag, Jerry; Yee, Kenneth M P; Wa, Christianne A; Huang, Laura C; Sadun, Alfredo A

    2014-06-01

    Floaters impact vision but the mechanism is unknown. We hypothesize that floaters reduce contrast sensitivity function, which can be normalized by vitrectomy, and that minimally invasive vitrectomy will have lower incidences of retinal tears (reported at 30%) and cataracts (50-76%). Seventy-six eyes (34 phakic) with floaters were evaluated in 2 separate studies. Floater etiologies were primarily posterior vitreous detachment in 61 of 76 eyes (80%) and myopic vitreopathy in 24 of 76 eyes (32%). Minimally invasive 25G vitrectomy was performed without posterior vitreous detachment induction, leaving anterior vitreous, and using nonhollow probes for cannula extraction. Efficacy was studied prospectively (up to 9 months) in 16 floater cases with Freiburg Acuity Contrast Testing (Weber index [%W] reproducibility = 92.1%) and the National Eye Institute Visual Function Questionnaire. Safety was separately evaluated in 60 other cases followed up on an average of 17.5 months (range, 3-51 months). Floater eyes had 67% contrast sensitivity function attenuation (4.0 ± 2.3 %W; control subjects = 2.4 ± 0.9 %W, P < 0.013). After vitrectomy, contrast sensitivity function normalized in each case at 1 week (2.0 ± 1.4 %W, P < 0.01) and remained normal at 1 month (2.0 ± 1.0 %W, P < 0.003) and 3 months to 9 months (2.2 ± 1.5 %W, P < 0.018). Visual Function Questionnaire was 28.3% lower in floater patients (73.2 ± 15.6, N = 16) than in age-matched control subjects (93.9 ± 8.0, N = 12, P < 0.001), and postoperatively improved by 29.2% (P < 0.001). In the safety study of 60 floater cases treated with vitrectomy, none developed retinal breaks, infection, or glaucoma after a mean follow-up of 17.5 months. Only 8 of 34 cases (23.5%) required cataract surgery (none younger than 53 years) at an average of 15 months postvitrectomy. Floaters lower contrast sensitivity function, which normalizes after vitrectomy. Visual Function Questionnaire quantified improvement in satisfaction. Not

  9. Electronic Cigarettes Efficacy and Safety at 12 Months: Cohort Study

    PubMed Central

    Fiore, Maria; La Vecchia, Carlo; Marzuillo, Carolina; Gualano, Maria Rosaria; Liguori, Giorgio; Cicolini, Giancarlo; Capasso, Lorenzo; D'Amario, Claudio; Boccia, Stefania; Siliquini, Roberta; Ricciardi, Walter; Villari, Paolo

    2015-01-01

    Objective To evaluate the safety and efficacy as a tool of smoking cessation of electronic cigarettes (e-cigarettes), directly comparing users of e-cigarettes only, smokers of tobacco cigarettes only, and smokers of both. Design Prospective cohort study. Final results are expected in 2019, but given the urgency of data to support policies on electronic smoking, we report the results of the 12-month follow-up. Data Sources Direct contact and structured questionnaires by phone or via internet. Methods Adults (30–75 years) were included if they were smokers of ≥1 tobacco cigarette/day (tobacco smokers), users of any type of e-cigarettes, inhaling ≥50 puffs weekly (e-smokers), or smokers of both tobacco and e-cigarettes (dual smokers). Carbon monoxide levels were tested in a sample of those declaring tobacco smoking abstinence. Main Outcome Measures Sustained smoking abstinence from tobacco smoking at 12 months, reduction in the number of tobacco cigarettes smoked daily. Data Synthesis We used linear and logistic regression, with region as cluster unit. Results Follow-up data were available for 236 e-smokers, 491 tobacco smokers, and 232 dual smokers (overall response rate 70.8%). All e-smokers were tobacco ex-smokers. At 12 months, 61.9% of the e-smokers were still abstinent from tobacco smoking; 20.6% of the tobacco smokers and 22.0% of the dual smokers achieved tobacco abstinence. Adjusting for potential confounders, tobacco smoking abstinence or cessation remained significantly more likely among e-smokers (adjusted OR 5.19; 95% CI: 3.35–8.02), whereas adding e-cigarettes to tobacco smoking did not enhance the likelihood of quitting tobacco and did not reduce tobacco cigarette consumption. E-smokers showed a minimal but significantly higher increase in self-rated health than other smokers. Non significant differences were found in self-reported serious adverse events (eleven overall). Conclusions Adding e-cigarettes to tobacco smoking did not facilitate

  10. Efficacy and safety profile of xanthines in COPD: a network meta-analysis.

    PubMed

    Cazzola, Mario; Calzetta, Luigino; Barnes, Peter J; Criner, Gerard J; Martinez, Fernando J; Papi, Alberto; Gabriella Matera, Maria

    2018-06-30

    Theophylline can still have a role in the management of stable chronic obstructive pulmonary disease (COPD), but its use remains controversial, mainly due to its narrow therapeutic window. Doxofylline, another xanthine, is an effective bronchodilator and displays a better safety profile than theophylline. Therefore, we performed a quantitative synthesis to compare the efficacy and safety profile of different xanthines in COPD.The primary end-point of this meta-analysis was the impact of xanthines on lung function. In addition, we assessed the risk of adverse events by normalising data on safety as a function of person-weeks. Data obtained from 998 COPD patients were selected from 14 studies and meta-analysed using a network approach.The combined surface under the cumulative ranking curve (SUCRA) analysis of efficacy (change from baseline in forced expiratory volume in 1 s) and safety (risk of adverse events) showed that doxofylline was superior to aminophylline (comparable efficacy and significantly better safety), bamiphylline (significantly better efficacy and comparable safety), and theophylline (comparable efficacy and significantly better safety).Considering the overall efficacy/safety profile of the investigated agents, the results of this quantitative synthesis suggest that doxofylline seems to be the best xanthine for the treatment of COPD. Copyright ©ERS 2018.

  11. Efficacy and Safety of Ethanol Ablation for Branchial Cleft Cysts.

    PubMed

    Ha, E J; Baek, S M; Baek, J H; Shin, S Y; Han, M; Kim, C-H

    2017-12-01

    Branchial cleft cyst is a common congenital lesion of the neck. This study evaluated the efficacy and safety of ethanol ablation as an alternative treatment to surgery for branchial cleft cyst. Between September 2006 and October 2016, ethanol ablation was performed in 22 patients who refused an operation for a second branchial cleft cyst. After the exclusion of 2 patients who were lost to follow-up, the data of 20 patients were retrospectively evaluated. All index masses were confirmed as benign before treatment. Sonography-guided aspiration of the cystic fluid was followed by injection of absolute ethanol (99%) into the lesion. The injected volume of ethanol was 50%-80% of the volume of fluid aspirated. Therapeutic outcome, including the volume reduction ratio, therapeutic success rate (volume reduction ratio of >50% and/or no palpable mass), and complications, was evaluated. The mean index volume of the cysts was 26.4 ± 15.7 mL (range, 3.8-49.9 mL). After ablation, the mean volume of the cysts decreased to 1.2 ± 1.1 mL (range, 0.0-3.5 mL). The mean volume reduction ratio at last follow-up was 93.9% ± 7.9% (range, 75.5%-100.0%; P < .001). Therapeutic success was achieved in all nodules (20/20, 100%), and the symptomatic ( P < .001) and cosmetic ( P < .001) scores had improved significantly by the last follow-up. In 1 patient, intracystic hemorrhage developed during the aspiration; however, no major complications occurred in any patient. Ethanol ablation is an effective and safe treatment for patients with branchial cleft cysts who refuse, or are ineligible for, an operation. © 2017 by American Journal of Neuroradiology.

  12. Safety and Efficacy of Warfarin Therapy in Kawasaki Disease.

    PubMed

    Baker, Annette L; Vanderpluym, Christina; Gauvreau, Kimberly A; Fulton, David R; de Ferranti, Sarah D; Friedman, Kevin G; Murray, Jenna M; Brown, Loren D; Almond, Christopher S; Evans-Langhorst, Margaret; Newburger, Jane W

    2017-10-01

    To describe the safety and efficacy of warfarin for patients with Kawasaki disease and giant coronary artery aneurysms (CAAs, ≥8 mm). Giant aneurysms are managed with combined anticoagulation and antiplatelet therapies, heightening risk of bleeding complications. We reviewed the time in therapeutic range; percentage of international normalization ratios (INRs) in range (%); bleeding events, clotting events; INRs ≥6; INRs ≥5 and <6; and INRs <1.5. In 9 patients (5 male), median age 14.4 years (range 7.1-22.8 years), INR testing was prescribed weekly to monthly and was done by home monitor (n = 5) or laboratory (n = 3) or combined (1). Median length of warfarin therapy was 7.2 years (2.3-13.3 years). Goal INR was 2.0-3.0 (n = 6) or 2.5-3.5 (n = 3), based on CAA size and history of CAA thrombosis. All patients were treated with aspirin; 1 was on dual antiplatelet therapy and warfarin. The median time in therapeutic range was 59% (37%-85%), and median percentage of INRs in range was 68% (52%-87%). INR >6 occurred in 3 patients (4 events); INRs ≥5 <6 in 7 patients (12 events); and INR <1.5 in 5 patients (28 events). The incidence of major bleeding events and clinically relevant nonmajor bleeding events were each 4.3 per 100 patient-years (95% CI 0.9-12.6). New asymptomatic coronary thrombosis was detected by imaging in 2 patients. Bleeding and clotting complications are common in patients with Kawasaki disease on warfarin and aspirin, with INRs in range only two-thirds of the time. Future studies should evaluate the use of direct oral anticoagulants in children as an alternative to warfarin. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Efficacy and safety of topical tranexamic acid in knee arthroplasty.

    PubMed

    López-Hualda, Álvaro; Dauder-Gallego, Cristina; Ferreño-Márquez, David; Martínez-Martín, Javier

    2018-02-26

    Tranexamic acid (TXA) is commonly used to control postoperative blood loss in total knee arthroplasty. In order to avoid adverse effects associated with intravenous administration, topical use has been proposed as an alternative. Our aim was to evaluate the efficacy and safety of topical TXA in total knee arthroplasty. A total of 90 patients scheduled for unilateral total knee arthroplasty were included in a prospective randomised study. All surgeries were performed under spinal anaesthesia, tourniquet and the same postoperative protocol. Patients were allocated to one of the 3 groups according to the application of TXA: group A (n=30) 1g of topical TXA; group B (n=30) 1g of TXA intravenous and in group C or the control group (n=30) no drug was administrated. Parameters related to blood loss and drain outputs were compared between the 3 groups. The results revealed that post-operative decrease in haemoglobin level was significantly lower in group A (1.95g/dL) than group B (2.25g/dL) and group C (2.96g/dL), P<.01. Total postoperative blood loss was lower in group A (195mL) than group B (466mL) and group C (718mL), P<.01. There was no significant difference in complications and allogenic blood transfusion rate between the 3 groups. According to the results, topical application of 1g TXA significantly reduced blood loss in patients undergoing total knee arthroplasty more than intravenous or no administration of TXA. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

  14. Efficacy and safety of OK-432 immunotherapy of lymphatic malformations.

    PubMed

    Smith, Mark C; Zimmerman, M Bridget; Burke, Diane K; Bauman, Nancy M; Sato, Yutaka; Smith, Richard J H

    2009-01-01

    To determine the efficacy and safety of the immunostimulant OK-432 (Picibanil) as a treatment option in the management of children with cervicofacial lymphatic malformations. A prospective, randomized, multi-institutional phase II clinical trial at 27 U.S. academic medical centers. 182 patients with lymphatic malformations (LM) were enrolled between January 1998 and November 2004. Of the 151 patients with complete case report forms, 117 patients were randomized into immediate or delayed treatment groups; 34 patients were nonrandomized and assigned to the open-label group. Treatment consisted of a four-dose intralesional injection series of OK-432 at eight-week intervals. Patients randomized into the delayed treatment group served as observational controls for spontaneous regression. Response to therapy was measured radiographically by quantitating change in lesion size and graded as complete (90%-100%), substantial (60%-89%), intermediate (20%-59%), or none (<20%). Of 117 patients randomized with intent-to-treat, 68% demonstrated a complete or substantial response to OK-432 immunotherapy. Response data for macrocystic LM were higher, with a complete or substantial response in 94% of patients; 63% of patients with mixed macrocystic-microcystic LM responded to treatment; no patients with microcystic LM responded to treatment. Spontaneous resolution occurred in less than 2% of patients. Median follow-up of 2.9 years demonstrated a 9% recurrence rate. Major adverse effects related to therapy occurred in 11 patients. As compared to historical surgical data on LM, OK-432 immunotherapy is more effective (P < .001) and has a lower morbidity (P < .001). OK-432 immunotherapy is an effective, safe, and simple treatment option for the management of macrocystic cervicofacial LM. ClinicalTrials.gov Identifier: NCT00010452.

  15. Abstinence Self-Efficacy and Abstinence 1 Year After Substance Use Disorder Treatment

    ERIC Educational Resources Information Center

    Ilgen, Mark; McKellar, John; Tiet, Quyen

    2005-01-01

    To better understand the relationship between abstinence self-efficacy and treatment outcomes in substance use disorder patients, experts in the field need more information about the levels of abstinence self-efficacy most predictive of treatment outcomes. Participants (N = 2,967) from 15 residential substance use disorder treatment programs were…

  16. Efficacy of alprazolam sublingual tablets in the treatment of the acute phase of panic disorders.

    PubMed

    Márquez, Miguel; Arenoso, Hector; Caruso, Norberto

    2011-01-01

    Panic disorder affects 2-5% of the general population. In Argentina, one million people would be affected with a 91% rate of psychiatric comorbidity. AIM; To compare efficacy parameters between sublingual (ALP-SL) and conventional (ALP-CT) tablets of alprazolam in the treatment of acute phase of panic disorder with and without agoraphobia. A comparative, multicenter (6 sites), double blind, randomized study was carried out. A total of 190 outpatients with (n=117) and without (n=73) agoraphobia were treated with ALP-SL or ALP-CT for 12 weeks. Outcome was assessed with the Clinical Global Impressions (CGI-S/CGI-I), Hamilton Rating Scale for Anxiety (HAM-A), Arizona Sexual Experiences Scale (ASEX), Patient Global Impression (PGI), Psychological General Well-Being Index (PGWBI), Panic Disorder Severity Scale (PDSS) also by the number of panic attacks and extension and intensity of panic attacks and anticipatory anxiety. RESULTS. Both treatments resulted in statistically significant clinical improvement in all measures. ASEX presented no changes during the study. The average dose of alprazolam for 12 weeks was 1.36 ± 0.70 mg/day (1.39 ± 0.77 ALP-CT and 1.33 ± 0.64 ALP-SL). With ALP-SL, panic attacks were shorter (p < 0.05) with shorter extension (p=0.16) and intensity of anticipatory anxiety (p=0.14). The treatment was well tolerated, there being no differences between both groups. Alprazolam has been demonstrated to have efficacy, safety and good tolerability in the treatment of the acute phase of panic disorder, the sublingual tablets showing some comparative advantages.

  17. Safety and efficacy of antihypertensive prescription at emergency department discharge.

    PubMed

    Brody, Aaron; Rahman, Tahsin; Reed, Brian; Millis, Scott; Ference, Brian; Flack, John M; Levy, Phillip D

    2015-05-01

    Poor blood pressure (BP) control is a primary risk factor for target organ damage in the heart, brain, and kidney. Uncontrolled hypertension is common among emergency department (ED) patients, particularly in underresourced settings, but it is unclear what role ED providers should play in the management of chronic antihypertensive therapy. The objective was to evaluate the safety and efficacy of prescribing antihypertensive therapy from the ED. This was a retrospective study of data pooled from two prospective, longitudinal, randomized controlled trials, both of which enrolled ED patients with asymptomatic hypertension. Antihypertensives were prescribed at emergency physician discretion, and this was not related to randomization arm. Demographic data, BP at screening and randomization visit, and data on adverse effects potentially related to antihypertensive therapy were compiled. Means were compared using Student's t-tests, and proportions were compared using chi-square tests. The effect of antihypertensive therapy on BP control was further analyzed using multivariable regression modeling controlling for age, race, sex, hypertension history, study cohort, and ED BP. Data were abstracted for 217 subjects. The median interval from ED visit to randomization was 12 days. Seventy-six subjects (35%) received one or more prescriptions for antihypertensive therapy. Age, sex, race, hypertension history, and mean duration of hypertension were equivalent between groups. Although mean ED BP was higher among those who received prescriptions, the mean systolic BP (sBP) reduction from ED to randomization was significantly greater (difference = 19 mm Hg, 95% confidence interval = 12 to 26 mm Hg). No patient in either group had an sBP less than 100 mm Hg at randomization. On multiple regression modeling, randomization sBP reduction was independently associated with antihypertensive prescription (p = 0.001). The incidence of adverse effects was equivalent and low in

  18. Diode laser cyclophotocoagulation in Indian eyes: efficacy and safety.

    PubMed

    Singh, Kirti; Jain, Divya; Veerwal, Vikas

    2017-02-01

    Diode laser cyclophotocoagulation (DLCP) has emerged as a time-tested procedure for end-stage glaucoma with fewer complications. By means of this study, we have evaluated its wide indications, its efficacy, and safety in darkly pigmented Asian Indian eyes. Ninety-one eyes with uncontrolled glaucoma presenting to glaucoma clinic of a tertiary care center over a period of 6 years were scheduled for DLCP. The semiconductor diode laser with a G probe was used with laser energy delivered about 1.5 mm behind the surgical limbus. The extent of clock hours of laser application was determined by pretreatment intraocular pressure (IOP) and superior area was spared in cases where future filtration surgery was contemplated. The DLCP was repeated earliest at 1 month in case of non-response and a maximum of three laser procedures were performed for any patient. Ninety-one eyes of 89 patients (40 males, 49 females) were included. Common indications included secondary glaucoma (37.3 %), failed trabeculectomies (27.4 %), angle closure glaucoma (17.5 %), etc. Laser power delivered ranged from 990 to 1800 mW, (mean 1396 + 182.14 mW) with an average of 17 spots. Patients improved from pretreatment IOP of 38.18 + 8.96 mmHg (range 20.6-64) to post treatment IOP of 17.86 + 7.75 mmHg (range 10-42). Qualified success was defined as final IOP of 20 mm Hg or less on topical medications that could be achieved in 70 % eyes with one or repeat treatment. Pre op visual acuity ranged from PL+ to 6/18 showing a slight improvement to PL+ to 6/12 post op. A 58.5 % reduction of IOP was noted. No incidence of serious complications was noted during follow-up ranging from 9 months to 3 years. DLCP is an effective and safe tool to be used in Indian population for control of IOP. It can be safely used as a primary modality to bring IOP to permissible levels before trabeculectomy.

  19. Evaluation of the efficacy and safety of bromocriptine QR in type 2 diabetes.

    PubMed

    Ramteke, Karuna Balwant; Ramanand, Sunita Jaiprakash; Ramanand, Jaiprakash B; Jain, Suyog Subhas; Raparti, Girish Tulsidas; Patwardhan, Milind Hari; Murthy, Mangala; Ghanghas, Ravi G

    2011-07-01

    Diabetes mellitus is a chronic metabolic disorder of endocrinal origin with multiorgan involement. Today's physician has a lot many options to choose for treating type 2 diabetes, but does not always manages to achieve optimal glycemic control. The newer drug bromocriptine acts by novel hypothalamic circadian rhythm resetting mechanism. To evaluate the efficacy and safety of bromocriptine QR in type 2 diabetes. 105 patients according to inclusion and exclusion criteria were randomized into three groups by simple randomization. Group 1 received bromocriprine 2.4 mg once daily, group 2 received metformin 500 mg twice daily while group 3 received bromocriprine 1.6 mg daily and metformin 500 mg twice daily. Baseline measurement of fasting and postprandial blood sugar, HbA1(C) and BMI were followed up at 6(th) and 12(th) weeks. Safety evaluation was done by questioning the patient and also through routine hematological and biochemical parameters. Z test was used for analysis. Group 1 showed significant reduction in fasting and postprandial sugar and HbA(1c) at 12 weeks. While groups 2 and 3 showed even higher reduction in these parameters albeit with slightly more adverse drug events like nausea, vomiting compared to group 1. Bromocriptine QR is an effective and safe antidiabetic drug which can be employed as monotherapy or in conjuction with metformin to achieve and maintain optimal glycemic control.

  20. Office Visits to Monitor Stimulant Medication Safety and Efficacy: Recommended Care.

    PubMed

    Zima, Bonnie T; Norquist, Grayson S; Altchuler, Steven I; Behrens, Jacob; Iles-Shih, Matthew D; Ng, Yiu Kee Warren; Schaepper, Mary Ann

    2018-06-01

    The clinical guidance based on the research article, "Specific Components of Pediatricians' Medication-Related Care Predict Attention-Deficit/Hyperactivity Disorder Improvement," published in the June 2017 issue, 1 might be premature. The authors, Epstein et al., suggest that "Physicians do not need to necessarily rely on office visits to monitor medication response and side effects in the week(s) after initially prescribing medication, but instead could use phone calls or email correspondence to check in with the family" (p. 489). However, this advice has the potential to be misinterpreted that phone or email contact is acceptable clinical practice to monitor stimulant medication safety and efficacy, especially during the maintenance phase. It also could be erroneously interpreted that phone or email contact is sufficient for follow-up care for children receiving medication treatment for attention-deficit/hyperactivity disorder (ADHD) for national quality measures. Copyright © 2018 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  1. Efficacy and safety of a new topical keratolytic treatment for localized hyperkeratosis in adults.

    PubMed

    Sadick, Neil S; Coutanceau, Christine; Sibaud, Vincent; Merial-Kieny, Christelle

    2010-12-01

    Palmoplantar keratoderma (PPK) is a heterogeneous group of skin disorders characterized by symmetrical diffuse or patchy areas of hyperkeratosis on the palms and soles. This study aimed to evaluate the efficacy and safety of a topical keratolytic treatment for localized hyperkeratosis. International, randomized, vehicle-controlled, double-blind, intra-individual comparative study. Clinical signs assessed by the investigator significantly improved in both group from baseline to day 10 and day 21 (P<0.001). Mean improvement was significantly more marked on the treated side than the control side (except pruritus) at day 10 for hyperkeratosis (-0.58 ± 0.59 versus -0.41 ± 0.51, P=0.009), desquamation (-0.62 ± 0.69 versus -0.47 ± 0.67, P=0.042) and dryness (-0.75 ± 0.67 versus -0.57 ± 0.67, P=0.014). At day 21, dryness (-1.16 ± 0.80 versus -1.00 ± 0.79, P=0.036) was significantly improved but only a trend for hyperkeratosis (-0.86 ± 0.76 versus -0.72 ± 0.72, P=0.158) and desquamation (-0.83 ± 0.85 versus -0.65 ± 0.85, P=0.057) was observed. Tolerance was considered to be good or very good in more than 92 percent patients. Both patients and investigators were satisfied in more than 84 percent of cases with the topical keratolytic treatment efficacy. Safety profile was highly satisfactory. This topical keratolytic treatment represents a valuable first-line option for mild to moderate hyperkeratosis.

  2. Efficacy and Safety of an Injectable Combination Hormonal Contraceptive for Men.

    PubMed

    Behre, Hermann M; Zitzmann, Michael; Anderson, Richard A; Handelsman, David J; Lestari, Silvia W; McLachlan, Robert I; Meriggiola, M Cristina; Misro, Man Mohan; Noe, Gabriela; Wu, Frederick C W; Festin, Mario Philip R; Habib, Ndema A; Vogelsong, Kirsten M; Callahan, Marianne M; Linton, Kim A; Colvard, Doug S

    2016-12-01

    The development of a safe and effective reversible method of male contraception is still an unmet need. Evaluation of suppression of spermatogenesis and contraceptive protection by coadministered im injections of progestogen and testosterone. Prospective multicentre study. Ten study centers. Healthy men, aged 18-45 years, and their 18- to 38-year-old female partners, both without known fertility problems. Intramuscular injections of 200-mg norethisterone enanthate combined with 1000-mg testosterone undecanoate, administered every 8 weeks. Suppression of spermatogenesis by ejaculate analysis, contraceptive protection by pregnancy rate. Of the 320 participants, 95.9 of 100 continuing users (95% confidence interval [CI], 92.8-97.9) suppressed to a sperm concentration less than or equal to 1 million/mL within 24 weeks (Kaplan-Meier method). During the efficacy phase of up to 56 weeks, 4 pregnancies occurred among the partners of the 266 male participants, with the rate of 1.57 per 100 continuing users (95% CI, 0.59-4.14). The cumulative reversibility of suppression of spermatogenesis after 52 weeks of recovery was 94.8 per 100 continuing users (95% CI, 91.5-97.1). The most common adverse events were acne, injection site pain, increased libido, and mood disorders. Following the recommendation of an external safety review committee the recruitment and hormone injections were terminated early. The study regimen led to near-complete and reversible suppression of spermatogenesis. The contraceptive efficacy was relatively good compared with other reversible methods available for men. The frequencies of mild to moderate mood disorders were relatively high.

  3. Safety Needs Mediate Stressful Events Induced Mental Disorders.

    PubMed

    Zheng, Zheng; Gu, Simeng; Lei, Yu; Lu, Shanshan; Wang, Wei; Li, Yang; Wang, Fushun

    2016-01-01

    "Safety first," we say these words almost every day, but we all take this for granted for what Maslow proposed in his famous theory of Hierarchy of Needs : safety needs come second to physiological needs. Here we propose that safety needs come before physiological needs. Safety needs are personal security, financial security, and health and well-being, which are more fundamental than physiological needs. Safety worrying is the major reason for mental disorders, such as anxiety, phobia, depression, and PTSD. The neural basis for safety is amygdala, LC/NE system, and corticotrophin-releasing hormone system, which can be regarded as a "safety circuitry," whose major behavior function is "fight or flight" and "fear and anger" emotions. This is similar to the Appraisal theory for emotions: fear is due to the primary appraisal, which is related to safety of individual, while anger is due to secondary appraisal, which is related to coping with the unsafe situations. If coping is good, the individual will be happy; if coping failed, the individual will be sad or depressed.

  4. Safety Needs Mediate Stressful Events Induced Mental Disorders

    PubMed Central

    Gu, Simeng; Lei, Yu; Lu, Shanshan

    2016-01-01

    Safety first,” we say these words almost every day, but we all take this for granted for what Maslow proposed in his famous theory of Hierarchy of Needs: safety needs come second to physiological needs. Here we propose that safety needs come before physiological needs. Safety needs are personal security, financial security, and health and well-being, which are more fundamental than physiological needs. Safety worrying is the major reason for mental disorders, such as anxiety, phobia, depression, and PTSD. The neural basis for safety is amygdala, LC/NE system, and corticotrophin-releasing hormone system, which can be regarded as a “safety circuitry,” whose major behavior function is “fight or flight” and “fear and anger” emotions. This is similar to the Appraisal theory for emotions: fear is due to the primary appraisal, which is related to safety of individual, while anger is due to secondary appraisal, which is related to coping with the unsafe situations. If coping is good, the individual will be happy; if coping failed, the individual will be sad or depressed. PMID:27738527

  5. Stimulant Use in Patients with Sturge-Weber Syndrome: Safety and Efficacy

    PubMed Central

    Lance, Eboni I.; Lanier, Kira E.; Zabel, T. Andrew; Comi, Anne M.

    2015-01-01

    BACKGROUND Sturge Weber Syndrome (SWS) is characterized by a facial port-wine birthmark, vascular eye abnormalities, and a leptomeningeal angioma. Attention and behavioral issues are common in SWS; however, literature evidence for stimulant treatment is minimal. This study evaluates stimulant medication safety and efficacy in SWS patients. METHODS The research database of the Hunter Nelson Sturge-Weber Center (n = 210 subjects with SWS brain involvement) was reviewed for stimulant use. Twelve subjects (mean age 10.5 years, age range 4 to 21 years) on stimulants were seen between 2003 and 2012. A retrospective chart review obtained co-morbid diagnoses, stimulant type and dosage, medication side effects, vital signs, and medication efficacy. RESULTS All twelve subjects had brain involvement (unilateral - nine; bilateral – three). Additional co-morbidities included epilepsy (twelve), hemi-paresis (eight), headaches (eight), and vision deficits (seven). Eight subjects reported side effects, primarily appetite suppression (four) and headaches (three). There were no statistically significant changes in weight or blood pressure six months after medication initiation. Medication efficacy was subjectively reported in eleven subjects. Seven patients remained on stimulants at their most recent follow up visit. CONCLUSIONS This study preliminarily evaluates stimulant medication use in a small group of SWS patients. Stimulants were tolerated and effective in most subjects. Side effects were mostly minor and medication did not negatively impact growth or vital signs. Stimulant medication may be a safe and effective intervention for SWS children with attention issues/attention deficit hyperactivity disorder (ADHD). Further studies with larger sample sizes are needed. PMID:25439578

  6. Efficacy and Safety of Sirolimus in the Treatment of Complicated Vascular Anomalies

    PubMed Central

    Trenor, Cameron C.; Hammill, Adrienne M.; Vinks, Alexander A.; Patel, Manish N.; Chaudry, Gulraiz; Wentzel, Mary Sue; Mobberley-Schuman, Paula S.; Campbell, Lisa M.; Brookbank, Christine; Gupta, Anita; Chute, Carol; Eile, Jennifer; McKenna, Jesse; Merrow, Arnold C.; Fei, Lin; Hornung, Lindsey; Seid, Michael; Dasgupta, A. Roshni; Dickie, Belinda H.; Elluru, Ravindhra G.; Lucky, Anne W.; Weiss, Brian; Azizkhan, Richard G.

    2016-01-01

    BACKGROUND AND OBJECTIVES: Complicated vascular anomalies have limited therapeutic options and cause significant morbidity and mortality. This Phase II trial enrolled patients with complicated vascular anomalies to determine the efficacy and safety of treatment with sirolimus for 12 courses; each course was defined as 28 days. METHODS: Treatment consisted of a continuous dosing schedule of oral sirolimus starting at 0.8 mg/m2 per dose twice daily, with pharmacokinetic-guided target serum trough levels of 10 to 15 ng/mL. The primary outcomes were responsiveness to sirolimus by the end of course 6 (evaluated according to functional impairment score, quality of life, and radiologic assessment) and the incidence of toxicities and/or infection-related deaths. RESULTS: Sixty-one patients were enrolled; 57 patients were evaluable for efficacy at the end of course 6, and 53 were evaluable at the end of course 12. No patient had a complete response at the end of course 6 or 12 as anticipated. At the end of course 6, a total of 47 patients had a partial response, 3 patients had stable disease, and 7 patients had progressive disease. Two patients were taken off of study medicine secondary to persistent adverse effects. Grade 3 and higher toxicities attributable to sirolimus included blood/bone marrow toxicity in 27% of patients, gastrointestinal toxicity in 3%, and metabolic/laboratory toxicity in 3%. No toxicity-related deaths occurred. CONCLUSIONS: Sirolimus was efficacious and well tolerated in these study patients with complicated vascular anomalies. Clinical activity was reported in the majority of the disorders. PMID:26783326

  7. Safety and Efficacy of Memantine in Children with Autism: Randomized, Placebo-Controlled Study and Open-Label Extension

    PubMed Central

    Findling, Robert L.; Hardan, Antonio Y.; Hendren, Robert L.; Melmed, Raun D.; Kehinde-Nelson, Ola; Hsu, Hai-An; Trugman, Joel M.; Palmer, Robert H.; Graham, Stephen M.; Gage, Allyson T.; Perhach, James L.; Katz, Ephraim

    2017-01-01

    Abstract Objective: Abnormal glutamatergic neurotransmission is implicated in the pathophysiology of autism spectrum disorder (ASD). In this study, the safety, tolerability, and efficacy of the glutamatergic N-methyl-d-aspartate (NMDA) receptor antagonist memantine (once-daily extended-release [ER]) were investigated in children with autism in a randomized, placebo-controlled, 12 week trial and a 48 week open-label extension. Methods: A total of 121 children 6–12 years of age with Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR)-defined autistic disorder were randomized (1:1) to placebo or memantine ER for 12 weeks; 104 children entered the subsequent extension trial. Maximum memantine doses were determined by body weight and ranged from 3 to 15 mg/day. Results: There was one serious adverse event (SAE) (affective disorder, with memantine) in the 12 week study and one SAE (lobar pneumonia) in the 48 week extension; both were deemed unrelated to treatment. Other AEs were considered mild or moderate and most were deemed not related to treatment. No clinically significant changes occurred in clinical laboratory values, vital signs, or electrocardiogram (ECG). There was no significant between-group difference on the primary efficacy outcome of caregiver/parent ratings on the Social Responsiveness Scale (SRS), although an improvement over baseline at Week 12 was observed in both groups. A trend for improvement at the end of the 48 week extension was observed. No improvements in the active group were observed on any of the secondary end-points, with one communication measure showing significant worsening with memantine compared with placebo (p = 0.02) after 12 weeks. Conclusions: This trial did not demonstrate clinical efficacy of memantine ER in autism; however, the tolerability and safety data were reassuring. Our results could inform future trial design in this population and may facilitate the investigation of

  8. Safety and Efficacy of Memantine in Children with Autism: Randomized, Placebo-Controlled Study and Open-Label Extension.

    PubMed

    Aman, Michael G; Findling, Robert L; Hardan, Antonio Y; Hendren, Robert L; Melmed, Raun D; Kehinde-Nelson, Ola; Hsu, Hai-An; Trugman, Joel M; Palmer, Robert H; Graham, Stephen M; Gage, Allyson T; Perhach, James L; Katz, Ephraim

    2017-06-01

    Abnormal glutamatergic neurotransmission is implicated in the pathophysiology of autism spectrum disorder (ASD). In this study, the safety, tolerability, and efficacy of the glutamatergic N-methyl-d-aspartate (NMDA) receptor antagonist memantine (once-daily extended-release [ER]) were investigated in children with autism in a randomized, placebo-controlled, 12 week trial and a 48 week open-label extension. A total of 121 children 6-12 years of age with Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR)-defined autistic disorder were randomized (1:1) to placebo or memantine ER for 12 weeks; 104 children entered the subsequent extension trial. Maximum memantine doses were determined by body weight and ranged from 3 to 15 mg/day. There was one serious adverse event (SAE) (affective disorder, with memantine) in the 12 week study and one SAE (lobar pneumonia) in the 48 week extension; both were deemed unrelated to treatment. Other AEs were considered mild or moderate and most were deemed not related to treatment. No clinically significant changes occurred in clinical laboratory values, vital signs, or electrocardiogram (ECG). There was no significant between-group difference on the primary efficacy outcome of caregiver/parent ratings on the Social Responsiveness Scale (SRS), although an improvement over baseline at Week 12 was observed in both groups. A trend for improvement at the end of the 48 week extension was observed. No improvements in the active group were observed on any of the secondary end-points, with one communication measure showing significant worsening with memantine compared with placebo (p = 0.02) after 12 weeks. This trial did not demonstrate clinical efficacy of memantine ER in autism; however, the tolerability and safety data were reassuring. Our results could inform future trial design in this population and may facilitate the investigation of memantine ER for other clinical applications.

  9. Intervention efficacy and intensity for children with speech sound disorder.

    PubMed

    Allen, Melissa M

    2013-06-01

    Clinicians do not have an evidence base they can use to recommend optimum intervention intensity for preschool children who present with speech sound disorder (SSD). This study examined the effect of dose frequency on phonological performance and the efficacy of the multiple oppositions approach. Fifty-four preschool children with SSD were randomly assigned to one of three intervention conditions. Two intervention conditions received the multiple oppositions approach either 3 times per week for 8 weeks (P3) or once weekly for 24 weeks (P1). A control (C) condition received a storybook intervention. Percentage of consonants correct (PCC) was evaluated at 8 weeks and after 24 sessions. PCC gain was examined after a 6-week maintenance period. The P3 condition had a significantly better phonological outcome than the P1 and C conditions at 8 weeks and than the P1 condition after 24 weeks. There were no significant differences between the P1 and C conditions. There was no significant difference between the P1 and P3 conditions in PCC gain during the maintenance period. Preschool children with SSD who received the multiple oppositions approach made significantly greater gains when they were provided with a more intensive dose frequency and when cumulative intervention intensity was held constant.

  10. Implications of Pain in Generalized Anxiety Disorder: Efficacy of Duloxetine

    PubMed Central

    Hartford, James T.; Endicott, Jean; Kornstein, Susan G.; Allgulander, Christer; Wohlreich, Madelaine M.; Russell, James M.; Perahia, David G. S.; Erickson, Janelle S.

    2008-01-01

    Objective: To conduct a post hoc evaluation of the prevalence of clinically significant pain and the efficacy of duloxetine in patients with generalized anxiety disorder (GAD) and concurrent pain. Method: Data from two 9- to 10-week double-blind, placebo-controlled, randomized clinical trials of duloxetine (60 to 120 mg) in DSM-IV–defined GAD were analyzed (study 1 was conducted from July 2004 to September 2005; study 2 was conducted from August 2004 to June 2005). Efficacy was assessed with the Hamilton Rating Scale for Anxiety (HAM-A), visual analog scales (VAS) for pain, the Hospital Anxiety Depression Scale (HADS), the Clinical Global Impressions-Improvement of Illness (CGI-I) scale, the Patient Global Impressions-Improvement (PGI-I) scale, and the Sheehan Disability Scale (SDS) global functional impairment scale. Results: Of 840 patients randomly assigned to treatment, 61.3% (302 duloxetine, 213 placebo) had VAS scores ≥ 30 mm on at least 1 of the pain scales, indicating clinically significant pain. Among those patients with concurrent pain at baseline, change from baseline to endpoint in the HAM-A total score (42.9% change in mean scores for duloxetine, 31.4% for placebo), HADS anxiety scale (40.3% vs. 22.8%), HADS depression scale (36.1% vs. 20.5%), HAM-A psychic factor (45.9% vs. 29.9%), and SDS global functional improvement score (45.5% vs. 22.1%) was significantly (all p's < .001) greater for duloxetine compared with placebo. Improvement on the CGI-I (p = .003) and PGI-I (p < .001) was also significantly greater for duloxetine. Response (HAM-A total score decrease ≥ 50%) (49% vs. 29%) and remission (HAM-A total score ≤ 7 at endpoint) (29% vs. 18%) rates were significantly greater for duloxetine compared with placebo (p < .001 and p = .041, respectively). Duloxetine demonstrated statistically significantly greater reduction in pain on all 6 VAS pain scales (all p's < .001 except headaches with p < .002) (for duloxetine, percent change in means from

  11. Zolpidem efficacy and safety in disorders of consciousness.

    PubMed

    Machado, Calixto; Estévez, Mario; Rodriguez-Rojas, Rafael

    2018-01-01

    Sutton and Clauss presented a detailed review about the effectiveness of zolpidem, discussing recoveries from brain damage due to strokes, trauma and hypoxia. A significant finding has been the unexpected and paradoxical increment of brain activity in vegetative state/unresponsive wakefulness syndrome (VS/UWS). On the contrary, zolpidem is considered one of the best sleep inducers in normal subjects. We have studied series of VS/UWS cases after zolpidem intake. We have demonstrated EEG activation, increment of BOLD signal in different brain regions, and an autonomic influence, mainly characterized by a vagolytic chronotropic effect without a significant increment of the vasomotor sympathetic tone. As this autonomic imbalance might induce cardio- circulatory complications, which we didn't find in any of our patients, we suggest developing future trials under control of physiological indices by bedside monitoring. However, considering that the paradoxical arousing zolpidem effect might be certainly related to brain function improvement, we agree with Sutton and Clauss that future multicentre and multinational clinical trials should be developed, but under control of physiological indices.

  12. The development and efficacy of safety training for commercial fishermen.

    PubMed

    Dzugan, Jerry

    2010-10-01

    Commercial fishing is still the most dangerous occupation in the United States. Efforts to have more stringent safety regulations in this industry beginning in the 1960s, culminated in the Commercial Fishing Vessel Safety Act of 1988. The purpose of this paper is to provide a short history of the development of safety training in the United States and the current training infrastructure. This paper will also review studies available regarding the effectiveness of safety training in reducing fatalities among fishermen. The lack of familiarity and practice with marine survival equipment such as life rafts, immersion suits, and emergency-locating beacons has been noted in National Transportation Safety Board and US Coast Guard casualty reports as a contributing factor in fatalities. These reports have demonstrated the importance of not just having survival equipment onboard, but training in how to use it effectively in an emergency. There is evidence that safety training has made a measurable impact in surviving an emergency at sea and that recent training (within 5 years) is most effective in saving lives. More recently, studies have been completed to understand how skills may diminish over time since initial training.

  13. Safety behaviors and judgmental biases in social anxiety disorder.

    PubMed

    Taylor, Charles T; Alden, Lynn E

    2010-03-01

    Two experiments were conducted to examine the link between safety behaviors and social judgments in social anxiety disorder (SAD). Safety behaviors were manipulated in the context of a controlled laboratory-based social interaction, and subsequent effects of the manipulation on the social judgments of socially anxious participants (N = 50, Study 1) and individuals meeting diagnostic criteria for generalized SAD (N = 80, Study 2) were examined. Participants were randomly assigned to either a safety behavior reduction plus exposure condition (SB + EXP) or a graduated exposure (EXP) control condition, and then took part in a conversation with a trained experimental confederate. Results revealed across both studies that participants in the SB + EXP group were less negative and more accurate in judgments of their performance following safety behavior reduction relative to EXP participants. Study 2 also demonstrated that participants in the SB + EXP group displayed lower judgments about the likelihood of negative outcomes in a subsequent social event compared to controls. Moreover, reduction in safety behaviors mediated change in participant self-judgments and future social predictions. The current findings are consistent with cognitive theories of anxiety, and support the causal role of safety behaviors in the persistence of negative social judgments in SAD. 2009 Elsevier Ltd. All rights reserved.

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

    PubMed Central

    2011-01-01

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

  15. Efficacy of Lisdexamfetamine in Adults With Moderate to Severe Binge-Eating Disorder

    PubMed Central

    McElroy, Susan L.; Ferreira-Cornwell, M. Celeste; Radewonuk, Jana; Gasior, Maria

    2017-01-01

    Importance The ability of pharmacotherapies to prevent relapse and maintain efficacy with long-term treatment in psychiatric conditions is important. Objective To assess lisdexamfetamine dimesylate maintenance of efficacy in adults with moderate to severe binge-eating disorder. Design, Setting, and Participants A multinational, phase 3, double-blind, placebo-controlled, randomized withdrawal study including 418 participants was conducted at 49 clinical research study sites from January 27, 2014, to April 8, 2015. Eligible adults met DSM-IV-R binge-eating disorder criteria and had moderate to severe binge eating disorder (≥3 binge-eating days per week for 14 days before open-label baseline; Clinical Global Impressions−Severity [CGI-S] scores ≥4 [moderate severity] at screening and open-label baseline). Following a 12-week, open-label phase (dose optimization, 4 weeks [lisdexamfetamine dimesylate, 50 or 70 mg]; dose maintenance, 8 weeks), lisdexamfetamine responders (≤1 binge eating day per week for 4 consecutive weeks and CGI-S scores ≤2 at week 12) were randomized to placebo or continued lisdexamfetamine during a 26-week, double-blind, randomized withdrawal phase. Interventions Lisdexamfetamine administration. Main Outcomes and Measures The primary outcome variable, time to relapse (≥2 binge-eating days per week for 2 consecutive weeks and ≥2-point CGI-S score increases from randomized withdrawal baseline), was analyzed using a log-rank test (primary analysis); the analysis was stratified for dichotomized 4-week cessation status. Safety assessments included treatment-emergent adverse events. Results Of the 418 participants enrolled in the open-label phase of the study, 411 (358 [87.1%] women; mean [SD] age, 38.3 [10.4] years) were included in the safety analysis set. Of 275 randomized lisdexamfetamine responders (placebo, n = 138; lisdexamfetamine, n = 137), the observed proportions of participants meeting relapse criteria were 3.7% (5 of 136

  16. Evaluation of the Efficacy and Safety of Rivaroxaban Using a Computer Model for Blood Coagulation

    PubMed Central

    Burghaus, Rolf; Coboeken, Katrin; Gaub, Thomas; Kuepfer, Lars; Sensse, Anke; Siegmund, Hans-Ulrich; Weiss, Wolfgang; Mueck, Wolfgang; Lippert, Joerg

    2011-01-01

    Rivaroxaban is an oral, direct Factor Xa inhibitor approved in the European Union and several other countries for the prevention of venous thromboembolism in adult patients undergoing elective hip or knee replacement surgery and is in advanced clinical development for the treatment of thromboembolic disorders. Its mechanism of action is antithrombin independent and differs from that of other anticoagulants, such as warfarin (a vitamin K antagonist), enoxaparin (an indirect thrombin/Factor Xa inhibitor) and dabigatran (a direct thrombin inhibitor). A blood coagulation computer model has been developed, based on several published models and preclinical and clinical data. Unlike previous models, the current model takes into account both the intrinsic and extrinsic pathways of the coagulation cascade, and possesses some unique features, including a blood flow component and a portfolio of drug action mechanisms. This study aimed to use the model to compare the mechanism of action of rivaroxaban with that of warfarin, and to evaluate the efficacy and safety of different rivaroxaban doses with other anticoagulants included in the model. Rather than reproducing known standard clinical measurements, such as the prothrombin time and activated partial thromboplastin time clotting tests, the anticoagulant benchmarking was based on a simulation of physiologically plausible clotting scenarios. Compared with warfarin, rivaroxaban showed a favourable sensitivity for tissue factor concentration inducing clotting, and a steep concentration–effect relationship, rapidly flattening towards higher inhibitor concentrations, both suggesting a broad therapeutic window. The predicted dosing window is highly accordant with the final dose recommendation based upon extensive clinical studies. PMID:21526168

  17. Efficacy and safety of minodronic acid hydrate in patients with steroid-induced osteoporosis.

    PubMed

    Kitamura, Noboru; Shiraiwa, Hidetaka; Inomata, Hirotake; Nozaki, Takamasa; Ikumi, Natsumi; Sugiyama, Kaita; Nagasawa, Yousuke; Karasawa, Hiromi; Iwata, Mitsuhiro; Matsukawa, Yoshihiro; Takei, Masami

    2018-04-01

    Minodronic acid hydrate, an oral bisphosphonate, has a greater inhibitory effect on bone resorption than do other approved drugs; however, this has been studied only in patients with primary osteoporosis. Here, we administered minodronic acid hydrate to patients with steroid-induced osteoporosis who have been treated with steroids for rheumatoid arthritis or other collagen diseases, and the efficacy and safety of minodronic acid hydrate were prospectively investigated. Twenty-five patients treated in our rheumatology clinic received minodronic acid hydrate 1 mg/day. The changes in bone mineral density (BMD) and bone turnover markers were investigated at 3 and 6 months, and adverse events, including the presence or absence of an incident osteoporotic fracture, were examined over a period of 6 months. Percent changes in BMD of the lumbar spine and femur significantly increased. The values of bone turnover markers significantly decreased. There were no patients with a radiographically apparent incident fracture. Adverse events included toothache for which the patient discontinued the treatment and three cases of gastrointestinal disorder that did not lead to discontinuation, and thus minodronic acid hydrate was well tolerated. Here, we show that minodronic acid hydrate is effectively and safely used for treatment of steroid-induced osteoporosis. © 2016 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

  18. Evaluation of the efficacy and safety of rivaroxaban using a computer model for blood coagulation.

    PubMed

    Burghaus, Rolf; Coboeken, Katrin; Gaub, Thomas; Kuepfer, Lars; Sensse, Anke; Siegmund, Hans-Ulrich; Weiss, Wolfgang; Mueck, Wolfgang; Lippert, Joerg

    2011-04-22

    Rivaroxaban is an oral, direct Factor Xa inhibitor approved in the European Union and several other countries for the prevention of venous thromboembolism in adult patients undergoing elective hip or knee replacement surgery and is in advanced clinical development for the treatment of thromboembolic disorders. Its mechanism of action is antithrombin independent and differs from that of other anticoagulants, such as warfarin (a vitamin K antagonist), enoxaparin (an indirect thrombin/Factor Xa inhibitor) and dabigatran (a direct thrombin inhibitor). A blood coagulation computer model has been developed, based on several published models and preclinical and clinical data. Unlike previous models, the current model takes into account both the intrinsic and extrinsic pathways of the coagulation cascade, and possesses some unique features, including a blood flow component and a portfolio of drug action mechanisms. This study aimed to use the model to compare the mechanism of action of rivaroxaban with that of warfarin, and to evaluate the efficacy and safety of different rivaroxaban doses with other anticoagulants included in the model. Rather than reproducing known standard clinical measurements, such as the prothrombin time and activated partial thromboplastin time clotting tests, the anticoagulant benchmarking was based on a simulation of physiologically plausible clotting scenarios. Compared with warfarin, rivaroxaban showed a favourable sensitivity for tissue factor concentration inducing clotting, and a steep concentration-effect relationship, rapidly flattening towards higher inhibitor concentrations, both suggesting a broad therapeutic window. The predicted dosing window is highly accordant with the final dose recommendation based upon extensive clinical studies.

  19. Safety and Efficacy of Donepezil in Children and Adolescents with Autism: Neuropsychological Measures

    PubMed Central

    Johnson, Cynthia R.; McAuliffe-Bellin, Sarah; Murray, Patricia Jo; Hardan, Antonio Y.

    2011-01-01

    Abstract Objective There has been recent interest in the use of cognitive enhancing drugs, such as cholinesterase inhibitors, as a possible treatment for executive functioning (EF) deficits in autism spectrum disorder (ASD). The goal of this study was to assess the tolerability, safety, and efficacy of donepezil on EF in a sample of children and adolescents with ASD. Method Thirty-four children and adolescents with ASD (age range 8–17 years; IQ >75) were enrolled in a 10-week, double-blind, placebo-controlled trial of donepezil (doses of 5 and 10 mg), followed by a 10-week open label trial for placebo nonresponders. Results The effect of donepezil treatment on EF was examined. Despite improvement on a number of EF measures, no statistically significant between-group differences were found (with gains observed for both the placebo and donepezil groups). Conclusions The results suggest that short-term treatment with donepezil may have limited impact on cognitive functioning in ASD. Future controlled trials may need to consider a longer treatment period to detect significant gains on EF measures. PMID:21309696

  20. Efficacy of Teacher In-Service Training for Attention-Deficit/Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Jones, Heather A.; Chronis-Tuscano, Andrea

    2008-01-01

    Children with attention-deficit/hyperactivity disorder (ADHD) evidence many problems in the classroom. Teacher in-service training is routinely used to inform school professionals about a number of special topics; however, the efficacy of such in-service training for ADHD has not been established. The present study examined the efficacy of brief…

  1. A naturalistic comparison of the efficacy and safety of intramuscular olanzapine and intramuscular haloperidol in agitated elderly patients with schizophrenia

    PubMed Central

    Gen, Keishi; Takahashi, Yuki

    2013-01-01

    Objective: This study was a comparative investigation of the clinical efficacy and safety of intramuscular (IM) olanzapine and IM haloperidol in agitated elderly patients with schizophrenia at 2 hours postdose. Methods: The subjects were 23 inpatients who had been diagnosed with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Their clinical symptoms were assessed using Positive and Negative Syndrome Scale Excited Component (PANSS-EC), PANSS and Agitation Calmness Evaluation Scale (ACES), and their safety were assessed using the Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia Rating Scale (BARS), Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) and laboratory tests. Results: The mean reduction from baseline on the PANSS-EC total score, the PANSS total score and the ACES score were significantly greater in the IM olanzapine injection group than in the IM haloperidol injection group. The mean changes from baseline on the AIMS score, the BARS score and the DIEPSS total score were significantly better in the IM olanzapine injection group than in the IM haloperidol injection group. No serious adverse events such as paralytic ileus, diabetic ketoacidosis, neuroleptic malignant syndrome or tardive dyskinesia occurred between the two groups. Conclusion: The results of this study suggest the possibility that agitated elderly patients may result in superior efficacy and safety after IM olanzapine without serious adverse events in comparison with IM haloperidol. PMID:24294484

  2. Testing cardiovascular drug safety and efficacy in randomized trials.

    PubMed

    FitzGerald, Garret A

    2014-03-28

    Randomized trials provide the gold standard evidence on which rests the decision to approve novel therapeutics for clinical use. They are large and expensive and provide average but unbiased estimates of efficacy and risk. Concern has been expressed about how unrepresentative populations and conditions that pertain in randomized trials might be of the real world, including concerns about the homogeneity of the biomedical and adherence characteristics of volunteers entered into such trials, the dose and constancy of drug administration and the mixture of additional medications that are restricted in such trials but might influence outcome in practice. A distinction has been drawn between trials that establish efficacy and those that demonstrate effectiveness, drugs that patients actually consume in the real world for clinical benefit. However, randomized controlled trials remain the gold standard for establishing efficacy and the testing of effectiveness with less rigorous approaches is a secondary, albeit important consideration. Despite this, there is an appreciation that average results may conceal considerable interindividual variation in drug response, leading to a failure to appreciate clinical value or risk in subsets of patients. Thus, attempts are now being made to individualize risk estimates by modulating those derived from large randomized trials with the individual baseline risk estimates based on demographic and biological criteria-the individual Numbers Needed to Treat to obtain a benefit, such as a life saved. Here, I will consider some reasons why large phase 3 trials-by far the most expensive element of drug development-may fail to address the unmet medical needs, which should justify such effort and investment.

  3. Gender Differences in the Efficacy and Safety of Chronic Nightly Zolpidem

    PubMed Central

    Roehrs, Timothy A.; Roth, Thomas

    2016-01-01

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

  4. Assuring the quality, safety, and efficacy of DNA vaccines.

    PubMed

    Robertson, J S; Griffiths, E

    2001-02-01

    Scientists in academia whose research is aimed at the development of a novel vaccine or approach to vaccination may not always be fully aware of the regulatory process by which a candidate vaccine becomes a licensed product. It is useful for such scientists to be aware of these processes as the development of a novel vaccine could be problematic owing to the starting material often being developed in a research laboratory under ill-defined conditions. This paper examines the regulatory process with respect to the development of a DNA vaccine. DNA vaccines present unusual safety considerations that must be addressed during preclinical safety studies, including adverse immunopathology, genotoxicity through integration into a vaccinees chromosomes, and the potential for the formation of anti-DNA antibodies.

  5. Assuring the quality, safety, and efficacy of DNA vaccines.

    PubMed

    Robertson, James S; Griffiths, Elwyn

    2006-01-01

    Scientists in academia whose research is aimed at the development of a novel vaccine or approach to vaccination may not always be fully aware of the regulatory process by which a candidate vaccine becomes a licensed product. It is useful for such scientists to be aware of these processes, as the development of a novel vaccine could be problematic as a result of the starting material often being developed in a research laboratory under ill-defined conditions. This chapter examines the regulatory process with respect to the development of a DNA vaccine. DNA vaccines present unusual safety considerations which must be addressed during nonclinical safety studies, including adverse immunopathology, genotoxicity through integration into a vaccinee's chromosomes and the potential for the formation of anti-DNA antibodies.

  6. Posttraumatic stress disorder and community collective efficacy following the 2004 Florida hurricanes.

    PubMed

    Ursano, Robert J; McKibben, Jodi B A; Reissman, Dori B; Liu, Xian; Wang, Leming; Sampson, Robert J; Fullerton, Carol S

    2014-01-01

    There is a paucity of research investigating the relationship of community-level characteristics such as collective efficacy and posttraumatic stress following disasters. We examine the association of collective efficacy with probable posttraumatic stress disorder and posttraumatic stress disorder symptom severity in Florida public health workers (n = 2249) exposed to the 2004 hurricane season using a multilevel approach. Anonymous questionnaires were distributed electronically to all Florida Department of Health personnel nine months after the 2004 hurricane season. The collected data were used to assess posttraumatic stress disorder and collective efficacy measured at both the individual and zip code levels. The majority of participants were female (80.42%), and ages ranged from 20 to 78 years (median = 49 years); 73.91% were European American, 13.25% were African American, and 8.65% were Hispanic. Using multi-level analysis, our data indicate that higher community-level and individual-level collective efficacy were associated with a lower likelihood of having posttraumatic stress disorder (OR = 0.93, CI = 0.88-0.98; and OR = 0.94, CI = 0.92-0.97, respectively), even after adjusting for individual sociodemographic variables, community socioeconomic characteristic variables, individual injury/damage, and community storm damage. Higher levels of community-level collective efficacy and individual-level collective efficacy were also associated with significantly lower posttraumatic stress disorder symptom severity (b = -0.22, p<0.01; and b = -0.17, p<0.01, respectively), after adjusting for the same covariates. Lower rates of posttraumatic stress disorder are associated with communities with higher collective efficacy. Programs enhancing community collective efficacy may be an important part of prevention practices and possibly lead to a reduction in the rate of posttraumatic stress disorder post-disaster.

  7. Efficacy and Safety of Pomegranate Medicinal Products for Cancer

    PubMed Central

    Vlachojannis, Christian

    2015-01-01

    Preclinical in vitro and in vivo studies demonstrate potent effects of pomegranate preparations in cancer cell lines and animal models with chemically induced cancers. We have carried out one systematic review of the effectiveness of pomegranate products in the treatment of cancer and another on their safety. The PubMed search provided 162 references for pomegranate and cancer and 122 references for pomegranate and safety/toxicity. We identified 4 clinical studies investigating 3 pomegranate products, of which one was inappropriate because of the low polyphenol content. The evidence of clinical effectiveness was poor because the quality of the studies was poor. Although there is no concern over safety with the doses used in the clinical studies, pomegranate preparations may be harmful by inducing synthetic drug metabolism through activation of liver enzymes. We have analysed various pomegranate products for their content of anthocyanins, punicalagin, and ellagic acid in order to compare them with the benchmark doses from published data. If the amount of coactive constituents is not declared, patients risk not benefiting from the putative pomegranate effects. Moreover, pomegranate end products are affected by many determinants. Their declaration should be incorporated into the regulatory guidance and controlled before pomegranate products enter the market. PMID:25815026

  8. Eating disorders, normative eating self-efficacy and body image self-efficacy: women in recovery homes.

    PubMed

    Czarlinski, Jennifer A; Aase, Darrin M; Jason, Leonard A

    2012-05-01

    Although eating disorders (EDs) and ED symptoms are common among individuals in recovery for substance abuse (SA), long-term SA treatment programmes rarely address these problems. The present study examined the prevalence of EDs among women residing in Oxford Houses--low-cost, self-governed recovery homes for SA. Further, among women both with and without an ED diagnosis, the association between duration of Oxford House residency and eating-related self-efficacy scores was examined as an indicator of potential treatment effects on ED symptoms. During a telephone assessment, participants were administered the Structured Clinical Interview for DSM-IV-TR Axis I Disorders and the Eating Disorder Recovery Self-Efficacy Questionnaire. Results indicated that 12 of the 31 women analysed met criteria for an ED (bulimia nervosa, 2; ED not otherwise specified, 10). Differential findings were evident for eating-related self-efficacy measures depending on ED diagnostic status and duration of residency. Potential interpretations, limitations and implications are discussed. Copyright © 2011 John Wiley & Sons, Ltd and Eating Disorders Association.

  9. Efficacy and Utility of Computer-Assisted Cognitive Behavioural Therapy for Anxiety Disorders

    ERIC Educational Resources Information Center

    Przeworski, Amy; Newman, Michelle G.

    2006-01-01

    Despite the efficacy of cognitive behavioural treatment for anxiety disorders, more than 70% of individuals with anxiety disorders go untreated every year. This is partially due to obstacles to treatment including limited access to mental health services for rural residents, the expense of treatment and the inconvenience of attending weekly…

  10. Moving from Efficacy to Effectiveness in Eating Disorders Prevention: The Sorority Body Image Program

    ERIC Educational Resources Information Center

    Becker, Carolyn Black; Ciao, Anna C.; Smith, Lisa M.

    2008-01-01

    Although eating disorders prevention research has begun to produce programs with demonstrated efficacy, many such programs simply target individuals as opposed to engaging broader social systems (e.g., schools, sororities, athletic teams) as participant collaborators in eating disorders prevention. Yet, social systems ultimately will be…

  11. Safety and efficacy of pirfenidone in severe Idiopathic Pulmonary Fibrosis: A real-world observational study.

    PubMed

    Tzouvelekis, Argyrios; Ntolios, Paschalis; Karampitsakos, Theodoros; Tzilas, Vasilios; Anevlavis, Stavros; Bouros, Evangelos; Steiropoulos, Paschalis; Koulouris, Nikolaos; Stratakos, Grigoris; Froudarakis, Marios; Bouros, Demosthenes

    2017-10-01

    Pirfenidone is a novel anti-fibrotic drug that has shown efficacy in five randomized multicenter clinical trials enrolling patients with Idiopathic Pulmonary Fibrosis of mild-to-moderate disease severity. Scarce data supports the use of pirfenidone in IPF patients with more advanced disease. To investigate the safety and efficacy profile of pirfenidone in IPF patients with severe lung function impairment. This was a retrospective study enrolling patients with advanced IPF (FVC%predicted < 50% and/or (DLco%predicted <35%) receiving pirfenidone for at least 6 months. Between September 2011 and March 2013, we identified 43 patients with severe IPF (baseline meanFVC%predicted±SD: 63.8 ± 20.3, meanDL CO %predicted: 27.3 ± 8.2), of mean age±SD: 66.3 + 9.7, 34 males (81%) that received pirfenidone (2.403 mg/daily) for one year. Pirfenidone treatment was associated with a trend towards decrease in functional decline compared to 6-months before treatment initiation but failed to show any benefit after one year of treatment (ΔFVC: -3.3 ± 4.6 vs 0.49 ± 11.4 and vs. -5.8 ± 11.8, p = 0.06 and p = 0.04, respectively and ΔDL CO : -13.3 ± 15.2 vs. -10.1 ± 16.6 and vs. 28.3 ± 19.2, p = 0.39 and p = 0.002, respectively). Gastrointestinal disorders (34.9%), fatigue (23.2%) and photosensitivity (18.6%) were the most common adverse events. Adverse events led to treatment discontinuation in 9 patients (20.9%) and dose reduction in 14 (32.5%). Pirfenidone appears to be safe when administered in patients with advanced IPF. Pirfenidone efficacy in IPF patients with severe lung function impairment may diminish after 6 months of treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Safety and efficacy of personal care products containing colloidal oatmeal.

    PubMed

    Criquet, Maryline; Roure, Romain; Dayan, Liliane; Nollent, Virginie; Bertin, Christiane

    2012-01-01

    Colloidal oatmeal is a natural ingredient used in the formulation of a range of personal care products for relief of skin dryness and itchiness. It is also used as an adjunctive product in atopic dermatitis. The safety of personal care products used on vulnerable skin is of particular importance and the risk of developing further skin irritations and/or allergies should be minimized. In a series of studies, we tested the safety of personal care products containing oatmeal (creams, cleansers, lotions) by assessing their irritant/allergenic potential on repeat insult patch testing, in safety-in-use and ocular studies using subjects with nonsensitive and sensitive skin. We also tested the skin moisturizing and repair properties of an oatmeal-containing skin care product for dry skin. We found that oatmeal-containing personal care products had very low irritant potential as well as a very low allergenic sensitization potential. Low-level reactions were documented in 1.0% of subjects during the induction phase of repeat insult patch testing; one of 2291 subjects developed a persistent but doubtful low-level reaction involving edema during the challenge phase in repeat insult patch testing. No allergies were reported by 80 subjects after patch testing after in-use application. Sustained skin moisturizing was documented in subjects with dry skin that lasted up to 2 weeks after product discontinuation. Our results demonstrate that colloidal oatmeal is a safe and effective ingredient in personal care products. No allergies were reported by consumers of 445,820 products sold during a 3-year period.

  13. Safety and efficacy of personal care products containing colloidal oatmeal

    PubMed Central

    Criquet, Maryline; Roure, Romain; Dayan, Liliane; Nollent, Virginie; Bertin, Christiane

    2012-01-01

    Background Colloidal oatmeal is a natural ingredient used in the formulation of a range of personal care products for relief of skin dryness and itchiness. It is also used as an adjunctive product in atopic dermatitis. The safety of personal care products used on vulnerable skin is of particular importance and the risk of developing further skin irritations and/or allergies should be minimized. Methods In a series of studies, we tested the safety of personal care products containing oatmeal (creams, cleansers, lotions) by assessing their irritant/allergenic potential on repeat insult patch testing, in safety-in-use and ocular studies using subjects with nonsensitive and sensitive skin. We also tested the skin moisturizing and repair properties of an oatmeal-containing skin care product for dry skin. Results We found that oatmeal-containing personal care products had very low irritant potential as well as a very low allergenic sensitization potential. Low-level reactions were documented in 1.0% of subjects during the induction phase of repeat insult patch testing; one of 2291 subjects developed a persistent but doubtful low-level reaction involving edema during the challenge phase in repeat insult patch testing. No allergies were reported by 80 subjects after patch testing after in-use application. Sustained skin moisturizing was documented in subjects with dry skin that lasted up to 2 weeks after product discontinuation. Conclusion Our results demonstrate that colloidal oatmeal is a safe and effective ingredient in personal care products. No allergies were reported by consumers of 445,820 products sold during a 3-year period. PMID:23204849

  14. Testing Cardiovascular Drug Safety and Efficacy in Randomized Trials

    PubMed Central

    FitzGerald, Garret A.

    2014-01-01

    Randomized trials provide the gold standard evidence on which rests the decision to approve novel therapeutics for clinical use. They are large and expensive and provide average, but unbiased estimates of efficacy and risk. Concern has been expressed about how “unrepresentative” populations and conditions that pertain in randomized trials might be of the “real world”, including concerns about the homogeneity of the biomedical and adherence characteristics of volunteers entered into such trials, the dose and constancy of drug administration and the mixture of additional medications that are restricted in such trials but might influence outcome in practice. A distinction has been drawn between trials which establish “efficacy” and those that demonstrate “effectiveness” - drugs that patients actually consume in the “real world” for clinical benefit1. However, randomized controlled trials remain the gold standard for establishing efficacy and the testing of “effectiveness” with less rigorous approaches is a secondary, albeit important consideration. Despite this, there is an appreciation that “average” results may conceal considerable inter-individual variation in drug response, leading to a failure to appreciate clinical value or risk in subsets of patients2,3Thus, attempts are now being made to individualize risk estimates by modulating those derived from large randomized trials with the individual baseline risk estimates based on demographic and biological criteria - the individual Numbers Needed to Treat to obtain a benefit, such as a life saved4. Here, I will consider some reasons why large phase 3 trials - by far the most expensive element of drug development - may fail to address the “unmet medical needs” which should justify such effort and investment. PMID:24677235

  15. Ibogaine: complex pharmacokinetics, concerns for safety, and preliminary efficacy measures.

    PubMed

    Mash, D C; Kovera, C A; Pablo, J; Tyndale, R F; Ervin, F D; Williams, I C; Singleton, E G; Mayor, M

    2000-09-01

    Ibogaine is an indole alkaloid found in the roots of Tabernanthe Iboga (Apocynaceae family), a rain forest shrub that is native to western Africa. Ibogaine is used by indigenous peoples in low doses to combat fatigue, hunger and thirst, and in higher doses as a sacrament in religious rituals. Members of American and European addict self-help groups have claimed that ibogaine promotes long-term drug abstinence from addictive substances, including psychostimulants and opiates. Anecdotal reports attest that a single dose of ibogaine eliminates opiate withdrawal symptoms and reduces drug craving for extended periods of time. The purported efficacy of ibogaine for the treatment of drug dependence may be due in part to an active metabolite. The majority of ibogaine biotransformation proceeds via CYP2D6, including the O-demethylation of ibogaine to 12-hydroxyibogamine (noribogaine). Blood concentration-time effect profiles of ibogaine and noribogaine obtained for individual subjects after single oral dose administrations demonstrate complex pharmacokinetic profiles. Ibogaine has shown preliminary efficacy for opiate detoxification and for short-term stabilization of drug-dependent persons as they prepare to enter substance abuse treatment. We report here that ibogaine significantly decreased craving for cocaine and heroin during inpatient detoxification. Self-reports of depressive symptoms were also significantly lower after ibogaine treatment and at 30 days after program discharge. Because ibogaine is cleared rapidly from the blood, the beneficial aftereffects of the drug on craving and depressed mood may be related to the effects of noribogaine on the central nervous system.

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

    PubMed Central

    Karbasi, Afsaneh; Haratian, Azadeh

    2018-01-01

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

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

    PubMed

    Karbasi, Afsaneh; Haratian, Azadeh

    2018-01-01

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

  18. Systematic review: cardiovascular safety profile of 5-HT(4) agonists developed for gastrointestinal disorders.

    PubMed

    Tack, J; Camilleri, M; Chang, L; Chey, W D; Galligan, J J; Lacy, B E; Müller-Lissner, S; Quigley, E M M; Schuurkes, J; De Maeyer, J H; Stanghellini, V

    2012-04-01

    The nonselective 5-HT(4) receptor agonists, cisapride and tegaserod have been associated with cardiovascular adverse events (AEs). To perform a systematic review of the safety profile, particularly cardiovascular, of 5-HT(4) agonists developed for gastrointestinal disorders, and a nonsystematic summary of their pharmacology and clinical efficacy. Articles reporting data on cisapride, clebopride, prucalopride, mosapride, renzapride, tegaserod, TD-5108 (velusetrag) and ATI-7505 (naronapride) were identified through a systematic search of the Cochrane Library, Medline, Embase and Toxfile. Abstracts from UEGW 2006-2008 and DDW 2008-2010 were searched for these drug names, and pharmaceutical companies approached to provide unpublished data. Retrieved articles on pharmacokinetics, human pharmacodynamics and clinical data with these 5-HT(4) agonists, are reviewed and summarised nonsystematically. Articles relating to cardiac safety and tolerability of these agents, including any relevant case reports, are reported systematically. Two nonselective 5-HT(4) agonists had reports of cardiovascular AEs: cisapride (QT prolongation) and tegaserod (ischaemia). Interactions with, respectively, the hERG cardiac potassium channel and 5-HT(1) receptor subtypes have been suggested to account for these effects. No cardiovascular safety concerns were reported for the newer, selective 5-HT(4) agonists prucalopride, velusetrag, naronapride, or for nonselective 5-HT(4) agonists with no hERG or 5-HT(1) affinity (renzapride, clebopride, mosapride). 5-HT(4) agonists for GI disorders differ in chemical structure and selectivity for 5-HT(4) receptors. Selectivity for 5-HT(4) over non-5-HT(4) receptors may influence the agent's safety and overall risk-benefit profile. Based on available evidence, highly selective 5-HT(4) agonists may offer improved safety to treat patients with impaired GI motility. © 2012 Blackwell Publishing Ltd.

  19. Systematic review: cardiovascular safety profile of 5-HT4 agonists developed for gastrointestinal disorders

    PubMed Central

    Tack, J; Camilleri, M; Chang, L; Chey, W D; Galligan, J J; Lacy, B E; Müller-Lissner, S; Quigley, E M M; Schuurkes, J; Maeyer, J H; Stanghellini, V

    2012-01-01

    Summary Background The nonselective 5-HT4 receptor agonists, cisapride and tegaserod have been associated with cardiovascular adverse events (AEs). Aim To perform a systematic review of the safety profile, particularly cardiovascular, of 5-HT4 agonists developed for gastrointestinal disorders, and a nonsystematic summary of their pharmacology and clinical efficacy. Methods Articles reporting data on cisapride, clebopride, prucalopride, mosapride, renzapride, tegaserod, TD-5108 (velusetrag) and ATI-7505 (naronapride) were identified through a systematic search of the Cochrane Library, Medline, Embase and Toxfile. Abstracts from UEGW 2006–2008 and DDW 2008–2010 were searched for these drug names, and pharmaceutical companies approached to provide unpublished data. Results Retrieved articles on pharmacokinetics, human pharmacodynamics and clinical data with these 5-HT4 agonists, are reviewed and summarised nonsystematically. Articles relating to cardiac safety and tolerability of these agents, including any relevant case reports, are reported systematically. Two nonselective 5-HT4 agonists had reports of cardiovascular AEs: cisapride (QT prolongation) and tegaserod (ischaemia). Interactions with, respectively, the hERG cardiac potassium channel and 5-HT1 receptor subtypes have been suggested to account for these effects. No cardiovascular safety concerns were reported for the newer, selective 5-HT4 agonists prucalopride, velusetrag, naronapride, or for nonselective 5-HT4 agonists with no hERG or 5-HT1 affinity (renzapride, clebopride, mosapride). Conclusions 5-HT4 agonists for GI disorders differ in chemical structure and selectivity for 5-HT4 receptors. Selectivity for 5-HT4 over non-5-HT4 receptors may influence the agent's safety and overall risk–benefit profile. Based on available evidence, highly selective 5-HT4 agonists may offer improved safety to treat patients with impaired GI motility. PMID:22356640

  20. Topical retinoids in acne vulgaris: update on efficacy and safety.

    PubMed

    Thielitz, Anja; Gollnick, Harald

    2008-01-01

    Topical retinoids represent a mainstay of acne treatment because they expel mature comedones, reduce microcomedone formation, and exert anti-inflammatory effects. The first-generation retinoid tretinoin (all-trans retinoic acid) and the synthetic third-generation polyaromatics adapalene and tazarotene are approved for acne treatment by the US FDA, whereas topical tretinoin, isotretinoin (13-cis retinoic acid), and adapalene are accredited in Canada and Europe. Topical retinoids have a favorable safety profile distinct from the toxicity of their systemic counterparts. Local adverse effects, including erythema, dryness, itching, and stinging, occur frequently during the early treatment phase. Their impact varies with the vehicle formation, skin type, frequency and mode of application, use of moisturizers, and environmental factors such as sun exposure or temperature. The broad anti-acne activity and safety profile of topical retinoids justifies their use as first-line treatment in most types of non-inflammatory and inflammatory acne. They are also suitable as long-term medications, with no risk of inducing bacterial resistance, for maintenance of remission after cessation of initial combination therapy.

  1. Mental Disorder Symptoms among Public Safety Personnel in Canada.

    PubMed

    Carleton, R Nicholas; Afifi, Tracie O; Turner, Sarah; Taillieu, Tamara; Duranceau, Sophie; LeBouthillier, Daniel M; Sareen, Jitender; Ricciardelli, Rose; MacPhee, Renee S; Groll, Dianne; Hozempa, Kadie; Brunet, Alain; Weekes, John R; Griffiths, Curt T; Abrams, Kelly J; Jones, Nicholas A; Beshai, Shadi; Cramm, Heidi A; Dobson, Keith S; Hatcher, Simon; Keane, Terence M; Stewart, Sherry H; Asmundson, Gordon J G

    2018-01-01

    Canadian public safety personnel (PSP; e.g., correctional workers, dispatchers, firefighters, paramedics, police officers) are exposed to potentially traumatic events as a function of their work. Such exposures contribute to the risk of developing clinically significant symptoms related to mental disorders. The current study was designed to provide estimates of mental disorder symptom frequencies and severities for Canadian PSP. An online survey was made available in English or French from September 2016 to January 2017. The survey assessed current symptoms, and participation was solicited from national PSP agencies and advocacy groups. Estimates were derived using well-validated screening measures. There were 5813 participants (32.5% women) who were grouped into 6 categories (i.e., call center operators/dispatchers, correctional workers, firefighters, municipal/provincial police, paramedics, Royal Canadian Mounted Police). Substantial proportions of participants reported current symptoms consistent with 1 (i.e., 15.1%) or more (i.e., 26.7%) mental disorders based on the screening measures. There were significant differences across PSP categories with respect to proportions screening positive based on each measure. The estimated proportion of PSP reporting current symptom clusters consistent with 1 or more mental disorders appears higher than previously published estimates for the general population; however, direct comparisons are impossible because of methodological differences. The available data suggest that Canadian PSP experience substantial and heterogeneous difficulties with mental health and underscore the need for a rigorous epidemiologic study and category-specific solutions.

  2. Efficacy of Atomoxetine in Children with Severe Autistic Disorders and Symptoms of ADHD: An Open-Label Study

    ERIC Educational Resources Information Center

    Charnsil, Chawanun

    2011-01-01

    Objective: This study aims to examine the efficacy of atomoxetine in treating symptoms of attention deficit hyperactivity disorder (ADHD) in children with severe autistic disorder. Method: Children with severe autistic disorder who had symptoms of ADHD were given atomoxetine for 10 weeks. The efficacy of atomoxetine was evaluated by using the…

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

    PubMed

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

    2013-11-01

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

  4. Safety and efficacy of over-the-counter cough and cold medicines for use in children.

    PubMed

    Vassilev, Zdravko P; Kabadi, Shaum; Villa, Raul

    2010-03-01

    Over-the-counter (OTC) cough and cold medications have been used widely for years and continue to be a preferred choice for temporary relief of symptoms of upper respiratory tract infections in children. These medications are being placed under extraordinary scrutiny in the pediatric population due to the lack of conclusive evidence about their therapeutic efficacy and increased reports of associations with serious adverse events and even mortality. A PubMed search was conducted to identify articles published up to August 2009 describing the efficacy and safety of OTC cough and cold medications in children. The objective was to provide an overview of the relevant literature and regulatory history and to comment on the available data on this important topic. The paper provides a detailed up-to-date review of the key efficacy and safety studies published on the subject. In addition, the reader is presented with an overview of the regulatory history and recent developments surrounding the use of OTC cough and cold medications in children in the US. This review confirms the lack of efficacy of OTC cough and cold products in children and reaffirms that although the overall incidence of related serious adverse events is low, such events continue to occur. The conclusions in this paper support a recommendation that OTC cough and cold medications should not be given to infants and very young children. Furthermore, additional research is needed to evaluate the safety and efficacy of these medicines in the broader pediatric population.

  5. Efficacy and safety of laxatives for chronic constipation in long-term care settings: A systematic review.

    PubMed

    Alsalimy, N; Madi, L; Awaisu, A

    2018-06-09

    Constipation is a common disorder among long-term care (LTC) patients due to several factors. However, there are no systematic reviews investigating the use of laxatives for chronic constipation in LTC settings. This study aims to explore the safety and efficacy of laxatives in LTC patients. A systematic review of randomized controlled trials (RCTs) describing the efficacy and safety of laxatives for chronic constipation in LTC patients was conducted using the following databases and search engines: MEDLINE, Cochrane Database of Systematic Reviews, ScienceDirect, ProQuest and Google Scholar. Two of the investigators independently performed the searches, and the data were extracted using a standardized data abstraction tool. Seven RCTs involving 444 patients were included in the review. These studies included senna (with or without fibre, ie Plantago ovata), lactulose, sodium picosulphate, docusate sodium, docusate calcium, isotonic and hypotonic polyethylene glycol and Chinese herbal medicine. Senna and lactulose were the most studied laxatives in LTC patients, and senna was found to be superior to or as effective as other laxatives. Generally, the frequency and severity of adverse drug reactions (ADRs) were similar between the arms of the studies, and no serious ADRs were reported. Considering the short duration of the trials, the lack of trials including newer laxatives and the low quality of some of the included trials, the long-term efficacy and safety of these laxatives are not conclusive. There is a need to conduct more robust RCTs that include newer agents to evaluate long-term outcomes. © 2018 John Wiley & Sons Ltd.

  6. Efficacy and Safety of Leucine Supplementation in the Elderly.

    PubMed

    Borack, Michael S; Volpi, Elena

    2016-12-01

    Leucine supplementation has grown in popularity due to the discovery of its anabolic effects on cell signaling and protein synthesis in muscle. The current recommendation is a minimum intake of 55 mg ⋅ kg -1 . d -1 Leucine acutely stimulates skeletal muscle anabolism and can overcome the anabolic resistance of aging. The value of chronic leucine ingestion for muscle growth is still unclear. Most of the research into leucine consumption has focused on efficacy. To our knowledge, very few studies have sought to determine the maximum safe level of intake. Limited evidence suggests that intakes of ≤1250 mg ⋅ kg -1 . d -1 do not appear to have any health consequences other than short-term elevated plasma ammonia concentrations. Similarly, no adverse events have been reported for the leucine metabolite β-hydroxy-β-methylbutyrate (HMB), although no studies have tested HMB toxicity in humans. Therefore, future research is needed to evaluate leucine and HMB toxicity in the elderly and in specific health conditions. © 2016 American Society for Nutrition.

  7. Oral versus intramuscular phytomenadione: safety and efficacy compared.

    PubMed

    von Kries, R

    1999-07-01

    Oral and intramuscular phytomenadione (vitamin K1) prophylaxis became an issue following the report of a potential carcinogenic effect of intramuscular but not oral phytomenadione prophylaxis. There is increasing evidence, however, that oral phytomenadione prophylaxis is less effective for the prevention of late vitamin K deficiency bleeding (VKDB) than intramuscular prophylaxis. Following a report of an increased cancer risk after intramuscular phytomenadione, a series of papers on this issue appeared. Although an increased risk for solid tumours could almost certainly be excluded, a potential risk for acute lymphatic leukaemia in childhood could not be ruled out definitively. Almost all cases of late VKDB are preventable with intramuscular phytomenadione prophylaxis administered once at birth, whereas a single oral dose given at birth is much less effective. Repeated oral phytomenadione doses given to breast-fed infants either weekly (1 mg) or daily (25 microg) seem to be as effective as intramuscular phytomenadione prophylaxis. The efficacy of 3 oral 2mg doses with the new mixed micellar preparation ('Konakion MM') remains to be established. Although a number of studies have failed to confirm a cancer risk with phytomenadione, these studies have been unable to rule out a risk definitely because absence of evidence is not evidence of absence. A meta-analysis of the available studies might provide 95% confidence intervals narrow enough to exclude even a small cancer risk with some certainty. Oral prophylaxis will probably be as safe as the intramuscular prophylaxis if given daily (25 microg) or weekly (1 mg).

  8. 76 FR 19375 - Safety and Efficacy of Hypnotic Drugs; Public Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-07

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Safety and Efficacy of Hypnotic Drugs; Public Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public meeting. The Food and Drug Administration (FDA) is announcing a public meeting to...

  9. Mathematical modeling of efficacy and safety for anticancer drugs clinical development.

    PubMed

    Lavezzi, Silvia Maria; Borella, Elisa; Carrara, Letizia; De Nicolao, Giuseppe; Magni, Paolo; Poggesi, Italo

    2018-01-01

    Drug attrition in oncology clinical development is higher than in other therapeutic areas. In this context, pharmacometric modeling represents a useful tool to explore drug efficacy in earlier phases of clinical development, anticipating overall survival using quantitative model-based metrics. Furthermore, modeling approaches can be used to characterize earlier the safety and tolerability profile of drug candidates, and, thus, the risk-benefit ratio and the therapeutic index, supporting the design of optimal treatment regimens and accelerating the whole process of clinical drug development. Areas covered: Herein, the most relevant mathematical models used in clinical anticancer drug development during the last decade are described. Less recent models were considered in the review if they represent a standard for the analysis of certain types of efficacy or safety measures. Expert opinion: Several mathematical models have been proposed to predict overall survival from earlier endpoints and validate their surrogacy in demonstrating drug efficacy in place of overall survival. An increasing number of mathematical models have also been developed to describe the safety findings. Modeling has been extensively used in anticancer drug development to individualize dosing strategies based on patient characteristics, and design optimal dosing regimens balancing efficacy and safety.

  10. Leadership Styles and Self-Efficacy in Determining Transfer Intentions of Safety Training

    ERIC Educational Resources Information Center

    Vignoli, Michela; Mariani, Marco Giovanni; Guglielmi, Dina; Violante, Francesco Saverio

    2018-01-01

    Purpose: This study aims to investigate the factors that can influence the transfer process of training in open skills, i.e. non-technical skills (NTS). Specifically, according to the model of the transfer process, the aim of this paper is to analyse the effects of both personal (e.g. self-efficacy) and work environment (e.g. safety leadership…

  11. Safety and efficacy of low-dose, subacute exposure of mature ewes to sodium chlorate

    USDA-ARS?s Scientific Manuscript database

    The objective was to determine the safety and efficacy of low-dose, subacute exposure of mature ewes to NaClO3 in the drinking water. Twenty-five ewes (BW = 62.5 ± 7.3 kg) were placed indoors in individual pens with ad libitum access to water and feed. After 7 d of adaptation, ewes were assigned ran...

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

    PubMed

    Veazey, Ronald S

    2008-09-01

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

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

    PubMed Central

    Veazey, Ronald S.

    2009-01-01

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

  14. Safety and efficacy assessment of standardized herbal formula PM012

    PubMed Central

    2012-01-01

    Background This study was conducted to evaluate the efficacy of the herbal formula PM012 on an Alzheimer's disease model, human presenilin 2 mutant transgenic mice (hPS2m), and also to evaluate the toxicity of PM012 in Sprague-Dawely rats after 4 or 26 weeks treatment with repeated oral administration. Methods Spatial learning and memory capacities of hPS2m transgenic mice were evaluated using the Morris Water Maze. Simultaneously, PM012 was repeatedly administered orally to male and female SD rats (15/sex/group) at doses of 0 (vehicle control), 500, 1,000 and 2,000 mg/kg/day for 4 or 26 weeks. To evaluate the recovery potential, 5 animals of each sex were assigned to vehicle control and 2,000 mg/kg/day groups during the 4-week recovery period. Results The results showed that PM012-treated hPS2m transgenic mice showed significantly reduced escape latency when compared with the hPS2m transgenic mice. The repeated oral administration of PM012 over 26 weeks in male and female rats induced an increase and increasing trend in thymus weight in the female treatment groups (main and recovery groups), but the change was judged to be toxicologically insignificant. In addition, the oral administration of the herbal medicine PM012 did not cause adverse effects as assessed by clinical signs, mortality, body weight, food and water consumption, ophthalmology, urinalysis, hematology, serum biochemistry, blood clotting time, organ weights and histopathology. The No Observed Adverse Effects Levels of PM012 was determined to be 2,000 mg/kg/day for both sexes, and the target organ was not identified. Conclusion These results suggest that PM012 has potential for use in the treatment of the Alzheimer's disease without serious adverse effects. PMID:22458507

  15. Efficacy and safety of Saccharomyces boulardii for acute diarrhea.

    PubMed

    Feizizadeh, Sahar; Salehi-Abargouei, Amin; Akbari, Vajihe

    2014-07-01

    The efficacy of Saccharomyces boulardii for treatment of childhood diarrhea remains unclear. Our objective was to systematically review data on the effect of S. boulardii on acute childhood diarrhea. Our data sources included Medline, Embase, CINAHL, Scopus, and The Cochrane Library up to September 2013 without language restrictions. Randomized controlled trials and non-randomized trials that evaluated effectiveness of S. boulardii for treatment of acute diarrhea in children were included. Two reviewers independently evaluated studies for eligibility and quality and extracted the data. In total, 1248 articles were identified, of which 22 met the inclusion criteria. Pooling data from trials showed that S. boulardii significantly reduced the duration of diarrhea (mean difference [MD], -19.7 hours; 95% confidence interval [CI], -26.05 to -13.34), stool frequency on day 2 (MD, -0.74; 95% CI, -1.38 to -0.10) and day 3 (MD, -1.24; 95% CI, -2.13 to -0.35), the risk for diarrhea on day 3 (risk ratio [RR], 0.41; 95% CI, 0.27 to 0.60) and day 4 (RR, 0.38; 95% CI, 0.24 to 0.59) after intervention compared with control. The studies included in this review were varied in the definition of diarrhea, the termination of diarrhea, inclusion and exclusion criteria, and their methodological quality. This review and meta-analysis show that S. boulardii is safe and has clear beneficial effects in children who have acute diarrhea. However, additional studies using head-to-head comparisons are needed to define the best dosage of S. boulardii for diarrhea with different causes. Copyright © 2014 by the American Academy of Pediatrics.

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

    PubMed

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

    2018-01-01

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

  17. Confidence in the efficacy and safety of dietary supplements among United States active duty army personnel.

    PubMed

    Carvey, Christina E; Farina, Emily K; Lieberman, Harris R

    2012-10-10

    United States Army Soldiers regularly use dietary supplements (DS) to promote general health, enhance muscle strength, and increase energy, but limited scientific evidence supports the use of many DS for these benefits. This study investigated factors associated with Soldiers' confidence in the efficacy and safety of DS, and assessed Soldiers' knowledge of federal DS regulatory requirements. Between 2006 and 2007, 990 Soldiers were surveyed at 11 Army bases world-wide to assess their confidence in the effectiveness and safety of DS, knowledge of federal DS regulations, demographic characteristics, lifestyle-behaviors and DS use. A majority of Soldiers were at least somewhat confident that DS work as advertised (67%) and thought they are safe to consume (71%). Confidence in both attributes was higher among regular DS users than non-users. Among users, confidence in both attributes was positively associated with rank, self-rated diet quality and fitness level, education, and having never experienced an apparent DS-related adverse event. Fewer than half of Soldiers knew the government does not require manufacturers to demonstrate efficacy, and almost a third incorrectly believed there are effective pre-market federal safety requirements for DS. Despite limited scientific evidence supporting the purported benefits and safety of many popular DS, most Soldiers were confident that DS are effective and safe. The positive associations between confidence and DS use should be considered when developing DS-related interventions or policies. Additionally, education to clarify Soldiers' misperceptions about federal DS safety and efficacy regulations is warranted.

  18. 78 FR 60290 - Availability of Masked and De-identified Non-Summary Safety and Efficacy Data; Reopening of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-01

    ...] Availability of Masked and De-identified Non-Summary Safety and Efficacy Data; Reopening of Comment Period... of Masked and De- identified Non-Summary Safety and Efficacy Data; Request for Comments,'' which... request for public comments from interested persons on the proposed availability of de-identified and...

  19. Efficacy and safety of sotagliflozin in treating diabetes type 1.

    PubMed

    Rendell, Marc S

    2018-02-01

    Sotagliflozin is the first dual SGLT1/SGLT2 inhibitor developed for use in diabetes. Sotagliflozin blocks SGLT2 in the kidneys and SGLT1 in the intestines resulting in reduced early phase glucose absorption and increased blood levels of GLP-1 and PYY. Urinary glucose excretion is lower than with other agents as a result of decreased glucose absorption. The primary development effort to date has been in Type 1 diabetes. Areas covered: The published information on sotagliflozin is reviewed, along with the recent results of several pivotal Type 1 diabetes trials. Expert opinion: Sotagliflozin treatment lowers HbA1c and reduces glucose variability, with a trend to less hypoglycemic events. In the Type 1 trials, sotagliflozin treated individuals experienced DKA at a higher rate than placebo treated patients. An additional safety issue arises from the as yet unknown potential risks in women of child bearing potential in whom DKA is of utmost concern. The sotagliflozin development program has now been extended to trials in Type 2 diabetes, and long term studies will be needed to assess the benefits and risks of the agent in comparison to other currently marketed SGLT2 inhibitors.

  20. Efficacy and Safety of Vedolizumab in Ulcerative Colitis and Crohn's Disease Patients Stratified by Age.

    PubMed

    Yajnik, Vijay; Khan, Nabeel; Dubinsky, Marla; Axler, Jeffrey; James, Alexandra; Abhyankar, Brihad; Lasch, Karen

    2017-02-01

    The efficacy and safety of vedolizumab, a gut-selective α 4 β 7 integrin antibody, were demonstrated in the GEMINI 1 and GEMINI 2 clinical trials of adults aged 18-80 years. We investigated the efficacy and safety of vedolizumab in patients stratified by age from the GEMINI trials. Safety and efficacy, including clinical response, clinical remission, and corticosteroid-free remission, at week 6 and/or 52 were determined post hoc in patients aged <35, 35 to <55, and ≥55 years. At baseline, 353, 412, and 130 ulcerative colitis (UC) and 582, 443, and 90 Crohn's disease (CD) patients were aged <35, 35 to <55, and ≥55. Of these patients, 56 were aged ≥65 years (UC: 33, CD: 23). Trends favoring vedolizumab over placebo were observed for most efficacy endpoints irrespective of patient age; some variability between subgroups was observed. Safety profiles of vedolizumab and placebo were similar in all age groups. Vedolizumab-treated patients aged ≥55 had the lowest incidence of serious infections (0.9 per 100 person-years) and adverse events leading to hospitalization (14.8 per 100 person-years). There were no age-related differences in the incidence of adverse hematological events, malignancy, or death. The safety and efficacy of vedolizumab in patients with UC or CD were similar for all age groups. The number of patients in the oldest age group in these analyses was small; thus further studies of vedolizumab in larger cohorts of elderly patients are warranted. Millennium Pharmaceuticals, Inc. (d/b/a Takeda Pharmaceuticals International Co.).

  1. Efficacy, safety and tolerability of rasagiline as adjunctive therapy in elderly patients with Parkinson's disease.

    PubMed

    Tolosa, E; Stern, M B

    2012-02-01

    Rasagiline, an MAO-B inhibitor, is indicated for the treatment of Parkinson's disease (PD). In this post hoc analysis, the efficacy, safety and tolerability of rasagiline as an adjunct to levodopa were compared with placebo in elderly (≥70 years) and younger (<70 years) patients with PD. Data were pooled from the Parkinson's Rasagiline: Efficacy and Safety on the Treatment of 'OFF' and Lasting effect in Adjunct therapy with Rasagiline Given Once daily randomized, double-blind, placebo-controlled trials with the primary efficacy end-point being the reduction from baseline in daily OFF time. Secondary efficacy end-points included scores for Clinical Global Improvement (CGI)-Examiner during ON time, Unified Parkinson's Disease Rating Scale (UPDRS)-ADL during OFF time, UPDRS-Motor during ON time and total daily ON time with and without troublesome dyskinesia. Tolerability was evaluated from adverse events (AEs) in the two age groups. Rasagiline decreased daily OFF time versus placebo (P<0.01) and improved CGI-Examiner score (P=0.001) and UPDRS-Motor ON score (P<0.05). Changes in UPDRS-ADL OFF score and total daily ON time without dyskinesia also favoured rasagiline but were not significant. Between-group comparisons (≥70 vs. <70 years) showed that efficacy was unaffected by age for all end-points (P>0.1), and rasagiline was well tolerated amongst both groups of patients with a comparable incidence of total and dopaminergic AEs (P>0.1). Adjunct rasagiline is efficacious and well tolerated in elderly non-demented patients (≥70 years) with moderate to advanced PD. Confirmation of the efficacy and safety of rasagiline in the elderly patient subgroup is especially relevant because of the increasing number of elderly patients with PD. © 2011 The Author(s). European Journal of Neurology © 2011 EFNS.

  2. Gender Differences in the Efficacy and Safety of Chronic Nightly Zolpidem.

    PubMed

    Roehrs, Timothy A; Roth, Thomas

    2016-03-01

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

  3. Efficacy Profiles of Psychopharmacology: Divalproex Sodium in Conduct Disorder

    ERIC Educational Resources Information Center

    Khanzode, Leena A.; Saxena, Kirti; Kraemer, Helena; Chang, Kiki; Steiner, Hans

    2006-01-01

    Little is known about how deeply medication treatment penetrates different levels of the mind/brain system. Psychopathology consists of relatively simple constructs (e.g., anger, irritability), or complex ones (e.g., responsibility). This study examines the efficacy of a specific compound, divalproex sodium (DVPX), on the various levels of…

  4. Subcutaneous venom immunotherapy in children: Efficacy and safety.

    PubMed

    Gür Çetinkaya, Pınar; Esenboğa, Saliha; Uysal Soyer, Özge; Tuncer, Ayfer; Şekerel, Bülent Enis; Şahiner, Ümit Murat

    2018-04-01

    Venom immunotherapy (VIT) is safe in children, although adverse effects can occur. To document adverse effects and to determine re-sting reactions and the efficacy of VIT in childhood. We retrospectively analyzed data from children who had taken VIT from 2002 through 2015. These patients were queried by telephone to determine reactions after re-stings during or after VIT. In total 107 children with a systemic reaction after Hymenoptera sting and with proved immunoglobulin E-mediated sensitization were enrolled. Participants had a median age of 10.0 years (7.2-12.4 years) at the beginning of immunotherapy. Fifty-two participants had allergic reactions during VIT; 40 of these reactions were local (37.4%), 5 were large local (4.7%), and 7 were systemic (6.5%). Of the 52 patients with adverse reactions, most reactions were local (n = 40, 89%) and were observed mainly in dose-increase periods (n = 25, 60%; P < .001). Although local reactions were more frequently seen with Vespula treatment (P = .047), systemic reactions were common with Apis treatment (P = .031). Sixty-eight patients (63.5%) were queried for re-sting, 33 (48.5%) had a re-sting and 24 (72.7%) of these 33 patients developed allergic reactions. The reactions were local (n = 19), large local (n = 1), and systemic (n = 4). Risk analysis for local and systemic reactions during VIT showed pre-existing asthma as an independent risk factor (odds ratio 4.1, 95% confidence interval 1.3-12.7, P = .016). In children, VIT appears to be safe and protective against severe reactions after re-sting. However, pre-existing asthma was identified as a risk factor for systemic and large local reactions during VIT in children. Copyright © 2018 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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

    PubMed Central

    West, Jonathan; Ogston, Simon; Foerster, John

    2016-01-01

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

  6. CYD-TDV dengue vaccine: systematic review and meta-analysis of efficacy, immunogenicity and safety.

    PubMed

    Godói, Isabella Piassi; Lemos, Livia Lovato Pires; de Araújo, Vânia Eloisa; Bonoto, Braúlio Cesar; Godman, Brian; Guerra Júnior, Augusto Afonso

    2017-03-01

    Dengue virus (DENV) is a serious global health problem. CYD-TDC (Dengvaxia ® ) was the first vaccine to gain regulatory approval to try and address this problem. Summarize all available evidence on the immunogenicity, efficacy and safety of the CYD-TDV dengue vaccine. Meta-analysis and systematic review. The best and worst immunogenicity results were for DENV4 and DENV1, respectively. Vaccine efficacy of 60% was derived from studies with participants aged 2-16 years old, with DENV4 and DENV2 presenting the best and worst results, respectively. Erythema and swelling were more frequent with CYD-TDV. No differences were detected for systemic adverse events. CYD-TDV showed moderate efficacy in children and adolescents. From the immunogenicity results in adults, we can expect satisfactory efficacy from vaccination in this population.

  7. The efficacy and safety of clotrimazole vaginal tablet vs. oral fluconazole in treating severe vulvovaginal candidiasis.

    PubMed

    Zhou, Xiaofang; Li, Ting; Fan, Shangrong; Zhu, Yuxia; Liu, Xiaoping; Guo, Xuedong; Liang, Yiheng

    2016-07-01

    To compare the efficacy and safety of two doses of clotrimazole vaginal tablet 500 mg with two doses of oral fluconazole 150 mg in treating severe vulvovaginal candidiasis (SVVC), 240 consecutive patients with SVVC were studied at the Department of Obstetrics and Gynaecology of Peking University Shenzhen Hospital between June 2014, and September 2015. Patients were randomly assigned in a 1 : 1 ratio to receive treatment with either two doses of clotrimazole vaginal tablet or two doses of oral fluconazole. The clinical cure rates in the clotrimazole group and the fluconazole group at days 7-14 follow-up were 88.7% (102/115) and 89.1% (98/110) respectively; the clinical cure rates at days 30-35 in the two groups were 71.9% (82/114) and 78.0% (85/109) respectively. The mycological cure rates at days 7-14 follow-up in the two groups were 78.3% (90/115) and 73.6% (81/110) respectively. The mycological cure rates of the patients at days 30-35 in the two groups were 54.4% (62/114) and 56.0% (61/109) respectively (P > 0.05). The adverse events of clotrimazole were mainly local. This study demonstrated that two doses of clotrimazole vaginal tablet 500 mg were as effective as two doses of oral fluconazole 150 mg in the treatment of patients with SVVC and could be an appropriate treatment for this disorder. © 2016 The Authors Mycoses Published by Blackwell Verlag GmbH.

  8. Feasibility, safety and efficacy of transcutaneous vagus nerve stimulation in chronic tinnitus: an open pilot study.

    PubMed

    Kreuzer, Peter M; Landgrebe, Michael; Resch, Markus; Husser, Oliver; Schecklmann, Martin; Geisreiter, Florian; Poeppl, Timm B; Prasser, Sarah J; Hajak, Goeran; Rupprecht, Rainer; Langguth, Berthold

    2014-01-01

    Vagus nerve stimulation represents an established treatment strategy for epilepsy and affective disorders. Recently, positive effects were also shown in animals and humans with tinnitus. Here we report the results of an open pilot study exploring feasibility, safety and efficacy of tVNS in the treatment of chronic tinnitus. Fifty patients with chronic tinnitus underwent tVNS in an open single-armed pilot study which was conducted in two phases applying two different stimulating devices (Cerbomed CM02 and NEMOS). Clinical assessment was based on Tinnitus Questionnaire (TQ), Tinnitus Handicap Inventory (THI), Beck Depression Inventory (BDI), WHO Quality of Life, and various numeric rating scales. Primary outcome was defined as change in TQ (baseline vs. final visit in week 24). The study has been registered with clinicaltrials.gov (NCT01176734). Primary analysis indicated mean TQ reductions of 3.7 points (phase 1) and 2.8 points (phase 2) significant for the first study phase. Secondary analyses indicated a significant BDI reduction for phase 1 (uncorrected for multiple testing), but no further systematic or significant effects. Adverse events included twitching and pressure at electrode placement site. The occurrence of one hospitalization because of palpations and the development of a left bundle branch block were considered as unrelated to the intervention. Cognitive testing revealed no significant changes. Our data demonstrate the feasibility of tVNS over a period of 6 months. There was no clinically relevant improvement of tinnitus complaints. Our data suggest tVNS to be considered safe in patients without a history of cardiac disease. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. [The efficacy and tolerability of pericyazine in the treatment of patients with schizotypal disorder, organic personality disorders and pathocharacterological changes within personality disorders].

    PubMed

    Danilov, D S

    To assess the efficacy and tolerability of pericyazine in the treatment of patients with mental disorders manifesting with psychopathic-like symptoms and correction of pathocharacterological disorders in patients with personality disorders during the short-term admission to the hospital or the long-term outpatient treatment. Sixty-three patients with schizotypal personality disorder and organic personality disorder with psychopathic-like symptoms and pathocharacterological changes within the diagnosis of dissocial personality disorder and borderline personality disorder were examined. Patients received pericyazine during the short-term admission to the hospital (6 weeks) or the long-term outpatient treatment (6 month). Efficacy, tolerability and compliance were assessed in the study. Treatment with pricyazine was effective in all patients. The improvement was seen in patients with organic personality disorders and patients with personality disorders (psychopathy). The maximal effect was observed in inpatients and this effect remained during outpatient treatment. The improvement of mental state of patients with schizotypal personality disorder achieved during inpatient treatment with pericyazine continued during the long-term outpatient treatment. Side-effects were restricted to extrapyramidal symptoms, the frequency of metabolic syndrome was low. During outpatient treatment, the compliance was higher if the patient was managed by the same psychiatrist during inpatient- and outpatient treatment.

  10. Safety and Efficacy of Glucomannan for Weight Loss in Overweight and Moderately Obese Adults

    PubMed Central

    Keithley, Joyce K.; Swanson, Barbara; Mikolaitis, Susan L.; DeMeo, Mark; Zeller, Janice M.; Fogg, Lou; Adamji, Jehan

    2013-01-01

    Background. Few safe and effective dietary supplements are available to promote weight loss. We evaluated the safety and efficacy of glucomannan, a water-soluble fiber supplement, for achieving weight loss in overweight and moderately obese individuals consuming self-selected diets. Methods. Participants were randomly assigned to take 1.33 grams of glucomannan or identically looking placebo capsules with 236.6 mL (8 ounces) of water one hour before breakfast, lunch, and dinner for 8 weeks. The primary efficacy outcome was change in body weight after 8 weeks. Other efficacy outcomes were changes in body composition, hunger/fullness, and lipid and glucose concentrations. Safety outcomes included gastrointestinal symptoms/tolerance and serum liver enzymes and creatinine levels. Results. A total of 53 participants (18–65 years of age; BMI 25–35 kg/m2) were enrolled and randomized. The two groups did not differ with respect to baseline characteristics and compliance with the study supplement. At 8 weeks, there was no significant difference between the glucomannan and placebo groups in amount of weight loss (−.40 ± .06 and −.43 ± .07, resp.) or other efficacy outcomes or in any of the safety outcomes. Conclusions. Glucomannan supplements administered over 8 weeks were well tolerated but did not promote weight loss or significantly alter body composition, hunger/fullness, or lipid and glucose parameters. This trial is registered with NCT00613600. PMID:24490058

  11. A review of the efficacy and safety of oral antidiabetic drugs

    PubMed Central

    Stein, Stephanie Aleskow; Lamos, Elizabeth Mary; Davis, Stephen N

    2014-01-01

    Introduction Additional oral antidiabetic agents to metformin, sulfonylureas (SU) and thiazolidinediones (TZD) are approved for the treatment of type 2 diabetes. Areas covered The efficacy and safety of metformin, SUs, TZDs, dipeptidyl peptidase-IV (DPP-4) inhibitors, meglitinide analogs, α-glucosidase inhibitors (AGIs), bile-acid sequestrants (BAS) and bromocriptine will be reviewed. Expert opinion Several new oral agents have been approved for type 2 diabetes management in recent years. It is important to understand the efficacy and safety of these medications in addition to the older agents to best maximize oral drug therapy for diabetes. Of the recently introduced oral hypoglycemic/antihyperglycemic agents, the DPP-4 inhibitors are moderately efficacious compared with mainstay treatment with metformin with a low side-effect profile and have good efficacy in combination with other oral agents and insulin. They are a recommended alternative when metformin use is limited by gastrointestinal (GI) side effects or when SU treatment results in significant hypoglycemia or weight gain. Meglitinide analogs are limited by their frequent dosing, expense and hypoglycemia (repaglinide > nateglinide), while AGIs are also limited by their dosing schedule and GI side-effect profile. BAS and bromocriptine have the lowest efficacy with regard to HbA1c reduction, also are plagued by GI adverse reactions, but have a low risk of hypoglycemia. PMID:23241069

  12. Safety and efficacy of physical restraints for the elderly. Review of the evidence.

    PubMed Central

    Frank, C.; Hodgetts, G.; Puxty, J.

    1996-01-01

    OBJECTIVE: To critically review evidence on the safety and efficacy of physical restraints for the elderly and to provide family physicians with guidelines for rational use of restraints. DATA SOURCES: Articles cited on MEDLINE (from 1989 to November 1994) and Cinahl (from 1982 to 1994) under the MeSH heading "physical restraints." STUDY SELECTION: Articles that specifically dealt with the safety and efficacy of restraints and current patterns of use, including prevalence, risk factors, and indications, were selected. Eight original research articles were identified and critically appraised. DATA EXTRACTION: Data extracted concerned the negative sequelae of restraints and the association between restraint use and fall and injury rates. General data about current patterns of restraint use were related to safety and efficacy findings. DATA SYNTHESIS: No randomized, controlled trials of physical restraint use were found in the literature. A variety of study design, including retrospective chart review, prospective cohort studies, and case reports, found little evidence that restraints prevent injury. Some evidence suggested that restraints might increase risk of falls and injury. Restraint-reduction programs have not been shown to increase fall or injury rates. Numerous case reports document injuries or deaths resulting from restraint use or misuse. CONCLUSIONS: Although current evidence does not support the belief that restraints prevent falls and injuries and questions their safety, further prospective and controlled studies are needed to clarify these issues. Information from review and research articles was synthesized in this paper to produce guidelines for the safe and rational use of restraints. PMID:8969858

  13. Automated discovery of safety and efficacy concerns for joint & muscle pain relief treatments from online reviews.

    PubMed

    Adams, David Z; Gruss, Richard; Abrahams, Alan S

    2017-04-01

    Product issues can cost companies millions in lawsuits and have devastating effects on a firm's sales, image and goodwill, especially in the era of social media. The ability for a system to detect the presence of safety and efficacy (S&E) concerns early on could not only protect consumers from injuries due to safety hazards, but could also mitigate financial damage to the manufacturer. Prior studies in the field of automated defect discovery have found industry-specific techniques appropriate to the automotive, consumer electronics, home appliance, and toy industries, but have not investigated pain relief medicines and medical devices. In this study, we focus specifically on automated discovery of S&E concerns in over-the-counter (OTC) joint and muscle pain relief remedies and devices. We select a dataset of over 32,000 records for three categories of Joint & Muscle Pain Relief treatments from Amazon's online product reviews, and train "smoke word" dictionaries which we use to score holdout reviews, for the presence of safety and efficacy issues. We also score using conventional sentiment analysis techniques. Compared to traditional sentiment analysis techniques, we found that smoke term dictionaries were better suited to detect product concerns from online consumer reviews, and significantly outperformed the sentiment analysis techniques in uncovering both efficacy and safety concerns, across all product subcategories. Our research can be applied to the healthcare and pharmaceutical industry in order to detect safety and efficacy concerns, reducing risks that consumers face using these products. These findings can be highly beneficial to improving quality assurance and management in joint and muscle pain relief. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    PubMed

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

    2000-10-01

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

  15. Long-term safety and efficacy of AAV gene therapy in the canine model of glycogen storage disease type Ia.

    PubMed

    Lee, Young Mok; Conlon, Thomas J; Specht, Andrew; Coleman, Kirsten E; Brown, Laurie M; Estrella, Ana M; Dambska, Monika; Dahlberg, Kathryn R; Weinstein, David A

    2018-05-25

    Viral mediated gene therapy has progressed after overcoming early failures, and gene therapy has now been approved for several conditions in Europe and the USA. Glycogen storage disease (GSD) type Ia, caused by a deficiency of glucose-6-phosphatase-α, has been viewed as an outstanding candidate for gene therapy. This follow-up report describes the long-term outcome for the naturally occurring GSD-Ia dogs treated with rAAV-GPE-hG6PC-mediated gene therapy. A total of seven dogs were treated with rAAV-GPE-hG6PC-mediated gene therapy. The first four dogs were treated at birth, and three dogs were treated between 2 and 6 months of age to assess the efficacy and safety in animals with mature livers. Blood and urine samples, radiographic studies, histological evaluation, and biodistribution were assessed. Gene therapy improved survival in the GSD-Ia dogs. With treatment, the biochemical studies normalized for the duration of the study (up to 7 years). None of the rAAV-GPE-hG6PC-treated dogs had focal hepatic lesions or renal abnormalities. Dogs treated at birth required a second dose of rAAV after 2-4 months; gene therapy after hepatic maturation resulted in improved efficacy after a single dose. rAAV-GPE-hG6PC treatment in GSD-Ia dogs was found to be safe and efficacious. GSD-Ia is an attractive target for human gene therapy since it is a monogenic disorder with limited tissue involvement. Blood glucose and lactate monitoring can be used to assess effectiveness and as a biomarker of success. GSD-Ia can also serve as a model for other hepatic monogenic disorders.

  16. Efficacies of roadway safety improvements across functional subclasses of rural two-lane highways.

    PubMed

    Labi, Samuel

    2011-08-01

    Highway crash occurrence is a leading cause of unnatural deaths, and highway agencies continually seek to identify engineering measures to reduce crashes and to assess the efficacy of such measures. Most past studies on the effectiveness of roadway improvements in terms of crash reduction considered all rural two-lane sections as a single category of roads. However, it may be hypothesized that the differences in the mobility and accessibility characteristics that are reflected in (and due to) the different design standards between different functional subclasses in the rural two-lane highway system can lead to differences in efficacies of safety improvements at these subclasses. This paper investigates the efficacy of roadway improvements, in terms of crash reduction, at the various subclasses of rural two-lane highways. An empirical analysis of safety performance at each of the three subclasses of rural two-lane highways was carried out using the negative binomial modeling technique. For each subclass, crash prediction models were developed separately for the three levels of crash severity: property-damage only, injury, and fatal/injury. The crash factors that were considered include lane width, shoulder width, pavement surface friction, pavement condition, and horizontal and vertical alignments. After having developed the safety performance functions, the effectiveness (in terms of the extent of crash reduction, for different levels of crash severity) of highway safety enhancements at each highway subclass were determined using the theoretical concepts established in past literature. These enhancements include widening lanes, widening shoulders, enhancing pavement surface friction, and improving the vertical or horizontal alignment. The study found that there is empirical evidence to justify the decomposition of the family of rural two-lane roads into its constituent subclasses for purposes of analyzing the effectiveness of safety enhancement projects and thus to

  17. Efficacy of transdiagnostic cognitive-behavioral group therapy for anxiety disorders and headache in adolescents.

    PubMed

    Sharma, Pragya; Mehta, Manju; Sagar, Rajesh

    2017-03-01

    Anxiety disorders and headache are both among the most prevalent disorders among adolescents. Although cognitive behavioral therapy (CBT) has proved its efficacy with each of these disorders individually, there are several barriers to its utilization, including cost, gaps in knowledge about treatment delivery and modes, and its utility with comorbid disorders. The current study examined the comparative efficacy of a 12 week TCBT Group treatment (n=32) versus treatment as usual group (n=31) (TAU) in adolescents with anxiety disorders and headache in a north Indian hospital based setting. Results from 63 adolescents suggested while both conditions improved significantly on the Headache Impact Test and Children's Global Assessment Scale, those receiving TCBT showed significantly greater improvement than those in the TAU condition. Participants receiving TCBT, but not those in the TAU condition, showed significant improvement on the State Trait Anxiety Inventory. The study provides evidence supporting the efficacy of TCBT in adolescents with anxiety disorders and headache. Further, group TCBT has the benefits of easy dissemination and increased access to evidence-based treatment, thus, lowering costs and therapist time. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Driving Safety and Fitness to Drive in Sleep Disorders.

    PubMed

    Tippin, Jon; Dyken, Mark Eric

    2017-08-01

    Driving an automobile while sleepy increases the risk of crash-related injury and death. Neurologists see patients with sleepiness due to obstructive sleep apnea, narcolepsy, and a wide variety of neurologic disorders. When addressing fitness to drive, the physician must weigh patient and societal health risks and regional legal mandates. The Driver Fitness Medical Guidelines published by the National Highway Traffic Safety Administration (NHTSA) and the American Association of Motor Vehicle Administrators (AAMVA) provide assistance to clinicians. Drivers with obstructive sleep apnea may continue to drive if they have no excessive daytime sleepiness and their apnea-hypopnea index is less than 20 per hour. Those with excessive daytime sleepiness or an apnea-hypopnea index of 20 per hour or more may not drive until their condition is effectively treated. Drivers with sleep disorders amenable to pharmaceutical treatment (eg, narcolepsy) may resume driving as long as the therapy has eliminated excessive daytime sleepiness. Following these guidelines, documenting compliance to recommended therapy, and using the Epworth Sleepiness Scale to assess subjective sleepiness can be helpful in determining patients' fitness to drive.

  19. [Legislation and inspection for the health and safety of workers. Efficacy and limits].

    PubMed

    Tozzi, G A

    2009-01-01

    To provide information regarding Occupational Health and Safety (OHS) Inspections in Europe. The dynamics that are transforming regulatory subsystems and complementary inspection services are described. Simplification initiatives, the limits and difficulties of applying the different models of Health and Safety Management Systems are discussed. Examples are given on how to evaluate legislation and technical standards during planning and enforcement. Different approaches for studying characteristics, methodologies and efficacy in practice of OHS Inspection are provided. Targeted inspections need to respond to the needs of enterprises and workers. Impartiality must be guaranteed and workers' participation should be facilitated.

  20. An open-label, flexible dose adaptive study evaluating the efficacy of vortioxetine in subjects with panic disorder.

    PubMed

    Shah, Anish; Northcutt, Joanne

    2018-01-01

    Despite the current treatments available for panic disorder (PD), as many as one-third of patients have persistent and treatment-resistant panic attacks. Vortioxetine is an approved medicine for major depressive disorder and has been shown to have anxiolytic properties. The purpose of this study was to evaluate its efficacy and safety in an adult population with a diagnosis of PD. The study design was open label with flexible dose strategies (5, 10, or 20 mg) with a treatment period of 10 weeks. 27 male and female subjects aged between 18 and 60 years, who met DSM-IV criteria for PD with or without agoraphobia, or who had a Panic Disorder Severity Scale (PDSS) score > 8 at baseline were enrolled. Statistical significance was established by the Student's T test. A statistically significant decrease in the occurrence of panic attacks was measured with the PDSS with vortioxetine. In addition, a moderate improvement in the quality of life and no significant side effects were observed using the Quality-of-Life Scale and Monitoring of Side Effects Scale, respectively. These results provide some support for the use of vortioxetine in the management of panic disorder. Trial registration ClinicalTrials.gov ID#: NCT02395510. Registered March 23, 2015, https://clinicaltrials.gov/ct2/show/NCT02395510.

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

    NASA Astrophysics Data System (ADS)

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

    2017-10-01

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

  2. Efficacy and Safety of Low-field Synchronized Transcranial Magnetic Stimulation (sTMS) for Treatment of Major Depression.

    PubMed

    Leuchter, Andrew F; Cook, Ian A; Feifel, David; Goethe, John W; Husain, Mustafa; Carpenter, Linda L; Thase, Michael E; Krystal, Andrew D; Philip, Noah S; Bhati, Mahendra T; Burke, William J; Howland, Robert H; Sheline, Yvette I; Aaronson, Scott T; Iosifescu, Dan V; O'Reardon, John P; Gilmer, William S; Jain, Rakesh; Burgoyne, Karl S; Phillips, Bill; Manberg, Paul J; Massaro, Joseph; Hunter, Aimee M; Lisanby, Sarah H; George, Mark S

    2015-01-01

    Transcranial Magnetic Stimulation (TMS) customarily uses high-field electromagnets to achieve therapeutic efficacy in Major Depressive Disorder (MDD). Low-field magnetic stimulation also may be useful for treatment of MDD, with fewer treatment-emergent adverse events. To examine efficacy, safety, and tolerability of low-field magnetic stimulation synchronized to an individual's alpha frequency (IAF) (synchronized TMS, or sTMS) for treatment of MDD. Six-week double-blind sham-controlled treatment trial of a novel device that used three rotating neodymium magnets to deliver sTMS treatment. IAF was determined from a single-channel EEG prior to first treatment. Subjects had baseline 17-item Hamilton Depression Rating Scale (HamD17) ≥ 17. 202 subjects comprised the intent-to-treat (ITT) sample, and 120 subjects completed treatment per-protocol (PP). There was no difference in efficacy between active and sham in the ITT sample. Subjects in the PP sample (N = 59), however, had significantly greater mean decrease in HamD17 than sham (N = 60) (-9.00 vs. -6.56, P = 0.033). PP subjects with a history of poor response or intolerance to medication showed greater improvement with sTMS than did treatment-naïve subjects (-8.58 vs. -4.25, P = 0.017). Efficacy in the PP sample reflects exclusion of subjects who received fewer than 80% of scheduled treatments or were inadvertently treated at the incorrect IAF; these subgroups failed to separate from sham. There was no difference in adverse events between sTMS and sham, and no serious adverse events attributable to sTMS. Results suggest that sTMS may be effective, safe, and well tolerated for treating MDD when administered as intended. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Safety and efficacy of tinea pedis and onychomycosis treatment in people with diabetes: a systematic review.

    PubMed

    Matricciani, Lisa; Talbot, Kerwin; Jones, Sara

    2011-12-04

    Effective treatment of tinea pedis and onychomycosis is crucial for patients with diabetes as these infections may lead to foot ulcers and secondary bacterial infections resulting in eventual lower limb amputation. Although numerous studies have assessed the effectiveness of antifungal drug and treatment regimens, most exclude patients with diabetes and examine otherwise healthy individuals. While these studies are useful, results cannot necessarily be extrapolated to patients with diabetes. The purpose of this study was to therefore identify the best evidence-based treatment interventions for tinea pedis or onychomycosis in people with diabetes. The question for this systemic review was: 'what evidence is there for the safety and/or efficacy of all treatment interventions for adults with tinea pedis and/or onychomycosis in people with diabetes'? A systematic literature search of four electronic databases (Scopus, EbscoHost, Ovid, Web of Science) was undertaken (6/1/11). The primary outcome measure for safety was self-reported adverse events likely to be drug-related, while the primary outcome measures assessed for 'efficacy' were mycological, clinical and complete cure. The systematic review identified six studies that examined the safety and/or efficacy of treatment interventions for onychomycosis in people with diabetes. No studies were identified that examined treatment for tinea pedis. Of the studies identified, two were randomised controlled trials (RCTs) and four were case series. Based on the best available evidence identified, it can be suggested that oral terbinafine is as safe and effective as oral itraconazole therapy for the treatment of onychomycosis in people with diabetes. However, efficacy results were found to be poor. This review indicates that there is good evidence (Level II) to suggest oral terbinafine is as safe and effective as itraconazole therapy for the treatment of onychomycosis in people with diabetes. Further research is needed to

  4. Safety and efficacy of autologous cell therapy in critical limb ischemia: a systematic review.

    PubMed

    Benoit, Eric; O'Donnell, Thomas F; Patel, Amit N

    2013-01-01

    Researchers have accumulated a decade of experience with autologous cell therapy in the treatment of critical limb ischemia (CLI). We conducted a systematic review of clinical trials in the literature to determine the safety and efficacy of cell therapy in CLI. We searched the literature for clinical trials of autologous cell therapy in CLI, including observational series of five or more patients to accrue a large pool of patients for safety analysis. Safety analysis included evaluation of death, cancer, unregulated angiogenesis, and procedural adverse events such as bleeding. Efficacy analysis included the clinical endpoints amputation and death as well as functional and surrogate endpoints. We identified 45 clinical trials, including seven RCTs, and 1,272 patients who received cell therapy. The overall adverse event rate was low (4.2%). Cell therapy patients did not have a higher mortality rate than control patients and demonstrated no increase in cancer incidence when analyzed against population rates. With regard to efficacy, cell therapy patients had a significantly lower amputation rate than control patients (OR 0.36, p = 0.0004). Cell therapy also demonstrated efficacy in a variety of functional and surrogate outcomes. Clinical trials differed in the proportion of patients with risk factors for clinical outcomes, and these influenced rates of amputation and death. Cell therapy presents a favorable safety profile with a low adverse event rate and no increase in severe events such as mortality and cancer and treatment with cell therapy decreases the risk of amputation. Cell therapy has a positive benefit-to-risk ratio in CLI and may be a valuable treatment option, particularly for those challenging patients who cannot undergo arterial reconstruction.

  5. Efficacy and safety of tranexamic acid versus ϵ-aminocaproic acid in cardiovascular surgery.

    PubMed

    Falana, Olabisi; Patel, Gourang

    2014-12-01

    Blood conservation is a major concern in the management of surgical patients because of transfusion-related complications, limited supply, and health care costs. Tranexamic acid (TXA) and ϵ-aminocaproic acid (ϵACA) are lysine analogue antifibrinolytics used to reduce surgical bleeding and transfusions. To evaluate the efficacy and safety of TXA compared with ϵACA in the management of cardiovascular surgical bleeding at an academic medical center. This single-center, retrospective, observational cohort study included 120 patients undergoing cardiovascular surgery with or without cardiopulmonary bypass, who received at least 1 dose of perioperative TXA or ϵACA. The efficacy outcome-massive perioperative bleeding-was a composite end point of chest tube drainage >1500 mL in any 8-hour period after surgery, perioperative transfusion of 10 or more units of packed red blood cells, reoperation for bleeding, or death from hemorrhage within 30 days. The safety outcomes were incidence of thromboembolic events, postoperative renal dysfunction, seizure, and 30-day all-cause mortality. The primary end point-massive perioperative bleeding-occurred in 10 patients (16.7%) in the TXA group compared with 5 patients (8.3%) in the ϵACA group (P = 0.17). There were no significant differences in the secondary end points of 30-day all-cause mortality, thromboembolic events, renal dysfunction, and seizure. There were no differences in the efficacy and safety outcomes between TXA and ϵACA in the management of cardiovascular surgical bleeding at our institution. Considering the substantial cost difference and comparable efficacy and safety, ϵACA may have better value over TXA for reducing cardiovascular surgical bleeding. © The Author(s) 2014.

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

    PubMed

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

    2016-04-01

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

  7. Integrated safety and efficacy analysis of once-daily fluticasone furoate for the treatment of asthma.

    PubMed

    O'Byrne, Paul M; Jacques, Loretta; Goldfrad, Caroline; Kwon, Namhee; Perrio, Michael; Yates, Louisa J; Busse, William W

    2016-11-24

    Fluticasone furoate is a once-daily inhaled corticosteroid. This report provides an overview of safety and efficacy data that support the use of once-daily fluticasone furoate 100 μg or 200 μg in adult and adolescent asthma patients. Fourteen clinical studies (six Phase II and eight Phase III) were conducted as part of the fluticasone furoate global clinical development programme in asthma. Safety data from 10 parallel-group, randomised, double-blind Phase II and III studies (including 3345 patients who received at least one dose of fluticasone furoate) were integrated to provide information on adverse events, withdrawals, laboratory assessments, vital signs and hypothalamic-pituitary-adrenal axis function. The efficacy of once-daily fluticasone furoate was evaluated in all included studies. Once-daily fluticasone furoate 100 μg and 200 μg safety profiles were consistent with those reported for other inhaled corticosteroids, and both doses consistently demonstrated efficacy versus placebo. In the integrated analysis, no dose-response relationship was observed for the overall incidence of adverse events and there were no significant effects of fluticasone furoate on hypothalamic-pituitary-adrenal axis function. Once-daily fluticasone furoate 100 μg and 200 μg had acceptable safety profiles and was efficacious in adult and adolescent patients with asthma. There was no evidence of cortisol suppression at studied doses. GSK (NCT01499446/FFA20001, NCT00398645/FFA106783, NCT00766090/112202, NCT00603746/FFA109684, NCT00603278/FFA109685, NCT00603382/FFA109687, NCT01436071/115283, NCT01436110/115285, NCT01159912/112059, NCT01431950/114496, NCT01165138/HZA106827, NCT01086384/106837, NCT01134042/HZA106829 and NCT01244984/1139879).

  8. Efficacy of Valbenazine (NBI-98854) in Treating Subjects with Tardive Dyskinesia and Schizophrenia or Schizoaffective Disorder

    PubMed Central

    Kane, John M.; Correll, Christoph U.; Liang, Grace S.; Burke, Joshua; O’Brien, Christopher F.

    2017-01-01

    Background Valbenazine (VBZ, NBI-98854) is a novel vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of tardive dyskinesia (TD). The KINECT 3 study (NCT02274558) evaluated the effects of VBZ on TD in subjects with schizophrenia/schizoaffective disorder (SCHZ) or mood disorder (mood disorder presented separately) who received up to 48 weeks of treatment. Methods KINECT 3 included: 6-week, double-blind, placebo (PBO)-controlled (DBPC) period (205 completers); 42-week VBZ extension (VE) period (124 completers): 4-week washout period (121 completers). Subjects entering the DBPC were randomized 1:1:1 to once-daily VBZ 80 mg, VBZ 40 mg, or PBO; stable concomitant antipsychotic medication regimens were allowed. Subjects completing the DBPC and entering the VE period were re-randomized (blinded) 1:1 from PBO to VBZ (80 or 40 mg) or continued VBZ treatment at the same dose. Efficacy assessments included: mean changes from baseline in Abnormal Involuntary Movement Scale (AIMS) total score (items 1–7); mean Clinical Global Impression of Change (CGI-TD) scores; AIMS responders (subjects with ≥50% score reduction from baseline): and CGI-TD responders (subjects with score ≤2 [“much improved” or “very much improved”]). Treatment effect sizes (Cohen’s d) and numbers needed to treat (NNTs) were analyzed for DBPC outcomes. Results Efficacy analyses were conducted in 148 subjects (DBPC) and 125 subjects (VE) with SCHZ. At Week 6 (end of DBPC), AIMS mean score improvements were greater in the VBZ groups (in a dose-related pattern) than in the PBO group (80 mg, -2.9, d = 0.88; 40 mg, -1.6, d = 0.52; PBO, +0.3). AIMS score changes at Week 48 (end of VE) showed continued TD improvement during long-term VBZ treatment (80 mg, -4.2; 40 mg, -2.5). By Week 52 (end of washout), AIMS scores were returning toward baseline levels, indicating re-emergence of TD. CGI-TD mean scores were as follows: Week 6 (80 mg, 3.0, d = 0.11; 40 mg, 2.9, d = 0.23; PBO

  9. Efficacy of Valbenazine (NBI-98854) in Treating Subjects with Tardive Dyskinesia and Mood Disorder.

    PubMed

    Correll, Christoph U; Josiassen, Richard C; Liang, Grace S; Burke, Joshua; O'Brien, Christopher F

    2017-08-01

    Valbenazine (VBZ, NBI-98854) is a novel vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of tardive dyskinesia (TD). The KINECT 3 study (NCT02274558) evaluated the effects of VBZ on TD in subjects with mood disorder or schizophrenia/schizoaffective disorder (SCHZ, presented separately) who received up to 48 weeks of treatment. KINECT 3 included: 6-week, double-blind, placebo (PBO)-controlled (DBPC) period (205 completers); 42-week VBZ extension (VE) period (124 completers); 4-week washout period (121 completers). Subjects entering the DBPC were randomized 1:1:1 to once-daily VBZ 80 mg, VBZ 40 mg, or PBO; stable concomitant antipsychotic medication regimens were allowed. Subjects completing the DBPC and entering the VE period were re-randomized (blinded) from PBO to VBZ (80 or 40 mg) or continued VBZ treatment at the same dose. Efficacy assessments included: mean changes from baseline in Abnormal Involuntary Movement Scale (AIMS) total score (items 1-7); mean Clinical Global Impression of Change (CGI-TD) scores; AIMS responders (subjects with ≥50% score reduction from baseline); and CGI-TD responders (subjects with score ≤2 ["much improved" or "very much improved"]). Treatment effect sizes (Cohen's d) and numbers needed to treat (NNTs) were analyzed for DBPC outcomes. Efficacy analyses were conducted in 77 subjects (DBPC) and 73 subjects (VE) with a mood disorder. At Week 6 (end of DBPC), AIMS mean score improvements were greater in the VBZ groups (in a dose-related pattern) than in the PBO group (80 mg, -3.6, d = 0.94; 40 mg, -2.4, d = 0.55; PBO, -0.7). AIMS mean score changes at Week 48 (end of VE) showed continued TD improvement during long-term VBZ treatment (80 mg, -5.8; 40 mg, -4.2). By Week 52 (end of washout), AIMS mean scores in both dose groups were returning toward baseline levels, indicating re-emergence of TD. CGI-TD scores showed a similar pattern: Week 6 (80 mg, 2.7, d = 0.64; 40 mg, 2.9, d = 0.39; PBO, 3.2), Week 48

  10. Efficacy of Valbenazine (NBI-98854) in Treating Subjects with Tardive Dyskinesia and Mood Disorder

    PubMed Central

    Correll, Christoph U.; Josiassen, Richard C.; Liang, Grace S.; Burke, Joshua; O’Brien, Christopher F.

    2017-01-01

    Background Valbenazine (VBZ, NBI-98854) is a novel vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of tardive dyskinesia (TD). The KINECT 3 study (NCT02274558) evaluated the effects of VBZ on TD in subjects with mood disorder or schizophrenia/schizoaffective disorder (SCHZ, presented separately) who received up to 48 weeks of treatment. Methods KINECT 3 included: 6-week, double-blind, placebo (PBO)-controlled (DBPC) period (205 completers); 42-week VBZ extension (VE) period (124 completers); 4-week washout period (121 completers). Subjects entering the DBPC were randomized 1:1:1 to once-daily VBZ 80 mg, VBZ 40 mg, or PBO; stable concomitant antipsychotic medication regimens were allowed. Subjects completing the DBPC and entering the VE period were re-randomized (blinded) from PBO to VBZ (80 or 40 mg) or continued VBZ treatment at the same dose. Efficacy assessments included: mean changes from baseline in Abnormal Involuntary Movement Scale (AIMS) total score (items 1–7); mean Clinical Global Impression of Change (CGI-TD) scores; AIMS responders (subjects with ≥50% score reduction from baseline); and CGI-TD responders (subjects with score ≤2 [“much improved” or “very much improved”]). Treatment effect sizes (Cohen’s d) and numbers needed to treat (NNTs) were analyzed for DBPC outcomes. Results Efficacy analyses were conducted in 77 subjects (DBPC) and 73 subjects (VE) with a mood disorder. At Week 6 (end of DBPC), AIMS mean score improvements were greater in the VBZ groups (in a dose-related pattern) than in the PBO group (80 mg, -3.6, d = 0.94; 40 mg, -2.4, d = 0.55; PBO, -0.7). AIMS mean score changes at Week 48 (end of VE) showed continued TD improvement during long-term VBZ treatment (80 mg, -5.8; 40 mg, -4.2). By Week 52 (end of washout), AIMS mean scores in both dose groups were returning toward baseline levels, indicating re-emergence of TD. CGI-TD scores showed a similar pattern: Week 6 (80 mg, 2.7, d = 0.64; 40

  11. Efficacy of Valbenazine (NBI-98854) in Treating Subjects with Tardive Dyskinesia and Schizophrenia or Schizoaffective Disorder.

    PubMed

    Kane, John M; Correll, Christoph U; Liang, Grace S; Burke, Joshua; O'Brien, Christopher F

    2017-08-01

    Valbenazine (VBZ, NBI-98854) is a novel vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of tardive dyskinesia (TD). The KINECT 3 study (NCT02274558) evaluated the effects of VBZ on TD in subjects with schizophrenia/schizoaffective disorder (SCHZ) or mood disorder (mood disorder presented separately) who received up to 48 weeks of treatment. KINECT 3 included: 6-week, double-blind, placebo (PBO)-controlled (DBPC) period (205 completers); 42-week VBZ extension (VE) period (124 completers): 4-week washout period (121 completers). Subjects entering the DBPC were randomized 1:1:1 to once-daily VBZ 80 mg, VBZ 40 mg, or PBO; stable concomitant antipsychotic medication regimens were allowed. Subjects completing the DBPC and entering the VE period were re-randomized (blinded) 1:1 from PBO to VBZ (80 or 40 mg) or continued VBZ treatment at the same dose. Efficacy assessments included: mean changes from baseline in Abnormal Involuntary Movement Scale (AIMS) total score (items 1-7); mean Clinical Global Impression of Change (CGI-TD) scores; AIMS responders (subjects with ≥50% score reduction from baseline): and CGI-TD responders (subjects with score ≤2 ["much improved" or "very much improved"]). Treatment effect sizes (Cohen's d) and numbers needed to treat (NNTs) were analyzed for DBPC outcomes. Efficacy analyses were conducted in 148 subjects (DBPC) and 125 subjects (VE) with SCHZ. At Week 6 (end of DBPC), AIMS mean score improvements were greater in the VBZ groups (in a dose-related pattern) than in the PBO group (80 mg, -2.9, d = 0.88; 40 mg, -1.6, d = 0.52; PBO, +0.3). AIMS score changes at Week 48 (end of VE) showed continued TD improvement during long-term VBZ treatment (80 mg, -4.2; 40 mg, -2.5). By Week 52 (end of washout), AIMS scores were returning toward baseline levels, indicating re-emergence of TD. CGI-TD mean scores were as follows: Week 6 (80 mg, 3.0, d = 0.11; 40 mg, 2.9, d = 0.23; PBO, 3.2), Week 48 (80 mg, 2.2; 40 mg, 2

  12. Efficacy and safety of once-monthly pasireotide in Cushing's disease: a 12 month clinical trial.

    PubMed

    Lacroix, André; Gu, Feng; Gallardo, Wilson; Pivonello, Rosario; Yu, Yerong; Witek, Przemysław; Boscaro, Marco; Salvatori, Roberto; Yamada, Masanobu; Tauchmanova, Libuse; Roughton, Michael; Ravichandran, Shoba; Petersenn, Stephan; Biller, Beverly M K; Newell-Price, John

    2018-01-01

    Cushing's disease is a rare debilitating endocrine disorder for which few prospective interventional studies have been done. We report results of the first phase 3 trial assessing long-acting intramuscular pasireotide in patients with Cushing's disease. In this phase 3 clinical trial we recruited patients aged 18 years or older with persistent, recurrent, or de-novo (non-surgical candidates) Cushing's disease who had a mean urinary free cortisol (mUFC) concentration (from three 24 h samples) of 1·5-5·0 times the upper limit of normal (ULN), a normal or greater than normal morning plasma adrenocorticotropic hormone concentration, and a pituitary source of Cushing's syndrome, from 57 sites across 19 countries. Exclusion criteria included previous pasireotide treatment, mitotane therapy within 6 months, and pituitary irradiation within 10 years. We randomly allocated patients 1:1 (block size of four) using an interactive-response-technology system to intramuscular pasireotide 10 mg or 30 mg every 4 weeks for 12 months (in the core phase). We stratified randomisation by screening mUFC concentration (1·5 to <2·0 × ULN and 2·0-5·0 × ULN). The dose could be uptitrated (from 10 mg to 30 mg or from 30 mg to 40 mg) at month 4 if the mUFC concentration was greater than 1·5 × ULN, and at month 7, month 9, or month 12 if the mUFC concentration was greater than 1·0 × ULN. Investigators, patients, site personnel, and those assessing outcomes were masked to dose group allocation. The primary endpoint was the proportion of patients in each group with an mUFC concentration of less than or equal to the ULN at month 7. Efficacy analyses were based on intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01374906. Between Dec 28, 2011, and Dec 9, 2014, we randomly allocated 150 patients to receive pasireotide 10 mg (74 [49%] patients) or 30 mg (76 [51%] patients). The primary efficacy endpoint was met by 31 (41·9% [95% CI 30·5-53

  13. Promoting Social Skill Development in Children with Pervasive Developmental Disorders: A Feasibility and Efficacy Study

    ERIC Educational Resources Information Center

    Koenig, Kathleen; White, Susan Williams; Pachler, Maryellen; Lau, Monika; Lewis, Moira; Klin, Ami; Scahill, Lawrence

    2010-01-01

    A randomized controlled design was employed to evaluate a social skills intervention for children with pervasive developmental disorders. Aims included evaluating the acceptability of the program and gathering preliminary evidence on efficacy. Forty-four children, ages 8-11 years, were randomly assigned to treatment or wait list. Treatment…

  14. Perceived Self-Efficacy in Parents of Adolescents and Adults with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Weiss, Jonathan A.; Tint, Ami; Paquette-Smith, Melissa; Lunsky, Yona

    2016-01-01

    Many parents of adolescents and adults with autism spectrum disorder experience difficulty accessing appropriate services for their children, and may report low levels of parent self-efficacy. In an effort to identify the factors that contribute to the difficulties these families face, this study examined the role of demographic, systemic, and…

  15. [Mentalization-Based Treatment for Adolescents with Borderline Personality Disorder - Concept and Efficacy].

    PubMed

    Taubner, Svenja; Volkert, Jana; Gablonski, Thorsten-Christian; Rossouw, Trudie

    2017-07-01

    Mentalization-Based Treatment for Adolescents with Borderline Personality Disorder - Concept and Efficacy In recent years, the concept of mentalization has become increasingly important in practice and research. It describes the imaginative ability to understand human behavior in terms of mental states. Mentalization is a central component to understand the etiology and to treat patients with borderline personality disorder (BPD). Both adult and adolescent patients with BPD have limited mentalization abilities, which can be reliably assessed using the Reflective Functioning Scale. Mentalization-Based Treatment (MBT) was originally developed as an integrative approach for the treatment of adult patients with BPD. It is a manualized psychotherapy with psychodynamic roots with the aim to increase mentalizing abilities of patients. Since then, MBT has been further developed for other mental disorders as well as for the treatment of different age groups. One of these developments is MBT for Adolescents (MBT-A). MBT-A includes both individual as well as family sessions and the average duration of therapy is about twelve months. MBT-A can be applied in inpatient and outpatient settings and aims to improve mentalizing abilities in emotionally important relationships and the whole family system. First studies have found evidence for the efficacy of MBT-A. A randomized controlled trial (RCT) is currently being carried out to evaluate the efficacy of MBT-A for adolescents with conduct disorder. However, further evidence for efficacy and further conceptual development is needed.

  16. Preliminary Efficacy of a Cognitive-Behavioral Treatment Program for Anxious Youth with Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    White, Susan W.; Ollendick, Thomas; Scahill, Lawrence; Oswald, Donald; Albano, Anne Marie

    2009-01-01

    Anxiety is a commonly occurring psychiatric concern in adolescents with autism spectrum disorders (ASD). This pilot study examined the preliminary efficacy of a manual-based intervention targeting anxiety and social competence in four adolescents with high-functioning ASD. Anxiety and social functioning were assessed at baseline, midpoint,…

  17. Efficacy of an Intervention Program for Attention and Reflexivity in Children with Attention Deficit Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Campeño-Martínez, Yoana; Santiago-Ramajo, Sandra; Navarro-Asencio, Enrique; Vergara-Moragues, Esperanza; Santiuste Bermejo, Victor

    2017-01-01

    There has been increasing evidence in recent years of the need to adapt intervention programs to the specific needs of children with attention deficit hyperactivity disorder (ADHD). The main goal of this research work was to study the efficacy of an educational intervention program to improve attention and reflexivity in school children with ADHD…

  18. Balancing efficacy against safety in sublingual immunotherapy with inhalant allergens: what is the best approach?

    PubMed

    Caminati, Marco; Dama, Annarita; Schiappoli, Michele; Senna, Gianenrico

    2013-10-01

    Over the last 20 years, studies and clinical trials have demonstrated efficacy, safety and cost-effectiveness of sublingual immunotherapy (SLIT) for respiratory allergic diseases. Nevertheless, it seems to be mostly used as a second-line therapeutic option, and adherence to treatment is not always optimal. Selective literature research was done in Medline and PubMed, including guidelines, position papers and Cochrane meta-analyses concerning SLIT in adult patients. The most recent reviews confirm SLIT as viable and efficacious treatment especially for allergic rhinitis, even if the optimal dosage, duration, schedule are not clearly established for most of the products. Despite an optimal safety profile, tolerability and patient-reported outcomes concerning SLIT have received poor attention until now. Recently, new tools have been specifically developed in order to investigate these aspects. Regular assessment of tolerability profile and SLIT-related patient-reported outcomes will allow balancing efficacy with tolerability and all the other patient-related variables that may affect treatment effectiveness beyond its efficacy.

  19. Excimer laser for the treatment of psoriasis: safety, efficacy, and patient acceptability

    PubMed Central

    Abrouk, Michael; Levin, Ethan; Brodsky, Merrick; Gandy, Jessica R; Nakamura, Mio; Zhu, Tian Hao; Farahnik, Benjamin; Koo, John; Bhutani, Tina

    2016-01-01

    Introduction The 308 nm excimer laser is a widely used device throughout the field of dermatology for many diseases including psoriasis. Although the laser has demonstrated clinical efficacy, there is a lack of literature outlining the safety, efficacy, and patient acceptability of the excimer laser. Methods A literature search on PubMed was used with combinations of the terms “excimer”, “excimer laser”, “308 nm”, “psoriasis”, “protocol”, “safety”, “efficacy”, acceptability”, “side effects”, and “dose”. The search results were included if they contained information pertaining to excimer laser and psoriasis treatment and description of the safety, efficacy, and patient acceptability of the treatment. Results The 308 nm excimer laser is generally safe and well tolerated with minimal side effects including erythema, blistering, and pigmentary changes. It has a range of efficacies depending on the protocol used with several different treatment protocols, including the induration protocol, the minimal erythema dose protocol, and the newer minimal blistering dose protocol. Conclusion Although the excimer laser is not a first-line treatment, it remains an excellent treatment option for psoriasis patients and has been demonstrated to be an effective treatment with little to no side effects. PMID:29387603

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

    PubMed

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

    2012-04-01

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

  1. Safety and Efficacy of Liposomal Cytarabine in the Treatment of Neoplastic Meningitis.

    PubMed

    Jahn, Franziska; Jordan, Karin; Behlendorf, Timo; Globig, Cordula; Schmoll, Hans-Joachim; Müller-Tidow, Carsten; Jordan, Berit

    2015-01-01

    Although rare, neoplastic meningitis (NM) has been increasingly observed in patients with cancer due to the prolonged course of the disease. Intrathecal chemotherapy with methotrexate or cytarabine with repeating injection schedules of 2-3 times per week is currently the mainstay of treatment. An efficacious and comfortable treatment alternative might be represented by liposomal cytarabine. In this retrospective study, we reviewed all patients with NM due to solid tumors or hematological malignancies treated with liposomal cytarabine at our institution between March 2004 and September 2011. The primary endpoint was treatment response, which was defined as improvement in neurological symptoms and/or conversion of the initial cerebrospinal fluid cytology and/or response in the radiological findings. The main secondary endpoint was safety. Fifty-one adult patients were evaluable for safety and 44 patients for efficacy. In 36 patients (81.8%), a treatment response was achieved. The median overall survival after diagnosis of NM was 11 months (95% confidence interval 8.8-13.2). Adverse events grade 1-4 occurred in 31 patients (60.8%), whereas grade 3-4 occurred in 18 patients (35.3%). The encouraging efficacy and safety data obtained in our analysis and the convenient administration schedule make intrathecal liposomal cytarabine a favorable treatment option for NM patients.

  2. A Review of the Efficacy, Safety, and Clinical Implications of Naturally Derived Dietary Supplements for Dyslipidemia.

    PubMed

    Thaipitakwong, Thanchanit; Aramwit, Pornanong

    2017-02-01

    Dyslipidemia is recognized as a major cause of cardiovascular disease. A number of evidence-based guidelines recommend conventional synthetic drugs as standard therapy for dyslipidemia in clinical practice. However, antihyperlipidemic drugs have some serious side effects. Naturally derived dietary supplements are becoming attractive as an alternative strategy because of their high efficacy and safety, as supported by numerous data. Moreover, they could be considered an initial treatment for dyslipidemia. The aims of this literature review were to demonstrate the efficacy, safety, and clinical implications of dietary supplements for treating dyslipidemia. We reviewed the literature, including data from in vitro, in vivo, and human studies, and clinical guideline recommendations. We classified dietary supplements by their proposed mechanisms of action on lipid metabolism and also collected daily dosage recommendations, interactions with concurrent drugs and/or foods, dosage forms, and examples of commercially available products. Various types of naturally derived dietary supplements exhibit lipid-improving properties. Efficacy and safety are acceptable; however, their use in clinical practice will require further well-designed investigations and the support of scientific data.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-03-14

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

  5. Safety and efficacy of repaglinide in type 2 diabetic patients with and without impaired renal function.

    PubMed

    Hasslacher, Christoph

    2003-03-01

    To evaluate the influence of renal impairment on the safety and efficacy of repaglinide in type 2 diabetic patients. This multinational, open-label study comprised a 6-week run-in period, continuing prestudy antidiabetic medication, followed by a titration period (1-4 weeks) and a 3-month maintenance period. Patients with normal renal function (n = 151) and various degrees of renal impairment (n = 130) were treated with repaglinide (maximal dose of 4 mg, three times daily). Safety and efficacy assessments were performed at baseline (end of run-in) and at the end of study treatment. The type and severity of adverse events during repaglinide treatment were similar to the run-in period. The number of patients with adverse events was not significantly related to renal function during run-in or repaglinide treatment. Percentage of patients with hypoglycemic episodes increased significantly (P = 0.007) with increasing severity of renal impairment during run-in but not during repaglinide treatment (P = 0.074). Metabolic control (HbA(1c) and fasting blood glucose) with repaglinide was unchanged from that on previous antidiabetic medication. Final repaglinide dose tended to be lower for patients with severe and extreme renal impairment than for patients with less severe renal impairment or normal renal function (P = 0.032). Repaglinide has a good safety and efficacy profile in type 2 diabetic patients complicated by renal impairment and is an appropriate treatment choice, even for individuals with more severe degrees of renal impairment.

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

    PubMed

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

    2018-05-01

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

  7. Simultaneous sequential monitoring of efficacy and safety led to masking of effects.

    PubMed

    van Eekelen, Rik; de Hoop, Esther; van der Tweel, Ingeborg

    2016-08-01

    Usually, sequential designs for clinical trials are applied on the primary (=efficacy) outcome. In practice, other outcomes (e.g., safety) will also be monitored and influence the decision whether to stop a trial early. Implications of simultaneous monitoring on trial decision making are yet unclear. This study examines what happens to the type I error, power, and required sample sizes when one efficacy outcome and one correlated safety outcome are monitored simultaneously using sequential designs. We conducted a simulation study in the framework of a two-arm parallel clinical trial. Interim analyses on two outcomes were performed independently and simultaneously on the same data sets using four sequential monitoring designs, including O'Brien-Fleming and Triangular Test boundaries. Simulations differed in values for correlations and true effect sizes. When an effect was present in both outcomes, competition was introduced, which decreased power (e.g., from 80% to 60%). Futility boundaries for the efficacy outcome reduced overall type I errors as well as power for the safety outcome. Monitoring two correlated outcomes, given that both are essential for early trial termination, leads to masking of true effects. Careful consideration of scenarios must be taken into account when designing sequential trials. Simulation results can help guide trial design. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Herbal Medicine in the United States: Review of Efficacy, Safety, and Regulation

    PubMed Central

    2008-01-01

    Introduction Herbal products have gained increasing popularity in the last decade, and are now used by approximately 20% of the population. Herbal products are complex mixtures of organic chemicals that may come from any raw or processed part of a plant, including leaves, stems, flowers, roots, and seeds. Under the current law, herbs are defined as dietary supplements, and manufacturers can therefore produce, sell, and market herbs without first demonstrating safety and efficacy, as is required for pharmaceutical drugs. Although herbs are often perceived as “natural” and therefore safe, many different side effects have been reported owing to active ingredients, contaminants, or interactions with drugs. Results Unfortunately, there is limited scientific evidence to establish the safety and efficacy of most herbal products. Of the top 10 herbs, 5 (ginkgo, garlic, St. John’s wort, soy, and kava) have scientific evidence suggesting efficacy, but concerns over safety and a consideration of other medical therapies may temper the decision to use these products. Conclusions Herbal products are not likely to become an important alternative to standard medical therapies unless there are changes to the regulation, standardization, and funding for research of these products. PMID:18415652

  9. Parenting Efficacy and Support in Mothers with Dual Disorders in a Substance Abuse Treatment Program

    PubMed Central

    Brown, Suzanne; Hicks, Laurel M.; Tracy, Elizabeth M.

    2016-01-01

    Objective Approximately 73% of women entering treatment for substance use disorders are mothers of children under the age of 18 (SAMHSA, 2009), and the high rate of mental health disorders among mothers with substance use disorders increases their vulnerability to poor parenting practices. Parenting efficacy and social support for parenting have emerged as significant predictors of positive parenting practices among families at risk for child maltreatment. The purpose of the current study was to examine the impact of parenting support and parenting efficacy on the likelihood of out-of-home placement and custody status among the children of mothers with dual substance use and mental health disorders. Methods This study examined the impact of parenting efficacy, and assistance with child-care on the likelihood of child out-of-home placement and custody status among 175 mothers diagnosed with a dual substance and mental health disorder and in treatment for substance dependence. Logistic regression was utilized to assess the contributions of parenting efficacy, and the number of individuals in mothers’ social networks who assist with child-care, to the likelihood of out-of-home placement and custody loss of children. Parenting efficacy was also examined as a mediator using bootstrapping in PROCESS for SPSS. Results Greater parenting efficacy was associated with lower likelihood of having at least one child in out-of-home placement (B = −.064, SE =.029, p = .027), and lower likelihood of loss of child custody (B = −.094, SE =.034, p = .006). Greater number of children in the 6–18 age range predicted greater likelihood of having at least one child in the custody of someone else (B = .409, SE = .171, p = .017) and in out-of-home placement (B = .651, SE = .167, p < .001). Additionally, mothers who identified as African-American were less likely to have a child in out-of-home placement (B = .927, SE = .382, p = .015) or to have lost custody of a child (B = −1

  10. Parenting Efficacy and Support in Mothers With Dual Disorders in a Substance Abuse Treatment Program.

    PubMed

    Brown, Suzanne; Hicks, Laurel M; Tracy, Elizabeth M

    2016-01-01

    Approximately 73% of women entering treatment for substance use disorders are mothers of children younger than 18, and the high rate of mental health disorders among mothers with substance use disorders increases their vulnerability to poor parenting practices. Parenting efficacy and social support for parenting have emerged as significant predictors of positive parenting practices among families at risk for child maltreatment. The purpose of the current study was to examine the impact of parenting support and parenting efficacy on the likelihood of out-of-home placement and custody status among the children of mothers with dual substance use and mental health disorders. This study examined the impact of parenting efficacy and assistance with childcare on the likelihood of child out-of-home placement and custody status among 175 mothers with diagnosed dual substance and mental health disorder and in treatment for substance dependence. Logistic regression was utilized to assess the contributions of parenting efficacy and the number of individuals in mothers' social networks who assist with childcare to the likelihood of out-of-home placement and custody loss of children. Parenting efficacy was also examined as a mediator using bootstrapping in PROCESS for SPSS. Greater parenting efficacy was associated with lower likelihood of having at least one child in out-of-home placement (B = -.064, SE = .029, p = .027) and lower likelihood of loss of child custody (B = -.094, SE = .034, p = .006). Greater number of children in the 6 to 18 age range predicted greater likelihood of having at least one child in the custody of someone else (B = .409, SE = .171, p = .017) and in out-of-home placement (B = .651, SE = .167, p < .001). In addition, mothers who identified as African American were less likely to have a child in out-of-home placement (B = .927, SE = .382, p = .015) or to have lost custody of a child (B = -1.31, SE = .456, p = .004). Finally, parenting efficacy mediated

  11. Confidence in the efficacy and safety of dietary supplements among United States active duty army personnel

    PubMed Central

    2012-01-01

    Background United States Army Soldiers regularly use dietary supplements (DS) to promote general health, enhance muscle strength, and increase energy, but limited scientific evidence supports the use of many DS for these benefits. This study investigated factors associated with Soldiers’ confidence in the efficacy and safety of DS, and assessed Soldiers’ knowledge of federal DS regulatory requirements. Methods Between 2006 and 2007, 990 Soldiers were surveyed at 11 Army bases world-wide to assess their confidence in the effectiveness and safety of DS, knowledge of federal DS regulations, demographic characteristics, lifestyle-behaviors and DS use. Results A majority of Soldiers were at least somewhat confident that DS work as advertised (67%) and thought they are safe to consume (71%). Confidence in both attributes was higher among regular DS users than non-users. Among users, confidence in both attributes was positively associated with rank, self-rated diet quality and fitness level, education, and having never experienced an apparent DS-related adverse event. Fewer than half of Soldiers knew the government does not require manufacturers to demonstrate efficacy, and almost a third incorrectly believed there are effective pre-market federal safety requirements for DS. Conclusions Despite limited scientific evidence supporting the purported benefits and safety of many popular DS, most Soldiers were confident that DS are effective and safe. The positive associations between confidence and DS use should be considered when developing DS-related interventions or policies. Additionally, education to clarify Soldiers’ misperceptions about federal DS safety and efficacy regulations is warranted. PMID:23051046

  12. Efficacy and safety testing of mycotoxin-detoxifying agents in broilers following the European Food Safety Authority guidelines.

    PubMed

    Osselaere, A; Devreese, M; Watteyn, A; Vandenbroucke, V; Goossens, J; Hautekiet, V; Eeckhout, M; De Saeger, S; De Baere, S; De Backer, P; Croubels, S

    2012-08-01

    Contamination of feeds with mycotoxins is a worldwide problem and mycotoxin-detoxifying agents are used to decrease their negative effect. The European Food Safety Authority recently stated guidelines and end-points for the efficacy testing of detoxifiers. Our study revealed that plasma concentrations of deoxynivalenol and deepoxy-deoxynivalenol were too low to assess efficacy of 2 commercially available mycotoxin-detoxifying agents against deoxynivalenol after 3 wk of continuous feeding of this mycotoxin at concentrations of 2.44±0.70 mg/kg of feed and 7.54±2.20 mg/kg of feed in broilers. This correlates with the poor absorption of deoxynivalenol in poultry. A safety study with 2 commercially available detoxifying agents and veterinary drugs showed innovative results with regard to the pharmacokinetics of 2 antibiotics after oral dosing in the drinking water. The plasma and kidney tissue concentrations of oxytetracycline were significantly higher in broilers receiving a biotransforming agent in the feed compared with control birds. For amoxicillin, the plasma concentrations were significantly higher for broilers receiving an adsorbing agent in comparison to birds receiving the biotransforming agent, but not to the control group. Mycotoxin-detoxifying agents can thus interact with the oral bioavailability of antibiotics depending on the antibiotic and detoxifying agent, with possible adverse effects on the health of animals and humans.

  13. Sources of Global Academic Self-Efficacy in Academically High-Achieving Females before the Onset of Disordered Eating

    ERIC Educational Resources Information Center

    Krafchek, Jennifer; Kronborg, Leonie

    2015-01-01

    There is limited research applying the four sources of self-efficacy (Bandura, 1997) to global academic self-efficacy. This qualitative study examined the sources of global academic self-efficacy in a sample of academically high-achieving females who developed disordered eating. Semistructured interviews were conducted with 14 participants to gain…

  14. A phase 2a multicenter, double-blind, placebo-controlled, crossover trial to investigate the efficacy, safety, and toleration of CP-866,087 (a high-affinity mu-opioid receptor antagonist) in premenopausal women diagnosed with female sexual arousal disorder (FSAD).

    PubMed

    Orri, Miguel; Abraham, Lucy; Giraldi, Annamaria

    2013-10-01

    Female sexual arousal disorder (FSAD) is a condition that can affect women of all ages and have a significant negative impact on emotional well-being. The aim of this study is to prospectively evaluate the effects of CP-866,087, a selective mu-opioid receptor antagonist, in premenopausal women with FSAD. The study included 51 women (20-45 years of age) with FSAD. All women received placebo and two of three planned doses of CP-866,087 (1, 3, and 10 mg) for 6 weeks in each of three double-blind treatment periods. Efficacy was determined through a series of measures to assess sexual functioning, sexual activity, sexual distress, and perceived meaningful benefit as a result of treatment. In addition, a semi-structured exit interview was conducted at the end of the fourth treatment period or withdrawal to provide a more in-depth, qualitative description of the participants' symptoms, response to treatment, and treatment satisfaction to augment the quantitative assessments. The within-subject differences from placebo in the change from baseline were compared across a range of measures of sexual function. Summary statistics and 90% confidence intervals were calculated. A qualitative analysis of the exit interview was conducted based on grounded theory methods. Although improvements were seen with CP-866,087 in the key efficacy end points, there was no clinical treatment benefit over placebo. The exit interview analysis suggested that being part of the study and taking positive action to search for a solution to the women's sexual disorder may have been a significant factor in the behavioral changes that were seen, as opposed to the drug treatment itself. Discerning the potential benefit of pharmacotherapy in a heterogeneous condition such as FSAD is challenging. Participation in a clinical trial combined with a commitment to actively engage in sexual activity may in itself create an environment that is conducive to symptom improvement. © 2013 International Society for

  15. Long-term safety and efficacy of sapropterin: the PKUDOS registry experience.

    PubMed

    Longo, Nicola; Arnold, Georgianne L; Pridjian, Gabriella; Enns, Gregory M; Ficicioglu, Can; Parker, Susan; Cohen-Pfeffer, Jessica L

    2015-04-01

    The Phenylketonuria (PKU) Demographics, Outcomes and Safety (PKUDOS) registry is designed to provide longitudinal safety and efficacy data on subjects with PKU who are (or have been) treated with sapropterin dihydrochloride. The PKUDOS population consists of 1189 subjects with PKU: N = 504 who were continuously exposed to sapropterin from date of registry enrollment, N = 211 who had intermittent exposure to the drug, and N = 474 with some other duration of exposure. Subjects continuously exposed to sapropterin showed an average 34% decrease in blood phenylalanine (Phe)--from 591 ± 382 μmol/L at baseline to 392 ± 239 μmol/L (p = 0.0009) after 5 years. This drop in blood Phe was associated with an increase in dietary Phe tolerance [from 1000 ± 959 mg/day (pre-sapropterin baseline) to 1539 ± 840 mg/day after 6 years]. Drug-related adverse events (AEs) were reported in 6% of subjects, were mostly considered non-serious, and were identified in the gastrointestinal, respiratory, and nervous systems. Serious drug-related AEs were reported in ≤ 1% of subjects. Similar safety and efficacy data were observed for children<4 years. Long-term data from the PKUDOS registry suggest that sapropterin has a tolerable safety profile and that continuous use is associated with a significant and persistent decrease in blood Phe and improvements in dietary Phe tolerance. Copyright © 2015. Published by Elsevier Inc.

  16. Safety and efficacy of fesoterodine fumarate in patients with overactive bladder: results of a post-marketing surveillance study in Korea.

    PubMed

    Kim, Tae Heon; Lee, Sang Eun; Lee, Hahn-Ey; Lee, Kyu-Sung

    2016-08-01

    The aim of this study was to evaluate the safety and efficacy of fesoterodine fumarate (fesoterodine; Toviaz ) in Korean patients with overactive bladder (OAB) in routine clinical practice. This was an open-label, non-interventional, prospective, post-marketing surveillance study submitted to the Korean Ministry of Food and Drug Safety. A total of 3109 patients aged ≥18 years with OAB symptoms were prescribed flexible doses of fesoterodine at the investigator's discretion. Safety was assessed based upon the reporting of adverse events (AEs). Efficacy was evaluated on the basis of patient self-assessment using a bladder diary as well as on the basis of investigator assessment in terms of overall clinical efficacy. A final analysis was performed on 3107 (99.9%) and 2978 (95.8%) patients for safety and efficacy analysis, respectively. The mean treatment duration of fesoterodine was 83.2 days. The incidence of AEs was 8.5% (265/3107). Common AEs that accounted for more than 1.0% of the total AE incidence included dry mouth (5.4%, 168/3107), constipation (1.5%, 48/3107) and micturition disorder (1.1%, 35/3107). Mean episodes of urinary frequency, urgency, and urgency urinary incontinence (UUI) per 24 hours decreased by 4.0, 2.4, and 0.8, respectively (all p < 0.001). At the final follow-up visit, the investigators found improvement in clinical efficacy for the majority of patients (90.1%, 2684/2978). Limitations of this study include the observational study design and the relatively short treatment duration. These results suggest that fesoterodine is a well tolerated and effective treatment for Korean patients with OAB in routine clinical practice.

  17. Impact of concomitant medication use on belimumab efficacy and safety in patients with systemic lupus erythematosus

    PubMed Central

    Dooley, M A; Roth, D A; Edwards, L; Thompson, A; Wilson, B

    2016-01-01

    Practicing physicians have requested efficacy and safety data for belimumab, when used with specific systemic lupus erythematosus (SLE) medications. This was a post hoc analysis of pooled efficacy and safety data from patients who received belimumab 10 mg/kg plus standard of care (SoC) or placebo (SoC) in two Phase III, randomized trials, BLISS-52 and BLISS-76. Patients were categorized into four groups based on baseline concomitant medication usage: steroids only; antimalarials (AM) only; steroids + AM; or steroids + AM + immunosuppressants (IS). The primary endpoint was the SLE Responder Index (SRI) at Week 52. SRI over time and individual SRI components were secondary endpoints. Time to first flare and changes in concomitant medications were exploratory endpoints. Safety was assessed using adverse event (AE) reporting. Across 834 patients, steroids + AM was the largest group (n = 346, 41.5%) and AM only was the smallest (n = 77, 9.2%). Disease duration was shortest in the steroids + AM group (5.7 years vs 6.4–7.1 years); SELENA-SLEDAI scores were similar across groups. At Week 52, the percentage of SRI responders was greatest in the steroids + AM group for belimumab 10 mg/kg (59%) compared with placebo (44%); treatment response and SRI component improvements were also observed across other groups. The probability of experiencing an SLE flare was reduced in the steroids-only group for patients who received belimumab 10 mg/kg compared with placebo (64.3% vs 78.1%; hazard ratio 0.64; 95% confidence interval: 0.42–0.96). There was little or no change in daily AM or IS dose in any group. For all groups, there was a general decrease in steroid dose over time; a quarter to a third of patients experienced decreased steroid doses at Week 52. The overall safety profile was similar across treatment arms and concomitant medication groups, with the exception of serious AEs in the steroids + AM group (belimumab 10 mg/kg 16

  18. Impact of concomitant medication use on belimumab efficacy and safety in patients with systemic lupus erythematosus.

    PubMed

    Schwarting, A; Dooley, M A; Roth, D A; Edwards, L; Thompson, A; Wilson, B

    2016-12-01

    Practicing physicians have requested efficacy and safety data for belimumab, when used with specific systemic lupus erythematosus (SLE) medications. This was a post hoc analysis of pooled efficacy and safety data from patients who received belimumab 10 mg/kg plus standard of care (SoC) or placebo (SoC) in two Phase III, randomized trials, BLISS-52 and BLISS-76. Patients were categorized into four groups based on baseline concomitant medication usage: steroids only; antimalarials (AM) only; steroids + AM; or steroids + AM + immunosuppressants (IS). The primary endpoint was the SLE Responder Index (SRI) at Week 52. SRI over time and individual SRI components were secondary endpoints. Time to first flare and changes in concomitant medications were exploratory endpoints. Safety was assessed using adverse event (AE) reporting. Across 834 patients, steroids + AM was the largest group (n = 346, 41.5%) and AM only was the smallest (n = 77, 9.2%). Disease duration was shortest in the steroids + AM group (5.7 years vs 6.4-7.1 years); SELENA-SLEDAI scores were similar across groups. At Week 52, the percentage of SRI responders was greatest in the steroids + AM group for belimumab 10 mg/kg (59%) compared with placebo (44%); treatment response and SRI component improvements were also observed across other groups. The probability of experiencing an SLE flare was reduced in the steroids-only group for patients who received belimumab 10 mg/kg compared with placebo (64.3% vs 78.1%; hazard ratio 0.64; 95% confidence interval: 0.42-0.96). There was little or no change in daily AM or IS dose in any group. For all groups, there was a general decrease in steroid dose over time; a quarter to a third of patients experienced decreased steroid doses at Week 52. The overall safety profile was similar across treatment arms and concomitant medication groups, with the exception of serious AEs in the steroids + AM group (belimumab 10 mg/kg 16%, placebo

  19. Efficacy and safety of metformin or oral contraceptives, or both in polycystic ovary syndrome.

    PubMed

    Yang, Young-Mo; Choi, Eun Joo

    2015-01-01

    Polycystic ovary syndrome (PCOS) is an endocrinopathy that affects approximately 10% of reproductive-aged women throughout their lives. Women with PCOS present with heterogeneous symptoms including ovulatory dysfunction, hyperandrogenism, and polycystic ovaries. Therefore, lifelong individualized management should be considered. Pharmacological agents commonly used to manage the symptoms are metformin and oral contraceptive pills. Although these medications have been beneficial in treating PCOS symptoms, their efficacy and safety are still not entirely elucidated. This study aimed to report the efficacy and safety of metformin, oral contraceptives, or their combination in the treatment of PCOS and to define their specific individual roles. A literature search of original studies published in PubMed and Scopus was conducted to identify studies comparing metformin with oral contraceptives or evaluating the combination of both in PCOS. Eight clinical trials involving 313 patients were examined in the review. The intervention dosage of metformin ranged from 1,000 to 2,000 mg/d and that of oral contraceptives was ethinylestradiol 35 µg and cyproterone acetate 2 mg. Lower body mass index was observed with regimens including metformin, but increased body mass index was observed in monotherapy with oral contraceptives. Administration of metformin or oral contraceptives, especially as monotherapy, had a negative effect on lipid profiles. In addition, there are still uncertainties surrounding the effects of metformin or oral contraceptives in the management of insulin level, although they improved total testosterone and sex hormone-binding globulin levels. In the included studies, significant side effects due to metformin or oral contraceptives were not reported. The clinical trials suggest that metformin or oral contraceptives are at least patient convenient, efficacious, and safe for the treatment of PCOS. However, well-designed, prospective, long-term, large

  20. Efficacy and safety of metformin or oral contraceptives, or both in polycystic ovary syndrome

    PubMed Central

    Yang, Young-Mo; Choi, Eun Joo

    2015-01-01

    Background Polycystic ovary syndrome (PCOS) is an endocrinopathy that affects approximately 10% of reproductive-aged women throughout their lives. Women with PCOS present with heterogeneous symptoms including ovulatory dysfunction, hyperandrogenism, and polycystic ovaries. Therefore, lifelong individualized management should be considered. Pharmacological agents commonly used to manage the symptoms are metformin and oral contraceptive pills. Although these medications have been beneficial in treating PCOS symptoms, their efficacy and safety are still not entirely elucidated. This study aimed to report the efficacy and safety of metformin, oral contraceptives, or their combination in the treatment of PCOS and to define their specific individual roles. Methods A literature search of original studies published in PubMed and Scopus was conducted to identify studies comparing metformin with oral contraceptives or evaluating the combination of both in PCOS. Results Eight clinical trials involving 313 patients were examined in the review. The intervention dosage of metformin ranged from 1,000 to 2,000 mg/d and that of oral contraceptives was ethinylestradiol 35 µg and cyproterone acetate 2 mg. Lower body mass index was observed with regimens including metformin, but increased body mass index was observed in monotherapy with oral contraceptives. Administration of metformin or oral contraceptives, especially as monotherapy, had a negative effect on lipid profiles. In addition, there are still uncertainties surrounding the effects of metformin or oral contraceptives in the management of insulin level, although they improved total testosterone and sex hormone-binding globulin levels. In the included studies, significant side effects due to metformin or oral contraceptives were not reported. Conclusion The clinical trials suggest that metformin or oral contraceptives are at least patient convenient, efficacious, and safe for the treatment of PCOS. However, well

  1. Efficacy, safety, tolerability and price of newly approved drugs in solid tumors.

    PubMed

    Barnes, Tristan A; Amir, Eitan; Templeton, Arnoud J; Gomez-Garcia, Susana; Navarro, Beatriz; Seruga, Bostjan; Ocana, Alberto

    2017-05-01

    New anti-cancer drugs utilize diverse mechanisms of action. Here we evaluate their differential efficacy, safety, tolerability and price. Drugs approved for solid tumor treatment between 2000 and 2015 were identified and analyzed in subgroups: agents targeting oncogenes (group 1), anti-angiogenics (group 2), immunotherapy (group 3), and chemotherapy (group 4). Hazard ratios (HRs) were extracted from the registration trials and pooled in a meta-analysis. Odds ratios for toxic death, treatment discontinuation and grade 3-4 toxicity were compared to control groups. The Micromedex Red Book was used to calculate the monthly price. Analysis included 74 studies comprising 48,527 patients. Progression-free survival (PFS) was improved to a greater degree with groups 1 and 2 than with groups 3 and 4, (pooled HR: 0.54, 0.56, 0.63, and 0.76 for groups 1-4 respectively, p for difference <0.001). Compared to PFS, there was a lower magnitude of improvement overall survival in all groups and the degree of benefit was less for group 4 than for other groups (pooled HR: 0.77, 0.78, 0.68, and 0.83 for groups 1-4 respectively, p for difference=0.007). Compared to control groups in individual trials, immunotherapy was associated with better safety and tolerability than other groups. Drug prices have increased over time with no significant difference between groups. There was no meaningful correlation between pricing and efficacy. Compared to control groups, immunotherapeutics and drugs targeting oncogenes or angiogenesis improve efficacy to a greater degree than chemotherapy. Immunotherapy appears to have better safety and tolerability profile compared to other cancer therapies. Market price of drugs is not related to efficacy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. The neuropharmacology of ADHD drugs in vivo: insights on efficacy and safety.

    PubMed

    Heal, D J; Cheetham, S C; Smith, S L

    2009-12-01

    Results from in vivo techniques, especially intracerebral microdialysis in freely-moving rats, have provided insights into potential mechanisms responsible for the efficacy and safety of catecholaminergic drugs for ADHD treatment. The drugs reviewed come from distinct pharmacological classes: psychostimulant releasing agents, eg d-amphetamine; psychostimulant reuptake inhibitors, eg dl-threo-methylphenidate (dl-MPH), and non-stimulant reuptake inhibitors, eg atomoxetine. Psychostimulants, which currently deliver the best efficacy in treating ADHD, exhibit the following characteristics on extraneuronal catecholamine concentrations in rodent brain in vivo: 1) They enhance the efflux and function of both noradrenaline and dopamine in the central nervous system. 2) The increase of dopamine efflux that they produce is not limited to cortical regions. 3) They have a rapid onset of action with no ceiling on drug effect. d-Amphetamine has a mechanism independent of neuronal firing rate, displacing intraneuronal stores of catecholamines, delaying their reuptake and inhibiting catabolism by monoamine oxidase. dl-MPH has an enigmatic, extraneuronal action that is neuronal firing rate-dependent and reuptake transporter-mediated, yet paradoxically, almost as powerful as that of d-amphetamine. In safety terms, these powerful catecholaminergic effects also make the psychostimulants liable for abuse. Since efficacy and safety derive from the same pharmacological mechanisms, it has not yet been possible to separate these two components. However, the development of once-daily psychostimulant formulations and a prodrug, lisdexamfetamine, has improved patient compliance and markedly reduced scope for their diversion/abuse. This review will discuss the in vivo pharmacological profiles of approved catecholaminergic drugs for treatment of ADHD and implications for their clinical efficacy and abuse liability.

  3. Efficacy and safety of biologic therapies for systemic lupus erythematosus treatment: systematic review and meta-analysis.

    PubMed

    Borba, Helena Hiemisch Lobo; Wiens, Astrid; de Souza, Thais Teles; Correr, Cassyano Januário; Pontarolo, Roberto

    2014-04-01

    The objectives of this study were to evaluate the efficacy, safety, and tolerability of biologic drugs compared with placebo for systemic lupus erythematosus (SLE) treatment. A systematic review evaluating the efficacy and safety of biologic therapies compared with placebo in adult SLE patients treatment was performed. Data from studies performed before September 2013 were collected from several databases (MEDLINE, Cochrane Library, SCIELO, Scopus, and International Pharmaceutical Abstracts). Study eligibility criteria included randomized, double-blind, placebo-controlled trials; regarding treatment with biologic agents in SLE adult patients; and published in English, German, Portuguese, and Spanish. Extracted data were statistically analyzed in a meta-analysis using the Review Manager (RevMan) 5.1 software. Efficacy outcomes included the SELENA-SLEDAI (Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index) score, the SRI (Systemic Lupus Erythematosus Responder Index), normalization of low C3 (<90 mg/dL), anti-double-stranded DNA positive to negative, and no new BILAG (British Isles Lupus Assessment Group index) 1A or 2B flares. Data on safety profile included adverse events, serious and severe adverse events, death, malignancy, infections, and infusion reactions. We also evaluated withdrawals from treatment due to lack of efficacy or adverse events. Thirteen randomized placebo-controlled trials met the criteria for data extraction for systematic review. A meta-analysis regarding the efficacy and safety of belimumab compared with placebo involving four of these trials was undertaken and the remainder contributed to a meta-analysis of the safety of biologic agents. In addition, two trials allowed the performance of a meta-analysis regarding the efficacy and safety of rituximab compared with placebo. Belimumab was more effective than placebo in most evaluated outcomes. No significant differences in the safety and

  4. Self-esteem, diet self-efficacy, body mass index, and eating disorders: modeling effects in an ethnically diverse sample.

    PubMed

    Saunders, Jessica F; Frazier, Leslie D; Nichols-Lopez, Kristin A

    2016-09-01

    Disordered eating patterns, particularly binge eating, are prevalent in Hispanic samples, yet the biopsychosocial risk factors remain understudied in minority populations. The relationship between diet self-efficacy and bulimic symptoms has been established in non-Hispanic white samples but not yet in Hispanics. This study sought to identify the direct role of diet self-efficacy on eating disorder risk and symptomology in a multicultural Hispanic sample, and to investigate the potential indirect relations among diet self-efficacy, self-esteem, body mass index (BMI), and eating disorder risk and symptomology in Hispanics and non-Hispanic whites. The present study surveyed 1339 college students from diverse ethnic backgrounds. Participants completed four standardized scales to assess acculturation, diet self-efficacy, global self-esteem, and eating disorder symptomology and risk. Self-reported height and weight were used for BMI calculations, and the data were analyzed in a robust maximum-likelihood structural equation modeling (SEM) framework. The findings highlighted diet self-efficacy as a predictor of eating disorder risk and symptomology. Diet self-efficacy partially explained the covariation between self-esteem and eating disorder risk and symptomology, and between BMI and eating disorder risk and symptomology for the entire sample. Diet self-efficacy emerged as an important construct to consider in developing eating disorder prevention and treatment models.

  5. Evaluating the safety and efficacy of dextromethorphan/quinidine in the treatment of pseudobulbar affect

    PubMed Central

    Schoedel, Kerri A; Morrow, Sarah A; Sellers, Edward M

    2014-01-01

    Pseudobulbar affect (PBA) is a common manifestation of brain pathology associated with many neurological diseases, including amyotrophic lateral sclerosis, Alzheimer’s disease, stroke, multiple sclerosis, Parkinson’s disease, and traumatic brain injury. PBA is defined by involuntary and uncontrollable expressed emotion that is exaggerated and inappropriate, and also incongruent with the underlying emotional state. Dextromethorphan/quinidine (DM/Q) is a combination product indicated for the treatment of PBA. The quinidine component of DM/Q inhibits the cytochrome P450 2D6-mediated metabolic conversion of dextromethorphan to its active metabolite dextrorphan, thereby increasing dextromethorphan systemic bioavailability and driving the pharmacology toward that of the parent drug and away from adverse effects of the dextrorphan metabolite. Three published efficacy and safety studies support the use of DM/Q in the treatment of PBA; significant effects were seen on the primary end point, the Center for Neurologic Study-Lability Scale, as well as secondary efficacy end points and quality of life. While concentration–effect relationships appear relatively weak for efficacy parameters, concentrations of DM/Q may have an impact on safety. Some special safety concerns exist with DM/Q, primarily because of the drug interaction and QT prolongation potential of the quinidine component. However, because concentrations of dextrorphan (which is responsible for many of the parent drug’s side effects) and quinidine are lower than those observed in clinical practice with these drugs administered alone, some of the perceived safety issues may not be as relevant with this low dose combination product. However, since patients with PBA have a variety of other medical problems and are on numerous other medications, they may not tolerate DM/Q adverse effects, or may be at risk for drug interactions. Some caution is warranted when initiating DM/Q treatment, particularly in patients

  6. Evaluating the safety and efficacy of dextromethorphan/quinidine in the treatment of pseudobulbar affect.

    PubMed

    Schoedel, Kerri A; Morrow, Sarah A; Sellers, Edward M

    2014-01-01

    Pseudobulbar affect (PBA) is a common manifestation of brain pathology associated with many neurological diseases, including amyotrophic lateral sclerosis, Alzheimer's disease, stroke, multiple sclerosis, Parkinson's disease, and traumatic brain injury. PBA is defined by involuntary and uncontrollable expressed emotion that is exaggerated and inappropriate, and also incongruent with the underlying emotional state. Dextromethorphan/quinidine (DM/Q) is a combination product indicated for the treatment of PBA. The quinidine component of DM/Q inhibits the cytochrome P450 2D6-mediated metabolic conversion of dextromethorphan to its active metabolite dextrorphan, thereby increasing dextromethorphan systemic bioavailability and driving the pharmacology toward that of the parent drug and away from adverse effects of the dextrorphan metabolite. Three published efficacy and safety studies support the use of DM/Q in the treatment of PBA; significant effects were seen on the primary end point, the Center for Neurologic Study-Lability Scale, as well as secondary efficacy end points and quality of life. While concentration-effect relationships appear relatively weak for efficacy parameters, concentrations of DM/Q may have an impact on safety. Some special safety concerns exist with DM/Q, primarily because of the drug interaction and QT prolongation potential of the quinidine component. However, because concentrations of dextrorphan (which is responsible for many of the parent drug's side effects) and quinidine are lower than those observed in clinical practice with these drugs administered alone, some of the perceived safety issues may not be as relevant with this low dose combination product. However, since patients with PBA have a variety of other medical problems and are on numerous other medications, they may not tolerate DM/Q adverse effects, or may be at risk for drug interactions. Some caution is warranted when initiating DM/Q treatment, particularly in patients with

  7. Safety and efficacy of rivastigmine in children with Down syndrome: A double blind placebo controlled trial.

    PubMed

    Spiridigliozzi, Gail A; Hart, Sarah J; Heller, James H; Schneider, Heather E; Baker, Jane Ann; Weadon, Cathleen; Capone, George T; Kishnani, Priya S

    2016-06-01

    Individuals with Down syndrome (DS) have decreased cholinergic function and an uneven profile of cognitive abilities, with more pronounced deficits in learning, memory, and expressive language. Cholinesterase inhibitors may improve cognitive function in adults and adolescents with DS, but studies in children with DS have been limited. This study aimed to: (i) investigate the safety and efficacy of rivastigmine treatment; (ii) build upon our open-label studies in children with DS in a double-blind, placebo-controlled clinical trial; and (iii) investigate specific cognitive domains that may respond to rivastigmine treatment. We conducted a 20-week double-blind, placebo-controlled trial to investigate the safety and efficacy of rivastigmine in 22 children and adolescents with DS aged 10-17 years. Safety measures included reports of adverse events, laboratory parameters, and electrocardiograms. Efficacy measures included parental assessments of adaptive behavior and executive function, and direct measures of language and memory. No group differences were found on safety measures and 22 of 24 participants that passed study screening completed the study. The results did not demonstrate evidence for significant improvement in aspects of cognition, language, or overall function in the children receiving rivastigmine. Our results suggest that rivastigmine is safe and well-tolerated for children and adolescents with DS, but may not be effective for improving performance on the selected measures in this study. However, larger samples and/or alternate measures could possibly reveal improvements in cognitive function with rivastigmine treatment. Further research is needed to define a battery of cognitive measures that is sensitive to treatment effects in DS. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  8. Efficacy and Safety of Pitavastatin in Children and Adolescents with Familial Hypercholesterolemia in Japan and Europe.

    PubMed

    Harada-Shiba, Mariko; Kastelein, John J P; Hovingh, G Kees; Ray, Kausik K; Ohtake, Akira; Arisaka, Osamu; Ohta, Takao; Okada, Tomoo; Suganami, Hideki; Wiegman, Albert

    2018-05-01

    Children with Familial Hypercholesterolemia (FH) are widely prescribed statins, and it has been suggested that the effects of statins differ among ethnicities. We compared the efficacy and safety of pitavastatin in children and adolescents with FH in clinical trials conducted in Japan and Europe. Low-density lipoprotein cholesterol (LDL-C) reductions, adjusted for confounding factors, and safety were compared between the studies in Japan and Europe. In the Japanese study, 14 males with heterozygous FH, aged 11.8±1.6 years, were randomized to 52-week double-blind treatment with 1 or 2 mg/day pitavastatin. In the European study, 106 children and adolescents with high risk hyperlipidemia (103 heterozygous FH), aged 10.6±2.9 years, were randomized to 12-week double-blind treatment with 1, 2 or 4 mg/day pitavastatin or placebo; 84 of these patients and 29 new patients participated in a 52-week open-label extension study. Age, body weight and baseline LDL-C were identified as factors influencing LDL-C reduction. There were no significant differences in the adjusted mean percentage reduction in LDL-C in Japanese and European children by pitavastatin (24.5% and 23.6%, respectively at 1 mg/day and 33.5% and 30.8%, respectively at 2 mg/day). Pitavastatin was well tolerated without any difference in the frequency or nature of adverse events between the treatment groups, or between the studies. There were no significant differences between the efficacy or safety of pitavastatin in Japanese and European children and adolescents with FH, suggesting no relevant ethnic differences in the safety or efficacy of pitavastatin.

  9. Anxiety sensitivity, catastrophic misinterpretations and panic self-efficacy in the prediction of panic disorder severity: towards a tripartite cognitive model of panic disorder.

    PubMed

    Sandin, Bonifacio; Sánchez-Arribas, Carmen; Chorot, Paloma; Valiente, Rosa M

    2015-04-01

    The present study examined the contribution of three main cognitive factors (i.e., anxiety sensitivity, catastrophic misinterpretations of bodily symptoms, and panic self-efficacy) in predicting panic disorder (PD) severity in a sample of patients with a principal diagnosis of panic disorder. It was hypothesized that anxiety sensitivity (AS), catastrophic misinterpretation of bodily sensations, and panic self-efficacy are uniquely related to panic disorder severity. One hundred and sixty-eight participants completed measures of AS, catastrophic misinterpretations of panic-like sensations, and panic self-efficacy prior to receiving treatment. Results of multiple linear regression analyses indicated that AS, catastrophic misinterpretations and panic self-efficacy independently predicted panic disorder severity. Results of path analyses indicated that AS was direct and indirectly (mediated by catastrophic misinterpretations) related with panic severity. Results provide evidence for a tripartite cognitive account of panic disorder. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Empowerment, feminism, and self-efficacy: relationships to body image and disordered eating.

    PubMed

    Kinsaul, Jessica A E; Curtin, Lisa; Bazzini, Doris; Martz, Denise

    2014-01-01

    Sociocultural norms pertaining to an ideal of thinness for women likely play a role in the development and maintenance of disturbance in body image, and by extension, disordered eating. However, competing norms associated with feminism may buffer women from pressures associated with achieving the thin ideal. The present study explored the relationship between feminist ideology, empowerment, and self-efficacy relative to body image and eating behavior with a sample of U.S. undergraduate women (N=318) attending a southeastern U.S. mid-sized university. In planned hierarchical multiple regression analyses, endorsement of feminist ideology predicted perceptions of positive body image, but did not appear to predict disordered eating. Self-efficacy emerged as a robust predictor of positive body image and lower disordered eating even after controlling for perceptions of personal empowerment and feminism. Results, although limited by correlational data, suggest that self-efficacy may protect college-aged women from disordered eating and negative body image. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Cognitive-behavioral therapy for body dysmorphic disorder: a review of its efficacy

    PubMed Central

    Prazeres, Angélica M; Nascimento, Antônio L; Fontenelle, Leonardo F

    2013-01-01

    The aim of this study was to review the efficacy of different methods of cognitive and/or behavioral therapies used to treat body dysmorphic disorder. We evaluated all case series, open studies, controlled trials, and meta-analyses of cognitive and/or behavioral treatment approaches to body dysmorphic disorder published up to July 2012, identified through a search in the PubMed/Medline, PsycINFO, ISI Web of Knowledge, and Scopus databases. Our findings indicate that individual and group cognitive behavioral therapies are superior to waiting list for the treatment of body dysmorphic disorder. While the efficacy of cognitive therapy is supported by one controlled trial, utility of behavioral therapy is suggested by one open study and one controlled relapse prevention follow-up study. There is a pressing need to conduct head-to-head studies, with appropriate, active, control treatment groups, in order to examine further the efficacy of cognitive and/or behavioral therapies for body dysmorphic disorder. PMID:23467711

  12. Efficacy and safety of glycosylated undenatured type-II collagen (UC-II) in therapy of arthritic dogs.

    PubMed

    Deparle, L A; Gupta, R C; Canerdy, T D; Goad, J T; D'Altilio, M; Bagchi, M; Bagchi, D

    2005-08-01

    DeParle L. A., Gupta R. C., Canerdy T. D., Goad J. T., D'Altilio M., Bagchi M., Bagchi D. Efficacy and safety of glycosylated undenatured type-II collagen (UC-II) in therapy of arthritic dogs. J. vet. Pharmacol. Therap.28, 385-390. In large breed dogs, arthritis is very common because of obesity, injury, aging, immune disorder, or genetic predispositions. This study was therefore undertaken to evaluate clinical efficacy and safety of undenatured type-II collagen (UC-II) in obese-arthritic dogs. Fifteen dogs in three groups received either no UC-II (Group I) or UC-II with 1 mg/day (Group II) or 10 mg/day (Group III) for 90 days. Lameness and pain were measured on a weekly basis for 120 days (90 days treatment plus 30 days post-treatment). Blood samples were assayed for creatinine and blood urea nitrogen (markers of renal injury); and alanine aminotransferase and aspartate aminotransferase (evidence of hepatic injury). Dogs receiving 1 mg or 10 mg UC-II/day for 90 days showed significant declines in overall pain and pain during limb manipulation and lameness after physical exertion, with 10 mg showed greater improvement. At either dose of UC-II, no adverse effects were noted and no significant changes were noted in serum chemistry, suggesting that UC-II was well tolerated. In addition, dogs receiving UC-II for 90 days showed increased physical activity level. Following UC-II withdrawal for a period of 30 days, all dogs experienced a relapse of overall pain, exercise-associated lameness, and pain upon limb manipulation. These results suggest that daily treatment of arthritic dogs with UC-II ameliorates signs and symptoms of arthritis, and UC-II is well tolerated as no adverse effects were noted.

  13. Focused ultrasound-mediated noninvasive blood-brain barrier modulation: preclinical examination of efficacy and safety in various sonication parameters.

    PubMed

    Shin, Jaewoo; Kong, Chanho; Cho, Jae Sung; Lee, Jihyeon; Koh, Chin Su; Yoon, Min-Sik; Na, Young Cheol; Chang, Won Seok; Chang, Jin Woo

    2018-02-01

    OBJECTIVE The application of pharmacological therapeutics in neurological disorders is limited by the ability of these agents to penetrate the blood-brain barrier (BBB). Focused ultrasound (FUS) has recently gained attention for its potential application as a method for locally opening the BBB and thereby facilitating drug delivery into the brain parenchyma. However, this method still requires optimization to maximize its safety and efficacy for clinical use. In the present study, the authors examined several sonication parameters of FUS influencing BBB opening in small animals. METHODS Changes in BBB permeability were observed during transcranial sonication using low-intensity FUS in 20 adult male Sprague-Dawley rats. The authors examined the effects of FUS sonication with different sonication parameters, varying acoustic pressure, center frequency, burst duration, microbubble (MB) type, MB dose, pulse repetition frequency (PRF), and total exposure time. The focal region of BBB opening was identified by Evans blue dye. Additionally, H & E staining was used to identify blood vessel damage. RESULTS Acoustic pressure amplitude and burst duration were closely associated with enhancement of BBB opening efficiency, but these parameters were also highly correlated with tissue damage in the sonicated region. In contrast, MB types, MB dose, total exposure time, and PRF had an influence on BBB opening without conspicuous tissue damage after FUS sonication. CONCLUSIONS The study aimed to identify these influential conditions and provide safety and efficacy values for further studies. Future work based on the current results is anticipated to facilitate the implementation of FUS sonication for drug delivery in various CNS disease states in the near future.

  14. Safety and Efficacy Endpoints for Mesenchymal Stromal Cell Therapy in Renal Transplant Recipients.

    PubMed

    Bank, J R; Rabelink, T J; de Fijter, J W; Reinders, M E J

    2015-01-01

    Despite excellent short-term graft survival after renal transplantation, the long-term graft outcome remains compromised. It has become evident that a combination of sustained alloreactivity and calcineurin-inhibitor- (CNI-) related nephrotoxicity results in fibrosis and consequently dysfunction of the graft. New immunosuppressive regimens that can minimize or eliminate side effects, while maintaining efficacy, are required to improve long-term graft survival. In this perspective mesenchymal stromal cells (MSCs) are an interesting candidate, since MSCs have immunosuppressive and regenerative properties. The first clinical trials with MSCs in renal transplantation showed safety and feasibility and displayed promising results. Recently, the first phase II studies have been started. One of the most difficult and challenging aspects in those early phase trials is to define accurate endpoints that can measure safety and efficacy of MSC treatment. Since both graft losses and acute rejection rates declined, alternative surrogate markers such as renal function, histological findings, and immunological markers are used to measure efficacy and to provide mechanistic insight. In this review, we will discuss the current status of MSCs in renal transplantation with a focus on the endpoints used in the different experimental and clinical studies.

  15. [Safety and efficacy of a prothrombin complex concentrate in patients with coagulopathy and hemorrhage].

    PubMed

    Martínez-Calle, N; Marcos-Jubilar, M; Alfonso, A; Hernández, M; Hidalgo, F; Lecumberri, R; Páramo, Ja

    2014-01-01

    Prothrombin complex concentrates (PCC) are approved for urgent reversal of vitamin K antagonists (VKA). Recently, PCC have been used in the management of massive bleeding-associated coagulopathy. The present work evaluates safety and efficacy of PCC in a case series of both VKA reversal and massive bleeding. Retrospective review of cases treated with CCP (January 2010 to February 2013). Safety endpoints were infusion reactions and incidence of thromboembolic events. Efficacy endpoints were: 1) VKA reversal efficacy and 2) Massive bleeding coagulopathy reversal and 24h mortality. Thirty-one patients were included (22 male), median age 61 years (range 30-86). No infusion reactions were detected, and only 1 thrombotic episode was observed. VKA reversal was effective in 100% of patients (6/6), all of them with complete reversal of INR value. In massive bleeding, 24-hour survival was 64% (16/25). Invasive hemostatic procedures were required in 28% of patients (7/25). CCP use was correlated with bleeding control in 44% of cases (11/25), and also significantly associated with survival (p=0.01). CCP are safe and effective for the novel indication of adjuvant treatment in massive bleeding patients, as well as for traditional urgent reversal of VKA.

  16. Effects of genetic, processing, or product formulation changes on efficacy and safety of probiotics.

    PubMed

    Sanders, Mary Ellen; Klaenhammer, Todd R; Ouwehand, Arthur C; Pot, Bruno; Johansen, Eric; Heimbach, James T; Marco, Maria L; Tennilä, Julia; Ross, R Paul; Franz, Charles; Pagé, Nicolas; Pridmore, R David; Leyer, Greg; Salminen, Seppo; Charbonneau, Duane; Call, Emma; Lenoir-Wijnkoop, Irene

    2014-02-01

    Commercial probiotic strains for food or supplement use can be altered in different ways for a variety of purposes. Production conditions for the strain or final product may be changed to address probiotic yield, functionality, or stability. Final food products may be modified to improve flavor and other sensory properties, provide new product formats, or respond to market opportunities. Such changes can alter the expression of physiological traits owing to the live nature of probiotics. In addition, genetic approaches may be used to improve strain attributes. This review explores whether genetic or phenotypic changes, by accident or design, might affect the efficacy or safety of commercial probiotics. We highlight key issues important to determining the need to re-confirm efficacy or safety after strain improvement, process optimization, or product formulation changes. Research pinpointing the mechanisms of action for probiotic function and the development of assays to measure them are greatly needed to better understand if such changes have a substantive impact on probiotic efficacy. © 2014 New York Academy of Sciences.

  17. Safety and preliminary efficacy of deep transcranial magnetic stimulation in MS-related fatigue

    PubMed Central

    Gaede, Gunnar; Tiede, Marina; Lorenz, Ina; Brandt, Alexander U.; Pfueller, Caspar; Dörr, Jan; Bellmann-Strobl, Judith; Piper, Sophie K.; Roth, Yiftach; Zangen, Abraham; Schippling, Sven

    2017-01-01

    Objective: To conduct a randomized, sham-controlled phase I/IIa study to evaluate the safety and preliminary efficacy of deep brain H-coil repetitive transcranial magnetic stimulation (rTMS) over the prefrontal cortex (PFC) and the primary motor cortex (MC) in patients with MS with fatigue or depression (NCT01106365). Methods: Thirty-three patients with MS were recruited to undergo 18 consecutive rTMS sessions over 6 weeks, followed by follow-up (FU) assessments over 6 weeks. Patients were randomized to receive high-frequency stimulation of the left PFC, MC, or sham stimulation. Primary end point was the safety of stimulation. Preliminary efficacy was assessed based on changes in Fatigue Severity Scale (FSS) and Beck Depression Inventory scores. Randomization allowed only analysis of preliminary efficacy for fatigue. Results: No serious adverse events were observed. Five patients terminated participation during treatment due to mild side effects. Treatment resulted in a significant median FSS decrease of 1.0 point (95%CI [0.45,1.65]), which was sustained during FU. Conclusions: H-coil rTMS is safe and well tolerated in patients with MS. The observed sustained reduction in fatigue after subthreshold MC stimulation warrants further investigation. ClinicalTrials.gov identifier: NCT01106365. Classification of evidence: This study provides Class III evidence that rTMS of the prefrontal or primary MC is not associated with serious adverse effects, although this study is underpowered to state this with any precision. PMID:29259998

  18. Risperidone long-acting injection: a review of its long term safety and efficacy

    PubMed Central

    Rainer, Michael K

    2008-01-01

    A long-acting form of the second-generation antipsychotic drug risperidone is now broadly available for the treatment of schizophrenia and closely related psychiatric conditions. It combines the advantage of previously available depot formulations for first-generation drugs with the favorable characteristics of the modern “atypical” antipsychotics, namely higher efficacy in the treatment of the negative symptoms of schizophrenia and reduced motor disturbances. Published clinical studies show an objective clinical efficacy (as per psychiatric symptom scores and relapse data) that exceeds that of oral atypical antipsychotics when patients are switched to the long-acting injectable form, a low incidence of treatment-emergent extrapyramidal side effects, and very good acceptance by patients. Available data for maintenance treatment of bipolar disorder show equivalence with the oral form instead of superiority, but are still limited. As it seems likely that efficacy benefits are mostly due to the fact that the injectable form reduces the demand for patient compliance to one physician visit every 2 weeks instead of self-administration on a daily or twice-daily basis, additional potential could exist in other psychiatric disorders where atypical antipsychotic drugs are of benefit but where patient adherence to treatment schedules is typically low. PMID:19183782

  19. Efficacy of Desvenlafaxine Compared With Placebo in Major Depressive Disorder Patients by Age Group and Severity of Depression at Baseline.

    PubMed

    Mosca, Daniel; Zhang, Min; Prieto, Rita; Boucher, Matthieu

    2017-04-01

    This post hoc meta-analysis evaluated the efficacy and safety of desvenlafaxine 50 and 100 mg versus placebo across age groups and severity of depression at baseline in patients with major depressive disorder. Data from placebo and desvenlafaxine 50-mg and 100-mg dose arms were pooled from 9 short-term, placebo-controlled, major depressive disorder studies (N = 4279). Effects of age (18-40 years, >40 to <55 years, 55-<65 years, and ≥65 years) and baseline depression severity (mild, 17-item Hamilton Rating Scale for Depression total score [HAM-D17] ≤18; moderate, HAM-D17 >18 to <25; severe, HAM-D17 ≥25) on desvenlafaxine efficacy were assessed using analysis of covariance for continuous end points and logistic regression for categorical end points. Desvenlafaxine-treated (50 or 100 mg/d) patients had significantly (P < 0.05, 2-sided) greater improvement in most measures of depression and function compared with placebo for patients 18 to 40 years, older than 40 to younger than 55 years, and 55 to younger than 65 years, with no significant evidence of an effect of age. Desvenlafaxine significantly improved most measures of depression and function in moderately and severely depressed patients. There was a significant baseline severity by treatment interaction for HAM-D17 total score only (P = 0.027), with a larger treatment effect for the severely depressed group. Desvenlafaxine significantly improved depressive symptoms in patients younger than 65 years and in patients with moderate or severe baseline depression. Sample sizes were not adequate to assess desvenlafaxine efficacy in patients 65 years or older or with mild baseline depression.

  20. False Safety Behavior Elimination Therapy: A randomized study of a brief individual transdiagnostic treatment for anxiety disorders.

    PubMed

    Riccardi, Christina J; Korte, Kristina J; Schmidt, Norman B

    2017-03-01

    In response to the ever-growing number of CBT based therapy protocols, transdiagnostic approaches to anxiety treatment, based on models of anxiety emphasizing common elements across anxiety disorders, have been increasingly explored. The aim of the current study was to test the efficacy of an individually administered, brief (5-session) transdiagnostic treatment for anxiety disorders. The current treatment (called F-SET) focuses chiefly on the elimination of anxiety maintaining behaviors and cognitive strategies (so-called "safety" aids) among individuals suffering from a range of anxiety disorders including generalized anxiety disorder (GAD), social anxiety disorder (SAD) and panic disorder (PD). Patients (N=28; mean age=28.5years; 75% female; 71% White) were randomly assigned to F-SET or waitlist control conditions. Participants were assessed prior to, immediately after, and 1-month following treatment. In addition to independent assessments of diagnostic status, standardized self-report measures and assessor ratings of severity and distress associated with anxiety symptoms were used. Participants in the F-SET condition experienced significantly less anxiety (Cohen's d=2.01) and depression (Cohen's d=2.16) than those in the WL condition. Mediational analysis showed that change in avoidance strategies mediated the group changes in anxiety symptoms. The results from the current study are an important first step in identifying a simpler, focused form of CBT that can be delivered with minimal therapist training, at a low cost and with minimal client contact time. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Efficacy and safety of a clinically relevant foamy vector design in human hematopoietic repopulating cells.

    PubMed

    Everson, Elizabeth M; Hocum, Jonah D; Trobridge, Grant D

    2018-06-23

    Previous studies have shown that foamy viral (FV) vectors are a promising alternative to gammaretroviral and lentiviral vectors and insulators can improve FV vector safety. However, in a previous analysis of insulator effects on FV vector safety, strong viral promoters were used to elicit genotoxic events. Here we developed and analyzed the efficacy and safety of a high-titer, clinically relevant FV vector driven by the housekeeping promoter elongation factor-1α and insulated with an enhancer blocking A1 insulator (FV-EGW-A1). Human CD34 + cord blood cells were exposed to an enhanced green fluorescent protein expressing vector, FV-EGW-A1, at a multiplicity of infection of 10 and then maintained in vitro or transplanted into immunodeficient mice. Flow cytometry was used to measure engraftment and marking in vivo. FV vector integration sites were analyzed to assess safety. FV-EGW-A1 resulted in high-marking, multi-lineage engraftment of human repopulating cells with no evidence of silencing. Engraftment was highly polyclonal with no clonal dominance and a promising safety profile based on integration site analysis. An FV vector with an elongation factor-1α promoter and an A1 insulator is a promising vector design for use in the clinic. This article is protected by copyright. All rights reserved.

  2. Differentiated Evaluation of Extract-Specific Evidence on Cimicifuga racemosa's Efficacy and Safety for Climacteric Complaints

    PubMed Central

    Beer, A.-M.; Neff, A.

    2013-01-01

    Past reviews on Cimicifuga racemosa (CR) without differentiation between extracts, quality, and indication altogether led to inconsistent data. Therefore, for the first time, we meet the requirements of the system's logic of evidence-based phytotherapy by taking into consideration extracts, pharmaceutical quality (reflected in a regulatory status as medicinal product), and indication. A literature search for clinical studies examining CR's efficacy and safety for menopausal complaints was conducted. The results were sorted by type of extract, regulatory status, and indication. Accordingly, Oxford Levels of Evidence (LOE) and Grades of Recommendation (GR) were determined. CR extracts demonstrated a good to very good safety in general, on estrogen-sensitive organs and the liver. However, only registered CR medicinal products were able to prove their efficacy. Best evidence was provided by the isopropanolic CR extract (iCR): the multitude of studies including more than 11,000 patients demonstrated consistent confirmatory evidence of LOE 1b (LOE 1a for safety) leading to GR A. The studies on the ethanolic extract BNO 1055 including more than 500 patients showed exploratory evidence of LOE 2b resulting in GR B. A positive benefit-risk profile is stated and limited to Cimicifuga racemosa products holding a marketing authorisation for treating climacteric complaints. PMID:24062793

  3. Safety and anti-hyperglycemic efficacy of various tea types in mice

    PubMed Central

    Han, Manman; Zhao, Guangshan; Wang, Yijun; Wang, Dongxu; Sun, Feng; Ning, Jingming; Wan, Xiachun; Zhang, Jinsong

    2016-01-01

    Tea, a beverage consumed worldwide, has proven anti-hyperglycemic effects in animal models. Better efficacies of tea beverages are frequently associated with high-dose levels, whose safety attracts considerable attention. Based on the inherent nature of tea catechin oxidation, fresh tea leaves are manufactured into diverse tea types by modulating the oxidation degree of catechins. The present study aimed to assess various tea types for their safety properties and anti-hyperglycemic effects. Mice were allowed free access to tea infusion (1:30, w/v) for one week, and the rare smoked tea caused salient adverse reactions, including hepatic and gastrointestinal toxicities; meanwhile, the widely-consumed green and black teas, unlike the rare yellow tea, suppressed growth in fast-growing healthy mice. When mice were fed a high-fat diet and allowed free access to tea infusion (1:30, w/v) for 25 days, only yellow tea significantly reduced blood glucose. Therefore, various teas showed different safety profiles as well as anti-hyperglycemic efficacy strengths. To achieve an effective and safe anti-hyperglycemic outcome, yellow tea, which effectively suppressed high-fat diet-induced early elevation of hepatic thioredoxin-interacting protein, is an optimal choice. PMID:27531374

  4. Differentiated Evaluation of Extract-Specific Evidence on Cimicifuga racemosa's Efficacy and Safety for Climacteric Complaints.

    PubMed

    Beer, A-M; Neff, A

    2013-01-01

    Past reviews on Cimicifuga racemosa (CR) without differentiation between extracts, quality, and indication altogether led to inconsistent data. Therefore, for the first time, we meet the requirements of the system's logic of evidence-based phytotherapy by taking into consideration extracts, pharmaceutical quality (reflected in a regulatory status as medicinal product), and indication. A literature search for clinical studies examining CR's efficacy and safety for menopausal complaints was conducted. The results were sorted by type of extract, regulatory status, and indication. Accordingly, Oxford Levels of Evidence (LOE) and Grades of Recommendation (GR) were determined. CR extracts demonstrated a good to very good safety in general, on estrogen-sensitive organs and the liver. However, only registered CR medicinal products were able to prove their efficacy. Best evidence was provided by the isopropanolic CR extract (iCR): the multitude of studies including more than 11,000 patients demonstrated consistent confirmatory evidence of LOE 1b (LOE 1a for safety) leading to GR A. The studies on the ethanolic extract BNO 1055 including more than 500 patients showed exploratory evidence of LOE 2b resulting in GR B. A positive benefit-risk profile is stated and limited to Cimicifuga racemosa products holding a marketing authorisation for treating climacteric complaints.

  5. Efficacy and Safety of Fish Oil in Treatment of Knee Osteoarthritis.

    PubMed

    Peanpadungrat, Pornrawee

    2015-04-01

    To study efficacy and safety of fish oil in treatment of knee osteoarthritis. 75 participants had divided into three groups of 25 people to study efficacy results after taking fish oil 1,000 mg and 2,000 mg once a day for 8 weeks. 1,000 mg of fish oil have EPA 400 mg and DHA 200 mg. All participants had complete visual analog scale for measuring knee pain and knee function. They also had measured 100 meters walking velocity and three steps walking time before taking fish oil. Then they had re-measured all parameters again at 8-12 weeks after taking fish oil to compare the results. All parameters had statistically significant better differences in the group of participants who had taken fish oil when compared to the control group. The average score of patient's satisfaction was 9.06 of 10 and also by verbal response of 50 participants; everyone felt good and happy with fish oil. One participant had hematuriafrom silent CA bladder at 10th week but the other 49 participants were safe without any complications from fish oil. Fish oil 1,000-2,000 mg daily supplementation had significant efficacy to improve knee performance and also are safe in mild to moderate stages of knee osteoarthritics patients. However higher dose 2,000 mg of fish oil had not significant higher efficacy than 1,000 mg of fish oil.

  6. Topical microbicide use by adolescent girls: concerns about timing, efficacy, and safety.

    PubMed

    Short, Mary B; Mills, Lisa; Majkowski, Jasmine M; Stanberry, Lawrence R; Rosenthal, Susan L

    2003-11-01

    Adolescent girls could benefit from topical microbicide use if the product is acceptable to them. The goal was to evaluate girls', mothers', experienced healthcare providers', and medical students' views on timing of use, efficacy, and safety of topical microbicide use by adolescents. Focus groups were conducted with girls, mothers, healthcare providers, and medical students. All groups were videotaped, transcribed, and coded for relevant themes. A delay between insertion and coitus presented a problem, and pre- and postcoital use had advantages depending on the group. Efficacy was evaluated by timing of use, smell, ability to feel the product, and confidence that it would spread sufficiently. There were concerns about physical side effects and the impact on normal vaginal flora. This study demonstrated the importance of understanding the unique needs and perspectives of adolescent girls and the adults who have an influence on their use.

  7. The efficacy and safety of high-intensity focused ultrasound ablation of benign thyroid nodules.

    PubMed

    Lang, Brian H; Wu, Arnold L H

    2018-04-01

    High-intensity focused ultrasound (HIFU) is a promising form of thermal ablation of benign thyroid nodules, but evidence supporting its use is scarce. The present review evaluated the efficacy and safety of single-session HIFU treatment of benign thyroid nodules. As reported in the literature, the extent of nodule shrinkage following treatment ranged from 48.8% to 68.8%. Like other forms of ablation, the shrinkage rate was greatest in the first 3-6 months, and the best responders were patients with small (≤10 mL) nodules. Complications were uncommon, but temporary vocal cord palsy occurred in 3%-4% of patients, and was related to the distance between the HIFU beam and the recurrent laryngeal nerve. Despite being safe and efficacious, a larger-scale prospective trial is required.

  8. Botanical medicine and cancer: a review of the safety and efficacy.

    PubMed

    Boon, Heather; Wong, Jacqueline

    2004-12-01

    It is currently estimated that > 50% of all patients diagnosed with cancer explore complementary and alternative medicine - especially herbal medicine. We conducted a comprehensive review to assess the safety and efficacy of herbal medicines commonly used by patients in an attempt to: prevent cancer; treat cancer; and treat adverse effects associated with conventional cancer treatments. Current evidence suggests that Asian ginseng, garlic, green tea, tomatoes and soy intake as part of the diet may be useful in preventing various cancers; additional research is needed in order to determine the efficacy of essiac, evening primrose oil, mistletoe, reishi, shiitake and turmeric as cancer treatments; and ginger may be effective in treating chemotherapy-induced nausea and vomiting.

  9. Efficacy of peroral endoscopic myotomy compared with other invasive treatment options for the different esophageal motor disorders.

    PubMed

    Estremera-Arévalo, Fermín; Albéniz, Eduardo; Rullán, María; Areste, Irene; Iglesias, Rosa; Vila, Juan José

    2017-08-01

    Peroral endoscopic myotomy (POEM) has been performed since 2008 on more than 5,000 patients. It has proven to be highly effective in the treatment of achalasia and has shown promising outcomes for other esophageal motility spastic disorders. A literature review of the efficacy of POEM compared to the previous invasive treatments for different esophageal motility disorders was performed. The application in the pediatric and elderly populations and its role as a rescue therapy after other procedures are also outlined. Short-term outcomes are similar to laparoscopic Heller myotomy (LHM) and pneumatic endoscopic dilation (PD) (clinical success > 90%) for achalasia subtypes I and II. Mid-term outcomes are comparable to LHM and overcome the results obtained after PD (> 90% vs ~50%). With regard to type III achalasia, POEM efficacy is 98% compared to 80.8% for LHM and the PD success remains at 40%. With regard to spastic esophageal disorders (SED), POEM has an effectiveness of 88% and 70% for distal esophageal spasm (DES) and jackhammer esophagus (JE) respectively. A response of 95% in patients with sigmoid esophagus has been reported. POEM has been performed in pediatric and elderly populations and has obtained a higher efficacy than PD in pediatric series (100% vs 33%) without greater adverse events. Previous treatments do not seem to hinder POEM results with excellent response rates, including 97% in post LHM and 100% in a re-POEM series. Final considerations: POEM has shown excellent short and mid-term results for all subtypes of achalasia but long-term results are not yet available. The promising results in SED may make POEM the first-line treatment for SED. A high-safety profile and efficacy have been shown in elderly and pediatric populations. Previous treatments do not seem to diminish the success rate of POEM. Core tip: POEM has emerged as an efficient treatment option for all subtypes of achalasia and other scenarios (including previous treatments and elderly

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

    PubMed

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

    2015-06-01

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

  11. Population analyses of efficacy and safety of ABT-594 in subjects with diabetic peripheral neuropathic pain.

    PubMed

    Dutta, Sandeep; Hosmane, Balakrishna S; Awni, Walid M

    2012-06-01

    ABT-594, a neuronal nicotinic acetylcholine receptor ligand, is 30- to 100-fold more potent than morphine in animal models of nociceptive and neuropathic pain. Efficacy and safety of ABT-594 in subjects with painful diabetic polyneuropathy was evaluated in a phase 2 study. The objective of this work was to use a nonlinear mixed effects model-based approach for characterizing the relationship between dose and response (efficacy and safety) of ABT-594. Subjects (N = 266) were randomized into four groups in a double-blind, placebo-controlled, 7-week study to receive twice daily regimens of placebo or 150, 225, and 300 μg of ABT-594. The primary efficacy variable, pain score (11-point Likert scale), was assessed on five occasions. The probability of change from baseline pain score of ≥1, ≥2, and ≥3 was modeled using cumulative logistic regression with dose and days of treatment as explanatory variables. The incidence of five most frequently occurring adverse events (AEs) was modeled using linear logistic regression. ABT-594 ED(50) values (improvement in 50% of subjects) for improvement in pain scores of ≥1, ≥2, and ≥3 were 50, 215, and 340 μg, respectively, for the average number of days (33) on treatment. The rank order of ED(50) values for AEs was nausea, vomiting, dizziness, headache, and abnormal dreams; nicotine users were less sensitive to AEs. Population pharmacodynamic models developed to characterize the improvement in pain score and incidence of adverse events indicate an approximately twofold separation between the ED(50) values for efficacy and AEs.

  12. Durability, safety, and efficacy of rilpivirine in clinical practice: results from the SCOLTA Project.

    PubMed

    Bagella, Paola; De Socio, Giuseppe Vl; Ricci, Elena; Menzaghi, Barbara; Martinelli, Canio; Squillace, Nicola; Maggi, Paolo; Orofino, Giancarlo; Calza, Leonardo; Carenzi, Laura; Celesia, Benedetto Maurizio; Penco, Giovanni; Di Biagio, Antonio; Valsecchi, Laura; Vichi, Francesca; Colombo, Valeria; Parruti, Giustino; Dentone, Chiara; Falasca, Katia; Bonfanti, Paolo; Madeddu, Giordano

    2018-01-01

    Rilpivirine is associated with a good efficacy and safety profile. However, data from real-life settings are scarce. We investigated the durability, safety and efficacy of Rilpivirine-based antiretroviral therapy in a prospective, observational, multicenter study. We enrolled 499 HIV-infected patients, 360 (72.1%) males, mean age 43.4 ± 10.5 years, mean CD4 600 ± 327 cell/μL, mean HIV-RNA 3.80 ± 1.15 log 10 cp/mL. After a median follow up of 16 months, 81 (16.2%) interruptions were reported, 36 (7.2%) of which for adverse events (16 of grade ≥3), most commonly neurological and gastrointestinal. We observed virological failures in only 8 (1.6%) patients. Naive patients showed a significant reduction in eGFR at week 24, 48 and 72 and in total cholesterol (TC)/HDL ratio at week 48 ( p =0.007). In patients switching from PI we found a significant decrease at week 24 and 48 in TC and triglycerides at week 24, 48 and 72. eGFR showed a significant decrease at week 48 and 72. TC/HDL ratio showed a statistically significant decrease at week 24 ( p =0.0008) and 72 ( p =0.04). A significant increase at week 24 and 48 in AST and ALT values was observed. Patients switching from TDF/FTC/EFV showed a reduction in HDL, total cholesterol and triglycerides at week 24 and 48 and in eGFR at all follow up times. TC/HDL ratio showed a significant decrease at week 48 ( p =0.01). CDC stage C and antiretroviral-experience (especially Protease Inhibitors) were associated with RPV discontinuation. In conclusion, our data confirm Rilpivirine efficacy, safety and tolerability with improvement in lipid profile. Although hepatic and renal events rarely caused discontinuation, liver and kidney parameters should be monitored.

  13. Efficacy, safety, quality control, marketing and regulatory guidelines for herbal medicines (phytotherapeutic agents).

    PubMed

    Calixto, J B

    2000-02-01

    This review highlights the current advances in knowledge about the safety, efficacy, quality control, marketing and regulatory aspects of botanical medicines. Phytotherapeutic agents are standardized herbal preparations consisting of complex mixtures of one or more plants which contain as active ingredients plant parts or plant material in the crude or processed state. A marked growth in the worldwide phytotherapeutic market has occurred over the last 15 years. For the European and USA markets alone, this will reach about $7 billion and $5 billion per annum, respectively, in 1999, and has thus attracted the interest of most large pharmaceutical companies. Insufficient data exist for most plants to guarantee their quality, efficacy and safety. The idea that herbal drugs are safe and free from side effects is false. Plants contain hundreds of constituents and some of them are very toxic, such as the most cytotoxic anti-cancer plant-derived drugs, digitalis and the pyrrolizidine alkaloids, etc. However, the adverse effects of phytotherapeutic agents are less frequent compared with synthetic drugs, but well-controlled clinical trials have now confirmed that such effects really exist. Several regulatory models for herbal medicines are currently available including prescription drugs, over-the-counter substances, traditional medicines and dietary supplements. Harmonization and improvement in the processes of regulation is needed, and the general tendency is to perpetuate the German Commission E experience, which combines scientific studies and traditional knowledge (monographs). Finally, the trend in the domestication, production and biotechnological studies and genetic improvement of medicinal plants, instead of the use of plants harvested in the wild, will offer great advantages, since it will be possible to obtain uniform and high quality raw materials which are fundamental to the efficacy and safety of herbal drugs.

  14. The role of attitudes about vaccine safety, efficacy, and value in explaining parents' reported vaccination behavior.

    PubMed

    Lavail, Katherine Hart; Kennedy, Allison Michelle

    2013-10-01

    To explain vaccine confidence as it related to parents' decisions to vaccinate their children with recommended vaccines, and to develop a confidence measure to efficiently and effectively predict parents' self-reported vaccine behaviors. A sample of parents with at least one child younger than 6 years (n = 376) was analyzed using data from the HealthStyles 2010 survey. Questions were grouped into block variables to create three confidence constructs: value, safety, and efficacy. Regression equations controlling for demographic characteristics were used to identify the confidence construct(s) that best predicted parents' self-reported vaccination decisions (accept all, some, or none of the recommended childhood vaccines). Among the three constructs evaluated, confidence in the value of vaccines, that is the belief that vaccines are important and vaccinating one's children is the right thing to do, was the best predictor of parents' vaccine decisions, F(2, 351) = 119.199, p < .001. When combined into a block variable for analysis, two survey items measuring confidence in the value of vaccines accounted for 40% of the variance in parents' self-reported vaccine decisions. Confidence in the safety or efficacy of vaccines failed to account for additional significant variance in parent-reported vaccination behavior. Confidence in the value of vaccines is a helpful predictor of parent-reported vaccination behavior. Attitudinal constructs of confidence in the safety and efficacy of vaccines failed to account for additional significant variance in parents' vaccination behaviors. Future research should assess the role of vaccine knowledge and tangible barriers, such as access and cost, to further explain parents' vaccination behaviors.

  15. [Efficacy and safety of vardenafil in patients with erectile dysfunction. Results of the Mexican Multicentric Study].

    PubMed

    Sotomayor-de-Zavaleta, Mariano; Rubio-Aurioles, Eusebio; Feria-Bernal, Guillermo; Mendoza-Valdés, Arturo; Quinzaños-Sordo, Luis Fernando; Ugarte-y-Romano, Fernando; Hurtado-Coll, Antonio; Telich-Vidal, Martín; Barreto-Fernández, Miguel Angel; Tapia-Serrano, María del Rosario; Ureta-Sánchez, Sergio Ermen; Jaspersen-Gastelum, Jorge; Pacheco-Gahbler, Carlos; Sentíes-Hernández, Ignacio R; Olguin, Jorge; Pérez-García, Javier

    2004-01-01

    The objective of the present study was to determine the efficacy and safety of a fixed dose of vardenafil in the treatment of patients with erectile dysfunction (ED). This was an open label, prospective and multicentric trial. After a 4-week wash out period, all patients received 20 mg of vardenafil given on demand for 12 weeks. Primary efficacy variables were the erectile function domain of the International Index of Erectile Function (IIEF), answers to questions 2 and 3 of the Sexual Encounter Profile (SEP) and the Global Assessment Question (GAQ). All adverse events were recorded and reported. 229 patients were screened. 177 received at least one dose of vardenafil and were included in the safety analysis. Mean age was 54.4 years old. Etiology of ED was organic or mixed in 77% of the patients. Erectile function domain of the IIEF changed from a basal mean score of 14.8 to 25.5 at the end of the study. 80.5% of the patients reported erections of rigidity and duration enough for satisfactory sexual intercourse and 93.3% improved their erections at the end of the study. Adverse events were mild to moderate and the most common were headache, dyspepsia, rhinitis and facial flushing. The drop out rate due to adverse events was 1.7%. This multicenter study confirms the high efficacy of this new phosphodiesterase type 5 inhibitor, vardenafil. There was a low rate of discontinuations due to adverse events and a favorable safety profile. The results of this study are similar to the results of other studies conducted in other parts of the world.

  16. Safety and efficacy of pharmacologic thromboprophylaxis following blunt head injury: a systematic review.

    PubMed

    Reeves, Fairleigh; Batty, Lachlan; Pitt, Veronica; Chau, Marisa; Pattuwage, Loyal; Gruen, Russell L

    2013-10-01

    Patients with blunt head injury are at high risk of venous thromboembolism. However, pharmacologic thromboprophylaxis (PTP) may cause progression of intracranial hemorrhage, and clinicians must often weigh up the risks and benefits. This review aimed to determine whether adding PTP to mechanical prophylaxis confers net benefit or harm and the optimal timing, dose, and agent for PTP in patients with blunt head injury. We searched MEDLINE, EMBASE, The Cochrane Library Central Register of Controlled Trials (CENTRAL), and www.clinicaltrials.gov on April 24, 2013, to identify controlled studies and ongoing trials that assessed the efficacy or safety of thromboprophylaxis interventions in the early management of head-injured patients. Studies were classified based on types of interventions and comparisons, and the quality of included studies was assessed using Cochrane risk-of-bias tool and the Newcastle-Ottawa Quality Assessment Scale. We intended to undertake a meta-analysis if studies were sufficiently similar. Sixteen studies met the inclusion criteria, including four randomized controlled trials. At least two randomized controlled trials were at high risk of bias owing to inadequate randomization and concealment of allocation, and observational studies were potentially confounded by substantial differences between comparison groups. Heterogeneity of included studies precluded meta-analysis. Results were mixed, with some studies supporting and others refuting addition of PTP to mechanical interventions. Little evidence was available about dose or choice of agent. The safety and efficacy of early PTP in patients without early progression of hemorrhage is unclear. There is currently insufficient evidence to guide thromboprophylaxis in patients with blunt head injury. Standardized definitions and outcome measurements would facilitate comparison of outcomes across future studies. Studies in mixed populations should report head-injured specific subgroup data. Future

  17. A Comparative Study of Efficacy and Safety of Eberconazole versus Terbinafine in Patients of Tinea Versicolor.

    PubMed

    Sharma, Jyoti; Kaushal, Jyoti; Aggarwal, Kamal

    2018-01-01

    Tinea versicolor (TV) is characterised by the appearance of maculosquamous lesions sometimes associated with mild erythema and pruritus in characteristic areas of the body. Eberconazole and terbinafine though drugs of different classes provide both mycological and clinical cure. This study aims to compare the efficacy and safety of eberconazole versus terbinafine in patients of TV. An open-label, randomised, comparative clinical trial was conducted on 60 patients. The patients were randomly divided into two study groups. Group A: Eberconazole 1% cream once daily and Group B: Terbinafine 1% cream once daily for 2 weeks. Efficacy assessment was done by observing signs and symptoms, i.e., Physician assessment 4-point scale, microscopic KOH examination, Wood's lamp examination, global clinical response assessment, and patient's assessment on visual analog scale at the end of 2 weeks and subsequently patients were reassessed at the end of 4 and 8 weeks to check any relapse. Safety assessment was also done. There was a significant improvement in all the parameters in both groups over a period of 2 weeks. Both the treatment groups, i.e., eberconazole and terbinafine were found to be safe and efficacious at the end of 2 weeks, and no statistically significant difference was observed between the two groups regarding complete cure, i.e., mycological and clinical cure (80% vs. 63.33%), respectively. However, early response (at the end of week 1) was observed with eberconazole. No relapse was seen with eberconazole, but one patient had relapse at 8 weeks with terbinafine. Both drugs had similar safety profile. Although both the drugs cured the disease, eberconazole showed better response as clinical cure and mycological cure were observed earlier and no patient relapsed in the follow-up.

  18. Durability, safety, and efficacy of rilpivirine in clinical practice: results from the SCOLTA Project

    PubMed Central

    Bagella, Paola; De Socio, Giuseppe VL; Ricci, Elena; Menzaghi, Barbara; Martinelli, Canio; Squillace, Nicola; Maggi, Paolo; Orofino, Giancarlo; Calza, Leonardo; Carenzi, Laura; Celesia, Benedetto Maurizio; Penco, Giovanni; Di Biagio, Antonio; Valsecchi, Laura; Vichi, Francesca; Colombo, Valeria; Parruti, Giustino; Dentone, Chiara; Falasca, Katia; Bonfanti, Paolo; Madeddu, Giordano

    2018-01-01

    Rilpivirine is associated with a good efficacy and safety profile. However, data from real-life settings are scarce. Methods We investigated the durability, safety and efficacy of Rilpivirine-based antiretroviral therapy in a prospective, observational, multicenter study. Results We enrolled 499 HIV-infected patients, 360 (72.1%) males, mean age 43.4 ± 10.5 years, mean CD4 600 ± 327 cell/μL, mean HIV-RNA 3.80 ± 1.15 log10 cp/mL. After a median follow up of 16 months, 81 (16.2%) interruptions were reported, 36 (7.2%) of which for adverse events (16 of grade ≥3), most commonly neurological and gastrointestinal. We observed virological failures in only 8 (1.6%) patients. Naive patients showed a significant reduction in eGFR at week 24, 48 and 72 and in total cholesterol (TC)/HDL ratio at week 48 (p=0.007). In patients switching from PI we found a significant decrease at week 24 and 48 in TC and triglycerides at week 24, 48 and 72. eGFR showed a significant decrease at week 48 and 72. TC/HDL ratio showed a statistically significant decrease at week 24 (p=0.0008) and 72 (p=0.04). A significant increase at week 24 and 48 in AST and ALT values was observed. Patients switching from TDF/FTC/EFV showed a reduction in HDL, total cholesterol and triglycerides at week 24 and 48 and in eGFR at all follow up times. TC/HDL ratio showed a significant decrease at week 48 (p=0.01). CDC stage C and antiretroviral-experience (especially Protease Inhibitors) were associated with RPV discontinuation. Conclusion In conclusion, our data confirm Rilpivirine efficacy, safety and tolerability with improvement in lipid profile. Although hepatic and renal events rarely caused discontinuation, liver and kidney parameters should be monitored. PMID:29731650

  19. Efficacy and Safety of 5 Anesthetics in Adult Zebrafish (Danio rerio)

    PubMed Central

    Collymore, Chereen; Tolwani, Angela; Lieggi, Christine; Rasmussen, Skye

    2014-01-01

    Although the safety and efficacy of tricaine methanesulfonate (MS222) for anesthesia of fish are well established, other anesthetics used less commonly in fish have been less extensively evaluated. Therefore, we compared gradual cooling, lidocaine hydrochloride (300, 325, and 350 mg/L), metomidate hydrochloride (2, 4, 6, 8, and 10 mg/L), and isoflurane (0.5 mL/L) with MS222 (150 mg/L) for anesthesia of adult zebrafish. The efficacy and safety of each agent was evaluated by observing loss of equilibrium, slowing of opercular movement, response to tail-fin pinch, recovery time, and anesthesia-associated mortality rates. At 15 min after anesthetic recovery, we used a novel-tank test to evaluate whether anesthetic exposure influenced short-term anxiety-like behavior. Behavioral parameters measured included latency to enter and number of transitions to the upper half of the tank, number of erratic movements, and number of freezing bouts. Behavior after anesthesia was unaltered regardless of the anesthetic used. Efficacy and safety differed among the anesthetics evaluated. Gradual cooling was useful for short procedures requiring immobilization only, but all instrumentation and surfaces that come in contact with fish must be maintained at approximately 10 °C. MS222 and lidocaine hydrochloride at 325 mg/L were effective as anesthetic agents for surgical procedures in adult zebrafish, but isoflurane and high-dose lidocaine hydrochloride were unsuitable as sole anesthetic agents due to high (30%) mortality rates. Although MS222 remains the best choice for generating a surgical plane of anesthesia, metomidate hydrochloride and gradual cooling were useful for sedation and immobilization for nonpainful procedures. PMID:24602548

  20. Attention-deficit hyperactivity disorder medication use: factors involved in prescribing, safety aspects and outcomes.

    PubMed

    Martinez-Raga, Jose; Ferreros, Amparo; Knecht, Carlos; de Alvaro, Raquel; Carabal, Eloisa

    2017-03-01

    While treatment of patients with attention-deficit hyperactivity disorder (ADHD) is based on a multimodal approach that combines medication with specific psychological interventions, pharmacotherapy alone is generally considered an essential and cost-effective element. This paper aims to comprehensively and critically review factors involved in prescribing and medication use in individuals diagnosed with ADHD, focusing on the difficulties facing patients with ADHD seeking treatment, as well as the safety and tolerability aspects of ADHD pharmacotherapies, with particular attention on the cardiovascular adverse events and the potential risk of misuse or diversion of ADHD medications. A comprehensive and systematic literature search of PubMed/MEDLINE database was conducted to identify studies published in peer-reviewed journals until 1 August 2016. Children, adolescents and adults often encounter significant difficulties in the process of accessing specialist assessment and treatment for ADHD as a consequence of disparities in service organization and available treatment provision. Despite the well-established efficacy and overall safety profile, ADHD medications are not exempt from adverse events. The cardiovascular safety of pharmacotherapies used for treating individuals with ADHD has raised particular concerns; however there is little evidence of serious cardiovascular adverse events, including no serious corrected QT (QTc) abnormalities associated with stimulants, atomoxetine or α2-adrenergic receptor agonists. Although the abuse of prescription stimulant drugs, particularly, short-acting stimulants is a prevalent and growing problem, nonmedical use of prescription stimulants within the clinical context is very limited. In addition, nonstimulant ADHD medications lack any reinforcing effects and consequently any abuse potential.

  1. The role of safety behaviors in exposure-based treatment for panic disorder and agoraphobia: associations to symptom severity, treatment course, and outcome.

    PubMed

    Helbig-Lang, Sylvia; Richter, Jan; Lang, Thomas; Gerlach, Alexander L; Fehm, Lydia; Alpers, Georg W; Ströhle, Andreas; Kircher, Tilo; Deckert, Jürgen; Gloster, Andrew T; Wittchen, Hans-Ulrich

    2014-12-01

    The potentially detrimental effects of safety behaviors during exposure therapy are still subject to debate. Empirical findings are inconsistent, and few studies have investigated effects of idiosyncratic safety behavior manifestations during exposure or in everyday life. These limitations might be due to a lack of appropriate measures that address individual safety behaviors. We examined psychometric properties and predictive value of the Texas Safety Maneuver Scale (TSMS), a questionnaire specifically targeting safety behaviors in panic disorder and agoraphobia. Effects of safety behavior use, both during everyday life and during therapy, were examined using data from a multicenter RCT of N=268 patients that aimed at evaluating efficacy and mechanisms of action of two variants of an exposure-based therapy. The TSMS total score demonstrated good internal consistency (α=0.89), and it showed significant correlations with selected measures of baseline anxiety and impairment. The proposed factor structure could not be replicated. Frequent safety behavior use at baseline was associated with actual safety behavior during exposure exercises. Pronounced in-situ safety behavior, but not baseline safety behavior was associated to detrimental treatment outcome. The results underline the relevance of a rigorous safety behavior assessment in therapy. The actual relationship between safety behavior use and treatment outcome is yet to determine. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Safety and efficacy of tinea pedis and onychomycosis treatment in people with diabetes: a systematic review

    PubMed Central

    2011-01-01

    Background Effective treatment of tinea pedis and onychomycosis is crucial for patients with diabetes as these infections may lead to foot ulcers and secondary bacterial infections resulting in eventual lower limb amputation. Although numerous studies have assessed the effectiveness of antifungal drug and treatment regimens, most exclude patients with diabetes and examine otherwise healthy individuals. While these studies are useful, results cannot necessarily be extrapolated to patients with diabetes. The purpose of this study was to therefore identify the best evidence-based treatment interventions for tinea pedis or onychomycosis in people with diabetes. Methods The question for this systemic review was: 'what evidence is there for the safety and/or efficacy of all treatment interventions for adults with tinea pedis and/or onychomycosis in people with diabetes'? A systematic literature search of four electronic databases (Scopus, EbscoHost, Ovid, Web of Science) was undertaken (6/1/11). The primary outcome measure for safety was self-reported adverse events likely to be drug-related, while the primary outcome measures assessed for 'efficacy' were mycological, clinical and complete cure. Results The systematic review identified six studies that examined the safety and/or efficacy of treatment interventions for onychomycosis in people with diabetes. No studies were identified that examined treatment for tinea pedis. Of the studies identified, two were randomised controlled trials (RCTs) and four were case series. Based on the best available evidence identified, it can be suggested that oral terbinafine is as safe and effective as oral itraconazole therapy for the treatment of onychomycosis in people with diabetes. However, efficacy results were found to be poor. Conclusions This review indicates that there is good evidence (Level II) to suggest oral terbinafine is as safe and effective as itraconazole therapy for the treatment of onychomycosis in people with

  3. Efficacy of venlafaxine extended-release capsules in nondepressed outpatients with generalized anxiety disorder: A 6-month randomized controlled trial.

    PubMed

    Gelenberg, A J; Lydiard, R B; Rudolph, R L; Aguiar, L; Haskins, J T; Salinas, E

    2000-06-21

    Generalized anxiety disorder (GAD) is a chronic disorder that is associated with debilitating psychic and somatic symptoms. Venlafaxine extended-release (XR) capsules have been shown to be effective in short-term treatment of patients with GAD without major depressive disorder (MDD), but long-term data are needed to establish whether this agent confers persistent benefits. To compare the 6-month efficacy and safety of a flexible dosage of venlafaxine XR in outpatients with GAD without associated MDD. Six-month, randomized, double-blind, placebo-controlled, parallel-group trial conducted May 1996 to October 1997. Fourteen outpatient clinics and private psychiatric practices in the United States. A total of 251 outpatients aged 18 years or older who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for GAD, had sufficient symptoms to require treatment, and did not have coexisting MDD. Participants were randomly assigned to receive either placebo (n=127) or venlafaxine XR (75, 150, or 225 mg/d, as required to control symptoms; n=124) for 28 weeks. Changes from baseline in the Hamilton Rating Scale for Anxiety (HAM-A) total score, the HAM-A psychic anxiety factor score, and the Clinical Global Impressions (CGI) scale Severity of Illness and Global Improvement scores, compared by intervention group. During weeks 6 through 28, response rates in the venlafaxine XR group were 69% or higher compared with rates of 42% to 46% in the placebo group (P<.001). By an evaluable-patient analysis, venlafaxine XR compared with placebo significantly improved anxiety scores from week 1 or 2 through week 28 on all primary efficacy measures, including the HAM-A total (P<.001), the HAM-A psychic anxiety factor (P<.001), and the CGI scale scores (P<.001). Adjusted mean changes from baseline to week 28 using last-observation-carried-forward methods were for HAM-A, venlafaxine XR -13.4, placebo -8.7 (P<.001); for HAM-A psychic anxiety score

  4. Efficacy, safety, and patient preference of monoamine oxidase B inhibitors in the treatment of Parkinson's disease.

    PubMed

    Robottom, Bradley J

    2011-01-20

    Parkinson's disease (PD) is the second most common neurodegenerative disease and the most treatable. Treatment of PD is symptomatic and generally focuses on the replacement or augmentation of levodopa. A number of options are available for treatment, both in monotherapy of early PD and to treat complications of advanced PD. This review focuses on rasagiline and selegiline, two medications that belong to a class of antiparkinsonian drugs called monoamine oxidase B (MAO-B) inhibitors. Topics covered in the review include mechanism of action, efficacy in early and advanced PD, effects on disability, the controversy regarding disease modification, safety, and patient preference for MAO-B inhibitors.

  5. Resistance training among young athletes: safety, efficacy and injury prevention effects.

    PubMed

    Faigenbaum, A D; Myer, G D

    2010-01-01

    A literature review was employed to evaluate the current epidemiology of injury related to the safety and efficacy of youth resistance training. Several case study reports and retrospective questionnaires regarding resistance exercise and the competitive sports of weightlifting and powerlifting reveal that injuries have occurred in young lifters, although a majority can be classified as accidental. Lack of qualified instruction that underlies poor exercise technique and inappropriate training loads could explain, at least partly, some of the reported injuries. Current research indicates that resistance training can be a safe, effective and worthwhile activity for children and adolescents provided that qualified professionals supervise all training sessions and provide age-appropriate instruction on proper lifting procedures and safe training guidelines. Regular participation in a multifaceted resistance training programme that begins during the preseason and includes instruction on movement biomechanics may reduce the risk of sports-related injuries in young athletes. Strategies for enhancing the safety of youth resistance training are discussed.

  6. Oral medications regarding their safety and efficacy in the management of patent ductus arteriosus

    PubMed Central

    Oncel, Mehmet Yekta; Erdeve, Omer

    2016-01-01

    Patent ductus arteriosus (PDA) is a common clinical condition in preterm infants which is inversely related to birth weight and gestational age. Cyclooxygenase inhibitors such as indomethacin and ibuprofen which block the prostaglandin conversion from arachidonic acid are the most commonly used drugs for ductal closure. This review focuses on the safety and efficacy oral medications in the management of PDA in preterm infants. Ibuprofen seems to be the first choice due to its higher safety profile, as it is associated with fewer gastrointestinal and renal side effects when compared to indomethacin. PDA closure rates are better with oral than with intravenous ibuprofen probably due to the pharmacokinetic of the drug. However, these medications were reported to be associated with several adverse including transient renal failure, gastrointestinal bleeding and perforation, hyperbilirubinemia and platelet dysfunction. Paracetamol seems be an alternative to PDA therapy with lower adverse events and side effects. PMID:26862505

  7. Benzocaine as a fish anesthetic: efficacy and safety for spawning-phase salmon

    USGS Publications Warehouse

    Gilderhus, P.A.

    1990-01-01

    The anesthetic benzocaine was tested for efficacy and safety for spawning-phase chinook salmon (Oncorhynchus tshawytscha) and Atlantic salmon (Salmo salar) at federal fish hatcheries. Tests were conducted in the existing hatchery water supplies (soft water; temperatures, 10–13 °C. Crystalline benzocaine was dissolved in ethanol (1 g/30 mL), and aliquots of that stock solution were added to the water in test tanks. Benzocaine concentrations of 25–30 mg/L anesthetized most fish in less than 3.5 min, and most fish recovered in less than 10 min after 15 min of exposure. Safety margins were narrow; both species tolerated 30 mg/L for about 20 min, but 25 min of exposure caused deaths. For 15 min exposures, concentrations of 35 mg/L for chinook salmon and 40 mg/L for Atlantic salmon were lethal.

  8. Ragweed sublingual tablet immunotherapy: part I - evidence-based clinical efficacy and safety.

    PubMed

    Creticos, Peter Socrates; Pfaar, Oliver

    2018-06-01

    Sublingual tablet immunotherapy provides an attractive alternative approach to allergen immunotherapy, as the allergen is administered as a rapidly dissolving sublingual tablet. Part I of this two-part series on the ragweed sublingual tablet describes the dose-ranging clinical work, the safety studies and the clinical outcomes from the pivotal trials which provide clear evidence for statistically significant and clinically meaningful benefit in the treatment of patients suffering from ragweed-induced seasonal allergic rhinitis-conjunctivitis with or without milder asthma. The robust results observed in the clinical trials performed with the ragweed sublingual tablet are defined by the quality of their study design, their use of a standardized allergen extract, their consistent reproducibility in demonstrating therapeutic efficacy and their properly quantified and graded safety data.

  9. Efficacy and Safety of Pembrolizumab in Patients Enrolled in KEYNOTE-030 in the United States: An Expanded Access Program.

    PubMed

    Gangadhar, Tara C; Hwu, Wen-Jen; Postow, Michael A; Hamid, Omid; Daud, Adil; Dronca, Roxana; Joseph, Richard; O'Day, Steven J; Hodi, F S; Pavlick, Anna C; Kluger, Harriet; Oxborough, Romina P; Yang, Aiming; Gazdoiu, Mihaela; Kush, Debra A; Ebbinghaus, Scot; Salama, April K S

    KEYNOTE-030 (ClinicalTrials.gov ID, NCT02083484) was a global expanded access program that allowed access to pembrolizumab, an antiprogrammed death 1 antibody, for patients with advanced melanoma before its regulatory approval. Patients with unresectable stage III/IV melanoma that progressed after standard-of-care therapy, including ipilimumab and, if BRAF mutant, a BRAF inhibitor, were eligible to receive pembrolizumab 2 mg/kg every 3 weeks. Response was assessed by immune-related response criteria by investigator review. Adverse events (AEs) were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. In the United States, 979 patients enrolled between April and September 2014. Of the 947 evaluable patients, 621 (65.6%) remained on treatment and transitioned to receive commercial pembrolizumab following approval by the Food and Drug Administration, whereas 326 (34.4%) discontinued, most commonly for disease progression (39.6%) or death (26.4%). Objective response rate was 14.5% (95% confidence interval, 12.2%-16.8%) in the treated population (n=947) and 22.1% (95% confidence interval, 18.8%-25.5%) in patients who had ≥1 response assessment reported (n=619). Twelve patients achieved complete response. One hundred eighty-one (19.1%) patients experienced ≥1 treatment-related AE, most commonly general disorders (8.0%), skin/subcutaneous tissue disorders (7.3%), and gastrointestinal disorders (6.4%); 29 (3.1%) patients experienced ≥1 grade 3/4 treatment-related AE. Immune-mediated AEs were also reported. There were no treatment-related deaths. The safety and efficacy observed in this expanded access program were consistent with those previously reported for similar populations and support the use of pembrolizumab for patients with advanced melanoma.

  10. Long-term safety and efficacy of adalimumab for intestinal Behçet's disease in the open label study following a phase 3 clinical trial.

    PubMed

    Inoue, Nagamu; Kobayashi, Kiyonori; Naganuma, Makoto; Hirai, Fumihito; Ozawa, Morio; Arikan, Dilek; Huang, Bidan; Robinson, Anne M; Thakkar, Roopal B; Hibi, Toshifumi

    2017-07-01

    Intestinal Behçet's disease (BD) is an immune-mediated inflammatory disorder. We followed up the patients and evaluated safety profile and effectiveness of adalimumab for the treatment of intestinal BD through 100 weeks rolled over from the 52 week clinical trial (NCT01243671). Patients initiated adalimumab therapy at 160 mg at week 0, followed by 80 mg at week 2, followed by 40 mg every other week until the end of the study. Long-term safety and all adverse events (AEs) were examined. The efficacy was assessed on the basis of marked improvement (MI) and complete remission (CR) using a composite efficacy index, which combined global gastrointestinal symptoms and endoscopic assessments. Twenty patients were enrolled in this study; 15 patients received adalimumab treatment until study completion. The incidence of AEs through week 100 was 544.4 events/100 person-years, which was comparable to the incidence through week 52 (560.4 events/100 person-years). No unexpected trend was observed and adalimumab was well tolerated. At weeks 52 and 100, 60.0% and 40.0% of patients showed MI, respectively, and 20.0% and 15.0% of patients showed CR, respectively. This report demonstrates 2 years safety and effectiveness of adalimumab in intestinal BD patients. Patients with intestinal BD refractory to conventional treatment receiving up to 2 years of adalimumab treatment demonstrated safety outcomes consistent with the known profile of adalimumab, and the treatment led to sustained reduction of clinical and endoscopic disease activity.

  11. Relationship between internalized stigma and treatment efficacy in mixed neurotic spectrum and depressive disorders.

    PubMed

    Ociskova, Marie; Prasko, Jan; Kamaradova, Dana; Grambal, Ales; Latalova, Klara; Sigmundova, Zuzana

    2014-01-01

    Many psychiatric patients suffer from self-stigma. One consequence of these internalized prejudices is decreased treatment efficacy. Much has been written about the effects of self-stigma in patients with severe mental disorders. However, individuals with minor psychiatric disorders also suffer from self-stigma. It is therefore necessary to explore the effect of self-stigma on treatment efficacy of neurotic patients. Aim of out study was to investigate relationship between self-stigma, severity of symptoms, and presence of comorbidit disorder and treatment outcome in neurotic patients. Patients were treated by combined psycho and pharmacotherapy. Level of self-stigma was measured by Internalized Stigma Of Mental Illness scale. Severity of anxiety and depressive symptoms was assed by Beck Anxiety Inventory, Beck Depressive Inventory and Clinical Global Impression Scale. Level of self-stigma was significantly correlated with the levels of anxiety, depression and global evalutions of a mental state on the beginnig of the therapy. Up to our results patients with higher level of self-stigmatization had lower improvement after combined treatmet in respect to perceived anxiety symptoms. Self-stigma seems to be an important factor influencing efficacy of combined treatment. More researches focused on self-stigmatization should be done to find an optimal therapeutic strategy for patients with higher level of self-stigmatization.

  12. Efficacy and safety of lacosamide in infants and young children with refractory focal epilepsy.

    PubMed

    Grosso, Salvatore; Parisi, Pasquale; Spalice, Alberto; Verrotti, Alberto; Balestri, Paolo

    2014-01-01

    Lacosamide is effective and well-tolerated antiepileptic drug (AED) in both children and adults. This multicentric, prospective study investigates the efficacy and safety of lacosamide adjunctive therapy in children aged less than four years presenting with refractory focal seizures. Lacosamide was added to the baseline therapy at a starting dose of 1-2 mg/kg/day and titrated to the final dose, ranging from 7 to 15.5 mg/kg/day. Efficacy was evaluated after a three-month period of therapy. When possible, we compared the initial efficacy and the retention after a minimum of 12 months of lacosamide, with regard to loss of efficacy (defined as the return to the baseline seizure frequency). Twenty-four children were enrolled in the study. Mean age was 2.7 years. After a minimum three-month period of lacosamide add-on therapy, ten (42%) patients were responders (more than a 50% decrease in seizure frequency), of whom 4 (17%) became seizure free. Retention rate, after a minimum of 12 months of lacosamide, was evaluated in a group of 18 patients. In the latter group, eight patients (44%) were initial responders (three of whom seizure free). After 12 months of follow-up, four of them (22%) maintained the improvement, 2 (11%) of whom remained seizure free. A loss of efficacy was observed in 4 of the initial responders (50%). Adverse events were seen in 8 (33%) patients. We conclude that lacosamide is an effective and a well-tolerated antiepileptic drug in an etiologically wide range of focal seizures. Therefore, lacosamide might represent a possible therapeutic option in infants and young children affected by uncontrolled focal epilepsy. Copyright © 2013 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  13. Electronic nicotine delivery systems ("e-cigarettes"): review of safety and smoking cessation efficacy.

    PubMed

    Harrell, Paul Truman; Simmons, Vani Nath; Correa, John Bernard; Padhya, Tapan Ashvin; Brandon, Thomas Henry

    2014-09-01

    Cigarette smoking is common among cancer patients and is associated with negative outcomes. Electronic nicotine delivery systems ("e-cigarettes") are rapidly growing in popularity and use, but there is limited information on their safety or effectiveness in helping individuals quit smoking. The authors searched PubMed, Web of Science, and additional sources for published empirical data on safety and use of electronic cigarettes as an aid to quit smoking. We conducted a structured search of the current literature up to and including November 2013. E-cigarettes currently vary widely in their contents and are sometimes inconsistent with labeling. Compared to tobacco cigarettes, available evidence suggests that e-cigarettes are often substantially lower in toxic content, cytotoxicity, associated adverse effects, and secondhand toxicity exposure. Data on the use of e-cigarettes for quitting smoking are suggestive but ultimately inconclusive. Clinicians are advised to be aware that the use of e-cigarettes, especially among cigarette smokers, is growing rapidly. These devices are unregulated, of unknown safety, and of uncertain benefit in quitting smoking. In the absence of further data or regulation, oncologists are advised to discuss the known and unknown safety and efficacy information on e-cigarettes with interested patients and to encourage patients to first try FDA-approved pharmacotherapies for smoking cessation. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.

  14. Electronic Nicotine Delivery Systems (“E-Cigarettes”): Review of Safety and Smoking Cessation Efficacy

    PubMed Central

    Harrell, Paul Truman; Simmons, Vani Nath; Correa, John Bernard; Padhya, Tapan Ashvin; Brandon, Thomas Henry

    2015-01-01

    Background and Objectives Cigarette smoking is common among cancer patients and is associated with negative outcomes. Electronic nicotine delivery systems (“e-cigarettes”) are rapidly growing in popularity and use, but there is limited information on their safety or effectiveness in helping individuals quit smoking. Data Sources The authors searched PubMed, Web of Science, and additional sources for published empirical data on safety and use of electronic cigarettes as an aid to quit smoking. Review Methods We conducted a structured search of the current literature up to and including November 2013. Results E-cigarettes currently vary widely in their contents and are sometimes inconsistent with labeling. Compared to tobacco cigarettes, available evidence suggests that e-cigarettes are often substantially lower in toxic content, cytotoxicity, associated adverse effects, and secondhand toxicity exposure. Data on the use of e-cigarettes for quitting smoking is suggestive, but ultimately inconclusive. Conclusions Clinicians are advised to be aware that the use of e-cigarettes, especially among cigarette smokers, is growing rapidly. These devices are unregulated, of unknown safety, and of uncertain benefit in quitting smoking. Implications for Practice In the absence of further data or regulation, oncologists are advised to discuss the known and unknown safety and efficacy information on e-cigarettes with interested patients, and to encourage patients to first try FDA-approved pharmacotherapies for smoking cessation. PMID:24898072

  15. Evidence report : musculoskeletal disorders II, and commercial motor vehicle driver safety.

    DOT National Transportation Integrated Search

    2009-05-29

    The purpose of this evidence report is to address several key questions posed by the Federal Motor Carrier Safety Administration (FMSCA). 1. Do musculoskeletal disorders of the hand, wrist, elbow, or shoulder ... increase crash risk and/or affect dri...

  16. A study on the safety and efficacy of reveglucosidase alfa in patients with late-onset Pompe disease.

    PubMed

    Byrne, Barry J; Geberhiwot, Tarekegn; Barshop, Bruce A; Barohn, Richard; Hughes, Derralynn; Bratkovic, Drago; Desnuelle, Claude; Laforet, Pascal; Mengel, Eugen; Roberts, Mark; Haroldsen, Peter; Reilley, Kristin; Jayaram, Kala; Yang, Ke; Walsh, Liron

    2017-08-24

    Late-onset Pompe disease is a rare genetic neuromuscular disorder caused by lysosomal acid alpha-glucosidase (GAA) deficiency that ultimately results in mobility loss and respiratory failure. Current enzyme replacement therapy with recombinant human (rh)GAA has demonstrated efficacy in subjects with late-onset Pompe disease. However, long-term effects of rhGAA on pulmonary function have not been observed, likely related to inefficient delivery of rhGAA to skeletal muscle lysosomes and associated deficits in the central nervous system. To address this limitation, reveglucosidase alfa, a novel insulin-like growth factor 2 (IGF2)-tagged GAA analogue with improved lysosomal uptake, was developed. This study evaluated the pharmacokinetics, safety, and exploratory efficacy of reveglucosidase alfa in 22 subjects with late-onset Pompe disease who were previously untreated with rhGAA. Reveglucosidase alfa plasma concentrations increased linearly with dose, and the elimination half-life was <1.2 h. Eighteen of 22 subjects completed 72 weeks of treatment. The most common adverse events were hypoglycemia (63%), dizziness, fall, headache, and nausea (55% for each). Serious adverse events included hypersensitivity (n = 1), symptomatic hypoglycemia (n = 2), presyncope (n = 1), and acute cardiac failure (n = 1). In the dose-escalation study, all treated subjects tested positive for anti-reveglucosidase alfa, anti-rhGAA, anti-IGF1, and anti-IGF2 antibodies at least once. Subjects receiving 20 mg/kg of reveglucosidase alfa demonstrated increases in predicted maximum inspiratory pressure (13.9%), predicted maximum expiratory pressure (8.0%), forced vital capacity (-0.4%), maximum voluntary ventilation (7.4 L/min), and mean absolute walking distance (22.3 m on the 6-min walk test) at 72 weeks. Additional studies are needed to further assess the safety and efficacy of this approach. Improvements in respiratory muscle strength, lung function, and walking endurance

  17. Silodosin for the treatment of clinical benign prostatic hyperplasia: safety, efficacy, and patient acceptability.

    PubMed

    Cho, Hee Ju; Yoo, Tag Keun

    2014-01-01

    α1-Adrenergic receptor antagonists are commonly used to treat male lower urinary tract symptoms and benign prostatic hyperplasia (BPH). We performed a literature search using PubMed, Medline via Ovid, Embase, and the Cochrane Library databases to identify studies on the treatment of BPH by silodosin. Silodosin is a novel α1-adrenergic receptor antagonist whose affinity for the α1A-adrenergic receptor is greater than that for the α1B-adrenergic receptor. Therefore, silodosin does not increase the incidence of blood pressure-related side effects, which may result from the inhibition of the α1B-adrenergic receptor. Patients receiving silodosin at a daily dose of 8 mg showed a significant improvement in the International Prostate Symptom Score and maximum urinary flow rate compared with those receiving a placebo. Silodosin also improved both storage and voiding symptoms, indicating that silodosin is effective, even during early phases of BPH treatment. Follow-up extension studies performed in the United States, Europe, and Asia demonstrated its long-term safety and efficacy. In the European study, silodosin significantly reduced nocturia compared to the placebo. Although retrograde or abnormal ejaculation was the most commonly reported symptom in these studies, only a few patients discontinued treatment. The incidence of adverse cardiovascular events was also very low. Evidence showing solid efficacy and cardiovascular safety profiles of silodosin will provide a good solution for the treatment of lower urinary tract symptoms associated with BPH in an increasingly aging society.

  18. Silodosin for the treatment of clinical benign prostatic hyperplasia: safety, efficacy, and patient acceptability

    PubMed Central

    Cho, Hee Ju; Yoo, Tag Keun

    2014-01-01

    α1-Adrenergic receptor antagonists are commonly used to treat male lower urinary tract symptoms and benign prostatic hyperplasia (BPH). We performed a literature search using PubMed, Medline via Ovid, Embase, and the Cochrane Library databases to identify studies on the treatment of BPH by silodosin. Silodosin is a novel α1-adrenergic receptor antagonist whose affinity for the α1A-adrenergic receptor is greater than that for the α1B-adrenergic receptor. Therefore, silodosin does not increase the incidence of blood pressure-related side effects, which may result from the inhibition of the α1B-adrenergic receptor. Patients receiving silodosin at a daily dose of 8 mg showed a significant improvement in the International Prostate Symptom Score and maximum urinary flow rate compared with those receiving a placebo. Silodosin also improved both storage and voiding symptoms, indicating that silodosin is effective, even during early phases of BPH treatment. Follow-up extension studies performed in the United States, Europe, and Asia demonstrated its long-term safety and efficacy. In the European study, silodosin significantly reduced nocturia compared to the placebo. Although retrograde or abnormal ejaculation was the most commonly reported symptom in these studies, only a few patients discontinued treatment. The incidence of adverse cardiovascular events was also very low. Evidence showing solid efficacy and cardiovascular safety profiles of silodosin will provide a good solution for the treatment of lower urinary tract symptoms associated with BPH in an increasingly aging society. PMID:25328864

  19. Safety and Efficacy of Uninterrupted Apixaban Therapy Versus Warfarin During Atrial Fibrillation Ablation.

    PubMed

    Shah, Ruchit R; Pillai, Ajay; Schafer, Pascha; Meggo, David; McElderry, Tom; Plumb, Vance; Yamada, Takumi; Kumar, Vineet; Doppalapudi, Harish; Gunter, Alicia; Pentecost, Emily; Maddox, William R

    2017-08-01

    Thromboembolic cerebrovascular accident remains a rare but potentially devastating complication of catheter-based atrial fibrillation (AF) ablation. Uninterrupted oral anticoagulant therapy with warfarin has become the standard of care when performing catheter-based AF ablation. Compared with warfarin, apixaban, a factor Xa inhibitor, has been shown to reduce the risk of stroke and major bleeding in nonvalvular AF. With an increase in apixaban use for stroke prophylaxis in patients with AF, there is an increased interest in the safety and efficacy of uninterrupted apixaban therapy during AF ablation. We compared the safety and efficacy of uninterrupted OA therapy with either warfarin or apixaban in all patients who underwent catheter-based AF ablation at the University of Alabama at Birmingham and at Augusta University Medical Center from January 7, 2013, to February 25, 2016. All patients underwent a transesophageal echocardiogram on the day of their ablation to assess for the presence of intracardiac thrombi. All complications were identified and classified as bleeding, thromboembolic events, or other. A total of 627 patients were analyzed as described earlier. There were 310 patients in the warfarin group and 317 patients in the apixaban group. There were 8 complications in the warfarin group and 5 complications in the apixaban group (p = 0.38). There were no thromboembolic complications in either group. In conclusion, the use of apixaban is as safe and effective as warfarin for uninterrupted OA therapy during catheter-based ablation of AF. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. The efficacy and safety of external cephalic version after a previous caesarean delivery.

    PubMed

    Weill, Yishay; Pollack, Raphael N

    2017-06-01

    External cephalic version (ECV) in the presence of a uterine scar is still considered a relative contraindication despite encouraging studies of the efficacy and safety of this procedure. We present our experience with this patient population, which is the largest cohort published to date. To evaluate the efficacy and safety of ECV in the setting of a prior caesarean delivery. A total of 158 patients with a fetus presenting as breech, who had an unscarred uterus, had an ECV performed. Similarly, 158 patients with a fetus presenting as breech, and who had undergone a prior caesarean delivery also underwent an ECV. Outcomes were compared. ECV was successfully performed in 136/158 (86.1%) patients in the control group. Of these patients, 6/136 (4.4%) delivered by caesarean delivery. In the study group, 117/158 (74.1%) patients had a successful ECV performed. Of these patients, 12/117 (10.3%) delivered by caesarean delivery. There were no significant complications in either of the groups. ECV may be successfully performed in patients with a previous caesarean delivery. It is associated with a high success rate, and is not associated with an increase in complications. © 2016 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  1. Safety and Efficacy of Rivastigmine in Adolescents with Down Syndrome: Long-Term Follow-Up

    PubMed Central

    Spiridigliozzi, Gail A.; Crissman, Blythe G.; McKillop, Jane Anne; Yamamoto, Haru; Kishnani, Priya S.

    2010-01-01

    Abstract Following the completion of a 20-week, open-label study of the safety and efficacy of liquid rivastigmine for adolescents with Down syndrome, 5 of the 10 adolescents in the clinical trial continued long-term rivastigmine therapy and 5 did not. After an average period of 38 months, all 10 subjects returned for a follow-up assessment to determine the safety and efficacy of long-term rivastigmine use. Rivastigmine was well tolerated and overall health appeared to be unaffected by long-term rivastigmine use. Performance change on cognitive and language measures administered at the termination of the open-label clinical trial was compared between the two groups. No between-group difference in median performance change across the long-term period was found, suggesting that the long-term use of rivastigmine does not improve cognitive and language performance. However, two subjects demonstrated remarkable improvement in adaptive function over the long-term period. Both subjects had received long-term rivastigmine therapy. The discussion addresses the challenge of assessing cognitive change in clinical trials using adolescents with Down syndrome as subjects and the use of group versus individual data to evaluate the relevance of medication effects. PMID:21186971

  2. Randomised multicentre trial on safety and efficacy of rivastigmine in cognitively impaired multiple sclerosis patients.

    PubMed

    Mäurer, M; Ortler, S; Baier, M; Meergans, M; Scherer, P; Hofmann, We; Tracik, F

    2013-04-01

    Cognitive decline has been recognised as a frequent symptom in multiple sclerosis (MS). Cholinesterase inhibitors (ChEIs) are employed for the treatment of Alzheimer's disease, but there is some evidence that ChEIs might also be effective in MS patients with cognitive deficits, particularly deficits of memory function. The aim of this study was to evaluate efficacy on memory function and safety of the ChEI rivastigmine in MS patients with cognitive deficits as measured by the change from baseline of the total recall score of the selective reminding test (SRT) after 16 weeks of treatment. Efficacy and safety of rivastigmine were analysed in a 16-week, multicentre, double-blind, randomised, placebo-controlled study, followed by an optional one-year open-label treatment phase. Effects of rivastigmine and placebo were compared by an analysis of covariance. In total, 86 patients were enrolled. Patients who received rivastigmine (n = 43) showed a non-significant increase in total recall score (sum of all words immediately recalled over all six trials) over placebo (n = 38) after 16 weeks of treatment (p = 0.2576). Other outcome measures provided no evidence supporting benefits of rivastigmine. Treatment with rivastigmine was well tolerated. With the results of this study, the need for an effective therapy in cognitively impaired MS patients is still required. Thus, intensive and continued clinical research is required to explore therapeutic options for cognitive deficits in MS patients.

  3. Efficacy and safety of topical Trikatu preparation in, relieving mosquito bite reactions: a randomized controlled trial.

    PubMed

    Maenthaisong, Ratree; Chaiyakunapruk, Nathorn; Tiyaboonchai, Waree; Tawatsin, Apiwat; Rojanawiwat, Archawin; Thavara, Usavadee

    2014-02-01

    Trikatu is composed of dried fruits of Piper nigrum L and Piper retrofractum Vahl, and dried rhizomes of Zingiber officinale R. Although this preparation has been used to relieve pruritis, pain, and inflammation for a long time, there is no clinical evidence to confirm its efficacy and safety. Therefore, we performed a double-blind, within person-randomized controlled study of 30 healthy volunteers to determine efficacy and safety of topical Trikatu on mosquito bite reactions. All subjects were bitten by Aedes aegypti laboratory mosquitoes on their forearms and they were randomly assigned arms to apply either Trikatu or reference product on the mosquito bite papule. The main outcome was the difference of papule size reduction at 30 min, measured by a caliper, between the Trikatu and reference arms. Pruritis, redness, pain, and patient satisfaction were assessed at 15, 30, 60, 180, and 360 min as secondary outcomes. There were no significant differences between treatment and reference arms on any outcome at any time of measurement. Trikatu did not show additional effects for relieving mosquito bite reaction as compared with the reference product containing camphor, menthol, and eucalyptus. For further study, it is very important to consider a proper selection of subjects, comparator product, and concentration of extract when Trikatu preparation is investigated. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4.  Efficacy and safety of ursodeoxycholic acid in patients with intrahepatic cholestasis of pregnancy.

    PubMed

    Parízek, Antonín; Simják, Patrik; Cerný, Andrej; Sestinová, Alena; Zdenková, Anna; Hill, Martin; Dusková, Michaela; Vlk, Radovan; Kokrdová, Zuzana; Koucký, Michal; Vítek, Libor

    2016-01-01

     Background and aims. Patients with intrahepatic cholestasis of pregnancy (ICP) benefit from ursodeoxycholic acid (UDCA) treatment. Since there is still certain reluctance to use UDCA in pregnant women, mainly due to warnings in the official SPC information in respective drug leaflets, our objective was to assess the efficacy and safety of UDCA during pregnancy. Our retrospective multicentric study was performed on 191 consecutive pregnant women with ICP treated with UDCA. Any maternal and/or fetal complications of the UDCA treatment were searched for; healthy pregnant women (n = 256) served as controls. The UDCA treatment improved liver disease status in the majority of the affected women (86.1%). This treatment was well tolerated, with only negligible skin reactions (0.5%) and mild diarrhea (4.7%). No complications attributable to UDCA treatment were detected during the fetal life, delivery, or the early neonatal period. We confirmed the good efficacy and safety of UDCA treatment in pregnancy for both mothers and fetuses/neonates.

  5. Efficacy, safety, and cost of pomalidomide in relapsed and refractory multiple myeloma.

    PubMed

    Gueneau, Pauline; Chretien, Marie-Lorraine; Cransac-Miet, Amelie; Aho, Ludwig Serge; Lafon, Ingrid; Favennec, Camille; Guy, Julien; Caillot, Denis; Boulin, Mathieu

    2018-05-01

    To investigate the efficacy, safety, and cost of a pomalidomide-dexamethasone regimen in patients with relapsed and refractory multiple myeloma (RRMM). All patients (n = 63) treated with pomalidomide-dexamethasone for RRMM in our university hospital between August 2013 and October 2015 were included. Pomalidomide was discontinued early due to progression (before the 4th cycle) in 17 (27%) patients. No case was discontinued for intolerance. The only independent factor that predicted early pomalidomide discontinuation was time from diagnosis to pomalidomide initiation <3 years. Overall response rate was 51% including complete response in 8%, very good partial response in 25%, and partial response in 19% patients. Thirteen (33%) patients showed stable disease. Median overall survival was 6.4 months in the 17 patients who discontinued pomalidomide early vs 26.8 months in the 14 patients with stable disease vs not achieved in the 32 responders (log-rank; P < 10 -3 ). The most common grade ≥3 adverse events were neutropenia (14%) and infections (25%). The incremental cost-effectiveness ratio of pomalidomide-dexamethasone compared with dexamethasone alone was estimated at €39 911 per life-year gained. The study demonstrated that pomalidomide-dexamethasone regimen has a long-term favorable safety-efficacy profile in RRMM patients. The survival benefit is substantial even in patients with stable disease. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Efficacy and safety of rituximab in pemphigus: experience of the German Registry of Autoimmune Diseases.

    PubMed

    Kasperkiewicz, Michael; Eming, Rüdiger; Behzad, Melika; Hunzelmann, Nicolas; Meurer, Michael; Schulze-Koops, Hendrik; von Wussow, Peter; Hertl, Michael; Zillikens, Detlef; Freivogel, Klaus; Dörner, Thomas; Schmidt, Enno

    2012-10-01

    Rituximab has been reported to be effective in various small case series of patients with severe and/or refractory pemphigus. However, no systematic evaluation is available to corroborate this observation. The aim of this study was to systematically determine efficacy and safety of rituximab in treatment-resistant pemphigus. Multicenter retrospective, observational study of 36 patients with severe pemphigus vulgaris (n = 33) and pemphigus foliaceus (n = 3) treated with rituximab before August 31(st) , 2008 and enrolled in a national observational registery between December 2008 and June 2009. Within a mean period of observation of 11 (1-37) months, 21 (58 %) pemphigus patients showed complete, 13 (36 %) partial, and 2 (6 %) no response to rituximab treatment. This correlates with a mean improvement of the visual analog scale for well-being of 34 (20-60) at baseline to 75 (40-95) at the last control visit. In 4 (11 %) patients, severe adverse events were recorded including 1 (3 %) serious infection. Data collected in this systematic registry indicate that rituximab is an effective and relatively safe adjuvant treatment option for refractory pemphigus. To further extend our knowledge on efficacy and safety of this drug, controlled prospective trials are required. © The Authors • Journal compilation © Blackwell Verlag GmbH, Berlin.

  7. The Influence of Safety, Efficacy, and Medical Condition Severity on Natural versus Synthetic Drug Preference.

    PubMed

    Meier, Brian P; Lappas, Courtney M

    2016-11-01

    Research indicates that there is a preference for natural v. synthetic products, but the influence of this preference on drug choice in the medical domain is largely unknown. We present 5 studies in which participants were asked to consider a hypothetical situation in which they had a medical issue requiring pharmacological therapy. Participants ( N = 1223) were asked to select a natural, plant-derived, or synthetic drug. In studies 1a and 1b, approximately 79% of participants selected the natural v. synthetic drug, even though the safety and efficacy of the drugs were identical. Furthermore, participants rated the natural drug as safer than the synthetic drug, and as that difference increased, the odds of choosing the natural over synthetic drug increased. In studies 2 and 3, approximately 20% of participants selected the natural drug even when they were informed that it was less safe (study 2) or less effective (study 3) than the synthetic drug. Finally, in study 4, approximately 65% of participants chose a natural over synthetic drug regardless of the severity of a specific medical condition (mild v. severe hypertension), and this choice was predicted by perceived safety and efficacy differences. Overall, these data indicate that there is a bias for natural over synthetic drugs. This bias could have implications for drug choice and usage. © The Author(s) 2015.

  8. Safety, efficacy and immunogenicity evaluation of the SAG2 oral rabies vaccine in Formosan ferret badgers.

    PubMed

    Hsu, Ai-Ping; Tseng, Chun-Hsien; Barrat, Jacques; Lee, Shu-Hwae; Shih, Yu-Hua; Wasniewski, Marine; Mähl, Philippe; Chang, Chia-Chia; Lin, Chun-Ta; Chen, Re-Shang; Tu, Wen-Jane; Cliquet, Florence; Tsai, Hsiang-Jung

    2017-01-01

    Since 2013, rabies cases have been reported among Formosan ferret badgers in Taiwan, and they have been shown to be the major reservoirs for Taiwanese enzootics. To control and eradicate rabies, the authorities plan to implement a vaccination programme. Before distributing live vaccines in the field, this study assessed the safety, efficacy, and immunogenicity of SAG2 vaccine on ferret badgers by direct oral instillation. After application of 109 TCID50/dose, no virus was excreted into the oral cavity 1-7 days post-application, and safety was also satisfactorily verified over a 266-day period. Moreover, despite the low level of rabies virus neutralising antibodies induced after vaccination of a 108 TCID50/dose, the efficacy assessment revealed a 100% survival rate (15/15) of vaccinees and an 87.5% fatality rate (7/8) in control animals after a challenge on the 198th day post-vaccination. The immunisation and protection rates obtained more than 6 months after a single vaccination dose demonstrated that SAG2 is an ideal vaccine candidate to protect Formosan ferret badgers against rabies in Taiwan.

  9. Safety, efficacy and immunogenicity evaluation of the SAG2 oral rabies vaccine in Formosan ferret badgers

    PubMed Central

    Hsu, Ai-Ping; Tseng, Chun-Hsien; Barrat, Jacques; Lee, Shu-Hwae; Shih, Yu-Hua; Wasniewski, Marine; Mähl, Philippe; Chang, Chia-Chia; Lin, Chun-Ta; Chen, Re-Shang; Tu, Wen-Jane; Cliquet, Florence

    2017-01-01

    Since 2013, rabies cases have been reported among Formosan ferret badgers in Taiwan, and they have been shown to be the major reservoirs for Taiwanese enzootics. To control and eradicate rabies, the authorities plan to implement a vaccination programme. Before distributing live vaccines in the field, this study assessed the safety, efficacy, and immunogenicity of SAG2 vaccine on ferret badgers by direct oral instillation. After application of 109 TCID50/dose, no virus was excreted into the oral cavity 1–7 days post-application, and safety was also satisfactorily verified over a 266-day period. Moreover, despite the low level of rabies virus neutralising antibodies induced after vaccination of a 108 TCID50/dose, the efficacy assessment revealed a 100% survival rate (15/15) of vaccinees and an 87.5% fatality rate (7/8) in control animals after a challenge on the 198th day post-vaccination. The immunisation and protection rates obtained more than 6 months after a single vaccination dose demonstrated that SAG2 is an ideal vaccine candidate to protect Formosan ferret badgers against rabies in Taiwan. PMID:28977009

  10. Efficacy and safety of a modified vaccinia Ankara (MVA) vectored plague vaccine in mice

    PubMed Central

    Brewoo, Joseph N.; Powell, Tim D.; Stinchcomb, Dan T.; Osorio, Jorge E.

    2010-01-01

    The efficacy and safety of plague vaccines based on the modified vaccinia Ankara (MVA) viral vector was evaluated. MVA recombinants were constructed expressing Yersinia pestis antigens under the translational control of the encephalomyocarditis virus (EMCV) internal ribosomal entry site (IRES) and/or fused to the tissue plasminogen activator (tPA) secretory signal. A MVA/Y. pestis recombinant that expressed a truncated version of the low-calcium response V antigen (MVA/IRES/tPA/V307), conferred significant protection (87.5%–100%) against intranasal or intraperitoneal challenge with CO92 (encapsulated) or Java 9 (non-encapsulated) strains of Y pestis, respectively. In contrast, a MVA/Y. pestis recombinant that expressed the full-length V antigen provided only 37.5% protection against challenge with CO92 or Java 9 strains, respectively. Interestingly, a MVA/Y. pestis recombinant that expressed the capsular protein (F1) did not elicit significant antibody titers but still conferred 50% and 25% protection against CO92 or Java 9 challenge, respectively. The MVA/Y. pestis recombinant viruses did not demonstrate any mortality or morbidity in SCID mice. Based on their safety and efficacy in mice, these MVA/Y. pestis recombinants are candidates for further development as biodefense and public health vaccines. PMID:20638759

  11. Efficacy and Safety of Gabapentin in the Treatment of Chronic Cough: A Systematic Review.

    PubMed

    Shi, Guanglin; Shen, Qin; Zhang, Caixin; Ma, Jun; Mohammed, Anaz; Zhao, Huan

    2018-06-19

    Despite recent clinical guidelines, the optimal therapeutic strategy for the management of refractory chronic cough is still a challenge. The present systematic review was designed to assess the evidence for efficacy and safety of gabapentin in the treatment of chronic cough. A systematic search of PubMed, Embase, Cochrane Library databases, and publications cited in bibliographies was performed. Articles were searched by two reviewers with a priori criteria for study selection. Seven relevant articles were identified, including two randomized controlled trials, one prospective case-series designed with consecutive patients, one retrospective case series of consecutive patients, one retrospective case series with unknown consecutive status, and two case reports comprising six and two patients, respectively. Improvements were detected in cough-specific quality of life (Leicester Cough Questionnaire score) and cough severity (visual analogue scale score) following gabapentin treatment in randomized controlled trials. The results of prospective case-series showed that the rate of overall improvement of cough and sensory neuropathy with gabapentin was 68%. Gabapentin treatment of patients with chronic cough showed superior efficacy and a good safety record compared with placebo or standard medications. Additional randomized and controlled trials are needed. Copyright©2018. The Korean Academy of Tuberculosis and Respiratory Diseases.

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

    PubMed

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

    2017-03-01

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

  13. Managing blood pressure control in Asian patients: safety and efficacy of losartan.

    PubMed

    Cheung, Tommy Tsang; Cheung, Bernard Man Yung

    2014-01-01

    Hypertension is common in Asian populations and is a major cause of cardiovascular diseases. The prevalence of hypertension is increasing in many Asian countries. The overall prevalence of hypertension in India and the People's Republic of China has been estimated to be 20.6% in men and 22.6% in women. However, the rates of detection, treatment, and control of hypertension remain low in Asia. This reflects a low level of literacy and education, as well as a low level of access to medical care. To overcome these obstacles, strategies targeted at education, promotion, and optimization of medical care, are crucial to achieve target blood pressure control. Angiotensin receptor blockers are one of the first-line treatments for essential hypertension because they confer better cardiovascular outcomes. Losartan has been widely evaluated for the management of hypertension. Although some studies suggested that the blood pressure-lowering effect of losartan is perhaps lower than for other angiotensin receptor blockers, losartan has been demonstrated to be beneficial in terms of renal protection in patients with diabetes, heart failure resulting from either systolic or diastolic dysfunction, and diuretic-induced hyperuricemia. However, most of these data were obtained from Caucasian populations. The efficacy and safety of losartan in Asian populations may be different because of genetic and ethnic variations. Therefore, the efficacy and safety of losartan in Asian patients with hypertension warrant further study.

  14. Efficacy and safety of miconazole for oral candidiasis: a systematic review and meta-analysis.

    PubMed

    Zhang, L-W; Fu, J-Y; Hua, H; Yan, Z-M

    2016-04-01

    The objective of this study is to assess the efficacy and safety of miconazole for treating oral candidiasis. Twelve electronic databases were searched for randomized controlled trials evaluating treatments for oral candidiasis and complemented by hand searching. The clinical and mycological outcomes, as well as adverse effects, were set as the primary outcome criteria. Seventeen trials were included in this review. Most studies were considered to have a high or moderate level of bias. Miconazole was more effective than nystatin for thrush. For HIV-infected patients, there was no significant difference in the efficacy between miconazole and other antifungals. For denture wearers, microwave therapy was significantly better than miconazole. No significant difference was found in the safety evaluation between miconazole and other treatments. The relapse rate of miconazole oral gel may be lower than that of other formulations. This systematic review and meta-analysis indicated that miconazole may be an optional choice for thrush. Microwave therapy could be an effective adjunct treatment for denture stomatitis. Miconazole oral gel may be more effective than other formulations with regard to long-term results. However, future studies that are adequately powered, large-scale, and well-designed are needed to provide higher-quality evidence for the management of oral candidiasis. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Preclinical efficacy and safety of herbal formulation for management of wounds.

    PubMed

    Ogwang, P E; Nyafuono, J; Agwaya, Moses; Omujal, F; Tumusiime, H R; Kyakulaga, A H

    2011-09-01

    Medicinal plants in Uganda and other developing countries have been scientifically demonstrated to have medicinal benefits but few or none have been translated to products for clinical use. Most herbal products developed by local herbalists and sold to the public are not standardized and lack efficacy and safety data to support use. To formulate from two Ugandan medicinal plants a herbal product for wound management and test its preclinical safety and efficacy using rat models. Thirty (30) Wistar albino rats were randomly divided into three groups and wounds were surgically created on the mid-dorsal region. The wounds were treated topically with distilled water (group I), Jena(®) (group II)and Neomycin sulfate cream (group III). The effects of the treatments on rate of wound closure, epithelialisation time and histological organization of tissue were assessed. The herbal formulation (Jena) had a significantly higher rate of wound closure than neomycin (p<0.05) which itself was better than distilled water. Epithelialisation time was also significantly shorter for the herbal product (p<0.01). Histological picture revealed more collagen fibers, less inflammation and better tissue remodeling for rats treated with herbal product. The herbal formulation Jena(®) systematically designed and formulated based on two Ugandan medicinal plants is according to this study better than neomycin and probably other imported products for wound management in Uganda. We recommend its trial in a clinical setting as an alternative in wound management.

  16. Efficacy and safety of acupuncture for chronic dizziness: study protocol for a randomized controlled trial

    PubMed Central

    2013-01-01

    Background Dizziness is one of the most challenging symptoms in medicine. No medication for dizziness in current use has well-established curative or prophylactic value or is suitable for long-term palliative use. Unconventional remedies, such as acupuncture, should be considered and scientifically evaluated. However, there has been relatively little evidence in randomized controlled clinical trials on acupuncture to treat chronic dizziness. The aim of our study is to evaluate the efficacy and safety of acupuncture in patients with dizziness. Methods/Design This trial is a randomized, single-blind, controlled study. A total of 80 participants will be randomly assigned to two treatment groups receiving acupuncture and sham acupuncture treatment, respectively, for 4 weeks. The primary outcome measures are the Dizziness Handicap Inventory (DHI) and the Vertigo Symptom Scale (VSS). Treatment will be conducted over a period of 4 weeks, at a frequency of two sessions per week. The assessment is at baseline (before treatment initiation), 4 weeks after the first acupuncture session, and 8 weeks after the first acupuncture session. Discussion The results from this study will provide clinical evidence on the efficacy and safety of acupuncture in patients with chronic dizziness. Trial registration International Standard Randomized Controlled Trial Number Register: ISRCTN52695239 PMID:24330810

  17. Safety and Efficacy of Topical Lime Sulfur in Mice Infested with Myocoptes musculinus

    PubMed Central

    Wood, Jennifer S; Courtney, Cynthia L; Lieber, Karen A; Lee, Vanessa K

    2013-01-01

    Current treatment options for murine fur mites have limitations in safety and efficacy. This study evaluated whether topical lime sulfur (LS) is an adjunct or alternative to traditional treatment options for Myocoptes musculinus. To evaluate the safety of topical LS, mice were dipped in a 3% LS solution at 34 and 41 d of age. Mice were observed daily for side effects and mortality, with blood work and necropsy at 42 d of age to evaluate for pathologic changes. To determine the efficacy of topical LS, postweanling mice infested with M. musculinus were treated with LS once weekly for 2 wk and then housed with uninfested sentinel mice for 4 wk. Weekly tape tests and postmortem tape tests and skin scrapings were performed on all mice. Treated postweanling mice had significantly lower Hgb levels and higher BUN levels than did control animals. In mite-infested mice, the number of positive cages at euthanasia was the same between treated and control animals. Although topical LS did not cause gross or microscopic changes to organ systems, it may cause clinicopathologic changes, and topical LS is not effective as a sole treatment for M. musculinus infestation of postweanling mice. PMID:23849408

  18. Efficacy and safety of local steroids for urethra strictures: a systematic review and meta-analysis.

    PubMed

    Zhang, Kaile; Qi, Er; Zhang, Yumeng; Sa, Yinglong; Fu, Qiang

    2014-08-01

    Local steroids have been used as an adjuvant therapy to patients undergoing internal urethrotomy (IU) in treating urethral strictures. Whether this technique is effective and safe is still controversial. The aim of this study is to determine the efficacy and safety of local steroids as applied with the IU procedure. A systematic review of the literature was performed by searching Medline, Embase, Cochrane Library Databases, and the Web of Science. We included only prospective randomized, controlled trials that compared the efficacy and safety between IU procedures with applied local steroids and those without. Eight studies were found eligible for further analysis. In total, 203 patients undergoing IU were treated with steroid injection or catheter lubrication. Time to recurrence is statistically significant (mean: 10.14 and 5.07 months, P<0.00001).The number of patients with recurrent stricture formation significantly decreased at different follow-up time points (P=0.05).No statistically significant differences were found between the recurrence rates, adverse effects, and success rates of second IUs in patients with applied local steroids and those without. The use of local steroids with IU seems to prolong time to stricture recurrence but does not seem to affect the high stricture recurrence rate following IU. When local steroids are applied with complementary intention, the disease control outcomes are encouraging. Further robust comparative effectiveness studies are now required.

  19. Managing blood pressure control in Asian patients: safety and efficacy of losartan

    PubMed Central

    Cheung, Tommy Tsang; Cheung, Bernard Man Yung

    2014-01-01

    Hypertension is common in Asian populations and is a major cause of cardiovascular diseases. The prevalence of hypertension is increasing in many Asian countries. The overall prevalence of hypertension in India and the People’s Republic of China has been estimated to be 20.6% in men and 22.6% in women. However, the rates of detection, treatment, and control of hypertension remain low in Asia. This reflects a low level of literacy and education, as well as a low level of access to medical care. To overcome these obstacles, strategies targeted at education, promotion, and optimization of medical care, are crucial to achieve target blood pressure control. Angiotensin receptor blockers are one of the first-line treatments for essential hypertension because they confer better cardiovascular outcomes. Losartan has been widely evaluated for the management of hypertension. Although some studies suggested that the blood pressure-lowering effect of losartan is perhaps lower than for other angiotensin receptor blockers, losartan has been demonstrated to be beneficial in terms of renal protection in patients with diabetes, heart failure resulting from either systolic or diastolic dysfunction, and diuretic-induced hyperuricemia. However, most of these data were obtained from Caucasian populations. The efficacy and safety of losartan in Asian populations may be different because of genetic and ethnic variations. Therefore, the efficacy and safety of losartan in Asian patients with hypertension warrant further study. PMID:24672231

  20. Review of clinical trials evaluating safety and efficacy of milk thistle (Silybum marianum [L.] Gaertn.).

    PubMed

    Tamayo, Carmen; Diamond, Suzanne

    2007-06-01

    Milk thistle extracts have been used as traditional herbal remedies for almost 2000 years. The extracts are still widely used to protect the liver against toxins and to control chronic liver diseases. Recent experimental and clinical studies suggest that milk thistle extracts also have anticancer, antidiabetic, and cardioprotective effects. This article reviews clinical trials of milk thistle conducted in the past 5 years including pharmacokinetic and toxicity studies, herb-drug interactions, and other safety issues. Several trials have studied the effects of milk thistle for patients with liver diseases, cancer, hepatitis C, HIV, diabetes, and hypercholesterolemia. Promising results have been reported in the protective effect of milk thistle in certain types of cancer, and ongoing trials will provide more evidence about this effect. In addition, new established doses and improvement on the quality and standardization of this herb will provide the much-awaited evidence about the efficacy of milk thistle in the treatment of liver diseases. Milk thistle extracts are known to be safe and well tolerated, and toxic or adverse effects observed in the reviewed clinical trials seem to be minimal. The future of milk thistle research is promising, and high-quality randomized clinical trials on milk thistle versus placebo may be needed to further demonstrate the safety and efficacy of this herb.

  1. Safety and efficacy of intravenous labetalol for hypertensive crisis in infants and small children.

    PubMed

    Thomas, Christopher A; Moffett, Brady S; Wagner, Jeffrey L; Mott, Antonio R; Feig, Daniel I

    2011-01-01

    To determine the efficacy and safety of labetalol for hypertensive crisis in children ≤ 24 months of age. Retrospective chart review. Statistical analysis utilized analysis of variance for continuous data, chi-square tests for nominal data, and linear regression. A 737-bed pediatric teaching institution. Twenty-seven patients ≤ 24 months of age were treated with 37 intravenous infusions of labetalol, nicardipine, or nitroprusside for hypertensive crisis or hypertensive urgency. None. The primary end point consisted of time to 20% reduction in systolic blood pressure. Primary safety end points measured the prevalence of deleterious effects of labetalol. Continuous infusion of labetalol reduced mean systolic blood pressure by at least 20% in < 8 hrs. This effect was similar to nicardipine and nitroprusside infusions. The reported side effects were similar in each group. Patients receiving labetalol and presenting with ischemic or traumatic brain injury were likely to develop hypotension requiring infusion discontinuation. Continuous intravenous labetalol infusion is efficacious for treatment of hypertensive crisis in children ≤ 24 months of age. Aside from patients presenting with ischemic or traumatic brain injury, labetalol was safe to use in this population for hypertensive emergencies and had a satisfactory adverse effect profile. Labetalol may reach dose saturation at a much lower dose in young children in comparison to adults. Clinicians should use caution when initiating labetalol infusions in young patients with brain injury.

  2. Efficacy, safety and risk of augmentation of rotigotine for treating restless legs syndrome.

    PubMed

    Inoue, Yuichi; Hirata, Koichi; Hayashida, Kenichi; Hattori, Nobutaka; Tomida, Takayuki; Garcia-Borreguero, Diego

    2013-01-10

    The present study aimed to examine the long-term efficacy and safety of rotigotine treatment for restless legs syndrome (RLS), as well as the rate of clinically significant augmentation, in a 1-year open-label study of Japanese subjects. Japanese patients with RLS who had been treated with rotigotine or placebo in a double-blind trial were enrolled in a 1-year, open-label, uncontrolled extension study and treated with rotigotine at a dose of up to 3 mg/24 h after an 8-week titration phase. Outcomes included International Restless Legs Syndrome Study Group rating scale (IRLS scale), Pittsburgh Sleep Quality Index (PSQI), safety, and investigator-/expert panel-assessed augmentation (including Augmentation Severity Rating Scale). Overall, 185 patients entered the open-label study and 133 completed the study. IRLS and PSQI total scores improved throughout the 52-week treatment period (IRLS, from 23.2±5.1 to 7.8±7.6 and PSQI, from 8.0±3.1 to 5.0±2.9). Treatment-emergent adverse events were mild to moderate in severity, and included application site reactions (52.4%) and nausea (28.6%). Clinically significant augmentation occurred in five patients (2.7%). These results indicate a good long-term efficacy of rotigotine for treating RLS, with a relatively low risk of clinically significant augmentation. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Safety and efficacy of extracorporeal shock wave myocardial revascularization therapy for refractory angina pectoris.

    PubMed

    Cassar, Andrew; Prasad, Megha; Rodriguez-Porcel, Martin; Reeder, Guy S; Karia, Darshak; DeMaria, Anthony N; Lerman, Amir

    2014-03-01

    To assess the safety and efficacy of extracorporeal shockwave myocardial revascularization (ESMR) therapy in treating patients with refractory angina pectoris. A single-arm multicenter prospective trial to assess safety and efficacy of the ESMR therapy in patients with refractory angina (class III/IV angina) was performed. Screening exercise treadmill tests and pharmacological single-photon emission computed tomography (SPECT) were performed for all patients to assess exercise capacity and ischemic burden. Patients were treated with 9 sessions of ESMR to ischemic areas over 9 weeks. Efficacy end points were exercise capacity by using treadmill test as well as ischemic burden on pharmacological SPECT at 4 months after the last ESMR treatment. Safety measures included electrocardiography, echocardiography, troponin, creatine kinase, and brain natriuretic peptide testing, and pain questionnaires. Fifteen patients with medically refractory angina and no revascularization options were enrolled. There was a statistically significant mean increase of 122.3±156.9 seconds (38% increase compared with baseline; P=.01) in exercise treadmill time from baseline (319.8±157.2 seconds) to last follow-up after the ESMR treatment (422.1±183.3 seconds). There was no improvement in the summed stress perfusion scores after pharmacologically induced stress SPECT at 4 months after the last ESMR treatment in comparison to that at screening; however, SPECT summed stress score revealed that untreated areas had greater progression in ischemic burden vs treated areas (3.69±6.2 vs 0.31±4.5; P=.03). There was no significant change in the mean summed echo score from baseline to posttreatment (0.4±5.1; P=.70). The ESMR therapy was performed safely without any adverse events in electrocardiography, echocardiography, troponins, creatine kinase, or brain natriuretic peptide. Pain during the ESMR treatment was minimal (a score of 0.5±1.2 to 1.1±1.2 out of 10). In this multicenter feasibility

  4. Telotristat ethyl in carcinoid syndrome: safety and efficacy in the TELECAST phase 3 trial.

    PubMed

    Pavel, Marianne; Gross, David J; Benavent, Marta; Perros, Petros; Srirajaskanthan, Raj; Warner, Richard R P; Kulke, Matthew H; Anthony, Lowell B; Kunz, Pamela L; Hörsch, Dieter; Weickert, Martin O; Lapuerta, Pablo; Jiang, Wenjun; Kassler-Taub, Kenneth; Wason, Suman; Fleming, Rosanna; Fleming, Douglas; Garcia-Carbonero, Rocio

    2018-03-01

    Telotristat ethyl, a tryptophan hydroxylase inhibitor, was efficacious and well tolerated in the phase 3 TELESTAR study in patients with carcinoid syndrome (CS) experiencing ≥4 bowel movements per day (BMs/day) while on somatostatin analogs (SSAs). TELECAST, a phase 3 companion study, assessed the safety and efficacy of telotristat ethyl in patients with CS (diarrhea, flushing, abdominal pain, nausea or elevated urinary 5-hydroxyindoleacetic acid (u5-HIAA)) with <4 BMs/day on SSAs (or ≥1 symptom or ≥4 BMs/day if not on SSAs) during a 12-week double-blind treatment period followed by a 36-week open-label extension (OLE). The primary safety and efficacy endpoints were incidence of treatment-emergent adverse events (TEAEs) and percent change from baseline in 24-h u5-HIAA at week 12. Patients ( N  = 76) were randomly assigned (1:1:1) to receive placebo or telotristat ethyl 250 mg or 500 mg 3 times per day (tid); 67 continued receiving telotristat ethyl 500 mg tid during the OLE. Through week 12, TEAEs were generally mild to moderate in severity; 5 (placebo), 1 (telotristat ethyl 250 mg) and 3 (telotristat ethyl 500 mg) patients experienced serious events, and the rate of TEAEs in the OLE was comparable. At week 12, significant reductions in u5-HIAA from baseline were observed, with Hodges-Lehmann estimators of median treatment differences from placebo of -54.0% (95% confidence limits, -85.0%, -25.1%, P  < 0.001) and -89.7% (95% confidence limits, -113.1%, -63.9%, P  < 0.001) for telotristat ethyl 250 mg and 500 mg. These results support the safety and efficacy of telotristat ethyl when added to SSAs in patients with CS diarrhea (ClinicalTrials.gov identifier: Nbib2063659). © 2018 The authors.

  5. Treatment of depression with comorbid anxiety disorders: differential efficacy of paroxetine versus moclobemide.

    PubMed

    Pini, Stefano; Amador, Xavier F; Dell'Osso, Liliana; Baldini Rossi, Nicolò; Cassano, Paolo; Savino, Mario; Cassano, Giovanni B

    2003-01-01

    To compare the efficacy and tolerability of moclobemide versus paroxetine for the treatment of depression with comorbid anxiety disorders. Outpatients fulfilling DSM-III-R criteria for major depression or dysthymia and for a co-occurring comorbid anxiety disorder (panic disorder, generalized anxiety disorder or obsessive-compulsive disorder) after a 1-week run-in phase were randomly assigned to open-label moclobemide (300-600 mg/day) or paroxetine (20-40 mg/day) for 4 months. Primary criterion for response was a 50% score reduction from baseline on Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale scores. Mean changes in Clinical Global Impressions Severity of Illness and Improvement Scales (CGI-I) were also used to evaluate treatment response. Of the 123 patients included in the study, 65 were randomly assigned to moclobemide and 58 to paroxetine. At study end, the two treatment groups did not differ significantly in terms of proportion of responders. Treatment group differences emerged when comorbid anxiety diagnoses were considered. In patients with comorbid panic disorder, paroxetine was superior to moclobemide in improving both anxiety and depression (five patients out of 18 in the moclobemide group and nine out of 14 in the paroxetine group were rated as responders according to CGI-I, P = 0.04). Neither medication was superior in treating comorbid generalized anxiety disorder. These findings indicate that both moclobemide and paroxetine are effective for treatment of depression with comorbid anxiety disorders. However, in the subgroup with comorbid panic disorder, paroxetine is more effective than moclobemide in reducing both depressive and anxiety symptoms.

  6. Efficacy and safety of tramadol/acetaminophen in the treatment of breakthrough pain in cancer patients.

    PubMed

    Ho, Ming-Lin; Chung, Chih-Yuan; Wang, Chuan-Cheng; Lin, Hsuan-Yu; Hsu, Nicholas C; Chang, Cheng-Shyong

    2010-12-01

    We evaluated the analgesic efficacy and safety of tramadol 37.5 mg/acetaminophen 325 mg combination tablet, for the treatment of breakthrough pain in cancer patients. This study was conducted at Changhua Christian Hospital, Changhua, Taiwan from January 2006 to February 2007. The single-center and open-label study enrolled 59 opioid-treated cancer patients with at least moderate breakthrough pain (visual analog scale [VAS] score ≥40mm on a 100-mm scale). The efficacy measures included VAS scores and adverse effect assessment 10, 30, and 60 minutes after the administration of tramadol/acetaminophen. Visual analog scale score at time of pain relief was reported. The mean VAS score when the breakthrough pain episode began (0 minute) was 77.8. Analysis showed significant better mean pain VAS scores at 10, 30, and 60 minutes after the administration of tramadol/acetaminophen (p≤0.001 versus 0 min for all 3 time points). The mean time to pain relief was 597.2 seconds and the mean VAS score at time of relief was 43.4. The effective rates, defined by more than 30% reduction of the VAS score, after 10 minutes of administration was 74.6%, 30 minutes 86.4%, and one hour 94.9% (p≤0.001 versus 0 minute for all 3 time points). Two cases of drowsiness were reported. Tramadol/acetaminophen might be efficacious and safe in the treatment of breakthrough pain in cancer.

  7. American rural women's exercise self-efficacy and awareness of exercise benefits and safety during pregnancy.

    PubMed

    Melton, Bridget; Marshall, Elaine; Bland, Helen; Schmidt, Michael; Guion, W Kent

    2013-12-01

    Though the positive link between physical activity and maternal health is well documented, physical activity declines during pregnancy and, internationally, rural mothers are less likely than urban mothers to engage in physical activity. Some evidence suggests that self-efficacy is related to sustained engagement in physical activity. The purpose of this study was to examine self-efficacy, perceived benefits, and knowledge of safe exercise among 88 rural pregnant women in a southeastern region of the United States. Exercise self-efficacy was significantly related to maternal age and gestation. Women over age 26 years, and those in the second and third trimesters, scored significantly higher than younger women or those in the first trimester. Fifty-two percent (n = 46) of participants perceived that activity would decrease energy levels, 37.5% (n = 33) did not know that exercise can decrease the risk of gestational diabetes, and 47.6% (n = 41) were unaware that a mother who is overweight is more likely to have an overweight child. Results confirm a need for education to improve women's knowledge about health benefits and safety information related to physical activity during pregnancy. © 2013 Wiley Publishing Asia Pty Ltd.

  8. Efficacy and safety of the subcutaneous implantable cardioverter defibrillator: a systematic review.

    PubMed

    Chue, Colin Dominic; Kwok, Chun Shing; Wong, Chun Wai; Patwala, Ashish; Barker, Diane; Zaidi, Amir; Mamas, Mamas A; Cunnington, Colin; Ahmed, Fozia Z

    2017-09-01

    Subcutaneous implantable cardioverter defibrillators (S-ICDs) are considered an alternative to conventional transvenous ICDs (TV-ICDs) in patients not requiring pacing. We searched MEDLINE and EMBASE for studies evaluating efficacy and safety outcomes in S-ICD patients. Outcomes were pooled across studies. Sixteen studies were included with 5380 participants (mean age range 33-56 years). Short-term follow-up data were available for 1670 subjects. The most common complication was pocket infection, affecting 2.7%. Other complications included delayed wound healing (0.6%) and wound discomfort (0.8%). 3.8% of S-ICDs were explanted, most commonly for pocket infection. Mortality rates in hospital (0.4%) and during follow-up (3.4% from 12 studies reporting) were low. Incidence of ventricular arrhythmia varied from 0% to 12%. Overall shock efficacy exceeded 96%. Inappropriate shocks affected 4.3% and was most commonly caused by T-wave oversensing. Although long-term randomised data are lacking, observational data suggest similar shock efficacy and short-term complication rates between the S-ICD and TV-ICD. © 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.

  9. Safety and efficacy of antiemetics used to treat nausea and vomiting in pregnancy.

    PubMed

    Leathem, A M

    1986-08-01

    The safety and efficacy of antiemetic drugs used in the treatment of nausea and vomiting during pregnancy are reviewed. Confirmation of the teratogenicity of drugs in humans is difficult; the risk can be estimated from results of cohort studies and case-control studies. The possible teratogenicity of Bendectin (doxylamine succinate and pyridoxine hydrochloride) was studied thoroughly; although the risk was minimal, the drug was withdrawn from the U.S. market. Whether phenothiazines are teratogenic has still not been conclusively determined. A large number of epidemiological studies have not shown meclizine to be teratogenic in humans. More information about metoclopramide is necessary before it can be safely recommended for use during pregnancy. The risks of using dimenhydrinate and diphenhydramine appear to be low. Pyridoxine is considered safe for use during pregnancy, but its efficacy in treating nausea and vomiting has not been determined. The relative efficacy of these agents has not been determined. The available data suggest that meclizine and dimenhydrinate are the antiemetics that present the lowest risk of teratogenicity; meclizine is the drug of first choice. Phenothiazines should be reserved for treating persistent vomiting that threatens the maternal nutritional status.

  10. Efficacy and safety of moxifloxacin in community acquired pneumonia: a prospective, multicenter, observational study (CAPRIVI).

    PubMed

    Kuzman, Ilija; Bezlepko, Alexandr; Kondova Topuzovska, Irena; Rókusz, László; Iudina, Liudmyla; Marschall, Hans-Peter; Petri, Thomas

    2014-06-30

    Community acquired pneumonia (CAP) is a major cause of morbidity, hospitalization, and mortality worldwide. Management of CAP for many patients requires rapid initiation of empirical antibiotic treatment, based on the spectrum of activity of available antimicrobial agents and evidence on local antibiotic resistance. Few data exist on the severity profile and treatment of hospitalized CAP patients in Eastern and Central Europe and the Middle East, in particular on use of moxifloxacin (Avelox®), which is approved in these regions. CAPRIVI (Community Acquired Pneumonia: tReatment wIth AVelox® in hospItalized patients) was a prospective observational study in 12 countries: Croatia, France, Hungary, Kazakhstan, Jordan, Kyrgyzstan, Lebanon, Republic of Moldova, Romania, Russia, Ukraine, and Macedonia. Patients aged >18 years were treated with moxifloxacin 400 mg daily following hospitalization with a CAP diagnosis. In addition to efficacy and safety outcomes, data were collected on patient history and disease severity measured by CRB-65 score. 2733 patients were enrolled. A low severity index (i.e., CRB-65 score <2) was reported in 87.5% of CAP patients assessed (n=1847), an unexpectedly high proportion for hospitalized patients. Moxifloxacin administered for a mean of 10.0 days (range: 2.0 to 39.0 days) was highly effective: 96.7% of patients in the efficacy population (n=2152) improved and 93.2% were cured of infection during the study. Severity of infection changed from "moderate" or "severe" in 91.8% of patients at baseline to "no infection" or "mild" in 95.5% at last visit. In the safety population (n=2595), 127 (4.9%) patients had treatment-emergent adverse events (TEAEs) and 40 (1.54%) patients had serious TEAEs; none of these 40 patients died. The safety results were consistent with the known profile of moxifloxacin. The efficacy and safety profiles of moxifloxacin at the recommended dose of 400 mg daily are characterized in this large observational study of

  11. Safety and efficacy of rivaroxaban compared with warfarin in patients undergoing peripheral arterial procedures.

    PubMed

    Talukdar, Anjan; Wang, S Keisin; Czosnowski, Lauren; Mokraoui, Nassim; Gupta, Alok; Fajardo, Andres; Dalsing, Michael; Motaganahalli, Raghu

    2017-10-01

    Rivaroxaban is a United States Food and Drug Administration-approved oral anticoagulant for venous thromboembolic disease; however, there is no information regarding the safety and its efficacy to support its use in patients after open or endovascular arterial interventions. We report the safety and efficacy of rivaroxaban vs warfarin in patients undergoing peripheral arterial interventions. This single-institution retrospective study analyzed all sequential patients from December 2012 to August 2014 (21 months) who were prescribed rivaroxaban or warfarin after a peripheral arterial procedure. Our study population was then compared using American College of Chest Physicians guidelines with patients then stratified as low, medium, or high risk for bleeding complications. Statistical analyses were performed using the Student t-test and χ 2 test to compare demographics, readmissions because of bleeding, and the need for secondary interventions. Logistic regression models were used for analysis of variables associated with bleeding complications and secondary interventions. The Fisher exact test was used for power analysis. There were 44 patients in the rivaroxaban group and 50 patients in the warfarin group. Differences between demographics and risk factors for bleeding between groups or reintervention rate were not statistically significant (P = .297). However, subgroup evaluation of the safety profile suggests that patients who were aged ≤65 years and on warfarin had an overall higher incidence of major bleeding (P = .020). Patients who were aged >65 years, undergoing open operation, had a significant risk for reintervention (P = .047) when they received rivaroxaban. Real-world experience using rivaroxaban and warfarin in patients after peripheral arterial procedures suggests a comparable safety and efficacy profile. Subgroup analysis of those requiring an open operation demonstrated a decreased bleeding risk when rivaroxaban was used (in those aged <65

  12. Safety and Efficacy of Acupuncture in Children A Review of the Evidence

    PubMed Central

    Jindal, Vanita; Ge, Adeline; Mansky, Patrick J.

    2008-01-01

    exclusively. Pain is often unresolved from drug therapy, thus there is a need for more studies in this setting. For seasonal allergic rhinitis, we reviewed studies conducted by Ng et al and Xue et al in children and adults, respectively. Both populations showed some relief of symptoms through acupuncture, but questions remain about treatment logistics. Additionally, there are limited indications that acupuncture may help cure children afflicted with nocturnal enuresis. Systematic reviews show that current published trials have suffered from low trial quality, including small sample sizes. Other areas of pediatric afflictions we reviewed that suffer from lack of research include asthma, other neurologic conditions, gastrointestinal disorders, and addiction. Acupuncture has become a dominant complementary and alternative modality in clinical practice today, but its associated risk has been questioned. The National Institutes of Health Consensus Statement states “one of the advantages of acupuncture is that the incidence of adverse effects is substantially lower than that of many drugs or other accepted procedures for the same conditions.” A review of serious adverse events by White et al found the risk of a major complication occurring to have an incidence between 1:10,000 and 1:100,000, which is considered “very low.” Another study found that the risk of a serious adverse event occurring from acupuncture therapy is the same as taking penicillin. The safety of acupuncture is a serious concern, particularly in pediatrics. Because acupuncture’s mechanism is not known, the use of needles in children becomes questionable. For example, acupoints on the vertex of infants should not be needled when the fontanel is not closed. It is also advisable to apply few needles or delay treatment to the children who have overeaten, are overfatigued, or are very weak. Through our review of pediatric adverse events, we found a 1.55 risk of adverse events occurring in 100 treatments of

  13. Safety, Efficacy, and Cost-effectiveness of Tranexamic Acid in Orthopedic Surgery.

    PubMed

    Lin, Zilan X; Woolf, Shane K

    2016-01-01

    Perioperative bleeding and postsurgical hemorrhage are common in invasive surgical procedures, including orthopedic surgery. Tranexamic acid (TXA) is a pharmacologic agent that acts through an antifibrinolytic mechanism to stabilize formed clots and reduce active bleeding. It has been used successfully in orthopedics to reduce perioperative blood loss, particularly in total hip and knee arthroplasty and spine surgery. Numerous research studies have reported favorable safety and efficacy in orthopedic cases, although there is no universal standard on its administration and its use has not yet become the standard of practice. Reported administration methods often depend on the surgeon's preference, with both topical and intravenous routes showing efficacy. The type and anatomic site of the surgery seem to influence the decision making but also result in conflicting opinions. Reported complication rates with TXA use are low. The incidence of both arterial and venous thromboembolic events, particularly deep venous thrombosis and pulmonary embolism, has not been found to be significantly different with TXA use for healthy patients. The route of administration and dosage do not appear to affect complication rates either. However, data on patients with higher-risk conditions are deficient. In addition, TXA has shown potential to reduce blood loss, transfusion rates and volumes, perioperative hemoglobin change, and hospital-related costs at various degrees among the published studies. Conservation of blood products, reduced laboratory costs, and shorter hospital stays are likely the major factors driving the cost savings associated with TXA use. This article reviews current data supporting the safety, efficacy, and cost-effectiveness of TXA in orthopedic surgery. Copyright 2016, SLACK Incorporated.

  14. Efficacy and safety of CPAP in low- and middle-income countries.

    PubMed

    Thukral, A; Sankar, M J; Chandrasekaran, A; Agarwal, R; Paul, V K

    2016-05-01

    We conducted a systematic review to evaluate the (1) feasibility and efficacy and (2) safety and cost effectiveness of continuous positive airway pressure (CPAP) therapy in low- and middle-income countries (LMIC). We searched the following electronic bibliographic databases-MEDLINE, Cochrane CENTRAL, CINAHL, EMBASE and WHOLIS-up to December 2014 and included all studies that enrolled neonates requiring CPAP therapy for any indication. We did not find any randomized trials from LMICs that have evaluated the efficacy of CPAP therapy. Pooled analysis of four observational studies showed 66% reduction in in-hospital mortality following CPAP in preterm neonates (odds ratio 0.34, 95% confidence interval (CI) 0.14 to 0.82). One study reported 50% reduction in the need for mechanical ventilation following the introduction of bubble CPAP (relative risk 0.5, 95% CI 0.37 to 0.66). The proportion of neonates who failed CPAP and required mechanical ventilation varied from 20 to 40% (eight studies). The incidence of air leaks varied from 0 to 7.2% (nine studies). One study reported a significant reduction in the cost of surfactant usage with the introduction of CPAP. Available evidence suggests that CPAP is a safe and effective mode of therapy in preterm neonates with respiratory distress in LMICs. It reduces the in-hospital mortality and the need for ventilation thereby minimizing the need for up-transfer to a referral hospital. But given the overall paucity of studies and the low quality evidence underscores the need for large high-quality studies on the safety, efficacy and cost effectiveness of CPAP therapy in these settings.

  15. Efficacy and safety of artemisinin combination therapy (ACT) for non-falciparum malaria: a systematic review.

    PubMed

    Visser, Benjamin J; Wieten, Rosanne W; Kroon, Daniëlle; Nagel, Ingeborg M; Bélard, Sabine; van Vugt, Michèle; Grobusch, Martin P

    2014-11-26

    Artemisinin combination therapy (ACT) is recommended as first-line treatment for uncomplicated Plasmodium falciparum malaria, whereas chloroquine is still commonly used for the treatment of non-falciparum species (Plasmodium vivax, Plasmodium ovale and Plasmodium malariae). A more simplified, more uniform treatment approach across all malaria species is worthwhile to be considered both in endemic areas and for malaria as an imported condition alike. A PROSPERO-registered systematic review to determine the efficacy and safety of ACT for the treatment of non-falciparum malaria was conducted, following PRISMA guidelines. Without language restrictions, Medline/PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, LILACS, Biosis Previews and the African Index Medicus were searched for studies published up to November 2014. The literature search identified 986 reports; 40 publications were found eligible for inclusion, all of them on non-falciparum malaria in endemic areas. Most evidence was available for P. vivax (n = 35). Five clinical trials in total were identified evaluating ACT for P. ovale, P. malariae and Plasmodium knowlesi. Most ACT presentations have high efficacy against P. vivax parasites; artemisinin-based combinations have shorter parasite and fever clearance times compared to chloroquine. ACT is as effective as chloroquine in preventing recurrent parasitaemia before day 28. Artemisinin-based combinations with long half-lives show significantly fewer recurrent parasitaemia up to day 63. The limited evidence available supports both the use of chloroquine and an ACT for P. ovale and P. malariae. ACT seems to be preferable for optimal treatment of P. knowlesi. ACT is at least equivalent to chloroquine in effectively treating non-falciparum malaria. These findings may facilitate development of simplified protocols for treating all forms of malaria with ACT, including returning travellers. Obtaining comprehensive efficacy and

  16. Efficacy and safety of intermittent preventive treatment for malaria in schoolchildren: a systematic review.

    PubMed

    Matangila, Junior R; Mitashi, Patrick; Inocêncio da Luz, Raquel A; Lutumba, Pascal T; Van Geertruyden, Jean-Pierre

    2015-11-14

    Intermittent preventive treatment (IPT) is a proven malaria control strategy in infants and pregnancy. School-aged children represent 26 % of the African population, and an increasing percentage of them are scholarized. Malaria is causing 50 % of deaths in this age group and malaria control efforts may shift the malaria burden to older age groups. Schools have been suggested as a platform for health interventions delivery (deworming, iron-folic acid, nutrients supplementation, (boost-)immunization) and as a possible delivery system for IPT in schoolchildren (IPTsc). However, the current evidence on the efficacy and safety of IPTsc is limited and the optimal therapeutic regimen remains controversial. A systematic search for studies reporting efficacy and safety of IPT in schoolchildren was conducted using PubMed, Web of Science, Clinicaltrials and WHO/ICTRP database, and abstracts from congresses with the following key words: intermittent, preventive treatment AND malaria OR Plasmodium falciparum AND schoolchildren NOT infant NOT pregnancy. Five studies were identified. Most IPTsc regimes demonstrated substantial protection against malaria parasitaemia, with dihydroartemisinin-piperaquine (DP) given monthly having the highest protective effect (PE) (94 %; 95 % CI 93-96). Contrarily, SP did not provide any PE against parasitaemia. However, no IPT regimen provided a PE above 50 % in regard to anaemia, and highest protection was provided by SP+ amodiaquine (AQ) given four-monthly (50 %; 95 % CI 41-53). The best protection against clinical malaria was observed in children monthly treated with DP (97 %; 95 % CI 87-98). However, there was no protection when the drug was given three-monthly. No severe adverse events were associated with the drugs used for IPTsc. IPTsc may reduce the malaria-related burden in schoolchildren. However, more studies assessing efficacy of IPT in particular against malaria-related anaemia and clinical malaria in schoolchildren must be conducted.

  17. Exposure-safety and efficacy response relationships and population pharmacokinetics of eslicarbazepine acetate.

    PubMed

    Gidal, B E; Jacobson, M P; Ben-Menachem, E; Carreño, M; Blum, D; Soares-da-Silva, P; Falcão, A; Rocha, F; Moreira, J; Grinnell, T; Ludwig, E; Fiedler-Kelly, J; Passarell, J; Sunkaraneni, S

    2018-05-06

    Eslicarbazepine acetate (ESL) is a once-daily (QD) oral antiepileptic drug (AED) for focal-onset seizures (FOS). Pharmacokinetic (PK) and pharmacodynamic (PD) models were developed to assess dose selection, identify significant AED drug interactions, and quantitate relationships between exposure and safety and efficacy outcomes from Phase 3 trials of adjunctive ESL. Eslicarbazepine (the primary active metabolite of ESL) population PK was evaluated using data from 1351 subjects enrolled in 14 studies (11 Phase 1 and three Phase 3 studies) after multiple oral doses ranging from 400 to 1200 mg. Population PK and PD models related individual eslicarbazepine exposures to safety outcomes and efficacy responses. Eslicarbazepine PK was described by a one-compartment model with linear absorption and elimination. The probability of a treatment-emergent adverse event (TEAE; dizziness, headache, or somnolence) was higher with an initial dose of ESL 800 mg than with an initial dose of ESL 400 mg QD. Body weight, sex, region, and baseline use of carbamazepine (CBZ) or lamotrigine were also found to influence the probability of TEAEs. Eslicarbazepine exposure influenced serum sodium concentration, standardized seizure frequency, and probability of response; better efficacy outcomes were predicted in patients not from Western Europe (WE; vs WE patients) and those not taking CBZ (vs taking CBZ) at baseline. Pharmacokinetic and PK/PD modeling were implemented during the development of ESL for adjunctive treatment of FOS in adults. This quantitative approach supported decision-making during the development of ESL, and contributed to dosing recommendations and labeling information related to drug interactions. © 2018 The Authors. Acta Neurologica Scandinavica Published by John Wiley & Sons Ltd.

  18. Efficacy and safety of CPAP in low- and middle-income countries

    PubMed Central

    Thukral, A; Sankar, M J; Chandrasekaran, A; Agarwal, R; Paul, V K

    2016-01-01

    We conducted a systematic review to evaluate the (1) feasibility and efficacy and (2) safety and cost effectiveness of continuous positive airway pressure (CPAP) therapy in low- and middle-income countries (LMIC). We searched the following electronic bibliographic databases—MEDLINE, Cochrane CENTRAL, CINAHL, EMBASE and WHOLIS—up to December 2014 and included all studies that enrolled neonates requiring CPAP therapy for any indication. We did not find any randomized trials from LMICs that have evaluated the efficacy of CPAP therapy. Pooled analysis of four observational studies showed 66% reduction in in-hospital mortality following CPAP in preterm neonates (odds ratio 0.34, 95% confidence interval (CI) 0.14 to 0.82). One study reported 50% reduction in the need for mechanical ventilation following the introduction of bubble CPAP (relative risk 0.5, 95% CI 0.37 to 0.66). The proportion of neonates who failed CPAP and required mechanical ventilation varied from 20 to 40% (eight studies). The incidence of air leaks varied from 0 to 7.2% (nine studies). One study reported a significant reduction in the cost of surfactant usage with the introduction of CPAP. Available evidence suggests that CPAP is a safe and effective mode of therapy in preterm neonates with respiratory distress in LMICs. It reduces the in-hospital mortality and the need for ventilation thereby minimizing the need for up-transfer to a referral hospital. But given the overall paucity of studies and the low quality evidence underscores the need for large high-quality studies on the safety, efficacy and cost effectiveness of CPAP therapy in these settings. PMID:27109089

  19. AbobotulinumtoxinA Efficacy and Safety in Children With Equinus Foot Previously Treated With Botulinum Toxin.

    PubMed

    Dabrowski, Edward; Bonikowski, Marcin; Gormley, Mark; Volteau, Magali; Picaut, Philippe; Delgado, Mauricio R

    2018-05-01

    The effects of botulinum toxin are transient, and repeat injections are required in children with lower-limb spasticity. However, the efficacy of botulinum toxin in patients who have received previous injections has remained largely unexplored. We present subgroup analyses of a phase III study conducted in ambulatory children (aged two to 17) with spastic equinus foot. Patients were randomized to single doses of abobotulinumtoxinA 10 U/kg/leg, 15 U/kg/leg, or placebo injected into the gastrocnemius-soleus complex (one or both legs). The first analysis was prespecified to review the effect of abobotulinumtoxinA in children previously treated with botulinum toxin versus those children new to the treatment; a second post hoc analysis evaluated the effect of abobotulinumtoxinA in children who changed botulinum toxin formulation. Of the 241 randomized patients, 113 had previously received botulinum toxin, including 86 who had been treated with another formulation. In both analyses, muscle tone (Modified Ashworth Scale) and the Physicians Global Assessment, at week 4, improved with abobotulinumtoxinA treatment versus placebo, regardless of baseline botulinum toxin status. Placebo responses in patients new to treatment were consistently higher than in the previously treated group. These results demonstrate similar abobotulinumtoxinA efficacy and safety profiles in children with spasticity who are new to botulinum toxin treatment and those children who were previously treated. The efficacy and safety of abobotulinumtoxinA treatment in these previously treated patients were comparable with the overall trial population, indicating that doses of 10 and 15 U/kg/leg are suitable starting doses for children with spasticity regardless of the previous botulinum toxin preparation used. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. Sensory integration dysfunction affects efficacy of speech therapy on children with functional articulation disorders.

    PubMed

    Tung, Li-Chen; Lin, Chin-Kai; Hsieh, Ching-Lin; Chen, Ching-Chi; Huang, Chin-Tsan; Wang, Chun-Hou

    2013-01-01

    Articulation disorders in young children are due to defects occurring at a certain stage in sensory and motor development. Some children with functional articulation disorders may also have sensory integration dysfunction (SID). We hypothesized that speech therapy would be less efficacious in children with SID than in those without SID. Hence, the purpose of this study was to compare the efficacy of speech therapy in two groups of children with functional articulation disorders: those without and those with SID. A total of 30 young children with functional articulation disorders were divided into two groups, the no-SID group (15 children) and the SID group (15 children). The number of pronunciation mistakes was evaluated before and after speech therapy. There were no statistically significant differences in age, sex, sibling order, education of parents, and pretest number of mistakes in pronunciation between the two groups (P > 0.05). The mean and standard deviation in the pre- and post-test number of mistakes in pronunciation were 10.5 ± 3.2 and 3.3 ± 3.3 in the no-SID group, and 10.1 ± 2.9 and 6.9 ± 3.5 in the SID group, respectively. Results showed great changes after speech therapy treatment (F = 70.393; P < 0.001) and interaction between the pre/post speech therapy treatment and groups (F = 11.119; P = 0.002). Speech therapy can improve the articulation performance of children who have functional articulation disorders whether or not they have SID, but it results in significantly greater improvement in children without SID. SID may affect the treatment efficiency of speech therapy in young children with articulation disorders.

  1. Sensory integration dysfunction affects efficacy of speech therapy on children with functional articulation disorders

    PubMed Central

    Tung, Li-Chen; Lin, Chin-Kai; Hsieh, Ching-Lin; Chen, Ching-Chi; Huang, Chin-Tsan; Wang, Chun-Hou

    2013-01-01

    Background Articulation disorders in young children are due to defects occurring at a certain stage in sensory and motor development. Some children with functional articulation disorders may also have sensory integration dysfunction (SID). We hypothesized that speech therapy would be less efficacious in children with SID than in those without SID. Hence, the purpose of this study was to compare the efficacy of speech therapy in two groups of children with functional articulation disorders: those without and those with SID. Method: A total of 30 young children with functional articulation disorders were divided into two groups, the no-SID group (15 children) and the SID group (15 children). The number of pronunciation mistakes was evaluated before and after speech therapy. Results: There were no statistically significant differences in age, sex, sibling order, education of parents, and pretest number of mistakes in pronunciation between the two groups (P > 0.05). The mean and standard deviation in the pre- and post-test number of mistakes in pronunciation were 10.5 ± 3.2 and 3.3 ± 3.3 in the no-SID group, and 10.1 ± 2.9 and 6.9 ± 3.5 in the SID group, respectively. Results showed great changes after speech therapy treatment (F = 70.393; P < 0.001) and interaction between the pre/post speech therapy treatment and groups (F = 11.119; P = 0.002). Conclusions: Speech therapy can improve the articulation performance of children who have functional articulation disorders whether or not they have SID, but it results in significantly greater improvement in children without SID. SID may affect the treatment efficiency of speech therapy in young children with articulation disorders. PMID:23355780

  2. Efficacy of Lisdexamfetamine in Adults With Moderate to Severe Binge-Eating Disorder: A Randomized Clinical Trial.

    PubMed

    Hudson, James I; McElroy, Susan L; Ferreira-Cornwell, M Celeste; Radewonuk, Jana; Gasior, Maria

    2017-09-01

    The ability of pharmacotherapies to prevent relapse and maintain efficacy with long-term treatment in psychiatric conditions is important. To assess lisdexamfetamine dimesylate maintenance of efficacy in adults with moderate to severe binge-eating disorder. A multinational, phase 3, double-blind, placebo-controlled, randomized withdrawal study including 418 participants was conducted at 49 clinical research study sites from January 27, 2014, to April 8, 2015. Eligible adults met DSM-IV-R binge-eating disorder criteria and had moderate to severe binge eating disorder (≥3 binge-eating days per week for 14 days before open-label baseline; Clinical Global Impressions-Severity [CGI-S] scores ≥4 [moderate severity] at screening and open-label baseline). Following a 12-week, open-label phase (dose optimization, 4 weeks [lisdexamfetamine dimesylate, 50 or 70 mg]; dose maintenance, 8 weeks), lisdexamfetamine responders (≤1 binge eating day per week for 4 consecutive weeks and CGI-S scores ≤2 at week 12) were randomized to placebo or continued lisdexamfetamine during a 26-week, double-blind, randomized withdrawal phase. Lisdexamfetamine administration. The primary outcome variable, time to relapse (≥2 binge-eating days per week for 2 consecutive weeks and ≥2-point CGI-S score increases from randomized withdrawal baseline), was analyzed using a log-rank test (primary analysis); the analysis was stratified for dichotomized 4-week cessation status. Safety assessments included treatment-emergent adverse events. Of the 418 participants enrolled in the open-label phase of the study, 411 (358 [87.1%] women; mean [SD] age, 38.3 [10.4] years) were included in the safety analysis set. Of 275 randomized lisdexamfetamine responders (placebo, n = 138; lisdexamfetamine, n = 137), the observed proportions of participants meeting relapse criteria were 3.7% (5 of 136) for lisdexamfetamine and 32.1% (42 of 131) for placebo. Lisdexamfetamine demonstrated superiority over

  3. Safety and Efficacy Profile of Commercial Veterinary Vaccines against Rift Valley Fever: A Review Study

    PubMed Central

    2016-01-01

    Rift Valley Fever (RVF) is an infectious illness with serious clinical manifestations and health consequences in humans as well as a wide range of domestic ruminants. This review provides significant information about the prevention options of RVF along with the safety-efficacy profile of commercial vaccines and some of RVF vaccination strategies. Information presented in this paper was obtained through a systematic investigation of published data about RVF vaccines. Like other viral diseases, the prevention of RVF relies heavily on immunization of susceptible herds with safe and cost-effective vaccine that is able to confer long-term protective immunity. Several strains of RVF vaccines have been developed and are available in commercial production including Formalin-Inactivated vaccine, live attenuated Smithburn vaccine, and the most recent Clone13. Although Formalin-Inactivated vaccine and live attenuated Smithburn vaccine are immunogenic and widely used in prevention programs, they proved to be accompanied by significant concerns. Despite Clone13 vaccine being suggested as safe in pregnant ewes and as highly immunogenic along with its potential for differentiating infected from vaccinated animals (DIVA), a recent study raised concerns about the safety of the vaccine during the first trimester of gestation. Accordingly, RVF vaccines that are currently available in the market to a significant extent do not fulfill the requirements of safety, potency, and DIVA. These adverse effects stressed the need for developing new vaccines with an excellent safety profile to bridge the gap in safety and immunity. Bringing RVF vaccine candidates to local markets besides the absence of validated serological test for DIVA remain the major challenges of RVF control. PMID:27689098

  4. In-situation safety behaviors among patients with panic disorder: descriptive and correlational study.

    PubMed

    Funayama, Tadashi; Furukawa, Toshi A; Nakano, Yumi; Noda, Yumiko; Ogawa, Sei; Watanabe, Norio; Chen, Junwen; Noguchi, Yuka

    2013-07-01

    In-situation safety behaviors play an important role in the maintenance of anxiety because they prevent patients from experiencing unambiguous disconfirmation of their unrealistic beliefs about feared catastrophes. Strategies for identifying particular safety behaviors, however, have not been sufficiently investigated. The aims of the present study were to (i) develop a comprehensive list of safety behaviors seen in panic disorder and to examine their frequency; and (ii) correlate the safety behaviors with panic attack symptoms, agoraphobic situations and treatment response. The subjects consisted of 46 consecutive patients who participated in group cognitive behavioral treatment (CBT) for panic disorder. All the patients completed a Safety Behavior List that was developed based on experiences with panic disorder patients. Carrying medications, distracting attention, carrying a plastic bottle, and drinking water were reported by more than half of the patients. The strongest correlations between panic symptoms and safety behaviors were found between symptoms of derealization and listening to music with headphones, paresthesia and pushing a cart while shopping, and nausea and squatting down. The strongest association between agoraphobic situations and safety behaviors was found between the fear of taking a bus or a train alone and moving around. Staying still predicted response to the CBT program, while concentrating on something predicted lack of response. An approximate guideline has been developed for identifying safety behaviors among patients with panic disorder and should help clinicians use CBT more effectively for these patients. © 2013 The Authors. Psychiatry and Clinical Neurosciences © 2013 Japanese Society of Psychiatry and Neurology.

  5. Safety and efficacy of aneurysm treatment with WEB: results of the WEBCAST study.

    PubMed

    Pierot, Laurent; Costalat, Vincent; Moret, Jacques; Szikora, Istvan; Klisch, Joachim; Herbreteau, Denis; Holtmannspötter, Markus; Weber, Werner; Januel, Anne-Christine; Liebig, Thomas; Sychra, Vojtech; Strasilla, Christoph; Cognard, Christophe; Bonafé, Alain; Molyneux, Andrew; Byrne, James V; Spelle, Laurent

    2016-05-01

    OBJECT WEB is an innovative intrasaccular treatment for intracranial aneurysms. Preliminary series have shown good safety and efficacy. The WEB Clinical Assessment of Intrasaccular Aneurysm Therapy (WEBCAST) trial is a prospective European trial evaluating the safety and efficacy of WEB in wide-neck bifurcation aneurysms. METHODS Patients with wide-neck bifurcation aneurysms for which WEB treatment was indicated were included in this multicentergood clinical practices study. Clinical data including adverse events and clinical status at 1 and 6 months were collected and independently analyzed by a medical monitor. Six-month follow-up digital subtraction angiography was also performed and independently analyzed by a core laboratory. Success was defined at 6 months as complete occlusion or stable neck remnant, no worsening in angiographic appearance from postprocedure, and no retreatment performed or planned. RESULTS Ten European neurointerventional centers enrolled 51 patients with 51 aneurysms. Treatment with WEB was achieved in 48 of 51 aneurysms (94.1%). Adjunctive implants (coils/stents) were used in 4 of 48 aneurysms (8.3%). Thromboembolic events were observed in 9 of 51 patients (17.6%), resulting in a permanent deficit (modified Rankin Scale [mRS] Score 1) in 1 patient (2.0%). Intraoperative rupture was not observed. Morbidity (mRS score > 2) and mortality were 2.0% (1 of 51 patients, related to rupture status on entry to study) and 0.0% at 1 month, respectively. Success was achieved at 6 months in 85.4% of patients treated with WEB: 23 of 41 patients (56.1%) had complete occlusion, 12 of 41 (29.3%) had a neck remnant, and 6 of 41 (14.6%) had an aneurysm remnant. CONCLUSIONS The WEBCAST study showed good procedural and short-term safety of aneurysm treatment with WEB and good 6-month anatomical results.

  6. Safety and Efficacy of Topical Chitogel- Deferiprone-Gallium Protoporphyrin in Sheep Model

    PubMed Central

    Ooi, Mian L.; Richter, Katharina; Drilling, Amanda J.; Thomas, Nicky; Prestidge, Clive A.; James, Craig; Moratti, Stephen; Vreugde, Sarah; Psaltis, Alkis J.; Wormald, Peter-John

    2018-01-01

    Objectives: Increasing antimicrobial resistance has presented new challenges to the treatment of recalcitrant chronic rhinosinusitis fuelling a continuous search for novel antibiofilm agents. This study aimed to assess the safety and efficacy of Chitogel (Chitogel®, Wellington New Zealand) combined with novel antibiofilm agents Deferiprone and Gallium Protoporphyrin (CG-DG) as a topical treatment against S. aureus biofilms in vivo. Methods: To assess safety, 8 sheep were divided into two groups of 7 day treatments (n = 8 sinuses per treatment); (1) Chitogel (CG) with twice daily saline flush, and (2) CG-DG gel with twice daily saline flush. Tissue morphology was analyzed using histology and scanning electron microscopy (SEM). To assess efficacy we used a S. aureus sheep sinusitis model. Fifteen sheep were divided into three groups of 7 day treatments (n = 10 sinuses per treatment); (1) twice daily saline flush (NT), (2) Chitogel (CG) with twice daily saline flush, and (3) CG-DG gel with twice daily saline flush. Biofilm biomass across all groups was compared using LIVE/DEAD BacLight stain and confocal scanning laser microscopy. Results: Safety study showed no cilia denudation on scanning electron microscopy and no change in sinus mucosa histopathology when comparing CG-DG to CG treated sheep. COMSTAT2 assessment of biofilm biomass showed a significant reduction in CG-DG treated sheep compared to NT controls. Conclusion: Results indicate that CG-DG is safe and effective against S. aureus biofilms in a sheep sinusitis model and could represent a viable treatment option in the clinical setting.

  7. Efficacy and safety of Suanzaoren decoction for primary insomnia: a systematic review of randomized controlled trials

    PubMed Central

    2013-01-01

    Background Insomnia is a widespread human health problem, but there currently are the limitations of conventional therapies available. Suanzaoren decoction (SZRD) is a well known classic Chinese herbal prescription for insomnia and has been treating people’s insomnia for more than thousand years. The objective of this study was to evaluate the efficacy and safety of SZRD for insomnia. Methods A systematic literature search was performed for 6 databases up to July of 2012 to identify randomized control trials (RCTs) involving SZRD for insomniac patients. The methodological quality of RCTs was assessed independently using the Cochrane Handbook for Systematic Reviews of Interventions. Results Twelve RCTs with total of 1376 adult participants were identified. The methodological quality of all included trials are no more than 3/8 score. Majority of the RCTs concluded that SZRD was more significantly effective than benzodiazepines for treating insomnia. Despite these positive outcomes, there were many methodological shortcomings in the studies reviewed, including insufficient information about randomization generation and absence of allocation concealment, lack of blinding and no placebo control, absence of intention-to-treat analysis and lack of follow-ups, selective publishing and reporting, and small number of sample sizes. A number of clinical heterogeneity such as diagnosis, intervention, control, and outcome measures were also reviewed. Only 3 trials reported adverse events, whereas the other 9 trials did not provide the safety information. Conclusions Despite the apparent reported positive findings, there is insufficient evidence to support efficacy of SZRD for insomnia due to the poor methodological quality and the small number of trials of the included studies. SZRD seems generally safe, but is insufficient evidence to make conclusions on the safety because fewer studies reported the adverse events. Further large sample-size and well-designed RCTs are needed

  8. Efficacy and safety of lipid lowering by alirocumab in chronic kidney disease.

    PubMed

    Toth, Peter P; Dwyer, Jamie P; Cannon, Christopher P; Colhoun, Helen M; Rader, Daniel J; Upadhyay, Ashish; Louie, Michael J; Koren, Andrew; Letierce, Alexia; Mandel, Jonas; Banach, Maciej

    2018-06-01

    Individuals with chronic kidney disease are at increased risk of premature cardiovascular disease. Among them, many with elevated low-density lipoprotein cholesterol (LDL-C) are unable to achieve optimal LDL-C on statins and require additional lipid-lowering therapy. To study this, we compared the LDL-C-lowering efficacy and safety of alirocumab in individuals with hypercholesterolemia with impaired renal function, defined as eGFR 30-59 ml/min/1.73 m 2 , to those without impaired renal function eGFR ≥60 ml/min/1.73 m 2 . A total of 4629 hypercholesterolemic individuals without or with impaired renal function, pooled from eight phase 3 ODYSSEY trials (double-blind treatments of 24-104 weeks), were on alirocumab 150 mg or 75/150 mg every two weeks vs. placebo or ezetimibe. Overall, 10.1% had impaired renal function and over 99% were receiving statin treatment. Baseline LDL-C in alirocumab and control groups was comparable in subgroups analyzed. LDL-C reductions at week 24 ranged from 46.1 to 62.2% or 48.3 to 60.1% with alirocumab among individuals with or without impaired renal function, respectively. Similar reductions were observed for lipoprotein (a), non-high-density lipoprotein cholesterol, apolipoprotein B, and triglycerides. Safety data were similar in both treatment subgroups, regardless of the degree of CKD. Renal function did not change over time in response to alirocumab. This post hoc efficacy analysis is limited by evaluation of alirocumab treatment effects on renal and lipid parameters by serum biochemistry. Thus, alirocumab consistently lowered LDL-C regardless of impaired renal function, with safety comparable to control, among individuals with hypercholesterolemia who nearly all were on statin treatment. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  9. Safety and efficacy of the switch to generic mycophenolate mofetil and tacrolimus in heart transplant patients.

    PubMed

    Söderlund, Carl; Rådegran, Göran

    2015-07-01

    Generic immunosuppressants may offer economic advantages, but their use is still controversial. At our center, 55 heart transplant patients were switched from CellCept(®) to Myfenax Teva(®) (MT) (n = 51, 18% female, 8.1 ± 6.6 yr post-transplantation) and/or Prograf(®) to Tacrolimus Sandoz(®) (TS) (n = 17, 41% female, 6.6 ± 5.8 yr post-transplantation). We conducted an acute monitoring and a retrospective follow-up with regard to safety and efficacy. Acute cellular rejections (ACRs) on endomyocardial biopsies (EMBs) four wk after the MT switch were specifically compared to a matched retrospective control group. Tacrolimus C0 levels (TS switch) as well as hemoglobin, leukocytes, and thrombocytes (MT switch) did not change (p = NS) during the three wk after each respective switch (8.7 ± 2.9 vs. 8.4 ± 1.9 μg/L, 129.1 ± 12.6 vs. 130.1 ± 12.8 g/L, 6.3 vs. 6.2 × 10(9) /L, and 217.4 ± 56.6 vs. 219.3 ± 61.8 × 10(9) /L, respectively). 0% of the EMBs in the MT switch vs. 3% of the EMBs in the control group showed ACR>grade 1R (p = NS). After six months, survival was 96% (MT switch) and 100% (TS switch), and the frequency of severe ACR was low. Safety parameters measured at the next annual follow-up were also stable following each switch. Switching to MT and/or TS several years after heart transplantation appeared safe in the short-term perspective, showing no detectable changes in tacrolimus C0 levels, safety or efficacy, during an average follow-up of six months. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. The magnetic navigation system allows safety and high efficacy for ablation of arrhythmias

    PubMed Central

    Bauernfeind, Tamas; Akca, Ferdi; Schwagten, Bruno; de Groot, Natasja; Van Belle, Yves; Valk, Suzanne; Ujvari, Barbara; Jordaens, Luc; Szili-Torok, Tamas

    2011-01-01

    Aims We aimed to evaluate the safety and long-term efficacy of the magnetic navigation system (MNS) in a large number of patients. The MNS has the potential for improving safety and efficacy based on atraumatic catheter design and superior navigation capabilities. Methods and results In this study, 610 consecutive patients underwent ablation. Patients were divided into two age- and sex-matched groups. Ablations were performed either using MNS (group MNS, 292) or conventional manual ablation [group manual navigation (MAN), 318]. The following parameters were analysed: acute success rate, fluoroscopy time, procedure time, complications [major: pericardial tamponade, permanent atrioventricular (AV) block, major bleeding, and death; minor: minor bleeding and temporary AV block]. Recurrence rate was assessed during follow-up (15 ± 9.5 months). Subgroup analysis was performed for the following groups: atrial fibrillation, isthmus dependent and atypical atrial flutter, atrial tachycardia, AV nodal re-entrant tachycardia, circus movement tachycardia, and ventricular tachycardia (VT). Magnetic navigation system was associated with less major complications (0.34 vs. 3.2%, P = 0.01). The total numbers of complications were lower in group MNS (4.5 vs. 10%, P = 0.005). Magnetic navigation system was equally effective as MAN in acute success rate for overall groups (92 vs. 94%, P = ns). Magnetic navigation system was more successful for VTs (93 vs. 72%, P < 0.05). Less fluoroscopy was used in group MNS (30 ± 20 vs. 35 ± 25 min, P < 0.01). There were no differences in procedure times and recurrence rates for the overall groups (168 ± 67 vs. 159 ± 75 min, P = ns; 14 vs. 11%, P = ns; respectively). Conclusions Our data suggest that the use of MNS improves safety without compromising efficiency of ablations. Magnetic navigation system is more effective than manual ablation for VTs. PMID:21508006

  11. The magnetic navigation system allows safety and high efficacy for ablation of arrhythmias.

    PubMed

    Bauernfeind, Tamas; Akca, Ferdi; Schwagten, Bruno; de Groot, Natasja; Van Belle, Yves; Valk, Suzanne; Ujvari, Barbara; Jordaens, Luc; Szili-Torok, Tamas

    2011-07-01

    We aimed to evaluate the safety and long-term efficacy of the magnetic navigation system (MNS) in a large number of patients. The MNS has the potential for improving safety and efficacy based on atraumatic catheter design and superior navigation capabilities. In this study, 610 consecutive patients underwent ablation. Patients were divided into two age- and sex-matched groups. Ablations were performed either using MNS (group MNS, 292) or conventional manual ablation [group manual navigation (MAN), 318]. The following parameters were analysed: acute success rate, fluoroscopy time, procedure time, complications [major: pericardial tamponade, permanent atrioventricular (AV) block, major bleeding, and death; minor: minor bleeding and temporary AV block]. Recurrence rate was assessed during follow-up (15±9.5 months). Subgroup analysis was performed for the following groups: atrial fibrillation, isthmus dependent and atypical atrial flutter, atrial tachycardia, AV nodal re-entrant tachycardia, circus movement tachycardia, and ventricular tachycardia (VT). Magnetic navigation system was associated with less major complications (0.34 vs. 3.2%, P=0.01). The total numbers of complications were lower in group MNS (4.5 vs. 10%, P=0.005). Magnetic navigation system was equally effective as MAN in acute success rate for overall groups (92 vs. 94%, P=ns). Magnetic navigation system was more successful for VTs (93 vs. 72%, P<0.05). Less fluoroscopy was used in group MNS (30±20 vs. 35±25 min, P<0.01). There were no differences in procedure times and recurrence rates for the overall groups (168±67 vs. 159±75 min, P=ns; 14 vs. 11%, P=ns; respectively). Our data suggest that the use of MNS improves safety without compromising efficiency of ablations. Magnetic navigation system is more effective than manual ablation for VTs.

  12. Safety and efficacy of ranirestat in patients with mild-to-moderate diabetic sensorimotor polyneuropathy.

    PubMed

    Polydefkis, Michael; Arezzo, Joseph; Nash, Marshall; Bril, Vera; Shaibani, Aziz; Gordon, Robert J; Bradshaw, Kate L; Junor, Roderick W J

    2015-12-01

    We examined the efficacy and safety of ranirestat in patients with diabetic sensorimotor polyneuropathy (DSPN). Patients (18-75 years) with stable type 1/2 diabetes mellitus and DSPN were eligible for this global, double-blind, phase II/III study (ClinicalTrials.gov NCT00927914). Patients (n = 800) were randomized 1 : 1 : 1 to placebo, ranirestat 40 mg/day or 80 mg/day (265 : 264 : 271). Change in peroneal motor nerve conduction velocity (PMNCV) from baseline to 24 months was the primary endpoint with a goal improvement vs. placebo ≥1.2 m/s. Other endpoints included symptoms, quality-of-life, and safety. Six hundred thirty-three patients completed the study. The PMNCV difference from placebo was significant at 6, 12, and 18 months in both ranirestat groups, but <1.2 m/s. The mean improvement from baseline at 24 months was +0.49, +0.95, and +0.90 m/s for placebo, ranirestat 40 mg and 80 mg, respectively (NS). The treatment difference vs. placebo reached significance when ranirestat groups were combined in a post hoc analysis (+0.44 m/s; p = 0.0237). There was no effect of ranirestat on safety assessments, secondary or exploratory endpoints vs. placebo. Ranirestat was well tolerated and improved PMNCV, but did not achieve any efficacy endpoints. The absence of PMNCV worsening in the placebo group underscores the challenges of DSPN studies in patients with well-controlled diabetes. © 2015 Peripheral Nerve Society.

  13. Antihypertensive efficacy and safety of the angiotensin receptor blocker azilsartan in elderly patients with hypertension.

    PubMed

    Kamada, Tomohito; Hayashi, Mutsuharu; Fujiwara, Wakaya; Yoshikawa, Daiji; Mukaide, Daisuke; Sugishita, Yoshinori; Yoshinaga, Masataka; Itoh, Takehiro; Yokoi, Hiroatsu; Ishii, Junichi; Watanabe, Eiichi; Ozaki, Yukio; Izawa, Hideo

    2017-01-01

    The number of elderly patients with hypertension has been steadily increasing. However, there are limited data on the safety and efficacy of the new angiotensin type 1 receptor blocker (ARB) azilsartan in elderly patients with hypertension. We investigated the clinical efficacy and safety of azilsartan in this population. The study population comprised 56 ambulatory patients with essential hypertension. We evaluated the reduction in blood pressure and safety after 12 weeks of treatment with azilsartan in 29 hypertensive patients ≥65 years of age (aged group) in comparison with the findings in 27 patients <65 years of age (non-aged group). Systolic blood pressure in the aged group declined significantly from 155 ± 18 mmHg at baseline to 138 ± 11 mmHg after 12 weeks of treatment with azilsartan, and that in the non-aged group also declined significantly from 152 ± 20 mmHg at baseline to 142 ± 13 mmHg after 12 weeks of treatment with azilsartan. There were no significant differences in the magnitude of change in blood pressures from pre-treatment to post-treatment with azilsartan between the non-aged and aged groups. There were no changes in clinical laboratory findings, including serum levels of creatinine, potassium, lipids, and other metabolic variables, after 12 weeks of treatment with azilsartan in both groups. Our findings suggest that azilsartan is effective in lowering blood pressure in elderly patients and may be safe. Therefore, azilsartan could be a valuable option for treating hypertension in elderly and non-elderly patients.

  14. A randomized trial of telemedicine efficacy and safety for nonacute headaches.

    PubMed

    Müller, Kai I; Alstadhaug, Karl B; Bekkelund, Svein I

    2017-07-11

    To evaluate long-term treatment efficacy and safety of one-time telemedicine consultations for nonacute headaches. We randomized, allocated, and consulted nonacute headache patients via telemedicine (n = 200) or in a traditional manner (n = 202) in a noninferiority trial. Efficacy endpoints, assessed by questionnaires at 3 and 12 months, included change from baseline in Headache Impact Test-6 (HIT-6) (primary endpoint) and pain intensity (visual analogue scale [VAS]) (secondary endpoint). The primary safety endpoint, assessed via patient records, was presence of secondary headache within 12 months after consultation. We found no differences between telemedicine and traditional consultations in HIT-6 ( p = 0.84) or VAS ( p = 0.64) over 3 periods. The absolute difference in HIT-6 from baseline was 0.3 (95% confidence interval [CI] -1.26 to 1.82, p = 0.72) at 3 months and 0.2 (95% CI -1.98 to 1.58, p = 0.83) at 12 months. The absolute change in VAS was 0.4 (95% CI -0.93 to 0.22, p = 0.23) after 3 months and 0.3 (95% CI -0.94 to 0.29, p = 0.30) at 12 months. We found one secondary headache in each group at 12 months. The estimated number of consultations needed to miss one secondary headache with the use of telemedicine was 20,200. Telemedicine consultation for nonacute headache is as efficient and safe as a traditional consultation. NCT02270177. This study provides Class III evidence that a one-time telemedicine consultation for nonacute headache is noninferior to a one-time traditional consultation regarding long-term treatment outcome and safety. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

  15. Intermediate term safety and efficacy of transscleral cyclophotocoagulation after tube shunt failure

    PubMed Central

    Ness, Peter J.; Khaimi, Mahmoud A.; Feldman, Robert M.; Tabet, Rania; Sarkisian, Steven R.; Skuta, Gregory L.; Chuang, Alice Z.; Mankiewicz, Kimberly A.

    2011-01-01

    Purpose To determine the efficacy and safety of diode transscleral cyclophotocoagulation (TSCPC) after tube shunt failure. Patients and Methods The patient population consisted of 32 eyes of 31 patients with uncontrolled glaucoma. Each eye had a previously implanted aqueous tube shunt and was currently on maximally tolerated medication. Each eye also underwent TSCPC treatment using the Iridex (Mountain View, CA) diode laser with a maximum of 360 degrees of treatment. All 31 charts were reviewed for data pertaining to demographics, treatment, ocular history, and follow-up clinical examinations. Safety was evaluated by complication data. Efficacy was evaluated in terms of TSCPC treatment parameters (number of laser applications, laser power, application duration, and degrees of ciliary body treated), intraocular pressure (IOP), number of hypotensive medications, and any further treatment required. Results With a mean (SD) follow-up of 17.1 (16.3) (median = 11.7) months from the last treatment, the mean IOP decreased from 28.6 (10.2) mmHg to 16.8 (7.5) mmHg (35% reduction) at 3 months (n = 30, p < 0.0001) and to 14.7 (7.9) mmHg (43% reduction) at 1 year (n = 13, p < 0.0001). Complications included hypotony (n = 4), hyphema (n = 2), failed corneal transplant (n = 1), and loss of light perception (n = 5). Conclusions TSCPC has a significant ocular hypotensive effect on glaucoma refractory to both tube shunt and medical therapy. The safety of this intervention remains unclear in this high risk patient population and warrants further study. PMID:21336148

  16. Safety and Efficacy of Topical Chitogel- Deferiprone-Gallium Protoporphyrin in Sheep Model.

    PubMed

    Ooi, Mian L; Richter, Katharina; Drilling, Amanda J; Thomas, Nicky; Prestidge, Clive A; James, Craig; Moratti, Stephen; Vreugde, Sarah; Psaltis, Alkis J; Wormald, Peter-John

    2018-01-01

    Objectives: Increasing antimicrobial resistance has presented new challenges to the treatment of recalcitrant chronic rhinosinusitis fuelling a continuous search for novel antibiofilm agents. This study aimed to assess the safety and efficacy of Chitogel (Chitogel®, Wellington New Zealand) combined with novel antibiofilm agents Deferiprone and Gallium Protoporphyrin (CG-DG) as a topical treatment against S. aureus biofilms in vivo . Methods: To assess safety, 8 sheep were divided into two groups of 7 day treatments ( n = 8 sinuses per treatment); (1) Chitogel (CG) with twice daily saline flush, and (2) CG-DG gel with twice daily saline flush. Tissue morphology was analyzed using histology and scanning electron microscopy (SEM). To assess efficacy we used a S. aureus sheep sinusitis model. Fifteen sheep were divided into three groups of 7 day treatments ( n = 10 sinuses per treatment); (1) twice daily saline flush (NT), (2) Chitogel (CG) with twice daily saline flush, and (3) CG-DG gel with twice daily saline flush. Biofilm biomass across all groups was compared using LIVE/DEAD BacLight stain and confocal scanning laser microscopy. Results: Safety study showed no cilia denudation on scanning electron microscopy and no change in sinus mucosa histopathology when comparing CG-DG to CG treated sheep. COMSTAT2 assessment of biofilm biomass showed a significant reduction in CG-DG treated sheep compared to NT controls. Conclusion: Results indicate that CG-DG is safe and effective against S. aureus biofilms in a sheep sinusitis model and could represent a viable treatment option in the clinical setting.

  17. A comprehensive review on the efficacy of S-Adenosyl-L-methionine in Major Depressive Disorder.

    PubMed

    De Berardis, Domenico; Orsolini, Laura; Serroni, Nicola; Girinelli, Gabriella; Iasevoli, Felice; Tomasetti, Carmine; de Bartolomeis, Andrea; Mazza, Monica; Valchera, Alessandro; Fornaro, Michele; Perna, Giampaolo; Piersanti, Monica; Di Nicola, Marco; Cavuto, Marilde; Martinotti, Giovanni; Di Giannantonio, Massimo

    2016-01-01

    To review the antidepressant efficacy of S-Adenosyl-L-Methionine (SAMe) both in monotherapy and/or in augmentation with antidepressants to better understand its potential role in the treatment of patients with Major Depressive Disorder (MDD) and Treatment-Resistant Depression (TRD). A MEDLINE/PubMed search was carried out by using the following set of keywords: ((SAMe OR SAdenosyl- L-Methionine) AND (major depressive disorder OR depression)). Data Selection and Data Extraction: No language or time restrictions were placed on the electronic searches. Randomized controlled trials and open trials involving humans were here included and analyzed. The references