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

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

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…

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

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.

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.

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.

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.

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

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.

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

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

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.

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

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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

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.

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

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.

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.

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.

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 (�

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.

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.

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.

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

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.

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

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

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

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

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.

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.

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.

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

PubMed

Veazey, Ronald S

2008-09-01

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

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

PubMed Central

Veazey, Ronald S.

2009-01-01

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

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.

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…

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.

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…

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.

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.

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

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.

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.

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

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.

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

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

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.

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

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.

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.

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

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

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

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.

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.

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…

The efficacy of cognitive-behavioral therapy for eating disorders: A systematic review and meta-analysis.

PubMed

Linardon, Jake; Wade, Tracey D; de la Piedad Garcia, Xochitl; Brennan, Leah

2017-11-01

This meta-analysis examined the efficacy of cognitive-behavioral therapy (CBT) for eating disorders. Randomized controlled trials of CBT were searched. Seventy-nine trials were included. Therapist-led CBT was more efficacious than inactive (wait-lists) and active (any psychotherapy) comparisons in individuals with bulimia nervosa and binge eating disorder. Therapist-led CBT was most efficacious when manualized CBT-BN or its enhanced version was delivered. No significant differences were observed between therapist-led CBT for bulimia nervosa and binge eating disorder and antidepressants at posttreatment. CBT was also directly compared to other specific psychological interventions, and therapist-led CBT resulted in greater reductions in behavioral and cognitive symptoms than interpersonal psychotherapy at posttreatment. At follow-up, CBT outperformed interpersonal psychotherapy only on cognitive symptoms. CBT for binge eating disorder also resulted in greater reductions in behavioral symptoms than behavioral weight loss interventions. There was no evidence that CBT was more efficacious than behavior therapy or nonspecific supportive therapies. CBT is efficacious for eating disorders. Although CBT was equally efficacious to certain psychological treatments, the fact that CBT outperformed all active psychological comparisons and interpersonal psychotherapy specifically, offers some support for the specificity of psychological treatments for eating disorders. Conclusions from this study are hampered by the fact that many trials were of poor quality. Higher quality RCTs are essential. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

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

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

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

[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.

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.

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.

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.

[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.

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

PubMed

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

2017-01-01

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

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.

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

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.

[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.

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.

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.

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…

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

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

PubMed Central

West, Jonathan; Ogston, Simon; Foerster, John

2016-01-01

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

Efficacy 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

[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.

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.

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

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

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.

Safety of Carbamazepine Extended-Release Capsules Used in Combination with Other Psychotropic Medications for the Treatment of Bipolar I Disorder

PubMed Central

Weisler, Richard H.; Kalali, Amir H.; Cutler, Andrew J.; Gazda, Thomas D.; Ginsberg, Lawrence

2008-01-01

Objective To evaluate the safety and efficacy of carbamazepine extended-release capsules (CBZ-ERC) in combination with other psychotropic medications for the treatment of bipolar I disorder. Design In this Phase IIIb, open-label, eight-week, observational, polypharmacy study, adult subjects were started on CBZ-ERC 200mg and titrated over four weeks to optimal dose (1600mg/d maximum). Concomitant lithium and atypical antipsychotics (olanzapine, risperidone, quetiapine, aripiprazole) were permitted. Safety assessments included adverse events, laboratory parameters, physical examination, medication history, vital signs, and electrocardiogram. Efficacy measures included the Young Mania Rating Scale (YMRS), Hamilton Rating Scale for Depression (HAM-D), Montgomery-Åsberg Depression Rating Scale (MADRS), and Clinical Global Impressions Scale–Bipolar Version (CGI-BP). All data were summarized using descriptive statistics. Results Overall, 45 (84.9%) subjects reported treatment-emergent adverse events (TEAEs); most were mild or moderate in severity. The most commonly reported TEAEs were somnolence (n=14, 26.4%), sedation (n=12, 22.6%), dizziness (n=11, 20.8%), headache (n=9, 17.0%), and nausea (n=7, 13.2%). There were no clinically significant changes in vital signs, including weight. Mean changes in laboratory parameters were small, with values that were within the normal range for the majority of subjects. Few changes relative to screening for other safety parameters occurred. Mean total YMRS score decreased from baseline at each study visit. HAM-D and MADRS scores decreased from baseline at Weeks 4 and 8, and all three CGI-BP components (overall bipolar disorder, mania, and depression) improved during the study. Conclusion CBZ-ERC appears to be safe and effective for use in combination with atypical antipsychotics and lithium for treatment of bipolar I disorder. PMID:19727252

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

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.

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

[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

Safety and efficacy of ipragliflozin in Japanese patients with type 2 diabetes in real-world clinical practice: interim results of the STELLA-LONG TERM post-marketing surveillance study.

PubMed

Nakamura, Ichiro; Maegawa, Hiroshi; Tobe, Kazuyuki; Tabuchi, Hiromi; Uno, Satoshi

2018-02-01

Data regarding the efficacy and safety of sodium-glucose cotransporter 2 inhibitors in the real-world setting in Japan are limited. The STELLA-LONG TERM study is an ongoing 3-year post-marketing surveillance study of ipragliflozin in type 2 diabetes (T2D) patients. Here, we report the interim results (including 3-, 12-, and 24-month data). All Japanese patients with T2D who were first prescribed ipragliflozin between 17 July 2014 and 16 October 2015 at participating centers in Japan were registered in STELLA-LONG TERM. At 3, 12, and 24 months, the safety analysis set comprised 11,053, 5475, and 138 patients, respectively; the efficacy analysis set comprised 8757 patients. Ipragliflozin treatment resulted in statistically significant improvements versus baseline in hemoglobin A1c, fasting plasma glucose concentration, body weight, blood pressure, heart rate, and serum concentrations of low-density lipoprotein cholesterol and triglycerides. The adverse drug reaction incidence rate was 10.71%, the most common reactions being renal and urinary disorders (5.06%), infections and infestations (1.24%), and skin and subcutaneous tissue disorders (1.14%). Ipragliflozin was well tolerated and effective in Japanese patients with T2D; no new safety issues were identified.

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.

Impact of IgG Fc-Oligosaccharides on Recombinant Monoclonal Antibody Structure, Stability, Safety, and Efficacy.

PubMed

Liu, Hongcheng; Nowak, Christine; Andrien, Bruce; Shao, Mei; Ponniah, Gomathinayagam; Neill, Alyssa

2017-09-01

Glycosylation of the conserved asparagine residue in the CH2 domain is the most common posttranslational modification of recombinant monoclonal antibodies. Ideally, a consistent oligosaccharide profile should be maintained from early clinical material to commercial material for the development of recombinant monoclonal therapeutics, though variation in the profile is a typical result of process changes. The risk of oligosaccharide variation posed to further development is required to be thoroughly evaluated based on its impact on antibody structure, stability, efficacy and safety. The variation should be controlled within a range so that there is no detrimental impact on safety and efficacy and thus allowing the use of early phase safety and efficacy data to support project advancement to later phase. This review article focuses on the current scientific understanding of the commonly observed oligosaccharides found in recombinant monoclonal antibodies and their impact on structure, stability and biological functions, which are the basis to evaluate safety and efficacy. It also provides a brief discussion on critical quality attribute (CQA) assessment with regard to oligosaccharides based on the mechanism of action (MOA). © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1173-1181, 2017. © 2017 American Institute of Chemical Engineers.

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…

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

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.).

Comparative efficacy and safety of six antidepressants and anticonvulsants in painful diabetic neuropathy: a network meta-analysis.

PubMed

Rudroju, Neelima; Bansal, Dipika; Talakokkula, Shiva Teja; Gudala, Kapil; Hota, Debasish; Bhansali, Anil; Ghai, Babita

2013-01-01

Anticonvulsants and antidepressants are mostly used in management of painful diabetic neuropathy (PDN). However there are few direct comparisons between drugs of these classes, making evidence-based decision-making in the treatment of painful diabetic neuropathy difficult. This study aimed to perform a network meta-analysis and benefit-risk analysis to evaluate the comparative efficacy and safety of these drugs in PDN treatment. Comparative effectiveness study. Medical Education and Research facility in India. A comprehensive data search was done in PubMed, Cochrane, and Embase up to August 2012. We then systematically reviewed the studies which compared any of 6 drugs for the management of PDN: amitriptyline, duloxetine, gabapentin, pregabalin, valproate, and venlafaxine or any of their combinations. We performed a random-effects network meta-analysis to rank treatments in terms of efficacy and safety. We chose the number of patients experiencing = 50% reduction in pain and number of patient withdrawals due to adverse events (AE) as primary outcomes for efficacy and safety, respectively. We also performed benefit-risk analysis, taking efficacy outcome as benefit and safety outcome as risk. Analysis was intention-to-treat. We included 21 published trials in the analysis. Duloxetine, gabapentin, pregabalin, and venlafaxine were shown to be significantly efficacious compared to placebo with odds ratios (OR) of 2.12, 3.98, 2.78, and 4.43, respectively. Amitriptyline (OR: 7.03, 95% confidence interval [CI]: 1.87, 29.05) and duloxetine (OR: 3.26, 95% CI: 1.04, 9.97) caused more withdrawals than gabapentin. The ranking order of efficacy was gabapentin, venlafaxine, pregabalin, duloxetine/gabapentin, duloxetine, amitriptyline, and placebo and the ranking order of safety was placebo, gabapentin, pregabalin, venlafaxine, duloxetine/gabapentin combination, duloxetine, and amitriptyline. Benefit-risk balance favored the order: gabapentin, venlafaxine, pregabalin, duloxetine

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.

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.

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.

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.

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

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...

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.

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

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.

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.

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…

Melatonin for disordered sleep in individuals with autism spectrum disorders: systematic review and discussion.

PubMed

Guénolé, Fabian; Godbout, Roger; Nicolas, Alain; Franco, Patricia; Claustrat, Bruno; Baleyte, Jean-Marc

2011-12-01

Sleep disturbance is common in autism spectrum disorders (ASD) and melatonin is widely prescribed in such cases despite a lack of guidelines. The aim of this paper is to provide a systematic review of efficacy and safety of exogenous melatonin for treating disordered sleep in individuals with ASD. We performed a Pubmed(®) documentary search enlarged by a manual review of references, which finally supplied 12 citations (4 case reports, 3 retrospective studies, 2 open-label clinical trials, and 3 placebo-controlled trials). As a whole, we found that the literature supports the existence of a beneficial effect of melatonin on sleep in individuals with ASD, with only few and minor side effects. However, considering the small number of studies and their methodological limits, these conclusions cannot yet be regarded as evidence-based. Randomized controlled trials and long-term follow-up data are still lacking to better assess efficacy and safety of exogenous melatonin for disordered sleep in individuals with ASD. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

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.

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.

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.

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.

Randomized Controlled Trial of Osmotic-Release Methylphenidate with Cognitive-Behavioral Therapy in Adolescents with Attention-Deficit/Hyperactivity Disorder and Substance Use Disorders

ERIC Educational Resources Information Center

Riggs, Paula D.; Winhusen, Theresa; Davies, Robert D.; Leimberger, Jeffrey D.; Mikulich-Gilbertson, Susan; Klein, Constance; Macdonald, Marilyn; Lohman, Michelle; Bailey, Genie L.; Haynes, Louise; Jaffee, William B.; Haminton, Nancy; Hodgkins, Candace; Whitmore, Elizabeth; Trello-Rishel, Kathlene; Tamm, Leanne; Acosta, Michelle C.; Royer-Malvestuto, Charlotte; Subramaniam, Geetha; Fishman, Marc; Holmes, Beverly W.; Kaye, Mary Elyse; Vargo, Mark A.; Woody, George E.; Nunes, Edward V.; Liu, David

2011-01-01

Objective: To evaluate the efficacy and safety of osmotic-release methylphenidate (OROS-MPH) compared with placebo for attention-deficit/hyperactivity disorder (ADHD), and the impact on substance treatment outcomes in adolescents concurrently receiving cognitive-behavioral therapy (CBT) for substance use disorders (SUD). Method: This was a…

[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.

Efficacy and Safety of Once-Weekly Semaglutide for the Treatment of Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

PubMed

Shi, Fang-Hong; Li, Hao; Cui, Min; Zhang, Zai-Li; Gu, Zhi-Chun; Liu, Xiao-Yan

2018-01-01

Background: Semaglutide, a newly once-weekly glucagon like peptide-1 (GLP-1) receptor agonist, has showed a favorable effect on glycaemic control and weight reduction in type 2 diabetes mellitus (T2DM). This meta-analysis was conducted to evaluate the clinical efficacy and safety of semaglutide in T2DM. Methods: A comprehensive searching was performed for Phase III randomized controlled trials (RCTs) which reported the efficacy and safety data of semaglutide and other therapies. The efficacy data expressed as weight mean difference (WMD) and the safety data expressed as risk ratios (RRs) were calculated by employing random-effects model. Heterogeneity was assessed through I 2 test, and subgroup analyses were performed by different control groups, dosage of semaglutide, and durations of follow up. Results: 9 RCTs including 9,773 subjects met the inclusion criteria. For efficacy, compared with other therapies, semaglutide resulted in a significant reduction in glycosylated hemoglobin (weight mean difference, WMD: -0.93%, 95% CI: -1.24 to -0.62, P < 0.001), fasting plasma glucose (WMD: -1.15 mmol/L, 95% CI: -1.67 to -0.63, P < 0.001), mean self-monitoring of plasma glucose (WMD: -1.19 mmol/L, 95% CI: -1.68 to -0.70, P < 0.001), body weight (WMD: -3.47 kg, 95% CI: -3.96 to -2.98, P < 0.001), body mass index (WMD: -1.25 kg/m 2 , 95% CI: -1.45 to -1.04, P < 0.001), systolic blood pressure (WMD: -2.55 mmHg, 95% CI: -3.22 to -1.88, P < 0.001), with the exception of negative result of diastolic blood pressure (WMD: -0.29 mmHg, 95% CI: -0.65 to 0.07, P = 0.113) and increased impact on pulse rate (WMD: -2.21, 95% CI: 1.54 to 2.88, P < 0.001). The results were consistent across the key subgroups. For safety, semaglutide did not increase the risk of any adverse events, hypoglycemia and pancreatitis, but induced a higher risk of gastrointestinal disorders when compared with other therapies (RR: 1.98, 95%CI: 1.49 to 2.62, P < 0.001). Conclusion: Semaglutide was effective and

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

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

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…

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

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.

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

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.

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

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.

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

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.

The efficacy of systemic therapy for childhood and adolescent externalizing disorders: a systematic review of 47 RCT.

PubMed

von Sydow, Kirsten; Retzlaff, Ruediger; Beher, Stefan; Haun, Markus W; Schweitzer, Jochen

2013-12-01

Systemic (family) therapy is a widely used psychotherapy approach. However, most systematic efficacy reviews have focused solely on "family-based treatment" rather than on the theoretic orientation "systemic therapy." We systematically review trials on the efficacy of systemic therapy for the treatment of childhood and adolescent externalizing disorders. All randomized (or matched) controlled trials (RCT) evaluating systemic/systems-oriented therapy in various forms (family, individual, group, multi-family group therapy) with child or adolescent index patients (0-17 years) suffering from mental disorders were identified by data base searches and cross-references. Inclusion criteria were as follows: index patient diagnosed with a DSM- or ICD-listed mental disorder, and trial published in any language up to the end of 2011. The RCTs were analyzed for their research methodology, interventions applied, and results (postintervention; follow-up). A total of 47 trials from the United States, Europe, and China, published in English, German, and Mandarin, were identified. A total of 42 of them showed systemic therapy to be efficacious for the treatment of attention deficit hyperactivity disorders, conduct disorders, and substance use disorders. Results were stable across follow-up periods of up to 14 years. There is a sound evidence base for the efficacy of systemic therapy for children and adolescents (and their families) diagnosed with externalizing disorders. © FPI, Inc.

[Relationship between perceptions of safety climate at workplace and depressive disorders in manufacturing workers].

PubMed

Liu, Xu-hua; Xiao, Ya-ni; Huang, Zhi-xiong; Huang, Shao-bin; Cao, Xiao-ou; Guan, Dong-bo; Chen, Wei-qing

2013-04-01

To investigate the risk factors for depressive disorders in manufacturing workers and to provide a basis for developing health promotion measures at workplace. A questionnaire survey was performed in 8085 front-line production workers from 33 manufacturing enterprises in Nanhai District of Foshan, Guangdong Province, China. The questionnaire contained a survey of demographic characteristics, the Safety Climate Scale, the Center for Epidemiological Studies Depression Scale, etc. The multilevel logistic regression analysis was applied to investigate the risk factors for depressive disorders in workers. A total of 6260 workers completed the survey; their mean age was 31.1 ± 8.6 years, and 53.2% of them were males. The multilevel logistic regression analysis showed that after adjustment for sociodemographic factors such as age, sex, and martial status, more depressive disorders were reported in the enterprises with higher score of "production safety training" than in those with lower score (OR = 1.46, 95%CI = 1.07 ∼ 1.97); fewer depressive disorders were reported in the enterprises with higher score of "colleagues concerned about production safety" than in those with lower score (OR = 0.08, 95%CI = 0.03 ∼ 0.26); the relationships of "safety warnings and precautions" and "managers concerned about production safety" with workers' depressive disorders were not statistically significant (OR = 0.78, 95%CI = 0.48 ∼ 1.28; OR = 1.08, 95%CI = 0.68 ∼ 1.72). Depressive disorders in manufacturing workers are related to the safety climate at workplace, which indicates that a good safety climate at workplace should be created to prevent and control depressive disorders in workers.

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

Pharmacotherapy of anxiety disorders: a critical review

PubMed Central

Koen, Nastassja; Stein, Dan J.

2011-01-01

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

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

Efficacy of multisystemic therapy in youths aged 10-17 with severe antisocial behaviour and emotional disorders: systematic review.

PubMed

Tan, Jia Xuan; Fajardo, Maria Lourdes Restrepo

2017-11-01

Antisocial behaviour and conduct disorders are the most common behavioural and mental health problems in children and young people globally. An efficacious intervention is needed to manage these antisocial behaviours that have costly consequences. Multisystemic Therapy (MST), an intensive home-based intervention for youths with psychosocial and behavioural problems, is recommended under National Institute for Health and Clinical Excellence guidelines for conduct disorder. However, reviews on the efficacy of MST are mixed. To review randomised controlled trials (RCTs) reporting efficacy of MST among youths presenting with antisocial behaviour and emotional disorder respectively. A systematic map term to subject heading search was conducted in PsycINFO, Embase, and Ovid Medline databases for articles up to November 2015. RCTs comparing MST vs.treatment as usual (TAU) in youths presenting with antisocial behaviour and emotional disorder were included. 12 RCTs ( n  = 1425) reported efficacy of MST vs. TAU in youths presenting with antisocial behaviour and emotional disorder. Clinically significant treatment effects of MST showed a reduction of antisocial behaviour which includes delinquency. MST, vs. psychiatric hospitalisation, was associated with a reduction of suicidal attempts in youths presenting with psychiatric emergencies. 4 studies showed that MST was less costly than TAU in the short term, with further analysis required for long-term cost-effectiveness. MST is an efficacious intervention for severe antisocial behaviours in reduction of delinquency and should be included in clinical practices. MST was shown to have a positive effect on emotional disorder but further research is needed to evaluate the efficacy of MST with emotional disorder. Further analysis is required to assess the services utilized for long-term cost effectiveness.

A Comparison Study of Quetiapine and Risperidone's Effectiveness and Safety on Treating Alcohol-induced Mental Disorder.

PubMed

Lv, Bei; Duan, Haishui

2016-08-25

Compared with Risperidone, Quetiapine's effectiveness and safety on treating alcohol-induced mental disorder is still unclear. To investigate the clinical effectiveness and safety of Quetiapine on treating alcohol-induced mental disorder. One hundred and forty-eight patients with alcohol-induced mental disorder were divided into the experimental group (75 patients) and the control group (73 patients) by the treatments they received. The patients in the experimental group were treated with Quetiapine by taking it three times per day orally. The mean (sd) maintenance dose was 151.2(27.3) mg/d, and the treatment cycle was 6 weeks. Patients in the control group received Risperidone once per day orally with a mean (sd) maintenance dose being 2.3(0.9) mg/d, and the treatment cycle was 6 weeks as well. The PANSS scale was used to assess patients' before and after treatment. The researchers also observed any adverse reactions in both treatment strategies and evaluated the effectiveness and safety of both treatment strategies. The mean (sd) PANSS scale score of the experimental group after two weeks of treatment was 71.9 (10.2), which was clearly better than the mean (sd) score before treatment (82.6 [11.4]), and was significantly better than the control group's mean (sd) score after two weeks (76.5[12.8]). Also, the experimental group's scores after 4 weeks of treatment and 6 weeks of treatment were significantly better than the control group. The experimental group's efficacy rate (94.7%) was higher than the control group's (90.4%); the cure rate of the experimental group (33.3%) was higher than that of the control group (24.7%), and the difference was statistically significant. The rates of adverse reactions in the experimental and control groups were 13.3% and 19.2% respectively, and they were significantly different from each other. Treating alcohol-induced mental disorder with Quetiapine is more effective than treating it with Risperidone. Quetiapine can improve

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.

Psychological Treatment of Depression in People Aged 65 Years and Over: A Systematic Review of Efficacy, Safety, and Cost-Effectiveness

PubMed Central

Jonsson, Ulf; Bertilsson, Göran; Gyllensvärd, Harald; Söderlund, Anne; Tham, Anne; Andersson, Gerhard

2016-01-01

Objectives Depression in elderly people is a major public health concern. As response to antidepressants is often unsatisfactory in this age group, there is a need for evidence-based non-pharmacological treatment options. Our objectives were twofold: firstly, to synthesize published trials evaluating efficacy, safety and cost-effectiveness of psychological treatment of depression in the elderly and secondly, to assess the quality of evidence. Method The electronic databases PubMed, EMBASE, Cochrane Library, CINAL, Scopus, and PsycINFO were searched up to 23 May 2016 for randomized controlled trials (RCTs) of psychological treatment for depressive disorders or depressive symptoms in people aged 65 years and over. Two reviewers independently assessed relevant studies for risk of bias. Where appropriate, the results were synthesized in meta-analyses. The quality of the evidence was graded according to GRADE (Grading of Recommendations Assessment, Development and Evaluation). Results Twenty-two relevant RCTs were identified, eight of which were excluded from the synthesis due to a high risk of bias. Of the remaining trials, six evaluated problem-solving therapy (PST), five evaluated other forms of cognitive behavioural therapy (CBT), and three evaluated life review/reminiscence therapy. In frail elderly with depressive symptoms, the evidence supported the efficacy of PST, with large but heterogeneous effect sizes compared with treatment as usual. The results for life-review/reminiscence therapy and CBT were also promising, but because of the limited number of trials the quality of evidence was rated as very low. Safety data were not reported in any included trial. The only identified cost-effectiveness study estimated an incremental cost per additional point reduction in Beck Depression Inventory II score for CBT compared with talking control and treatment as usual. Conclusion Psychological treatment is a feasible option for frail elderly with depressive symptoms

Efficacy and safety of tofacitinib in patients with active rheumatoid arthritis: review of key Phase 2 studies.

PubMed

Fleischmann, Roy; Kremer, Joel; Tanaka, Yoshiya; Gruben, David; Kanik, Keith; Koncz, Tamas; Krishnaswami, Sriram; Wallenstein, Gene; Wilkinson, Bethanie; Zwillich, Samuel H; Keystone, Edward

2016-12-01

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Here, the safety and efficacy data from five Phase 2 studies of tofacitinib in patients with RA are summarized. Tofacitinib 1-30 mg twice daily was investigated, as monotherapy and in combination with methotrexate, in patients with RA. Tofacitinib 20 mg once daily was investigated in one study. Tofacitinib 5 and 10 mg twice daily were selected for investigation in Phase 3 studies; therefore, the efficacy and safety of tofacitinib 5 and 10 mg twice daily in Phase 2 studies are the focus of this review. Tofacitinib ≥ 5 mg twice daily was efficacious in a dose-dependent manner, with statistically significant and clinically meaningful reductions in the signs and symptoms of RA and patient-reported outcomes. The safety profile was consistent across studies. The efficacy and safety profile of tofacitinib in Phase 2 studies supported its further investigation and the selection of tofacitinib 5 mg twice daily and tofacitinib 10 mg twice daily for evaluation in Phase 3 studies. © 2016 The Authors. International Journal of Rheumatic Diseases published by Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

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...

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

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.

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

PubMed

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

2012-04-01

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

Efficacy and safety of crizotinib among Chinese EML4-ALK-positive, advanced-stage non-small cell lung cancer patients.

PubMed

Cao, Yabing; Xiao, Guangli; Qiu, Xibin; Ye, Sheng; Lin, Tongyu

2014-01-01

We report the efficacy and safety of crizotinib treatment among Chinese patients with advanced-stage NSCLC. We retrospectively analyzed patients with EML4-ALK positive advanced NSCLC who were treated with crizotinib from May 2012 to Aug 2013. Baseline clinical parameters, treatment protocol, response to therapy and survival were noted. The primary goal was to evaluate the efficacy of crizotinib in patients who were previously treated patients or who had poor ECOG performance status (PS). Forty patients were evaluable for safety and efficacy. Median age was 43 years, 100% had adenocarcinoma and stage IV disease, and 42.5% were female. Six patients received frontline treatment with crizotinib, 17 patients had 1 prior treatment, and 17 patients had more than 2 lines of prior treatment. Patients received a median of 5 cycles of treatment (range 1-15 cycles). After the first cycle, 92.5% (37/40) patients archived partial remission (PR). At the end of the follow-up period, the overall PR rate was 70% (28/40), and progression of disease (PD) occurred in 30% of patients (12/40). The median PFS was 28 weeks (95% CI 15.4 to 40.5 weeks), and median OS was 40 weeks (95% CI 38.6 to 49.3 weeks). The most frequent treatment-related AEs were vomiting (47.5%), vision disorder (27.5%) and increased ALT/AST (42%); most toxicities were Grade 1/2. Observed treatment-related Grade 3/4 AEs included increased ALT/AST (10%) and vomiting (5%). The EML4-ALK fusion rate and number of prior chemotherapy cycles did not appear to significantly affect the efficacy of crizotinib. However, PS 0-2 patients had improved PFS (50 weeks vs. 24 weeks, p = 0.015). Crizotinib was safe, well-tolerated, and effective in Chinese patients with pre-treated ALK-rearranged NSCLC. QOL was improved and PS appears to have an effect on the efficacy of crizotinib, but prior treatment and ALK fusion rate do not.

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…

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.

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.

Potential role of anticonvulsants in the treatment of obsessive-compulsive and related disorders.

PubMed

Wang, Hee Ryung; Woo, Young Sup; Bahk, Won-Myong

2014-10-01

We reviewed the extant literature to evaluate the current evidence regarding the efficacy and safety of anticonvulsants in the treatment of obsessive-compulsive and related disorders. Relevant literature was accessed using the Cochrane database, embase and PubMed on 29 October 2013. Prospective studies examining the efficacy of anticonvulsants in obsessive-compulsive and related disorders were included. Case reports, case series, and retrospective studies were excluded. A total of 10 studies were included in this review. The studies of obsessive-compulsive disorder, except for two negative studies, showed favorable efficacy results of anticonvulsants. In one study on body dysmorphic disorder, levetiracetam showed favorable efficacy. In two lamotrigine studies for pathologic skin-picking, the efficacy findings were inconsistent. In one trichotillomania study, topiramate had reduced hair-pulling symptoms. Despite limited evidence, our review suggests that anticonvulsants have a potential role in the treatment of obsessive-compulsive and related disorders. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

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.

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

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

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.

The efficacy of systemic therapy for internalizing and other disorders of childhood and adolescence: a systematic review of 38 randomized trials.

PubMed

Retzlaff, Ruediger; von Sydow, Kirsten; Beher, Stefan; Haun, Markus W; Schweitzer, Jochen

2013-12-01

Systemic therapy (ST) is one of the most widely applied psychotherapeutic approaches in the treatment of children and adolescents, yet few systematic reviews exist on the efficacy of ST with this age group. Parallel to a similar study on adults, a systematic review was performed to analyze the efficacy of ST in the treatment of children and adolescents. All randomized or matched controlled trials (RCT) evaluating ST in any setting with child and adolescent index patients were identified by database searches and cross-references, as well as in existing meta-analyses and reviews. Inclusion criteria were: index patient diagnosed with a DSM-IV or ICD-10 listed psychological disorder, or suffering from other clinically relevant conditions, and trial published by December 2011. Studies were analyzed according to their sample, research methodology, interventions applied, and results at end-of-treatment and at follow-up. This article presents findings for internalizing and mixed disorders. Thirty-eight trials were identified, with 33 showing ST to be efficacious for the treatment of internalizing disorders (including mood disorders, eating disorders, and psychological factors in somatic illness). There is some evidence for ST being also efficacious in mixed disorders, anxiety disorders, Asperger disorder, and in cases of child neglect. Results were stable across follow-up periods of up to 5 years. Trials on the efficacy of ST for externalizing disorders are presented in a second article. There is a sound evidence base for the efficacy of ST as a treatment for internalizing disorders of child and adolescent patients. © FPI, Inc.

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.

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.

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.

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

Efficacy and Safety of Secukinumab in Elderly Subjects with Moderate to Severe Plaque Psoriasis: A Pooled Analysis of Phase III Studies.

PubMed

Körber, Andreas; Papavassilis, Charis; Bhosekar, Vaishali; Reinhardt, Maximilian

2018-02-01

Psoriasis is a chronic inflammatory skin disease, affecting patients of a wide age range, including elderly patients. Elderly patients can respond differently to drug treatments and can be more vulnerable to adverse reactions. There are limited data on biologic therapies for psoriasis in elderly subjects. Secukinumab, a fully human monoclonal antibody that selectively neutralizes IL-17A, has proven significant efficacy in the treatment of moderate to severe psoriasis. A post-hoc analysis of three phase III trials (ERASURE, FIXTURE and CLEAR) was performed to evaluate the efficacy and safety of secukinumab in elderly subjects. Studies were multicentre, randomized, parallel-group, double-blind, 52-week phase III trials in subjects with moderate to severe plaque psoriasis. For efficacy analyses, 67 elderly subjects (≥ 65 years) treated with secukinumab 300 mg were compared with 841 younger subjects (18-64 years). Psoriasis Area and Severity Index (PASI), Dermatological Life Quality Index (DLQI) and safety were analysed. Elderly subjects had higher baseline frequencies of cardiovascular and metabolic disorders. Secukinumab efficacy in elderly subjects was comparable to that in younger subjects throughout 52 weeks of treatment. PASI 75 response was reached by 81.8% of elderly subjects and 79.4% of younger subjects at Week 52. Similar rates of DLQI 0/1 response were observed. The total rate of adverse events was similar between elderly and younger subjects. Secukinumab at the recommended dose (300 mg) is effective and acceptably safe in subjects aged ≥ 65 years with moderate to severe psoriasis, with quality-of-life benefits, despite an increased prevalence of cardiovascular and metabolic comorbidities in this population.

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…

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

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

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

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.

Preventing necrotizing enterocolitis by food additives in neonates: A network meta-analysis revealing the efficacy and safety.

PubMed

Yu, Wentao; Sui, Wu; Mu, Linsong; Yi, Wenying; Li, Haijuan; Wei, Liqin; Yin, Weihong

2017-05-01

Necrotizing enterocolitis (NEC) is a serious multifactorial gastrointestinal disease which is often discovered in premature infants. Various additives have been used to prevent NEC; yet, their relative efficacy and safety remain disputed. This study aims to compare the efficacy and safety of 5 food additives, namely, probiotics, probiotics + fructo-oligosaccharides, pentoxifylline, arginine, and lactoferrin in preventing NEC in neonates. Embase, PubMed, and Cochrane Library had been searched for all eligible randomized control trials. Odds ratios (ORs) were estimated for dichotomous data and mean differences with 95% credible intervals (CrIs) were estimated for continuous data. Surface under the cumulative ranking curve was used to rank efficacy and safety of the prevention methods on each endpoint. A total of 27 eligible studies with 4649 preterm infants were included in this network meta-analysis (NMA), and the efficacy and safety of 5 food additives were evaluated. Probiotic and arginine exhibited better preventive efficacy compared with placebo (OR = 0.50, 95% CrIs: 0.32-0.73; OR = 0.30, 95% CrIs: 0.12-0.73, respectively). Only probiotic achieved a considerable decrease in the risk of mortality compared to placebo (OR = 0.68, 95% CrIs: 0.46-0.98). NEC patients with lactoferrin appeared to have lower incidence of sepsis than those of placebo (OR = 0.13, 95% CrIs: 0.03-0.61) or probiotic (OR = 0.18, 95% CrIs: 0.03-0.83). Based on this NMA, probiotics had the potential to be the most preferable additive, since it exhibited a significant superiority for NEC and mortality as well as a relatively balanced performance in safety.

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

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

Efficacy and Safety of Once-Weekly Semaglutide for the Treatment of Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

PubMed Central

Shi, Fang-Hong; Li, Hao; Cui, Min; Zhang, Zai-Li; Gu, Zhi-Chun; Liu, Xiao-Yan

2018-01-01

Background: Semaglutide, a newly once-weekly glucagon like peptide-1 (GLP-1) receptor agonist, has showed a favorable effect on glycaemic control and weight reduction in type 2 diabetes mellitus (T2DM). This meta-analysis was conducted to evaluate the clinical efficacy and safety of semaglutide in T2DM. Methods: A comprehensive searching was performed for Phase III randomized controlled trials (RCTs) which reported the efficacy and safety data of semaglutide and other therapies. The efficacy data expressed as weight mean difference (WMD) and the safety data expressed as risk ratios (RRs) were calculated by employing random-effects model. Heterogeneity was assessed through I2 test, and subgroup analyses were performed by different control groups, dosage of semaglutide, and durations of follow up. Results: 9 RCTs including 9,773 subjects met the inclusion criteria. For efficacy, compared with other therapies, semaglutide resulted in a significant reduction in glycosylated hemoglobin (weight mean difference, WMD: −0.93%, 95% CI: −1.24 to −0.62, P < 0.001), fasting plasma glucose (WMD: −1.15 mmol/L, 95% CI: −1.67 to −0.63, P < 0.001), mean self-monitoring of plasma glucose (WMD: −1.19 mmol/L, 95% CI: −1.68 to −0.70, P < 0.001), body weight (WMD: –3.47 kg, 95% CI: −3.96 to −2.98, P < 0.001), body mass index (WMD: –1.25 kg/m2, 95% CI: −1.45 to −1.04, P < 0.001), systolic blood pressure (WMD: −2.55 mmHg, 95% CI: −3.22 to −1.88, P < 0.001), with the exception of negative result of diastolic blood pressure (WMD: −0.29 mmHg, 95% CI: −0.65 to 0.07, P = 0.113) and increased impact on pulse rate (WMD: −2.21, 95% CI: 1.54 to 2.88, P < 0.001). The results were consistent across the key subgroups. For safety, semaglutide did not increase the risk of any adverse events, hypoglycemia and pancreatitis, but induced a higher risk of gastrointestinal disorders when compared with other therapies (RR: 1.98, 95%CI: 1.49 to 2.62, P < 0

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.

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.

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

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

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.

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

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.

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.

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2015-03-14

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

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.

Clinical efficacy, onset time and safety of bright light therapy in acute bipolar depression as an adjunctive therapy: A randomized controlled trial.

PubMed

Zhou, Tian-Hang; Dang, Wei-Min; Ma, Yan-Tao; Hu, Chang-Qing; Wang, Ning; Zhang, Guo-Yi; Wang, Gang; Shi, Chuan; Zhang, Hua; Guo, Bin; Zhou, Shu-Zhe; Feng, Lei; Geng, Shu-Xia; Tong, Yu-Zhen; Tang, Guan-Wen; He, Zhong-Kai; Zhen, Long; Yu, Xin

2018-02-01

Bright light therapy (BLT) is an effective treatment for seasonal affective disorder and non- seasonal depression. The efficacy of BLT in treating patients with bipolar disorder is still unknown. The aim of this study is to examine the efficacy, onset time and clinical safety of BLT in treating patients with acute bipolar depression as an adjunctive therapy (trial registration at ClinicalTrials.gov: NCT02009371). This was a multi-center, single blind, randomized clinical trial. Seventy-four participants were randomized in one of two treatment conditions: BLT and control (dim red light therapy, dRLT). Sixty-three participants completed the study (33 BLT, 30 dRLT). Light therapy lasted for two weeks, one hour every morning. All participants were required to complete several scales assessments at baseline, and at the end of weeks 1 and 2. The primary outcome measures were the clinical efficacy of BLT which was assessed by the reduction rate of HAMD-17 scores, and the onset time of BLT which was assessed by the reduction rate of QIDS-SR16 scores. The secondary outcome measures were rates of switch into hypomania or mania and adverse events. 1) Clinical efficacy: BLT showed a greater ameliorative effect on bipolar depression than the control, with response rates of 78.19% vs. 43.33% respectively (p < 0.01). 2) Onset day: Median onset day was 4.33 days in BLT group. 3) BLT-emergent hypomania: No participants experienced symptoms of hypomania. 4) Side effects: No serious adverse events were reported. BLT can be considered as an effective and safe adjunctive treatment for patients with acute bipolar depression. Copyright © 2017 Elsevier B.V. All rights reserved.

Efficacy and Safety of Oral Beclomethasone Dipropionate in Ulcerative Colitis: A Systematic Review and Meta-Analysis.

PubMed

Manguso, Francesco; Bennato, Raffaele; Lombardi, Giovanni; Riccio, Elisabetta; Costantino, Giuseppe; Fries, Walter

2016-01-01

We performed a systematic review and meta-analysis of all the available evidence comparing efficacy and safety of oral prolonged released beclomethasone dipropionate (BDP) to active oral controls in patients with mild-to-moderate ulcerative colitis (UC). A subgroup-analysis compared the effectiveness of BDP and 5-ASA. Literature research was performed in different databases, as well as manual search to identify abstracts from international meetings with data not included in extensive publications. Experts in the field and companies involved in BDP development and manufacture were contacted to identify unpublished studies used for registration purposes. Dichotomous data were pooled to obtain odds ratio meta-analysis. Five randomized controlled trials that compared oral BDP 5mg/day vs. all oral active controls in treating UC were identified as eligible. Efficacy and safety have been addressed after 4-week treatment period. One study evaluated efficacy and safety of BDP vs. prednisone and 4 of BDP vs. 5-ASA. Treatment with oral BDP 5 mg/day induces a significant better clinical response compared to oral 5-ASA (OR 1.86, 95% CI = 1.23-2.82, P = 0.003). The effect is detectable even when the comparison to prednisone is added (OR 1.41, 95% CI = 1.03-1.93, P = 0.03). Data on remission indicate that the potential clinical efficacy of BDP may be better than 5-ASA (OR 1.55, 95% CI = 1.00-2.40, P = 0.05). This difference is lost when the comparison with prednisone is added (OR 1.30, 95% CI = 0.76-2.23, P = 0.34). The safety analysis showed no differences between BDP and 5-ASA (OR 0.55, 95% CI = 0.24-1.27, P = 0.16). The lack of difference is maintained even when the study with prednisone is added (OR 0.67, 95% CI = 0.44-1.01, P = 0.06). However, the trend of difference is clear and indicates a more favourable safety profile of BDP compared to 5-ASA and PD. Oral prolonged release BDP showed a superior efficacy vs. oral 5-ASA in inducing clinical improvement of mild

Efficacy and Safety of Oral Beclomethasone Dipropionate in Ulcerative Colitis: A Systematic Review and Meta-Analysis

PubMed Central

Bennato, Raffaele; Lombardi, Giovanni; Riccio, Elisabetta; Costantino, Giuseppe; Fries, Walter

2016-01-01

Background and Aim We performed a systematic review and meta-analysis of all the available evidence comparing efficacy and safety of oral prolonged released beclomethasone dipropionate (BDP) to active oral controls in patients with mild-to-moderate ulcerative colitis (UC). A subgroup-analysis compared the effectiveness of BDP and 5-ASA. Methods Literature research was performed in different databases, as well as manual search to identify abstracts from international meetings with data not included in extensive publications. Experts in the field and companies involved in BDP development and manufacture were contacted to identify unpublished studies used for registration purposes. Dichotomous data were pooled to obtain odds ratio meta-analysis. Results Five randomized controlled trials that compared oral BDP 5mg/day vs. all oral active controls in treating UC were identified as eligible. Efficacy and safety have been addressed after 4-week treatment period. One study evaluated efficacy and safety of BDP vs. prednisone and 4 of BDP vs. 5-ASA. Treatment with oral BDP 5 mg/day induces a significant better clinical response compared to oral 5-ASA (OR 1.86, 95% CI = 1.23–2.82, P = 0.003). The effect is detectable even when the comparison to prednisone is added (OR 1.41, 95% CI = 1.03–1.93, P = 0.03). Data on remission indicate that the potential clinical efficacy of BDP may be better than 5-ASA (OR 1.55, 95% CI = 1.00–2.40, P = 0.05). This difference is lost when the comparison with prednisone is added (OR 1.30, 95% CI = 0.76–2.23, P = 0.34). The safety analysis showed no differences between BDP and 5-ASA (OR 0.55, 95% CI = 0.24–1.27, P = 0.16). The lack of difference is maintained even when the study with prednisone is added (OR 0.67, 95% CI = 0.44–1.01, P = 0.06). However, the trend of difference is clear and indicates a more favourable safety profile of BDP compared to 5-ASA and PD. Conclusions Oral prolonged release BDP showed a superior efficacy vs. oral

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).

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

Lurasidone for the Treatment of Irritability Associated with Autistic Disorder

ERIC Educational Resources Information Center

Loebel, Antony; Brams, Matthew; Goldman, Robert S.; Silva, Robert; Hernandez, David; Deng, Ling; Mankoski, Raymond; Findling, Robert L.

2016-01-01

The aim of this study was to evaluate the short-term efficacy and safety of lurasidone in treating irritability associated with autistic disorder. In this multicenter trial, outpatients age 6-17 years who met DSM-IV-TR criteria for autistic disorder, and who demonstrated irritability, agitation, and/or self-injurious behaviors were randomized to…

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.

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.

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

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

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.

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

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.

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…

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.

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.

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.

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.

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.

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.

Collective efficacy: How is it conceptualized, how is it measured, and does it really matter for understanding perceived neighborhood crime and disorder?

PubMed Central

Hipp, John R.

2016-01-01

Building on the insights of the self-efficacy literature, this study highlights that collective efficacy is a collective perception that comes from a process. This study emphasizes that 1) there is updating, as there are feedback effects from success or failure by the group to the perception of collective efficacy, and 2) this updating raises the importance of accounting for members' degree of uncertainty regarding neighborhood collective efficacy. Using a sample of 113 block groups in three rural North Carolina counties, this study finds evidence of updating as neighborhoods perceiving more crime or disorder reported less collective efficacy at the next time point. Furthermore, collective efficacy was only associated with lower perceived disorder at the next time point when it occurred in highly cohesive neighborhoods. Finally, neighborhoods with more perceived disorder and uncertainty regarding collective efficacy at one time point had lower levels of collective efficacy at the next time point, illustrating the importance of uncertainty along with updating. PMID:27069285

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.

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

PubMed

Breech, Lesley L; Braverman, Paula K

2010-08-09

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

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

PubMed Central

Breech, Lesley L; Braverman, Paula K

2010-01-01

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

Randomized controlled trial of false safety behavior elimination therapy: a unified cognitive behavioral treatment for anxiety psychopathology.

PubMed

Schmidt, Norman B; Buckner, Julia D; Pusser, Andrea; Woolaway-Bickel, Kelly; Preston, Jennifer L; Norr, Aaron

2012-09-01

We tested the efficacy of a unified cognitive-behavioral therapy protocol for anxiety disorders. This group treatment protocol, termed false safety behavior elimination therapy (F-SET), is a cognitive-behavioral approach designed for use across various anxiety disorders such as panic disorder (PD), social anxiety disorder (SAD), and generalized anxiety disorder (GAD). F-SET simplifies, as well as broadens, key therapeutic elements of empirically validated treatments for anxiety disorders to allow for easier delivery to heterogeneous groups of patients with anxiety psychopathology. Patients with a primary anxiety disorder diagnosis (N=96) were randomly assigned to F-SET or a wait-list control. Data indicate that F-SET shows good efficacy and durability when delivered to mixed groups of patients with anxieties (i.e., PD, SAD, GAD) by relatively inexperienced clinicians. Findings are discussed in the context of balancing treatment efficacy and clinical utility. Copyright © 2012. Published by Elsevier Ltd.

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.

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

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

ERIC Educational Resources Information Center

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

2006-01-01

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

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.

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.

Efficacy and safety of chloroquine for treatment in patients with uncomplicated Plasmodium vivax infections in endemic countries.

PubMed

Naing, Cho; Aung, Kyan; Win, Daw-Khin; Wah, Mak Joon

2010-11-01

Chloroquine (CQ) is a relatively inexpensive drug for treatment of malaria. If efficacy of CQ is still assumed, then it should be indicated in malaria treatment policies as the drug of choice for uncomplicated Plasmodium vivax malaria in endemic countries with resource constraints. The objective of this review is to summarize the existing evidence on the relative efficacy and safety of CQ in treating patients with uncomplicated P. vivax malaria in endemic countries. We searched online data bases (PUBMED, MEDLINE, EMBASE, The Cochrane Library) and the reference lists of the retrieved articles. Fifteen randomized controlled trials (n=6215) assessing the relative efficacy and safety of CQ for treatment of uncomplicated P. vivax malaria were included. CQ monotherapy was compared to CQ plus primaquine (PQ), artemisinin/artemether, artemisinin based combination therapy, quinine, CQ plus tafenoquine, chlorguanil plus dapsone, azithromycin, or placebo. Treatment efficacy was not significantly different between the CQ monotherapy group and that of the CQ with PQ 14 day group at 28 day follow-up (55/711, 7.7% vs 35/712, 4.9%; P=0.16). Evidence from the trials identified for this review draw a fairly clear conclusion about the relative efficacy and safety of CQ for treating uncomplicated P. vivax malaria infection. However, further research in this field with well powered, randomized, non-inferiority design, using the standardized protocol is needed. Copyright © 2010 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

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

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.

Preliminary examination of the efficacy and safety of a standardized chamomile extract for chronic primary insomnia: a randomized placebo-controlled pilot study.

PubMed

Zick, Suzanna M; Wright, Benjamin D; Sen, Ananda; Arnedt, J Todd

2011-09-22

Despite being the most commonly used herbal for sleep disorders, chamomile's (Matricaria recutita) efficacy and safety for treating chronic primary insomnia is unknown. We examined the preliminary efficacy and safety of chamomile for improving subjective sleep and daytime symptoms in patients with chronic insomnia. We performed a randomized, double-blind, placebo-controlled pilot trial in 34 patients aged 18-65 years with DSM-IV primary insomnia for ≥ 6-months. Patients were randomized to 270 mg of chamomile twice daily or placebo for 28-days. The primary outcomes were sleep diary measures. Secondary outcomes included daytime symptoms, safety assessments, and effect size of these measures. There were no significant differences between groups in changes in sleep diary measures, including total sleep time (TST), sleep efficiency, sleep latency, wake after sleep onset (WASO), sleep quality, and number of awakenings. Chamomile did show modest advantage on daytime functioning, although these did not reach statistical significance. Effect sizes were generally small to moderate (Cohen's d ≤ 0.20 to < 0.60) with sleep latency, night time awakenings, and Fatigue Severity Scale (FSS), having moderate effect sizes in favor of chamomile. However, TST demonstrated a moderate effect size in favor of placebo. There were no differences in adverse events reported by the chamomile group compared to placebo. Chamomile could provide modest benefits of daytime functioning and mixed benefits on sleep diary measures relative to placebo in adults with chronic primary insomnia. However, further studies in select insomnia patients would be needed to investigate these conclusions.

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.

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…

A Randomized Controlled Trial for Veterans with PTSD and Substance Use Disorder: Creating Change versus Seeking Safety.

PubMed

Najavits, Lisa M; Krinsley, Karen; Waring, Molly E; Gallagher, Matthew W; Skidmore, Christopher

2018-02-20

Posttraumatic stress disorder (PTSD) and substance use disorder (SUD) co-occur in military veterans and other populations. To conduct a randomized controlled trial to compare a new past-focused treatment (Creating Change; CC), to a well-established, evidence-based present-focused treatment for PTSD/SUD (Seeking Safety; SS), on symptoms of both disorders. CC guides patients to process the past through exploration of PTSD/SUD life themes and memories whereas SS focuses on coping skills in the present. Fifty-two male and female veterans with current PTSD/SUD were randomized (n = 26 per treatment) and assessed at baseline, end-of-treatment and 3-month follow-up. They received 17 individual one-hour sessions. Intent-to-treat analyses indicated that both conditions improved over time, with no difference between conditions, on PTSD, alcohol use, and drug use (our primary outcomes) as well as mental health symptoms, quality of life, self-efficacy, and SUD cognitions. Effect sizes were medium except for alcohol use, which was large. Change over time reflected improvement from baseline to end-of-treatment, with gains sustained at follow-up, although alcohol use showed continued improvement from end-of-treatment to follow-up. Both treatments evidenced a strong safety profile; and attendance, alliance, and treatment satisfaction were also very strong. Conclusions/importance: CC has promise as a PTSD/SUD therapy with strong public health relevance and the potential to fill important gaps in the field. We used minimal exclusionary criteria to obtain a real-world sample, which was severe-predominantly substance-dependent with chronic PTSD and additional psychiatric diagnoses. Future research is warranted, especially on nonveteran samples and treatment mechanisms of action.

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

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.

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.

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.

Swallowing disorders in Parkinson's disease.

PubMed

Mamolar Andrés, Sandra; Santamarina Rabanal, María Liliana; Granda Membiela, Carla María; Fernández Gutiérrez, María José; Sirgo Rodríguez, Paloma; Álvarez Marcos, César

Parkinson's disease is a type of chronic neurodegenerative pathology with a typical movement pattern, as well as different, less studied symptoms such as dysphagia. Disease-related disorders in efficacy or safety in the process of swallowing usually lead to malnutrition, dehydration or pneumonias. The aim of this study was identifying and analyzing swallowing disorders in Parkinson's disease. The initial sample consisted of 52 subjects with Parkinson's disease to whom the specific test for dysphagia SDQ was applied. Nineteen participants (36.5%) with some degree of dysphagia in the SDQ test were selected to be evaluated by volume-viscosity clinical exploration method and fiberoptic endoscopic evaluation of swallowing. Disorders in swallowing efficiency and safety were detected in 94.7% of the selected sample. With regards to efficiency, disorders were found in food transport (89.5%), insufficient labial closing (68.4%) and oral residues (47.4%), relating to duration of ingestion. Alterations in security were also observed: pharynx residues (52.7%), coughing (47.4%), penetration (31.64%), aspiration and decrease of SaO 2 (5.3%), relating to the diagnosis of respiratory pathology in the previous year. The SDQ test detected swallowing disorders in 36.5% of the subjects with Parkinson's disease. Disorders in swallowing efficiency and safety were demonstrated in 94.7% of this subset. Disorders of efficiency were more frequent than those of safety, establishing a relationship with greater time in ingestion and the appearance of respiratory pathology and pneumonias. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

PRISMA—Efficacy and Safety of Vedolizumab for Inflammatory Bowel Diseases

PubMed Central

Wang, Man Cai; Zhang, Ling Yi; Han, Wei; Shao, Yuan; Chen, Mo; Ni, Rui; Wang, Gen Nian; Wei, Feng Xian; Zhang, Ya Wu; Xu, Xiao Dong; Zhang, You Cheng

2014-01-01

Abstract Vedolizumab is an anti-inflammatory monoclonal antibody that exclusively targets the α4β7 integrin. We aimed to systematically review the efficacy and safety of vedolizumab for patients with inflammatory bowel diseases (IBDs). PubMed, EMBASE, and the Cochrane Library were searched up to May 2014. Randomized controlled trials examining the efficacy or safety of vedolizumab in patients with IBDs were eligible for inclusion. Data were extracted independently by 2 investigators and pooled using Review Manager 5.0 software (The Cochrane Collaboration, Copenhagen). Results were expressed as the relative risk (RR) with 95% confidence intervals (CIs). Six randomized controlled trials involving 2815 patients were eligible for inclusion. Vedolizumab was more effective than placebo for patients with ulcerative colitis and Crohn disease (CD) in clinical response (RR = 1.82, 95% CI, [1.43, 2.31]; RR = 1.46, 95% CI [1.18,1.81]) and clinical remission (RR = 2.23, 95% CI [1.35, 3.68]; RR = 1.71, 95% CI [1.25, 2.34]) during induction therapy. A superior effect was found during maintenance therapy in durable clinical/CD Activity Index-100 response (RR = 2.22, 95% CI [1.62, 3.05]; RR = 1.48, 95% CI [1.13, 1.94]) and clinical remission (RR = 2.55, 95% CI [1.38, 4.70]; RR = 1.15, 95% CI [0.75, 1.77]). However, vedolizumab may be associated with serious adverse events (RR = 1.25, 95% CI [1.03, 1.52]) and nasopharyngitis (RR = 1.56, 95% CI [1.08, 2.25]) for patients with CD. Vedolizumab was more effective than placebo as induction and maintenance therapy for IBDs, with an acceptable short-term safety profile, and achieving cure, although it may be associated with serious adverse events and nasopharyngitis for patients with CD. PMID:25526490

Psilocybin-Assisted Therapy: A Review of a Novel Treatment for Psychiatric Disorders.

PubMed

Thomas, Kelan; Malcolm, Benjamin; Lastra, Dan

2017-01-01

Recent research suggests that functional connectivity changes may be involved in the pathophysiology of psychiatric disorders. Hyperconnectivity in the default mode network has been associated with psychopathology, but psychedelic serotonin agonists like psilocybin may profoundly disrupt these dysfunctional neural network circuits and provide a novel treatment for psychiatric disorders. We have reviewed the current literature to investigate the efficacy and safety of psilocybin-assisted therapy for the treatment of psychiatric disorders. There were seven clinical trials that investigated psilocybin-assisted therapy as a treatment for psychiatric disorders related to anxiety, depression, and substance use. All trials demonstrated reductions in psychiatric rating scale scores or increased response and remission rates. There were large effect sizes related to improved depression and anxiety symptoms. Psilocybin may also potentially reduce alcohol or tobacco use and increase abstinence rates in addiction, but the benefits of these two trials were less clear due to open-label study designs without statistical analysis. Psilocybin-assisted therapy efficacy and safety appear promising, but more robust clinical trials will be required to support FDA approval and identify the potential role in clinical psychiatry.

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

PubMed

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

2017-11-01

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

[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.

Open-Label, Prospective Trial of Olanzapine in Adolescents with Subaverage Intelligence and Disruptive Behavioral Disorders

ERIC Educational Resources Information Center

Handen, Benjamin L.; Hardan, Antonio Y.

2006-01-01

Objective: Olanzapine, an atypical antipsychotic, has been shown to be efficacious for treatment of psychotic and mood disorders in adults. This prospective, open-label study was conducted to examine the safety and usefulness of olanzapine in treating disruptive behavior disorders in adolescents with subaverage intelligence. Method: Sixteen…

Immediate-Release Methylphenidate for ADHD in Children with Comorbid Chronic Multiple Tic Disorder

ERIC Educational Resources Information Center

Gadow, Kenneth D.; Sverd, Jeffrey; Nolan, Edith E.; Sprafkin, Joyce; Schneider, Jayne

2007-01-01

Objective: To examine the safety and efficacy of immediate-release methylphenidate (MPH-IR) for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children (ages 6-12 years) with Tourette's syndrome (96%) or chronic motor tic disorder (4%). Method: Two cohorts of prepubertal children (N = 71) received placebo and three doses of…

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.

5-HT1 receptor augmentation strategies as enhanced efficacy: therapeutics for psychiatric disorders.

PubMed

Dawson, Lee A; Bromidge, Steve M

2008-01-01

Since the initial observations linking 5-HT to psychiatric illness, evidence for a role of 5-HT and, in particular, a decreased brain serotonergic function in the pathology of a plethora of related disorders, has grown. However, it is the role of 5-HT in the pathogenesis of anxiety disorders and depression and the mechanism of action of antidepressants which has received the most attention. Thus enhanced serotonergic neurotransmission has become one of the unifying mechanisms of action of modern day antidepressants/anxiolytics such as monoamine oxidase inhibitors, tricyclic antidepressants, and serotonin reuptake inhibitors. Interestingly all of these treatments are associated with a delay to therapeutic efficacy and in some cases treatment resistance, despite immediate enhancements in serotonergic neurotransmission. The postulated reason for this is the need for temporal neuroplastic changes in the control of serotonergic neurotransmission, and more specifically changes in 5-HT(1) autoreceptor function. Thus significant research has gone into pharmacologically targeting these 5-HT(1) autoreceptors as a means of augmenting the efficacy of current therapeutic mechanisms. Here we will review the rationale behind the various augmentation strategies adopted and the progress made in identifying novel therapeutics for conditions such as depression and anxiety disorders.

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

Attention-deficit/hyperactivity disorder overview. Historical perspective, current controversies, and future directions.

PubMed

Stubbe, D E

2000-07-01

There have been "modern" descriptions of ADHD in the medical literature since 1902. Despite the burgeoning growth of information about the cause, pathophysiology, and effective treatments of the disorder, ADHD has been particularly steeped in controversy, especially regarding the use of medication (safety, efficacy, use or overuse, and concerns about medication treatment of preschool children). Changing diagnostic criteria, evolving conceptualizations of the disorder, and international differences in diagnosis, have enhanced and complicated ongoing research and understanding of the disorder. The recent Multimodal Treatment Study of Children with ADHD, a large, multisite study comparing efficacy of behavioral, medication, and combined treatments, and a recent NIH Consensus Conference on ADHD, represent true advances in the scientific understanding of the disorder and its treatment.

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

PubMed

Friedman, A J; Wheeler, J

1991-04-01

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

A review of the efficacy of atomoxetine in the treatment of attention-deficit hyperactivity disorder in children and adult patients with common comorbidities

PubMed Central

Clemow, David B; Bushe, Chris; Mancini, Michele; Ossipov, Michael H; Upadhyaya, Himanshu

2017-01-01

Attention-deficit hyperactivity disorder (ADHD) is a common neuropsychiatric disorder that is often diagnosed during childhood, but has also increasingly been recognized to occur in adults. Importantly, up to 52% of children (including adolescents) and 87% of adults with ADHD also have a comorbid psychiatric disorder. The presence of a comorbid disorder has the potential to impact diagnosis and could affect treatment outcomes. Atomoxetine is a nonstimulant treatment for ADHD. Despite numerous published studies regarding efficacy of atomoxetine in the treatment of ADHD in patients with comorbid disorders, there is limited information about the impact of individual common comorbid disorders on the efficacy of atomoxetine for ADHD, especially with regard to adults. Moreover, a cumulative review and assessment of these studies has not been conducted. For this reason, we performed a literature review to find, identify, and cumulatively review clinical studies that examined the efficacy of atomoxetine in the treatment of patients with ADHD and comorbid psychiatric disorders. We found a total of 50 clinical studies (37 in children; 13 in adults) that examined the efficacy of atomoxetine in patients with ADHD and a comorbid disorder. The comorbidities that were studied in children or in adults included anxiety, depression, and substance use disorder. Overall, the presence of comorbidity did not adversely impact the efficacy of atomoxetine in treatment of ADHD symptoms in both patient populations. In the studies identified and assessed in this review, atomoxetine did not appear to exacerbate any of the comorbid conditions and could, therefore, be an important therapy choice for the treatment of ADHD in the presence of comorbid disorders. PMID:28223809

Novel Medications to Treat Addictive Disorders

PubMed Central

Montoya, Iván D.; Vocci, Frank

2008-01-01

Recent discoveries about the effects of drugs of abuse on the brain and the mechanisms of their addictions; new chemical compounds, including immunotherapies; and new actions of available medications are offering many opportunities for the discovery and development of novel medications to treat addictive disorders. Furthermore, advancements in the understanding of the genetic and epigenetic basis of drug addiction and the pharmacogenetics of the safety and/or efficacy of the medications are providing opportunities for more individualized pharmacotherapy approaches. Although multiple medications have been investigated for treating addictions, only a handful have shown acceptable safety and efficacy and are approved by the US Food and Drug Administration. This article reviews the current medications that are medically safe and have shown promising results for treating opioid, cocaine, methamphetamine, and cannabis addictions. PMID:18803912

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

PubMed

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

2015-04-01

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

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

Neuromodulation Treatments for Geriatric Mood and Cognitive Disorders.

PubMed

McDonald, William M

2016-12-01

There is increasing evidence for the efficacy of neuromodulation in the treatment of resistant mood disorders and emerging data supporting the use of neuromodulation in cognitive disorders. A significant minority of depressed elders do not respond to pharmacotherapy and/or psychotherapy. This has led clinicians to recommend the increasing use of electroconvulsive therapy (ECT) in the treatment of medication-resistant or life-threatening geriatric depression. Multiple studies have supported the safety and efficacy of ECT in the elderly, yet ECT is associated with side effects including cardiovascular and cognitive side effects. Neuromodulation therapies have the potential for providing effective treatment for treatment-resistant older adults with reduced side effects and this review will outline the risks and benefits of neuromodulation treatment in geriatric psychiatry. There is also emerging evidence of the efficacy of neuromodulation devices in the treatment of cognitive disorders. Pharmacotherapy has been largely ineffective in changing the course of neurodegenerative diseases causing dementia and other treatments are clearly needed. This review will outline the available evidence for neuromodulation in the treatment of mood and cognitive disorders in the elderly. Copyright © 2016 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

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.

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.

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

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.

Preliminary examination of the efficacy and safety of a standardized chamomile extract for chronic primary insomnia: A randomized placebo-controlled pilot study

PubMed Central

2011-01-01

Background Despite being the most commonly used herbal for sleep disorders, chamomile's (Matricaria recutita) efficacy and safety for treating chronic primary insomnia is unknown. We examined the preliminary efficacy and safety of chamomile for improving subjective sleep and daytime symptoms in patients with chronic insomnia. Methods We performed a randomized, double-blind, placebo-controlled pilot trial in 34 patients aged 18-65 years with DSM-IV primary insomnia for ≥ 6-months. Patients were randomized to 270 mg of chamomile twice daily or placebo for 28-days. The primary outcomes were sleep diary measures. Secondary outcomes included daytime symptoms, safety assessments, and effect size of these measures. Results There were no significant differences between groups in changes in sleep diary measures, including total sleep time (TST), sleep efficiency, sleep latency, wake after sleep onset (WASO), sleep quality, and number of awakenings. Chamomile did show modest advantage on daytime functioning, although these did not reach statistical significance. Effect sizes were generally small to moderate (Cohen's d ≤ 0.20 to < 0.60) with sleep latency, night time awakenings, and Fatigue Severity Scale (FSS), having moderate effect sizes in favor of chamomile. However, TST demonstrated a moderate effect size in favor of placebo. There were no differences in adverse events reported by the chamomile group compared to placebo. Conclusion Chamomile could provide modest benefits of daytime functioning and mixed benefits on sleep diary measures relative to placebo in adults with chronic primary insomnia. However, further studies in select insomnia patients would be needed to investigate these conclusions. Trial Registration ClinicalTrials.gov Identifier NCT01286324 PMID:21939549

[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.

[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.

Pharmacokinetic drug evaluation of paliperidone in the treatment of schizoaffective disorder.

PubMed

Macaluso, Matthew; Oliver, Hannah; Sohail, Zohaib

2017-08-01

This paper reviews the pharmacokinetics, receptor binding, clinical efficacy and safety of paliperidone in the treatment of patients with schizoaffective disorder. Areas covered: We reviewed the literature using keywords 'paliperidone', 'schizoaffective disorder' and 'clinical trials' with a focus on seminal data papers and information that is clinically relevant to the treatment of schizoaffective disorder. The purpose of this paper is to provide a clinically oriented review of the pharmacokinetic and pharmacodynamic properties of paliperidone including receptor binding, clinical efficacy, safety and tolerability. Expert opinion: Paliperidone is currently the only medication FDA approved specifically for the treatment of schizoaffective disorder. Paliperidone is an active metabolite of risperidone, is minimally metabolized in the liver and is primarily known to be cleared through the kidneys. For this reason, paliperidone could be considered for some patients with schizoaffective disorder who also have hepatic impairment. After correcting for the reduced protein binding that is characteristic of hepatically impaired patients, the Cmax was 12% lower than in healthy subjects while the AUC and CL/F were comparable [14]. In addition, the availability of long acting injectable formulations may be useful for patients who are non-adherent with oral medications. The cost of paliperidone may be a disadvantage.

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

PubMed

Elbasty, Ahmed; Metcalf, James

2017-12-01

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

The effects of antenatal education on fear of childbirth, maternal self-efficacy and post-traumatic stress disorder (PTSD) symptoms following childbirth: an experimental study.

PubMed

Gökçe İsbir, Gözde; İnci, Figen; Önal, Hatice; Yıldız, Pelin Dıkmen

2016-11-01

Fear of birth and low childbirth self-efficacy is predictive of post-traumatic stress disorder symptoms following childbirth. The efficacy of antenatal education classes on fear of birth and childbirth self-efficacy has been supported; however, the effectiveness of antenatal classes on post-traumatic stress disorder symptoms after childbirth has received relatively little research attention. This study examined the effects of antenatal education on fear of childbirth, maternal self-efficacy and post-traumatic stress disorder symptoms following childbirth. Quasi-experimental study. The study was conducted in a city located in the Middle Anatolia region of Turkey and data were collected between December 2013 and May 2015. Two groups of women were compared-an antenatal education intervention group (n=44), and a routine prenatal care control group (n=46). The Wijma Delivery Expectancy/Experience Questionnaire, Version A and B, Childbirth Self-efficacy Inventory and Impact of Event Scale-Revised was used to assess fear of childbirth, maternal self-efficacy and PTSD symptoms following childbirth. Compared to the control group, women who attended antenatal education had greater childbirth self-efficacy, greater perceived support and control in birth, and less fear of birth and post-traumatic stress disorder symptoms following childbirth (all comparisons, p<0.05). Antenatal education appears to alleviate post-traumatic stress disorder symptoms after childbirth. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Efficacy and safety of acupuncture therapy for nerve deafness: a meta-analysis of randomized controlled trials.

PubMed

Jiang, Yuebo; Shi, Xian; Tang, Yan

2015-01-01

Acupuncture is one of the important parts of therapeutic methods in traditional Chinese medicine, and has been widely used for the treatment of nerve deafness in recent years. The current study was to evaluate the efficacy and safety of acupuncture therapy for nerve deafness compared with conventional medicine therapy. PubMed, the Chinese National Knowledge Infrastructure Database, the Chinese Science and Technology Periodical Database, the Chinese Biomedical Database, the Wanfang Database were searched for articles published to identify randomized controlled trials evaluating efficacy and side effects between acupuncture and conventional medicine therapies up to 2013/06. A total of 12 studies, including 527 patients assessed the efficacy and safety of acupuncture therapy for nerve deafness. Overall, the efficacy of acupuncture was significantly better than that of the conventional western medication (RR: 1.54, 95% CI: 1.36-1.74) or traditional Chinese medicines (RR: 1.51, 95% CI: 1.24-1.84), and the efficacy of acupuncture in combination with conventional western medication or traditional Chinese medicine was better than that of the conventional western medication alone (RR: 1.51, 95% CI: 1.29-1.77) or traditional Chinese medicine alone (RR: 1.59, 95% CI: 1.30-1.95). Based on the comparison of number of deafness patients who were completely cured, the efficacy of acupuncture in combination with traditional Chinese medicines was better than that of traditional Chinese medicine alone (RR: 4.62, 95% CI: 1.38-15.47). Acupuncture therapy can significantly improve the hearing of patients with nerve deafness, and the efficacy of acupuncture in combination with medication is superior to medication alone.

Efficacy and safety of direct oral anticoagulants approved for cardiovascular indications: Systematic review and meta-analysis.

PubMed

Makam, Raghavendra Charan P; Hoaglin, David C; McManus, David D; Wang, Victoria; Gore, Joel M; Spencer, Frederick A; Pradhan, Richeek; Tran, Hoang; Yu, Hong; Goldberg, Robert J

2018-01-01

Direct oral anticoagulants (DOACs) have emerged as promising alternatives to vitamin K antagonists (VKAs) for patients with non-valvular atrial fibrillation (NVAF) or venous thromboembolism (VTE). Few meta-analyses have included all DOACs that have received FDA approval for these cardiovascular indications, and their overall comparisons against VKAs have shortcomings in data and methods. We provide an updated overall assessment of the efficacy and safety of those DOACs at dosages currently approved for NVAF or VTE, in comparison with VKAs. We used data from Phase 3 randomized trials that compared an FDA-approved DOAC with VKA for primary prevention of stroke in patients with NVAF or for treatment of acute VTE. Among trial participants with NVAF, DOAC recipients had a lower risk of stroke or systemic embolism [Pooled Odds Ratio (OR) 0.76, 95% Confidence Interval (CI) (0.68-0.84)], any stroke (0.80, 0.73-0.88), systemic embolism (0.56, 0.34-0.93), and total mortality (0.89, 0.84-0.95). Safety outcomes also showed a lower risk of fatal, major, and intracranial bleeding but higher risk for gastrointestinal bleeding (GIB). Patients with acute VTE randomized to DOACs had comparable risk of recurrent VTE and death (OR 0.88, 95% CI 0.75-1.03), recurrent DVT (0.83, 0.66-1.05), recurrent non-fatal PE (0.97, 0.75-1.25), and total mortality (0.94, 0.79-1.12). Safety outcomes for DOACs showed a lower risk of major, fatal, and intracranial bleeding, but similar risk of GIB. Patients receiving DOACs for NVAF had predominantly superior efficacy and safety. Patients who were treated with DOACs for acute VTE had non-inferior efficacy, but an overall superior safety profile.

Sleep-Related Safety Behaviors and Dysfunctional Beliefs Mediate the Efficacy of Online CBT for Insomnia: A Randomized Controlled Trial.

PubMed

Lancee, Jaap; Eisma, Maarten C; van Straten, Annemieke; Kamphuis, Jan H

2015-01-01

Several trials have demonstrated the efficacy of online cognitive behavioral therapy (CBT) for insomnia. However, few studies have examined putative mechanisms of change based on the cognitive model of insomnia. Identification of modifiable mechanisms by which the treatment works may guide efforts to further improve the efficacy of insomnia treatment. The current study therefore has two aims: (1) to replicate the finding that online CBT is effective for insomnia and (2) to test putative mechanism of change (i.e., safety behaviors and dysfunctional beliefs). Accordingly, we conducted a randomized controlled trial in which individuals with insomnia were randomized to either online CBT for insomnia (n = 36) or a waiting-list control group (n = 27). Baseline and posttest assessments included questionnaires assessing insomnia severity, safety behaviors, dysfunctional beliefs, anxiety and depression, and a sleep diary. Three- and six-month assessments were administered to the CBT group only. Results show moderate to large statistically significant effects of the online treatment compared to the waiting list on insomnia severity, sleep measures, sleep safety behaviors, and dysfunctional beliefs. Furthermore, dysfunctional beliefs and safety behaviors mediated the effects of treatment on insomnia severity and sleep efficiency. Together, these findings corroborate the efficacy of online CBT for insomnia, and suggest that these effects were produced by changing maladaptive beliefs, as well as safety behaviors. Treatment protocols for insomnia may specifically be enhanced by more focused attention on the comprehensive fading of sleep safety behaviors, for instance through behavioral experiments.

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

 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.

The use of sibutramine in the management of obesity and related disorders: An update

PubMed Central

Tziomalos, Konstantinos; Krassas, Gerasimos E; Tzotzas, Themistoklis

2009-01-01

Aims: To review the major trials that evaluated the efficacy and safety of the use of sibutramine for weight loss and the impact of this agent on obesity-related disorders. Methods and results: The most important articles on sibutramine up to January 2009 were located by a PubMed and Medline search. Sibutramine reduces food intake and body weight more than placebo and has positive effects on the lipid profile (mainly triglycerides and high density lipoprotein cholesterol), glycemic control and inflammatory markers in studies for up to one year. Preliminary studies showed that sibutramine may also improve other obesity-associated disorders such as polycystic ovary syndrome, left ventricular hypertrophy, binge eating disorder and adolescent obesity. The high discontinuation rates and some safety issues mainly due to the increase in blood pressure and pulse rate have to be considered. Additionally, it has not yet been established that treatment with sibutramine will reduce cardiovascular events and total mortality. Conclusions: Sibutramine, in conjunction with lifestyle measures, is a useful drug for reducing body weight and improving associated cardiometabolic risk factors and obesity-related disorders. Studies of longer duration are required to determine the precise indications of the drug, to evaluate safety issues and to assess its efficacy on cardiovascular mortality. PMID:19475780

The use of sibutramine in the management of obesity and related disorders: an update.

PubMed

Tziomalos, Konstantinos; Krassas, Gerasimos E; Tzotzas, Themistoklis

2009-01-01

To review the major trials that evaluated the efficacy and safety of the use of sibutramine for weight loss and the impact of this agent on obesity-related disorders. The most important articles on sibutramine up to January 2009 were located by a PubMed and Medline search. Sibutramine reduces food intake and body weight more than placebo and has positive effects on the lipid profile (mainly triglycerides and high density lipoprotein cholesterol), glycemic control and inflammatory markers in studies for up to one year. Preliminary studies showed that sibutramine may also improve other obesity-associated disorders such as polycystic ovary syndrome, left ventricular hypertrophy, binge eating disorder and adolescent obesity. The high discontinuation rates and some safety issues mainly due to the increase in blood pressure and pulse rate have to be considered. Additionally, it has not yet been established that treatment with sibutramine will reduce cardiovascular events and total mortality. Sibutramine, in conjunction with lifestyle measures, is a useful drug for reducing body weight and improving associated cardiometabolic risk factors and obesity-related disorders. Studies of longer duration are required to determine the precise indications of the drug, to evaluate safety issues and to assess its efficacy on cardiovascular mortality.

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

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

The efficacy of motivational interviewing for disordered gambling: systematic review and meta-analysis.

PubMed

Yakovenko, Igor; Quigley, Leanne; Hemmelgarn, Brenda R; Hodgins, David C; Ronksley, Paul

2015-04-01

Motivational interviewing is a client-centered therapeutic intervention that aims to resolve ambivalence toward change. We conducted a systematic review and meta-analysis on the efficacy of motivational interviewing, compared to non-motivational interviewing controls, in the treatment of disordered gambling. Electronic databases were searched for randomized controlled trials that evaluated change in gambling behavior using motivational interviewing in adult disordered gamblers. The primary outcomes were the weighted mean difference (WMD) for change in average days gambled per month and average dollars lost per month. The search strategy yielded 447 articles, of which 20 met criteria for full text review. Overall, 8 studies (N=730) fulfilled the inclusion criteria for systematic review and 5 (N=477) were included in the meta-analysis. Motivational interviewing was associated with significant reduction in gambling frequency up to a year after treatment delivery. For gambling expenditure, motivational interviewing yielded significant reductions in dollars spent gambling compared to non-motivational controls at post-treatment only (1-3 months). Overall, the results of this review suggest that motivational interviewing is an efficacious style of therapy for disordered gambling in the short term. Whether treatment effects are maintained over time remains unclear. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

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

[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.

The efficacy of aerobic exercise and resistance training as transdiagnostic interventions for anxiety-related disorders and constructs: A randomized controlled trial.

PubMed

LeBouthillier, Daniel M; Asmundson, Gordon J G

2017-12-01

Evidence supports exercise as an intervention for many mental health concerns; however, randomized controlled investigations of the efficacy of different exercise modalities and predictors of change are lacking. The purposes of the current trial were to: (1) quantify the effects of aerobic exercise and resistance training on anxiety-related disorder (including anxiety disorders, obsessive-compulsive disorder, and posttraumatic stress disorder) status, symptoms, and constructs, (2) evaluate whether both modalities of exercise were equivalent, and (3) to determine whether exercise enjoyment and physical fitness are associated with symptom reduction. A total of 48 individuals with anxiety-related disorders were randomized to aerobic exercise, resistance training, or a waitlist. Symptoms of anxiety-related disorders, related constructs, and exercise enjoyment were assessed at pre-intervention and weekly during the 4-week intervention. Participants were further assessed 1-week and 1-month post-intervention. Both exercise modalities were efficacious in improving disorder status. As well, aerobic exercise improved general psychological distress and anxiety, while resistance training improved disorder-specific symptoms, anxiety sensitivity, distress tolerance, and intolerance of uncertainty. Physical fitness predicted reductions in general psychological distress for both types of exercise and reductions in stress for aerobic exercise. Results highlight the efficacy of different exercise modalities in uniquely addressing anxiety-related disorder symptoms and constructs. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

Efficacy of an Acceptance-Based Behavior Therapy for Generalized Anxiety Disorder: Evaluation in a Randomized Controlled Trial

ERIC Educational Resources Information Center

Roemer, Lizabeth; Orsillo, Susan M.; Salters-Pedneault, Kristalyn

2008-01-01

Generalized anxiety disorder (GAD) is a chronic anxiety disorder, associated with comorbidity and impairment in quality of life, for which improved psychosocial treatments are needed. GAD is also associated with reactivity to and avoidance of internal experiences. The current study examined the efficacy of an acceptance-based behavioral therapy…

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.

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

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.

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.

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…

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

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

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�

Safety of nicergoline as an agent for management of cognitive function disorders.

PubMed

Saletu, Bernd; Garg, Amit; Shoeb, Ahsan

2014-01-01

Nicergoline is a semisynthetic ergot derivative and has a selective alpha-1A adrenergic receptor blocking property and also other additional mechanisms of actions, both in the brain and in the periphery. It is in clinical use for over three decades in over fifty countries for conditions such as cerebral infarction, acute and chronic peripheral circulation disorders, vascular dementia, and Alzheimer's disease and has been found to be beneficial in a variety of other conditions. However, concerns about its safety have been raised, especially after the European medicines agency's (EMEA's) restriction in the use of all ergot derivatives including nicergoline. But, most of the available literature and data suggest that the adverse events with nicergoline are mild and transient. Further, none of the available treatment options for cognitive disorders afford definitive resolution of symptoms. In this backdrop, we discuss the pharmacology of nicergoline with special emphasis on the safety of this compound, especially when used in patients suffering from cognitive function disorders.

Safety of Nicergoline as an Agent for Management of Cognitive Function Disorders

PubMed Central

2014-01-01

Nicergoline is a semisynthetic ergot derivative and has a selective alpha-1A adrenergic receptor blocking property and also other additional mechanisms of actions, both in the brain and in the periphery. It is in clinical use for over three decades in over fifty countries for conditions such as cerebral infarction, acute and chronic peripheral circulation disorders, vascular dementia, and Alzheimer's disease and has been found to be beneficial in a variety of other conditions. However, concerns about its safety have been raised, especially after the European medicines agency's (EMEA's) restriction in the use of all ergot derivatives including nicergoline. But, most of the available literature and data suggest that the adverse events with nicergoline are mild and transient. Further, none of the available treatment options for cognitive disorders afford definitive resolution of symptoms. In this backdrop, we discuss the pharmacology of nicergoline with special emphasis on the safety of this compound, especially when used in patients suffering from cognitive function disorders. PMID:25243157

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.

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.

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

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.

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

Efficacy and Safety of Paliperidone Extended Release 1.5 mg/day-A Double-blind, Placebo- and Active-Controlled, Study in the Treatment of Patients with Schizophrenia.

PubMed

Coppola, Danielle; Melkote, Rama; Lannie, Caroline; Singh, Jaskaran; Nuamah, Isaac; Gopal, Srihari; Hough, David; Palumbo, Joseph

2011-05-15

Paliperidone extended-release (paliperidone ER) is an approved oral antipsychotic medication (dosing range 3-12 mg/day) for treatment of schizophrenia and schizoaffective disorder in adults. In this 3-arm, double-blind, placebo- and active-controlled, parallel-group study, paliperidone ER 1.5 mg was assessed to determine the lowest efficacious dose in patients (N = 201) with acute schizophrenia. Paliperidone ER 6 mg was included for assay sensitivity. Patients (intent-to-treat analysis set) had a mean age of 39.4 years; 74% were men, 43% Asian, and 40% black. The baseline mean (SD) Positive and Negative Syndrome Scale (PANSS) total score was 92.6 (13.02) and the mean (SD) change from baseline to endpoint was: placebo group, -11.4 (20.81); paliperidone ER 1.5 mg group, -8.9 (23.31); and paliperidone ER 6 mg group, -15.7 (26.25). Differences between paliperidone groups versus placebo were not significant (paliperidone ER 1.5 mg [p = 0.582], paliperidone ER 6 mg, [p = 0.308]). Safety results of paliperidone ER 1.5 mg and placebo were comparable. The most frequently reported treatment emergent adverse events (≥10%) were: placebo group-headache (15.6%) and psychotic disorder (14.1%); paliperidone ER 1.5 mg group-insomnia (13.6%); and paliperidone ER 6 mg group-headache (11.4%), insomnia (10%), and tremor (10%). In this study, paliperidone ER 1.5 mg did not demonstrate efficacy in patients with acute schizophrenia. A markedly high placebo response was noted. Assay sensitivity with the 6 mg dose was not established. Paliperidone ER 1.5 mg was generally tolerable with a safety profile comparable to placebo.

Self-efficacy toward physical activity and the physical activity behavior of children with and without Developmental Coordination Disorder.

PubMed

Batey, C A; Missiuna, C A; Timmons, B W; Hay, J A; Faught, B E; Cairney, J

2014-08-01

Affecting 5-6% of children, Developmental Coordination Disorder (DCD) is a prevalent chronic condition. The nature of the disorder - impaired motor coordination - makes avoidance of physical activity (PA) common. The purpose of this study was to examine the effect of barrier and task self-efficacy on PA behavior in children with DCD and a group of typically developing (TD) children. Children were compared on their perceived ability to complete different intensities and duration of PA (task efficacy) and their confidence in completing PA when faced with everyday barriers (barrier efficacy). An accelerometer was used to record their activity over the subsequent week. Children with DCD were found to have significantly lower task efficacy and barrier efficacy. They also spent significantly less time in moderate to vigorous physical activity (MVPA). Multivariate analyses revealed that gender modified the relationship for both groups. Separate multivariate regressions, were therefore conducted by gender. A direct effect of DCD on PA was observed for boys, but not for girls. Further analyses showed that neither task efficacy nor barrier efficacy influenced the relationship between DCD and PA. Results from this study confirm that children with DCD have lower task and barrier self-efficacy than TD children and that males have lower PA levels than their TD peers; however neither task or barrier self-efficacy mediated the relationship between DCD and PA. Copyright © 2013. Published by Elsevier B.V.

Impact of Venetoclax Exposure on Clinical Efficacy and Safety in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia.

PubMed

Freise, Kevin J; Jones, Aksana K; Eckert, Doerthe; Mensing, Sven; Wong, Shekman L; Humerickhouse, Rod A; Awni, Walid M; Salem, Ahmed Hamed

2017-05-01

Venetoclax is a selective, potent, first-in-class B-cell lymphoma-2 inhibitor that restores apoptosis in cancer cells and has demonstrated efficacy in a variety of hematological malignancies. The objective of this research was to characterize the relationship between venetoclax exposures and efficacy and safety in patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). A total of 272 and 338 patients from four clinical studies were pooled for the exposure-efficacy and exposure-safety analyses, respectively. Demographics, baseline disease characteristics, and select co-medications were evaluated for their impact on efficacy (lymphocytes, tumor size, objective response [OR]) and safety (neutropenia and infection). Higher venetoclax concentrations led to a more rapid decrease in lymphocyte counts and tumor size, which translated into patients more rapidly achieving OR. The 17p deletion somatic mutation was not identified, in any of the analyses, to affect the responsiveness of patients to venetoclax. Model-based simulations of lymphocyte counts and tumor size estimated an OR rate (ORR) of 84.8 % (95 % confidence interval 81.5-88.0 %) at a venetoclax dosage of 400 mg daily, with minimal increase in ORR at higher doses. The safety analyses of the adverse events (grade 3 or higher) of neutropenia and infection indicated that higher average venetoclax concentrations were not associated with an increase in adverse events. The exposure-response analyses indicated that a venetoclax dosage regimen of 400 mg daily results in a high (>80 %) probability of achieving OR in R/R CLL/SLL patients, with minimal probability of increasing neutropenia or infection with higher exposures.

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

PubMed Central

Elbasty, Ahmed; Metcalf, James

2017-01-01

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

A Randomized, Double-Blind, Placebo-Controlled Trial of Metoclopramide for the Treatment of Tourette's Disorder.

ERIC Educational Resources Information Center

Nicolson, Rob; Craven-Thuss, Beth; Smith, Judy; McKinlay, B. Duncan; Castellanos, F. Xavier

2005-01-01

Objective: The pattern of dopamine antagonism by metoclopramide suggests benefits in the treatment of tic disorders. The purpose of this study was to examine the efficacy and safety of metoclopramide in the treatment of children and adolescents with tic disorders. Method: Twenty-seven medication-free patients (age 11.9 [+ or -] 2.7 years) with…

Pre- and post-exposure safety and efficacy of attenuated rabies virus vaccines are enhanced by their expression of IFNγ

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

Barkhouse, Darryll A.; Center for Neurovirology 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107; Faber, Milosz

Consistent with evidence of a strong correlation between interferon gamma (IFNγ) production and rabies virus (RABV) clearance from the CNS, we recently demonstrated that engineering a pathogenic RABV to express IFNγ highly attenuates the virus. Reasoning that IFNγ expression by RABV vaccines would enhance their safety and efficacy, we reverse-engineered two proven vaccine vectors, GAS and GASGAS, to express murine IFNγ. Mortality and morbidity were monitored during suckling mice infection, immunize/challenge experiments and mixed intracranial infections. We demonstrate that GASγ and GASγGAS are significantly attenuated in suckling mice compared to the GASGAS vaccine. GASγ better protects mice from lethal DRV4more » RABV infection in both pre- and post-exposure experiments compared to GASGAS. Finally, GASγGAS reduces post-infection neurological sequelae, compared to control, during mixed intracranial infection with DRV4. These data show IFNγ expression by a vaccine vector can enhance its safety while increasing its efficacy as pre- and post-exposure treatment. - Highlights: • IFNγ expression improves attenuated rabies virus safety and immunogenicity. • IFNγ expression is safer and more immunogenic than doubling glycoprotein expression. • Co-infection with IFNγ-expressing RABV prevents wild-type rabies virus lethality. • Vaccine safety and efficacy is additive for IFNγ and double glycoprotein expression.« less

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.

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.

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.

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...

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.

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.

Comparable pharmacodynamics, efficacy, and safety of linagliptin 5 mg among Japanese, Asian and white patients with type 2 diabetes.

PubMed

Sarashina, Akiko; Friedrich, Christian; Crowe, Susanne; Patel, Sanjay; Graefe-Mody, Ulrike; Hayashi, Naoyuki; Horie, Yoshiharu

2016-09-01

The efficacy and safety of drugs can vary between different races or ethnic populations because of differences in the relationship of dose to exposure, pharmacodynamic response or clinical efficacy and safety. In the present post-hoc analysis, we assessed the influence of race on the pharmacokinetics, pharmacodynamics, efficacy and safety of monotherapy with the dipeptidyl peptidase-4 inhibitor, linagliptin, in patients with type 2 diabetes enrolled in two comparable, previously reported randomized phase III trials. Study 1 (with a 12-week placebo-controlled phase) recruited Japanese patients only (linagliptin, n = 159; placebo, n = 80); study 2 (24-week trial) enrolled Asian (non-Japanese; linagliptin, n = 156; placebo, n = 76) and white patients (linagliptin, n = 180; placebo, n = 90). Linagliptin trough concentrations were equivalent across study and race groups, and were higher than half-maximal inhibitory concentration, resulting in dipeptidyl peptidase-4 inhibition >80% at trough. Linagliptin inhibited plasma dipeptidyl peptidase-4 activity to a similar degree in study 1 and study 2. Linagliptin reduced fasting plasma glucose concentrations by a similar magnitude across groups, leading to clinically relevant reductions in glycated hemoglobin in all groups. Glycated hemoglobin levels decreased to a slightly greater extent in study 1 (Japanese) and in Asian (non-Japanese) patients from study 2. Linagliptin had a favorable safety profile in each race group. Trough exposure, pharmacodynamic response, and efficacy and safety of linagliptin monotherapy were comparable among Japanese, Asian (non-Japanese) and white patients, confirming that the recommended 5-mg once-daily dose of linagliptin is appropriate for use among different race groups. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Comparative efficacy and safety of antipsychotics in the treatment of schizophrenia: a network meta-analysis in a Japanese population.

PubMed

Kishi, Taro; Ikuta, Toshikazu; Matsunaga, Shinji; Matsuda, Yuki; Oya, Kazuto; Iwata, Nakao

2017-01-01

The relative efficacy and tolerability of antipsychotics for schizophrenia are considerably well studied. This study aimed to examine whether previous findings could be replicated in a genetically distinct and homogenous group (ie, Japanese patients with schizophrenia) and whether previous findings could be extended to a broader range of antipsychotics with previously unclear relative efficacy and tolerability. Bayesian network meta-analysis was performed in which randomized trials comparing any of the following interventions were included: second-generation antipsychotics, haloperidol, or placebo. The primary outcomes for efficacy and acceptability were the response rate and all-cause discontinuation. The secondary outcomes included the improvement of Positive and Negative Syndrome Scale scores, discontinuation because of adverse events, and individual adverse events. Eighteen relevant studies were identified (total n=3,446; aripiprazole =267, blonanserin =285, clozapine =47, clocapramine =295, haloperidol =857, mosapramine =493, olanzapine =179, paliperidone =136, perospirone =146, placebo =138, quetiapine =212, and risperidone =338; mean study duration =8.33±1.41 weeks). In primary outcomes, olanzapine and paliperidone showed efficacy than placebo, and olanzapine and paliperidone showed superior acceptability compared with placebo. There were differences in the incidences of individual adverse events (the best antipsychotic: extrapyramidal symptoms = olanzapine, hyperprolactinemia- related symptoms = quetiapine, sedation = paliperidone, and weight change = blonanserin) among antipsychotics. Although the current analysis exclusively included Japanese patients with schizophrenia, no remarkable differences were observed in efficacy and safety compared with previous meta-analyses. Diverse hierarchies in safety outcomes also support the implication that individual risk expectations for adverse events can guide clinical decisions. However, the sample size was

Comparative efficacy and safety of antipsychotics in the treatment of schizophrenia: a network meta-analysis in a Japanese population

PubMed Central

Kishi, Taro; Ikuta, Toshikazu; Matsunaga, Shinji; Matsuda, Yuki; Oya, Kazuto; Iwata, Nakao

2017-01-01

Background The relative efficacy and tolerability of antipsychotics for schizophrenia are considerably well studied. This study aimed to examine whether previous findings could be replicated in a genetically distinct and homogenous group (ie, Japanese patients with schizophrenia) and whether previous findings could be extended to a broader range of antipsychotics with previously unclear relative efficacy and tolerability. Methods Bayesian network meta-analysis was performed in which randomized trials comparing any of the following interventions were included: second-generation antipsychotics, haloperidol, or placebo. The primary outcomes for efficacy and acceptability were the response rate and all-cause discontinuation. The secondary outcomes included the improvement of Positive and Negative Syndrome Scale scores, discontinuation because of adverse events, and individual adverse events. Results Eighteen relevant studies were identified (total n=3,446; aripiprazole =267, blonanserin =285, clozapine =47, clocapramine =295, haloperidol =857, mosapramine =493, olanzapine =179, paliperidone =136, perospirone =146, placebo =138, quetiapine =212, and risperidone =338; mean study duration =8.33±1.41 weeks). In primary outcomes, olanzapine and paliperidone showed efficacy than placebo, and olanzapine and paliperidone showed superior acceptability compared with placebo. There were differences in the incidences of individual adverse events (the best antipsychotic: extrapyramidal symptoms = olanzapine, hyperprolactinemia- related symptoms = quetiapine, sedation = paliperidone, and weight change = blonanserin) among antipsychotics. Conclusion Although the current analysis exclusively included Japanese patients with schizophrenia, no remarkable differences were observed in efficacy and safety compared with previous meta-analyses. Diverse hierarchies in safety outcomes also support the implication that individual risk expectations for adverse events can guide clinical decisions

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

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

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.

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.

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

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.

Long-term safety and efficacy of deferasirox in young pediatric patients with transfusional hemosiderosis: Results from a 5-year observational study (ENTRUST).

PubMed

Vichinsky, Elliott; El-Beshlawy, Amal; Al Zoebie, Azzam; Kamdem, Annie; Koussa, Suzanne; Chotsampancharoen, Thirachit; Bruederle, Andreas; Gilotti, Geralyn; Han, Jackie; Elalfy, Mohsen

2017-09-01

Children with red blood cell disorders may receive regular transfusions from an early age and consequently accumulate iron. Adequate iron chelation therapy can prevent organ damage and delayed growth/development. Deferasirox is indicated for treatment of pediatric patients with chronic iron overload due to transfusional hemosiderosis; however, fewer than 10% of patients in the registration studies were aged 2 to less than 6 years. Deferasirox, a once-daily oral iron chelator, was evaluated in young pediatric patients with transfusional hemosiderosis during the observational 5-year ENTRUST study. Patients aged 2 to less than 6 years at enrollment received deferasirox according to local prescribing information, with the primary objective of evaluating safety, specifically renal and hepatic function. Serum ferritin was observed as a surrogate efficacy parameter. In total, 267 patients (mean age 3.2 years) predominantly with β-thalassemia (n = 176, 65.9%) were enrolled. Mean ± standard deviation deferasirox dose was 25.8 ± 6.5 mg/kg per day over a median of 59.9 months. A total of 145 patients (54.3%) completed 5 years' treatment. The proportion of patients with two or more consecutive postbaseline measurements (≥7 days apart) of serum creatinine higher than age-adjusted upper limit of normal (ULN) and alanine aminotransferase more than five times the ULN was 4.4% (95% confidence interval [CI]: 2.1-7.9) and 4.0% (95% CI: 1.8-7.4), respectively. Median serum ferritin decreased from 1,702 ng/ml at baseline to 1,127 ng/ml at 5 years. There were no new safety signals. Safety and efficacy of deferasirox in young pediatric patients in this long-term, observational study in everyday clinical practice were consistent with the known deferasirox profile. © 2017 The Authors. Pediatric Blood & Cancer Published by Wiley Periodicals, Inc.

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

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.

Economic implications of sleep disorders.

PubMed

Skaer, Tracy L; Sclar, David A

2010-01-01

Sleep disorders such as insomnia, obstructive sleep apnoea (OSA), excessive daytime sleepiness (EDS) and fatigue, sleep deprivation and restless legs syndrome (RLS) are increasingly seen in clinical practice. Sleep is considered vital for preserving daytime cognitive function and physiological well-being. Sleep insufficiency may have deleterious effects on work-life balance, overall health and safety. The consequential economic burden at both the individual and societal levels is significant. Moreover, sleep disorders are commonly associated with other major medical problems such as chronic pain, cardiovascular disease, mental illness, dementias, gastrointestinal disorders and diabetes mellitus. Thus, in order to properly care for patients presenting with sleep-related morbidity, and to reduce the consequential economic burden, accurate screening efforts and efficacious/cost-effective treatments need to be developed and employed.

A Systematic Review of Treatments for Anxiety in Youth with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Vasa, Roma A.; Carroll, Laura M.; Nozzolillo, Alixandra A.; Mahajan, Rajneesh; Mazurek, Micah O.; Bennett, Amanda E.; Wink, Logan K.; Bernal, Maria Pilar

2014-01-01

This study systematically examined the efficacy and safety of psychopharmacological and non-psychopharmacological treatments for anxiety in youth with autism spectrum disorders (ASD). Four psychopharmacological, nine cognitive behavioral therapy (CBT), and two alternative treatment studies met inclusion criteria. Psychopharmacological studies were…

Introduction of a closed-system cell processor for red blood cell washing: postimplementation monitoring of safety and efficacy.

PubMed

Acker, Jason P; Hansen, Adele L; Yi, Qi-Long; Sondi, Nayana; Cserti-Gazdewich, Christine; Pendergrast, Jacob; Hannach, Barbara

2016-01-01

After introduction of a closed-system cell processor, the effect of this product change on safety, efficacy, and utilization of washed red blood cells (RBCs) was assessed. This study was a pre-/postimplementation observational study. Efficacy data were collected from sequentially transfused washed RBCs received as prophylactic therapy by β-thalassemia patients during a 3-month period before and after implementation of the Haemonetics ACP 215 closed-system processor. Before implementation, an open system (TerumoBCT COBE 2991) was used to wash RBCs. The primary endpoint for efficacy was a change in hemoglobin (Hb) concentration corrected for the duration between transfusions. The primary endpoint for safety was the frequency of adverse transfusion reactions (ATRs) in all washed RBCs provided by Canadian Blood Services to the transfusion service for 12 months before and after implementation. Data were analyzed from more than 300 RBCs transfused to 31 recipients before implementation and 29 recipients after implementation. The number of units transfused per episode reduced significantly after implementation, from a mean of 3.5 units to a mean of 3.1 units (p < 0.005). The corrected change in Hb concentration was not significantly different before and after implementation. ATRs occurred in 0.15% of transfusions both before and after implementation. Safety and efficacy of washed RBCs were not affected after introduction of a closed-system cell processor. The ACP 215 allowed for an extended expiry time, improving inventory management and overall utilization of washed RBCs. Transfusion of fewer RBCs per episode reduced exposure of recipients to allogeneic blood products while maintaining efficacy. © 2015 AABB.

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.

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.

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.

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

Risperidone in the treatment of behavioral disorders associated with autism in children and adolescents

PubMed Central

Canitano, Roberto; Scandurra, Valeria

2008-01-01

This is a review of the clinical trials investigating the efficacy and safety of risperidone in the treatment of children with autistic spectrum disorders (ASD). The main clinical characteristics are impairment in social skills, communication difficulties, repetitive movements and behaviors, including stereotypies. Pharmacotherapy is mainly directed at the so-called target symptoms, ie, behavioral disorders and the various kinds of repetitions associated with ASD. According to the available data, risperidone seems to be moderately efficacious and safe for treating behavioral disorders. 4 double blind controlled trial. 3 reanalysis studies, and 12 open studies have documented the role of risperidone in children with ASD. Controlled studies have been thoroughly considered in this review. PMID:19043516

Risperidone in the treatment of behavioral disorders associated with autism in children and adolescents.

PubMed

Canitano, Roberto; Scandurra, Valeria

2008-08-01

This is a review of the clinical trials investigating the efficacy and safety of risperidone in the treatment of children with autistic spectrum disorders (ASD). The main clinical characteristics are impairment in social skills, communication difficulties, repetitive movements and behaviors, including stereotypies. Pharmacotherapy is mainly directed at the so-called target symptoms, ie, behavioral disorders and the various kinds of repetitions associated with ASD. According to the available data, risperidone seems to be moderately efficacious and safe for treating behavioral disorders. 4 double blind controlled trial. 3 reanalysis studies, and 12 open studies have documented the role of risperidone in children with ASD. Controlled studies have been thoroughly considered in this review.

A Randomized, Placebo-Controlled, Active-Reference, Double-Blind, Flexible-Dose Study of the Efficacy of Vortioxetine on Cognitive Function in Major Depressive Disorder

PubMed Central

Mahableshwarkar, Atul R; Zajecka, John; Jacobson, William; Chen, Yinzhong; Keefe, Richard SE

2015-01-01

This multicenter, randomized, double-blind, placebo-controlled, active-referenced (duloxetine 60 mg), parallel-group study evaluated the short-term efficacy and safety of vortioxetine (10–20 mg) on cognitive function in adults (aged 18–65 years) diagnosed with major depressive disorder (MDD) who self-reported cognitive dysfunction. Efficacy was evaluated using ANCOVA for the change from baseline to week 8 in the digit symbol substitution test (DSST)–number of correct symbols as the prespecified primary end point. The patient-reported perceived deficits questionnaire (PDQ) and physician-assessed clinical global impression (CGI) were analyzed in a prespecified hierarchical testing sequence as key secondary end points. Additional predefined end points included the objective performance-based University of San Diego performance-based skills assessment (UPSA) (ANCOVA) to measure functionality, MADRS (MMRM) to assess efficacy in depression, and a prespecified multiple regression analysis (path analysis) to calculate direct vs indirect effects of vortioxetine on cognitive function. Safety and tolerability were assessed at all visits. Vortioxetine was statistically superior to placebo on the DSST (P<0.05), PDQ (P<0.01), CGI-I (P<0.001), MADRS (P<0.05), and UPSA (P<0.001). Path analysis indicated that vortioxetine's cognitive benefit was primarily a direct treatment effect rather than due to alleviation of depressive symptoms. Duloxetine was not significantly different from placebo on the DSST or UPSA, but was superior to placebo on the PDQ, CGI-I, and MADRS. Common adverse events (incidence ⩾5%) for vortioxetine were nausea, headache, and diarrhea. In this study of MDD adults who self-reported cognitive dysfunction, vortioxetine significantly improved cognitive function, depression, and functionality and was generally well tolerated. PMID:25687662

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.

Psychopharmacology of aggression in children and adolescents with primary neuropsychiatric disorders: a review of current and potentially promising treatment options.

PubMed

Nevels, Robert M; Dehon, Erin E; Alexander, Katrina; Gontkovsky, Samuel T

2010-04-01

Research examining the role of pharmacological therapy in the treatment of children and adolescents with clinical disorders is growing. Clinical disorders that present with comorbid aggression can add a challenge to treatment. Child and adolescent neuropsychiatric disorders associated with aggression include attention-deficit hyperactivity disorder, various mood disorders and in particular bipolar disorders/pediatric mania, schizophrenia, mental retardation, oppositional defiant disorder, conduct disorder, and autism spectrum disorders. This review describes the psychopharmacy to treat these disorders and the aggression that often appears comorbidly. Existing literature regarding the efficacy and safety of psychotropics for youth with neuropsychiatric disorders also is discussed. In addition, general guidelines for psychopharmacy of aggression in children and adolescents are presented. Studies reviewed in this article provide evidence for the use of psychostimulants, alpha-2 agonists, beta blockers, lithium, anticonvulsant mood-stabilizers, atypical antipsychotics, traditional antipsychotics, and selective serotonin reuptake inhibitors in treating pediatric aggression with the choice of medication dependent on symptomology. Despite increased support for pediatric psychotropic use, there is a need for more long-term safety and efficacy studies of existing medications and newer, safer, and more effective agents with fewer side effects for the pharmacological treatment of all childhood disorders in which aggression is prominent. 2010 APA, all rights reserved

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 of published articles identified in the initial search process were also examined for any additional studies appropriate for the review. SAMe is an important physiologic compound, playing a central role as precursor molecule in several biochemical reactions. Numerous studies have shown that SAMe may affect the regulation of various critical components of monoaminergic neurotransmission involved in the pathophysiology of MDD. Some findings have suggested its antidepressant efficacy in treating MDD. Several randomized controlled trials have supported that the antidepressant efficacy of SAMe in monotherapy is superior to placebo and tricyclic antidepressants. Recent findings have also demonstrated its efficacy in patients nonresponsive to selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. Overall, SAMe is a well-tolerated medication, which may offer considerable advantages as an alternative to antidepressant drugs or as an add-on therapy in the treatment of MDD and TRD. More large-scale controlled trials are needed to gain a better understanding of the relative efficacy of this drug.

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.

Safety and efficacy of canagliflozin in elderly patients with type 2 diabetes mellitus: a 1-year post-marketing surveillance in Japan.

PubMed

Goda, Maki; Yamakura, Tomoko; Sasaki, Kazuyo; Tajima, Takumi; Ueno, Makoto

2018-02-01

To evaluate the safety and efficacy of canagliflozin in elderly patients with type 2 diabetes mellitus (T2DM) in clinical settings. The authors conducted a 1-year post-marketing surveillance (PMS) of canagliflozin in almost all the elderly patients (≥65 years old) with T2DM who began taking canagliflozin during the first 3 months after its launch in Japan. The main outcomes included the incidences of adverse drug reactions (ADRs), serious ADRs, and the changes of laboratory tests as well as efficacy variables. An ADR was reported in 9.09% (125 of 1375 patients) in the safety analysis set. The main ADRs were dehydration, constipation, thirst, pollakiuria, dizziness, cystitis, eczema, pruritus, and rash. The incidence of serious ADRs was 1.02% (14 patients), which included urinary tract infection, dehydration, hypoglycemia, and cerebral infarction (two patients each). ADRs of special interest that had been reported in clinical trials of SGLT2 inhibitors, such as hypoglycemia, volume depletion-related events, genital/urinary tract infection, polyuria/pollakiuria, and ketone body increased were also observed in this PMS. The safety profiles were similar to the results of a previous clinical study of canagliflozin, and new safety concerns were not identified in this survey. The mean change in HbA1c was -0.77% after 12 months of treatment in the efficacy analysis set. In this PMS, the safety and efficacy profiles of canagliflozin in elderly patients with T2DM were obtained in the clinical settings in Japan and the drug was well tolerated and effective in improving glycemic control.

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...

Efficacy and safety of statins and exercise combination therapy compared to statin monotherapy in patients with dyslipidaemia: A systematic review and meta-analysis.

PubMed

Gui, Ya-Jun; Liao, Cai-Xiu; Liu, Qiong; Guo, Yuan; Yang, Tao; Chen, Jing-Yuan; Wang, Ya-Ting; Hu, Jia-Hui; Xu, Dan-Yan

2017-06-01

Background Statin treatment in association with physical exercise can substantially reduce mortality in dyslipidaemic individuals. However, the available data to compare the efficacy and safety of statins and exercise combination therapy with statin monotherapy are limited. Design Systematic review and meta-analysis. Methods We systematically searched PubMed, Embase and the Cochrane Library from database inception until December 2016. We included randomised and non-randomised studies that compared the efficacy and safety of statins and exercise combination therapy with statin monotherapy in patients with dyslipidaemia. Standardised mean differences were calculated and pooled by means of fixed effects models. The risk of bias and heterogeneity among trials was also assessed. Seven articles were assessed in terms of the efficacy of therapy and 13 from the viewpoint of therapeutic safety. Results In terms of efficacy, statins and exercise combination decreased the incidence of diabetes mellitus, improved insulin sensitivity and inflammation, but caused no change in lipid profile compared to statins alone. In terms of safety, statins and exercise combination increased peak oxygen uptake (standardised mean difference 1.01, 95% confidence interval 0.46 to 1.57) compared to statins alone. In contrast to statin-induced myopathy, chronic exercise training prior to statin treatment could counteract statin-induced adverse effects in skeletal muscle. Conclusion Statins and exercise combination therapy is more effective than statin monotherapy in terms of insulin sensitivity, inflammation and exercise capacity. The small number of studies warrants the need for more randomised controlled trials evaluating the efficacy and safety of combination therapy.

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

The effectiveness of anticonvulsants in psychiatric disorders

PubMed Central

Grunze, Heinz C. R.

2008-01-01

Anticonvulsant drugs are widely used in psychiatric indications. These include mainly alcohol and benzodiazepine withdrawal syndromes, panic and anxiety disorders, dementia, schizophrenia, affective disorders, bipolar affective disorders in particular, and, to some extent, personality disorders, A further area in which neurology and psychiatry overlap is pain conditions, in which some anticonvulsants, and also typical psychiatric medications such as antidepressants, are helpful. From the beginning of their psychiatric use, anticonvulsants have also been used to ameliorate specific symptoms of psychiatric disorders independently of their causality and underlying illness, eg, aggression, and, more recently, cognitive impairment, as seen in affective disorders and schizophrenia. With new anticonvulsants currently under development, it is likely that their use in psychiatry will further increase, and that psychiatrists need to learn about their differential efficacy and safety profiles to the same extent as do neurologists. PMID:18472486

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.

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

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.

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

PubMed Central

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

2007-01-01

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

Tofacitinib, an Oral Janus Kinase Inhibitor: Pooled Efficacy and Safety Analyses in an Australian Rheumatoid Arthritis Population.

PubMed

Hall, Stephen; Nash, Peter; Rischmueller, Maureen; Bossingham, David; Bird, Paul; Cook, Nicola; Witcombe, David; Soma, Koshika; Kwok, Kenneth; Thirunavukkarasu, Krishan

2018-06-11

In Australia, there is an unmet need for improved treatments for rheumatoid arthritis (RA). Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. To provide an overview of key study outcomes for tofacitinib in Australian patients, we analyzed the efficacy and safety of tofacitinib in the Australian subpopulation of global RA phase III and long-term extension (LTE) studies. Data were pooled from the Australian subpopulation of four phase III studies and one LTE study (database not locked at cut-off date: January 2016). Patients in the phase III studies received tofacitinib 5 or 10 mg twice daily (BID), placebo (advancing to tofacitinib at months 3 or 6), or adalimumab, with background methotrexate or conventional synthetic disease-modifying antirheumatic drugs. Patients in the LTE study received tofacitinib 5 or 10 mg BID. Efficacy endpoints were American College of Rheumatology (ACR) 20/50/70 response rates, and change from baseline in the Disease Activity Score in 28 joints, erythrocyte sedimentation rate [DAS28-4(ESR)] and Health Assessment Questionnaire-Disability Index (HAQ-DI) scores. Safety endpoints included incidence of adverse events (AEs), serious AEs, and discontinuations due to AEs. AEs of special interest and laboratory parameters were analyzed in the LTE study. Across phase III studies (N = 100), ACR response rates and improvements in DAS28-4(ESR) and HAQ-DI scores were numerically greater with tofacitinib vs. placebo at month 3, and increased until month 12. The results were sustained in the LTE study (N = 99) after 60 months' observation. In general, the efficacy and safety profiles of tofacitinib were similar to those of the global RA population. In Australian patients with RA, tofacitinib therapy demonstrated sustained efficacy and consistent safety over ≥ 60 months' treatment. Pfizer Inc. TRIAL REGISTRATION NUMBERS (ALL CLINICALTRIALS.GOV): NCT00960440; NCT00847613; NCT00856544; NCT00853385; NCT00413699.

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.

Safety Behaviors in Adults With Social Anxiety: Review and Future Directions.

PubMed

Piccirillo, Marilyn L; Taylor Dryman, M; Heimberg, Richard G

2016-09-01

Safety behaviors are considered an important factor in the maintenance of social anxiety disorder (SAD). Safety behaviors are typically employed by socially anxious individuals to reduce anxiety in feared social situations. However, by preventing individuals with social anxiety from gathering evidence that would disconfirm their maladaptive beliefs about social situations, the use of safety behaviors ultimately maintains social anxiety over time. Twenty years ago, Wells and colleagues (1995) demonstrated that use of safety behaviors diminishes the efficacy of exposure treatment for SAD, suggesting that reduction in the use of safety behaviors during exposure can enhance treatment response. Research on safety behaviors has expanded considerably since Wells et al.'s seminal publication, and our understanding of the role safety behaviors may play in the maintenance of social anxiety has grown in breadth and depth. In this paper, we present a detailed review of the published research on safety behaviors relevant to social anxiety and social-anxiety-related processes. Finally, we evaluate the impact of safety behaviors on the outcome of treatment for SAD, and we look to the literature on safety behaviors in other anxiety disorders to inform our understanding of use of safety behaviors during exposure and to facilitate future research in SAD. Copyright © 2015. Published by Elsevier Ltd.

Unknown Safety and Efficacy of Smartphone Bolus Calculator Apps Puts Patients at Risk for Severe Adverse Outcomes.

PubMed

Hirsch, Irl B; Parkin, Christopher G

2016-07-01

Manual calculation of bolus insulin dosages can be challenging for individuals treated with multiple daily insulin injections (MDI) therapy. Automated bolus calculator capability has recently been made available via enhanced blood glucose meters and smartphone apps. Use of this technology has been shown to improve glycemic control and reduce glycemic variability without changing hypoglycemia; however, the clinical utility of app-based bolus calculators has not been demonstrated. Moreover, recent evidence challenges the safety and efficacy of these smartphone apps. Although the ability to automatically calculate bolus insulin dosages addresses a critical need of MDI-treated individuals, this technology raises concerns about efficacy of treatment and the protection of patient safety. This article discusses key issues and considerations associated with automated bolus calculator use. © 2016 Diabetes Technology Society.

Efficacy and Safety of Paliperidone Extended Release 1.5 mg/day—A Double-blind, Placebo- and Active-Controlled, Study in the Treatment of Patients with Schizophrenia

PubMed Central

Coppola, Danielle; Melkote, Rama; Lannie, Caroline; Singh, Jaskaran; Nuamah, Isaac; Gopal, Srihari; Hough, David; Palumbo, Joseph

2011-01-01

Background Paliperidone extended-release (paliperidone ER) is an approved oral antipsychotic medication (dosing range 3–12 mg/day) for treatment of schizophrenia and schizoaffective disorder in adults. Methods In this 3-arm, double-blind, placebo- and active-controlled, parallel-group study, paliperidone ER 1.5 mg was assessed to determine the lowest efficacious dose in patients (N = 201) with acute schizophrenia. Paliperidone ER 6 mg was included for assay sensitivity. Results Patients (intent-to-treat analysis set) had a mean age of 39.4 years; 74% were men, 43% Asian, and 40% black. The baseline mean (SD) Positive and Negative Syndrome Scale (PANSS) total score was 92.6 (13.02) and the mean (SD) change from baseline to endpoint was: placebo group, –11.4 (20.81); paliperidone ER 1.5 mg group, –8.9 (23.31); and paliperidone ER 6 mg group, –15.7 (26.25). Differences between paliperidone groups versus placebo were not significant (paliperidone ER 1.5 mg [p = 0.582], paliperidone ER 6 mg, [p = 0.308]). Safety results of paliperidone ER 1.5 mg and placebo were comparable. The most frequently reported treatment emergent adverse events (≥10%) were: placebo group—headache (15.6%) and psychotic disorder (14.1%); paliperidone ER 1.5 mg group—insomnia (13.6%); and paliperidone ER 6 mg group—headache (11.4%), insomnia (10%), and tremor (10%). Conclusions In this study, paliperidone ER 1.5 mg did not demonstrate efficacy in patients with acute schizophrenia. A markedly high placebo response was noted. Assay sensitivity with the 6 mg dose was not established. Paliperidone ER 1.5 mg was generally tolerable with a safety profile comparable to placebo. PMID:27738355

A Placebo-Controlled, Fixed-Dose Study of Aripiprazole in Children and Adolescents with Irritability Associated with Autistic Disorder

ERIC Educational Resources Information Center

Marcus, Ronald N.; Owen, Randall; Kamen, Lisa; Manos, George; McQuade, Robert D.; Carson, William H.; Aman, Michael G.

2009-01-01

Objective: To evaluate the short-term efficacy and safety of aripiprazole in the treatment of irritability in children and adolescents with autistic disorder. Method: Two hundred eighteen children and adolescents (aged 6-17 years) with a diagnosis of autistic disorder, and with behaviors such as tantrums, aggression, self-injurious behavior, or a…

Self esteem, dependency, self-efficacy and self-criticism in social anxiety disorder.

PubMed

Iancu, Iulian; Bodner, Ehud; Ben-Zion, Itzhak Z

2015-04-01

Social anxiety disorder (SAD) is characterized by fear and avoidance in social situations where one perceives being in danger of scrutiny by others. Low self-esteem, low self-efficacy, high self-criticism and high dependency are additional potential features of SAD, and thus their examination is warranted, as is the elucidation of their inter-relationship. Thirty-two SAD subjects diagnosed with the Mini-International Neuropsychiatric Interview and 30 healthy controls, were administered the Liebowitz Social Anxiety Scale (LSAS), the Rosenberg Self Esteem Scale, the Depressive Experiences Questionnaire (DEQ) that assesses self-criticism, dependency and self-efficacy, and a socio-demographic questionnaire. We hypothesized that the SAD group would present higher scores of dependency and self-criticism and lower self-esteem and self-efficacy. We also hypothesized that low self-esteem, low self-efficacy, high self-criticism and high dependency will predict the severity of SAD. In line with the hypotheses, SAD patients had higher scores of self-criticism and dependency and lower scores of self-esteem. The social anxiety score correlated negatively with self-esteem and self-efficacy, and positively with dependency and self-criticism. Self-criticism, but not the other measures, predicted the total LSAS score. Self-esteem, self-criticism, dependency and self-efficacy are related to SAD and their relations should be examined in future studies that will employ larger samples. It is suggested to search for ways to affect these factors through cognitive-behavioral interventions and additional psychotherapeutic treatments. Research should also focus on the specific role of self-criticism in SAD. Copyright © 2014 Elsevier Inc. All rights reserved.

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.

Resistance training among young athletes: safety, efficacy and injury prevention effects

PubMed Central

Faigenbaum, A D; Myer, G D

2012-01-01

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 power-lifting 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. PMID:19945973

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.

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.

Assessment of efficacy and safety of a fractionated bipolar radiofrequency device for the treatment of lower face wrinkles and laxity.

PubMed

Jiang, Yueqi; Zhang, Xuting; Lu, Zhong; Gold, Michael H

2018-04-18

Skin aging, as a natural course, is a gradual process. It can be classified as either intrinsic or photo-aging. In recent years, as the attention to lower face wrinkles and laxity has raised significantly, the demands to facial rejuvenation also increased, along with a variety of technologies coming into being. Fractional bipolar RF as a novel means of rejuvenation has been used in clinical practice, but questions remain in terms of its efficacy and safety. Considering a large population in our country and huge demands for skin tightening, we did this research to evaluate the efficacy and safety of fractional bipolar radiofrequency.

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.

Feasibility, safety, and preliminary efficacy of Low Amplitude Seizure Therapy (LAP-ST): A proof of concept clinical trial in man.

PubMed

Youssef, Nagy A; Sidhom, Emad

2017-11-01

Current pulse amplitude used in clinical ECT may be higher than needed. Reducing pulse amplitude may improve focality of the electric field and thus cognitive adverse effects. Here we examine the feasibility, safety, and whether Low Pulse Amplitude Seizure Therapy (LAP-ST, 0.5-0.6A) minimizes cognitive adverse effects while retaining efficacy. Patients with treatment-resistant primary mood (depressive episodes) or psychotic disorders who were clinically indicated to undergo ECT were offered to be enrolled in an open-label study. The study consisted of a full acute course of LAP-ST under standard anesthesia and muscle relaxation. The primary outcome was feasibility of seizure induction. Clinical outcome measures were: time to reorientation (TRO), Mini Mental State Examination, Montgomery Aberg Depression Scale, and Brief Psychiatric Rating Scale, and Clinical Global Impression Scale. Twenty-two patients consented for enrollment in the study. LAP-ST was feasible, and all patients had seizures in the first session. Participants had a quick orientation with median TRO of 4.5min. Treatment was efficacious for both depressive and psychotic symptoms. Relatively small sample size, non-blinded, and no randomization was performed in this initial proof of concept study. This first human preliminary data of a full course of focal LAP-ST demonstrates that seizure induction is feasible. These results, although preliminary, suggest that the LAP-ST compared to the standard ECT techniques may result in less cognitive side effects, but comparable efficacy. Larger studies are needed to replicate these findings. Copyright © 2017 Elsevier B.V. All rights reserved.

Gsk3 Signalling and Redox Status in Bipolar Disorder: Evidence from Lithium Efficacy

PubMed Central

2016-01-01

Objective. To discuss the link between glycogen synthase kinase-3 (GSK3) and the main biological alterations demonstrated in bipolar disorder (BD), with special attention to the redox status and the evidence supporting the efficacy of lithium (a GSK3 inhibitor) in the treatment of BD. Methods. A literature research on the discussed topics, using Pubmed and Google Scholar, has been conducted. Moreover, a manual selection of interesting references from the identified articles has been performed. Results. The main biological alterations of BD, pertaining to inflammation, oxidative stress, membrane ion channels, and circadian system, seem to be intertwined. The dysfunction of the GSK3 signalling pathway is involved in all the aforementioned “biological causes” of BD. In a complex scenario, it can be seen as the common denominator linking them all. Lithium inhibition of GSK3 could, at least in part, explain its positive effect on these biological dysfunctions and its superiority in terms of clinical efficacy. Conclusions. Deepening the knowledge on the molecular bases of BD is fundamental to identifying the biochemical pathways that must be targeted in order to provide patients with increasingly effective therapeutic tools against an invalidating disorder such as BD. PMID:27630757

Gsk3 Signalling and Redox Status in Bipolar Disorder: Evidence from Lithium Efficacy.

PubMed

Luca, Antonina; Calandra, Carmela; Luca, Maria

2016-01-01

Objective. To discuss the link between glycogen synthase kinase-3 (GSK3) and the main biological alterations demonstrated in bipolar disorder (BD), with special attention to the redox status and the evidence supporting the efficacy of lithium (a GSK3 inhibitor) in the treatment of BD. Methods. A literature research on the discussed topics, using Pubmed and Google Scholar, has been conducted. Moreover, a manual selection of interesting references from the identified articles has been performed. Results. The main biological alterations of BD, pertaining to inflammation, oxidative stress, membrane ion channels, and circadian system, seem to be intertwined. The dysfunction of the GSK3 signalling pathway is involved in all the aforementioned "biological causes" of BD. In a complex scenario, it can be seen as the common denominator linking them all. Lithium inhibition of GSK3 could, at least in part, explain its positive effect on these biological dysfunctions and its superiority in terms of clinical efficacy. Conclusions. Deepening the knowledge on the molecular bases of BD is fundamental to identifying the biochemical pathways that must be targeted in order to provide patients with increasingly effective therapeutic tools against an invalidating disorder such as BD.

Initial severity and antidepressant efficacy for anxiety disorders, obsessive-compulsive disorder, and posttraumatic stress disorder: An individual patient data meta-analysis.

PubMed

de Vries, Ymkje Anna; Roest, Annelieke M; Burgerhof, Johannes G M; de Jonge, Peter

2018-06-01

It has been suggested that antidepressant benefits are smaller for mild than severe depression. Because antidepressants are also used for anxiety disorders, obsessive-compulsive disorder (OCD), and posttraumatic stress disorder (PTSD), we examined the influence of severity for these disorders. We used individual patient data of eight trials (3,430 participants) for generalized anxiety disorder (GAD); four trials (1,195 participants) for social anxiety disorder (SAD); four trials (1,132 participants) for OCD; three trials (1,071 participants) for PTSD; and 10 trials (2,151 participants) for panic disorder (PD). Mixed-effects models were used to investigate an interaction between severity and treatment group. For GAD and PD, severity moderated antidepressant efficacy. The antidepressant-placebo difference was 1.4 (95% CI: 0.4-2.5; SMD: 0.21) Hamilton Anxiety Rating Scale (HAM-A) points for participants with mild GAD (baseline HAM-A = 10), increasing to 4.0 (3.4-4.6; SMD: 0.45) or greater for severely ill participants (HAM-A ≥ 30). For PD, the difference was 0.4 (0.3-0.6) panic attacks/2 weeks for participants with 10 panic attacks/2 weeks at baseline, increasing to 4.7 (3.0-6.4) for participants with 40. For SAD, OCD, and PTSD, no interaction was found. Across severity levels, the differences were 16.1 (12.9-19.3; SMD: 0.59) Liebowitz Social Anxiety Scale points, 3.4 (2.5-4.4, SMD: 0.39) Yale-Brown Obsessive-Compulsive Scale points, and 10.3 (6.9-13.6; SMD: 0.41) Clinician-Administered PTSD Scale points. Antidepressants are equally effective across severity levels for SAD, OCD, and PTSD. For GAD and PD, however, benefits are small at low severity, and the benefit-risk ratio may be unfavorable for these patients. © 2018 Wiley Periodicals, Inc.

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.

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.

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

Efficacy and safety of oral alitretinoin in severe oral lichen planus--results of a prospective pilot study.

PubMed

Kunz, M; Urosevic-Maiwald, M; Goldinger, S M; Frauchiger, A L; Dreier, J; Belloni, B; Mangana, J; Jenni, D; Dippel, M; Cozzio, A; Guenova, E; Kamarachev, J; French, L E; Dummer, R

2016-02-01

Patients with severe oral lichen planus refractory to standard topical treatment currently have limited options of therapy suitable for long-term use. Oral alitretinoin (9-cis retinoic acid) was never systematically investigated in clinical trials, although case reports suggest its possible efficacy. To assess the efficacy and safety of oral alitretinoin taken at 30 mg once daily for up to 24 weeks in the treatment of severe oral lichen planus refractory to standard topical therapy. We conducted a prospective open-label single arm pilot study to test the efficacy and safety of 30 mg oral alitretinoin once daily for up to 24 weeks in severe oral lichen planus. Ten patients were included in the study. Primary end point was reduction in signs and symptoms measured by the Escudier severity score. Secondary parameters included pain and quality of life scores. Safety parameters were assessed during a follow-up period of 5 weeks. A substantial response at the end of treatment, i.e. >50% reduction in disease severity measured by the Escudier severity score, was apparent in 40% of patients. Therapy was well tolerated. Adverse events were mild and included headache, mucocutaneous dryness, musculoskeletal pain, increased thyroid-stimulating hormone and dyslipidaemia. Alitretinoin given at 30 mg daily reduced disease severity of severe oral lichen planus in a substantial proportion of patients refractory to standard treatment, was well tolerated and may thus represent one therapeutic option for this special group of patients. © 2015 European Academy of Dermatology and Venereology.

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

Posttraumatic stress disorder, depression, and perceived safety 13 months after September 11.

PubMed

Grieger, Thomas A; Fullerton, Carol S; Ursano, Robert J

2004-09-01

This study assessed relationships between exposure to the September 11, 2001, terrorist attack, current posttraumatic stress disorder (PTSD), current major depression, and current safety perceptions in a sample of 212 Pentagon staff members 13 months after the attack. Forty-eight respondents (23 percent) had possible PTSD; eight (4 percent) had probable major depression. Respondents who were directly exposed to the attack were more likely to have PTSD and major depression and were less likely to have a perception of safety at work and in usual activities and travel only. In contrast, respondents with PTSD reported a lower perception of safety at home, at work, and in usual activities and travel.

Efficacy and safety of golimumab in Indian patients with rheumatoid arthritis: Subgroup data from GO-MORE study.

PubMed

Pal, Sarvajeet; Veeravalli, Sarath Chandra Mouli; Das, Siddharth Kumar; Shobha, Vineeta; Uppuluri, Ramakrishna Rao; Dharmanand, B G; Nadkar, Milind; Hsia, Elizabeth; Fei, Kaiyin; Yao, Ruji; Khalifa, Ahmed

2016-11-01

To conduct a subgroup analysis of GO-MORE trial Part 1, comparing efficacy and safety of add-on subcutaneous golimumab therapy in rheumatoid arthritis (RA) patients enrolled from and outside India. GO-MORE was an open-label, multicenter, prospective trial of add-on golimumab in biologic-naïve RA patients, having active disease despite being on conventional DMARD regimen(s). Part 1 of the study was chosen as the focus of this subgroup analysis because a substantial number of Indian patients (106) were enrolled compared to no Indian patients in Part 2. The primary efficacy outcome was proportion of patients achieving good to moderate DAS28-ESR (Disease Activity Score of 28 joints calculated using erythrocyte sedimentation rate) European League Against Rheumatism (EULAR) response at month 6. Efficacy evaluable population comprised of 105 and 3175 patients from India and outside India, respectively. Safety analysis included 106 patients enrolled from India and 3251 from outside India. A higher proportion of Indian patients had a high disease activity as measured by DAS28 ESR than outside India patients. At month 6, the proportion of Indian and non-Indian patients achieving DAS28-ESR, DAS28 - C-reactive protein, simplified disease activity index (SDAI) remission, and EuroQoL Quality-of-Life Questionnaire (EQ-5D) scores were comparable. Incidence of all adverse events was lower in Indian patients. There were no deaths, cases of tuberculosis or malignancy reported in the patients from India at month 6. The efficacy and safety results with add-on golimumab were consistent between RA patients from India and outside India, despite high baseline disease activity in the Indian patients. © 2016 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

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

PubMed Central

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

2016-01-01

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

Enhanced clinical outcome with manual massage following cryolipolysis treatment: a 4-month study of safety and efficacy.

PubMed

Boey, Gerald E; Wasilenchuk, Jennifer L

2014-01-01

Cryolipolysis procedures have been shown to safely and effectively reduce the thickness of fat in a treated region. This study was conducted to determine whether the addition of post-treatment manual massage would improve efficacy while maintaining the safety profile of the original cryolipolysis treatment protocol. The study population consisted of an efficacy group (n = 10) and a safety group (n = 7). Study subjects were treated on each side of the lower abdomen with a Cooling Intensity Factor of 42 (-72.9 mW/cm(2) ) for 60 minutes. One side of the abdomen was massaged post-treatment and the other side served as the control. Immediately post-treatment, the massage side was treated for 1 minute using a vigorous kneading motion followed by 1 minute of circular massage using the pads of the fingers. For the efficacy group, photos and ultrasound measurements were taken at baseline, 2 months, and 4 months post-treatment. For the safety group, histological analysis was completed at 0, 3, 8, 14, 30, 60, and 120 days post-treatment to examine the effects of massage on subcutaneous tissue over time. Post-treatment manual massage resulted in a consistent and discernible increase in efficacy over the non-massaged side. At 2 months post-treatment, mean fat layer reduction was 68% greater in the massage side than in the non-massage side as measured by ultrasound. By 4 months, mean fat layer reduction was 44% greater in the massage side. Histological results showed no evidence of necrosis or fibrosis resulting from the massage. Post-treatment manual massage is a safe and effective technique to enhance the clinical outcome from a cryolipolysis procedure. © 2013 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

Efficacy and safety of testosterone replacement gel for treating hypogonadism in men: Phase III open-label studies.

PubMed

Belkoff, L; Brock, G; Carrara, D; Neijber, A; Ando, M; Mitchel, J

2018-02-01

Efficacy and safety of testosterone gel 2% (TG) were evaluated in two phase 3, open-labelled, single-arm, multicentre studies (000023 and extension study 000077). Hypogonadal men having serum testosterone levels <300 ng/dl at two consecutive measurements were included. Study duration was 9 months (000023: 3 months; 000077: 6 months). Starting dose of TG (46 mg) was applied on upper arm/shoulder. The primary endpoint (000023) was responder rate (subjects with average 24-hour serum testosterone concentration 300-1050 ng/dl on Day 90). Study 000077 evaluated the safety of TG in patients rolling over from study 000023 over a period of 6 months. Of 180 subjects in 000023, 172 completed and 145 rolled over to 000077, with 127 completers. The responder rate was 85.5%. Fewer subjects in 000077 (12.7%) versus 000023 (31.8%) had maximum testosterone concentration (C max ) >1500 ng/dl, with no significant safety concerns. Significant improvements in sexual function and quality of life were noted in both studies. Subjects experienced few skin reactions without notable increases in prostate-specific antigen and haematocrit levels. TG was efficacious with an acceptable safety profile. C max >1500 ng/dl did not exhibit distinct impact on safety parameters. However, further optimisation of titration schema to reduce C max is warranted while maintaining the average steady state total testosterone concentration. © 2017 Blackwell Verlag GmbH.

Multi-ingredient, caffeine-containing dietary supplements: history, safety, and efficacy.

PubMed

Gurley, Bill J; Steelman, Susan C; Thomas, Sheila L

2015-02-01

Our objective was to review the history, safety, and efficacy of caffeine-containing dietary supplements in the United States and Canada. PubMed and Web of Science databases (1980-2014) were searched for articles related to the pharmacology, toxicology, and efficacy of caffeine-containing dietary supplements with an emphasis on Ephedra-containing supplements, Ephedra-free supplements, and energy drinks or shots. Among the first and most successful dietary supplements to be marketed in the United States were those containing Ephedra—combinations of ephedrine alkaloids, caffeine, and other phytochemicals. A decade after their inception, serious tolerability concerns prompted removal of Ephedra supplements from the US and Canadian markets. Ephedra-free products, however, quickly filled this void. Ephedra-free supplements typically contain multiple caffeine sources in conjunction with other botanical extracts whose purposes can often be puzzling and their pharmacologic properties difficult to predict. Ingestion of these products in the form of tablets, capsules, or other solid dosage forms as weight loss aids, exercise performance enhancers, or energy boosters have once again brought their tolerability and efficacy into question. In addition to Ephedra-free solid dosage forms, caffeine-containing energy drinks have gained a foothold in the world market along with concerns about their tolerability. This review addresses some of the pharmacologic and pharmaceutical issues that distinguish caffeine-containing dietary supplement formulations from traditional caffeine-containing beverages. Such distinctions may account for the increasing tolerability concerns affiliated with these products. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

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.

An open-label pilot study to assess the efficacy and safety of virgin coconut oil in reducing visceral adiposity.

PubMed

Liau, Kai Ming; Lee, Yeong Yeh; Chen, Chee Keong; Rasool, Aida Hanum G

2011-01-01

Introduction. This is an open-label pilot study on four weeks of virgin coconut oil (VCO) to investigate its efficacy in weight reduction and its safety of use in 20 obese but healthy Malay volunteers. Methodology. Efficacy was assessed by measuring weight and associated anthropometric parameters and lipid profile one week before and one week after VCO intake. Safety was assessed by comparing organ function tests one week before and one week after intake of VCO. Paired t-test was used to analyse any differences in all the measurable variables. Results. Only waist circumference (WC) was significantly reduced with a mean reduction of 2.86 cm or 0.97% from initial measurement (P = .02). WC reduction was only seen in males (P < .05). There was no change in the lipid profile. There was a small reduction in creatinine and alanine transferase levels. Conclusion. VCO is efficacious for WC reduction especially in males and it is safe for use in humans.

An Open-Label Pilot Study to Assess the Efficacy and Safety of Virgin Coconut Oil in Reducing Visceral Adiposity

PubMed Central

Liau, Kai Ming; Lee, Yeong Yeh; Chen, Chee Keong; Rasool, Aida Hanum G.

2011-01-01

Introduction. This is an open-label pilot study on four weeks of virgin coconut oil (VCO) to investigate its efficacy in weight reduction and its safety of use in 20 obese but healthy Malay volunteers. Methodology. Efficacy was assessed by measuring weight and associated anthropometric parameters and lipid profile one week before and one week after VCO intake. Safety was assessed by comparing organ function tests one week before and one week after intake of VCO. Paired t-test was used to analyse any differences in all the measurable variables. Results. Only waist circumference (WC) was significantly reduced with a mean reduction of 2.86 cm or 0.97% from initial measurement (P = .02). WC reduction was only seen in males (P < .05). There was no change in the lipid profile. There was a small reduction in creatinine and alanine transferase levels. Conclusion. VCO is efficacious for WC reduction especially in males and it is safe for use in humans. PMID:22164340

Efficacy of face-to-face versus self-guided treatments for disordered gambling: A meta-analysis.

PubMed

Goslar, Martina; Leibetseder, Max; Muench, Hannah M; Hofmann, Stefan G; Laireiter, Anton-Rupert

2017-06-01

Background and aims In the light of growing traditional and novel forms of gambling, the treatment of disordered gambling is gaining increasing importance and practical relevance. Most studies have examined face-to-face treatments. Although trials implementing self-guided treatments have recently been conducted, these options have not yet been systematically examined. The primary objective of this meta-analysis, therefore, was to analyze the efficacy of all types of psychological face-to-face and self-guided treatments. Methods A multilevel literature search yielded 27 randomized controlled studies totaling 3,879 participants to provide a comprehensive comparative evaluation of the short- and long-term efficacies of face-to-face and self-guided treatments for disordered gambling. Results As expected, the results revealed significantly higher effect sizes for face-to-face treatments (16 studies with Hedges's g ranging from 0.67 to 1.15) as compared with self-guided treatments (11 studies with Hedges's g ranging from 0.12 to 0.30) regarding the reduction of problematic gambling behavior. The intensity of treatment moderated the therapy effect, particularly for self-guided treatments. Discussion and Conclusions The results of this meta-analysis favor face-to-face treatments over self-guided treatments for the reduction of disordered gambling. Although the findings broaden the scope of knowledge about psychological treatment modalities for disordered gambling, further research is needed to identify the reasons for these differences with the goal to optimize the treatment for this disabling condition.

The Efficacy and Safety of Mainstream Medications for Patients With cDMARD-Naïve Rheumatoid Arthritis: A Network Meta-Analysis.

PubMed

Cai, Weiyan; Gu, Youyi; Cui, Huanqin; Cao, Yinyin; Wang, Xiaoliang; Yao, Yi; Wang, Mingyu

2018-01-01

Background: The mainstream medications for rheumatoid arthritis (RA) include conventional disease-modifying antirheumatic drugs (cDMARDs), which mostly are methotrexate (MTX), and biologic agents such as adalimumab (ADA), certolizumab (CZP), etanercept (ETN), golimumab (GOL), infliximab (IFX), and tocilizumab (TCZ). This network meta-analysis was aimed at evaluating the efficacy and safety of the medications above and interventions combining cDMARDs and biologic agents for patients with RA. Methods: PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov were searched systematically for eligible randomized controlled trials (RCTs). Outcomes concerning efficacy and safety were evaluated utilizing odds ratios (ORs) and 95% credible intervals ( CrI ). The outcomes of efficacy would be evaluated through remission and American College of Rheumatology (ACR) scores. The surface under the cumulative ranking curve (SUCRA) was calculated to rank each treatment on each index. Results: A total of 20 RCTs with 9,047 patients were included, and the efficacy and safety of the concerning interventions for RA were evaluated. Compared with cDMARDs alone, TCZ+MTX, ETN+MTX, IFX+MTX, TCZ, and ADA+MTX showed significant statistical advantage on ACR20, ACR50, and ACR70. Apart from that, as for remission, TCZ+MTX, IFX+MTX, TCZ, and CZP+MTX performed better compared to cDMARDs alone. The SUCRA ranking also indicated that TCZ+MTX was the intervention with best ranking in the entire four efficacy indexes followed by ETX+MTX and IFX+MTX. However, there was no obvious difference among these medications compared with cDMARDs when it comes to safety, which need more specific studies on that. Conclusion: TCZ+MTX was potentially the most recommended combination of medications for RA due to its good performance in all outcomes of efficacy. ETX+MTX and IFX+MTX, which also performed well, could be introduced as alternative treatments. However, considering the adverse events, the treatments

Emerging Drugs for the Treatment of Symptoms Associated with Autism Spectrum Disorders

PubMed Central

Wink, Logan K.; Plawecki, Martin H.; Erickson, Craig A.; Stigler, Kimberly A.; McDougle, Christopher J.

2010-01-01

Importance of the Field Autism spectrum disorders, or pervasive developmental disorders (PDDs), are neurodevelopmental disorders defined by qualitative impairment in social interaction, impaired communication, and stereotyped patterns of behavior. The most common forms of PDD are autstic disorder (autism), Asperger's disorder, and pervasive developmental disorder not otherwise specified (PDD NOS). Recent surveillance studies reveal an increase in the prevalence of autism and related PDDs. The use of pharmacologic agents in the treatment of these disorders can reduce the impact of interfering symptoms, providing relief for affected individuals and their families. Areas Covered in this Review This review examines results from neurobiologic research in an attempt to both elucidate the pathophysiology of autism and guide the development of pharmacologic agents for the treatment of associated symptoms. The safety and efficacy data of drugs currently in clinical use for the treatment of these symptoms, as well as pharmaceuticals currently under development, are discussed. What the Reader will Gain This comprehensive review will deepen the reader's current understanding of the research guiding the pharmacologic treatment of symptoms associated with autism and related PDDs. Areas of focus for future research are also discussed. The need for large-scale investigation of some commonly used pharmacologic agents, in addition to the development of drugs with improved efficacy and safety profiles, is made evident. Take Home Message Despite progress in the development of pharmacologic treatments for a number of interfering symptom domains associated with autism and other PDDs, a great deal of work remains. PMID:20470188

Evidence for the efficacy and safety of topical herbal drugs in dermatology: Part I: Anti-inflammatory agents.

PubMed

Hörmann, H P; Korting, H C

1994-09-01

Topical herbal drugs have for centuries been used for treating skin ailments. Although they are currently widely accepted by patients, their scientific esteem among dermatologists in particular is limited. A variety of herbal drugs for topical application deserves consideration regarding their widespread use or their still ill-defined potential with respect to their benefit/risk ratio. Clinically, camomile (Chamomilla recutita) and hamamelis preparations look particularly well documented. While the final proof of efficacy in common dermatoses such as atopic dermatitis is still lacking, there is fairly ample evidence for their activity against cutaneous inflammation in man, as may be deduced from experiments with normal volunteers. With Hamamelis virginiana this looks paricularly promising, as unwanted effects related to the drug are virtually absent. With camomile preparations the degree of safety seems to depend largely on the plant used. Some herbal drugs clearly need further analysis until their value can be determined. This includes the frequently-used aloe preparations. This is the more remarkable as huge numbers of in vitro studies are available. Arnica is fairly unique in so far as the lack of proof of efficacy strongly contrasts to its sensitization potential. So far, in particular dermatitis and related disorders can be considered potential indications for topical herbal antiinflammatory drugs. Studies in psoriasis vulgaris should also be performed addressing long-term application. In this context such fairly ill-defined drugs as Mahonia deserve attention. Copyright © 1994 Gustav Fischer Verlag, Stuttgart · Jena · New York. Published by Elsevier GmbH.. All rights reserved.

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.

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

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

PubMed Central

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

2014-01-01

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

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…

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,…

Safety and efficacy of subcutaneous tanezumab in patients with knee or hip osteoarthritis.

PubMed

Birbara, Charles; Dabezies, Eugene J; Burr, Aimee M; Fountaine, Robert J; Smith, Michael D; Brown, Mark T; West, Christine R; Arends, Rosalin H; Verburg, Kenneth M

2018-01-01

The objective of this study was to investigate the safety and efficacy of subcutaneous (SC) and intravenous (IV) tanezumab administration in osteoarthritis (OA) patients. Study 1027 (NCT01089725), a placebo-controlled trial, evaluated the efficacy of SC tanezumab (ie, 2.5, 5, and 10 mg) and the therapeutic equivalence of 10 mg tanezumab given subcutaneously versus intravenously every 8 weeks in the symptomatic treatment of OA. Coprimary endpoints were: change from baseline in Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) Pain and Physical Function indices, and Patient's Global Assessment (PGA) of OA. Study 1043 (NCT00994890) was a long-term, noncontrolled safety study of tanezumab (ie, 2.5, 5, and 10 mg) subcutaneously administered every 8 weeks. Both studies were discontinued prematurely due to a US Food and Drug Administration partial clinical hold. Due to the clinical hold, Study 1027 was underpowered, and no statistical analyses were performed. Mean (standard error [SE]) change from baseline to week 8 in WOMAC Pain in tanezumab groups ranged from -3.59 (0.26) to -3.89 (0.32), versus -2.74 (0.25) with placebo. Mean (SE) change from baseline to week 8 in WOMAC Physical Function ranged from -3.13 (0.25) to -3.51 (0.28) with tanezumab and was -2.26 (0.24) with placebo. PGA mean (SE) change from baseline to week 8 ranged from -0.90 (0.11) to -1.08 (0.12) with tanezumab and was -0.78 (0.10) with placebo. Similar effectiveness was associated with tanezumab in Study 1043. Few patients in either study (1.4%-5.2%) discontinued due to adverse events. Five patients required total joint replacements in Study 1027 (placebo, n=2 [2.8%]; tanezumab 2.5 mg, n=3 [4.1%]) and 34 patients in Study 1043 (tanezumab 2.5 mg, n=11 [4.8%]; tanezumab 5 mg, n=8 [3.6%]; tanezumab 10 mg, n=15 [6.6%]). Preliminary results show similar efficacy and safety for both SC and IV administration of tanezumab based on the direct comparisons reported here and indirect

A systematic review of the safety and efficacy of artemether-lumefantrine against uncomplicated Plasmodium falciparum malaria during pregnancy.

PubMed

Manyando, Christine; Kayentao, Kassoum; D'Alessandro, Umberto; Okafor, Henrietta U; Juma, Elizabeth; Hamed, Kamal

2012-05-01

Malaria during pregnancy, particularly Plasmodium falciparum malaria, has been linked to increased morbidity and mortality, which must be reduced by both preventive measures and effective case management. The World Health Organization (WHO) recommends artemisinin-based combination therapy (ACT) to treat uncomplicated falciparum malaria during the second and third trimesters of pregnancy, and quinine plus clindamycin during the first trimester. However, the national policies of many African countries currently recommend quinine throughout pregnancy. Therefore, the aim of this article is to provide a summary of the available data on the safety and efficacy of artemether-lumefantrine (AL) in pregnancy. An English-language search identified 16 publications from 1989 to October 2011 with reports of artemether or AL exposure in pregnancy, including randomized clinical trials, observational studies and systematic reviews. Overall, there were 1,103 reports of AL use in pregnant women: 890 second/third trimester exposures; 212 first trimester exposures; and one case where the trimester of exposure was not reported. In the second and third trimesters, AL was not associated with increased adverse pregnancy outcomes as compared with quinine or sulphadoxine-pyrimethamine, showed improved tolerability relative to quinine, and its efficacy was non-inferior to quinine. There is evidence to suggest that the pharmacokinetics of anti-malarial drugs may change in pregnancy, although the impact on efficacy and safety needs to be studied further, especially since the majority of studies report high cure rates and adequate tolerability. As there are fewer reports of AL safety in the first trimester, additional data are required to assess the potential to use AL in the first trimester. Though the available safety and efficacy data support the use of AL in the second and third trimesters, there is still a need for further information. These findings reinforce the WHO recommendation to

Pharmacodynamic and pharmacokinetic evaluation of buprenorphine + samidorphan for the treatment of major depressive disorder.

PubMed

Ragguett, Renee-Marie; Rong, Carola; Rosenblat, Joshua D; Ho, Roger C; McIntyre, Roger S

2018-04-01

Treatment resistant depression (TRD) represents approximately 20% of all individuals receiving care for major depressive disorder. The opioidergic system is identified as a novel target which hitherto has not been sufficiently investigated in adults with TRD. The combination product buprenorphine + samidorphan is an opioid modulatory agent which has demonstrated replicated evidence of efficacy in TRD without abuse liability. Areas covered: Databases Pubmed, Google Scholar and clinicaltrials.gov were searched from inception through December 2017 for clinical trial information, pharmacokinetics, and pharmacodynamics of buprenorphine + samidorphan. Herein we provide a summary of the available information. Eight clinical trials were identified for inclusion, of the eight trials, five trials had available results and are included in detail in our review. Expert opinion: Buprenorphine + samidorphan has demonstrated efficacy in TRD. Extant evidence surrounding the safety and tolerability profile of buprenorphine + samidorphan does not identify any significant safety concerns. Additional studies are needed in order to assess the long-term safety and efficacy of this product.

Systematic review of published studies on safety and efficacy of thoracoscopic and robot-assisted lobectomy for lung cancer.

PubMed

Nakamura, Hiroshige

2014-01-01

The safety and efficacy of thoracoscopic and robot-assisted lobectomies for primary lung cancer were reviewed in the literature. Thoracoscopic surgery is less invasive compared to thoracotomy, and it has been reported to be superior with regard to the outcome. In addition, the operability of a surgical robot (da Vinci) is favorable and supplements the disadvantages of conventional endoscopic surgery. Robot-assisted lobectomy has been reported to be comparable to thoracoscopic surgery with regard to the safety and efficacy based on analysis of perioperative results and superior with regard to the operability and length of the learning curve. However, a high cost and a long operative time are of concern. Since robot-assisted surgery has been performed only in early cases, the continuation of a comparative investigation may be necessary.

[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.

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.

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

Omega-3 Fatty Acids for Autistic Spectrum Disorder: A Systematic Review

ERIC Educational Resources Information Center

Bent, Stephen; Bertoglio, Kiah; Hendren, Robert L.

2009-01-01

We conducted a systematic review to determine the safety and efficacy of omega-3 fatty acids for autistic spectrum disorder (ASD). Articles were identified by a search of MEDLINE, EMBASE, and the Cochrane Database using the terms autism or autistic and omega-3 fatty acids. The search identified 143 potential articles and six satisfied all…

Short-Term Safety and Efficacy of Calcium Montmorillonite Clay (UPSN) in Children

PubMed Central

Mitchell, Nicole J.; Kumi, Justice; Aleser, Mildred; Elmore, Sarah E.; Rychlik, Kristal A.; Zychowski, Katherine E.; Romoser, Amelia A.; Phillips, Timothy D.; Ankrah, Nii-Ayi

2014-01-01

Recently, an association between childhood growth stunting and aflatoxin (AF) exposure has been identified. In Ghana, homemade nutritional supplements often consist of AF-prone commodities. In this study, children were enrolled in a clinical intervention trial to determine the safety and efficacy of Uniform Particle Size NovaSil (UPSN), a refined calcium montmorillonite known to be safe in adults. Participants ingested 0.75 or 1.5 g UPSN or 1.5 g calcium carbonate placebo per day for 14 days. Hematological and serum biochemistry parameters in the UPSN groups were not significantly different from the placebo-controlled group. Importantly, there were no adverse events attributable to UPSN treatment. A significant reduction in urinary metabolite (AFM1) was observed in the high-dose group compared with placebo. Results indicate that UPSN is safe for children at doses up to 1.5 g/day for a period of 2 weeks and can reduce exposure to AFs, resulting in increased quality and efficacy of contaminated foods. PMID:25135766

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

The Efficacy of Exposure Therapy for Anxiety-Related Disorders and Its Underlying Mechanisms: The Case of OCD and PTSD.

PubMed

Foa, Edna B; McLean, Carmen P

2016-01-01

In this review we describe the intricate interrelationship among basic research, conceptualization of psychopathology, treatment development, treatment outcome research, and treatment mechanism research and how the interactions among these areas of study further our knowledge about psychopathology and its treatment. In describing the work of Edna Foa and her colleagues in anxiety disorders, we demonstrate how emotional processing theory of anxiety-related disorders and their treatment using exposure therapy have generated hypotheses about the psychopathology of posttraumatic stress disorder and obsessive-compulsive anxiety disorder that have informed the development and refinement of specific treatment protocols for these disorders: prolonged exposure and exposure and response (ritual) prevention. Further, we have shown that the next step after the development of theoretically driven treatment protocols is to evaluate their efficacy. Once evidence for a treatment's efficacy has accumulated, studies of the mechanisms involved in the reduction of the targeted psychopathology are conducted, which in turn inform the theory and further refine the treatments. We conclude our review with a discussion of how the knowledge derived from Foa and colleagues' programmatic research together with knowledge emerging from basic research on extinction learning can inform future research on the psychopathology of anxiety disorders and their treatments.

Long-Term Safety and Efficacy of Enzyme Replacement Therapyfor Fabry Disease

PubMed Central

Wilcox, William R.; Banikazemi, Maryam; Guffon, Nathalie; Waldek, Stephen; Lee, Philip; Linthorst, Gabor E.; Desnick, Robert J.; Germain, Dominique P.

2004-01-01

Elsewhere, we reported the safety and efficacy results of a multicenter phase 3 trial of recombinant human α-galactosidase A (rh-αGalA) replacement in patients with Fabry disease. All 58 patients who were enrolled in the 20-wk phase 3 double-blind, randomized, and placebo-controlled study received subsequently 1 mg/kg of rh-αGalA (agalsidase beta, Fabrazyme, Genzyme Corporation) biweekly in an ongoing open-label extension study. Evidence of long-term efficacy, even in patients who developed IgG antibodies against rh-αGalA, included the continuously normal mean plasma globotriaosylceramide (GL-3) levels during 30 mo of the extension study and the sustained capillary endothelial GL-3 clearance in 98% (39/40) of patients who had a skin biopsy taken after treatment for 30 mo (original placebo group) or 36 mo (original enzyme-treated group). The mean serum creatinine level and estimated glomerular filtration rate also remained stable after 30–36 mo of treatment. Infusion-associated reactions decreased over time, as did anti-rh-αGalA IgG antibody titers. Among seroconverted patients, after 30–36 mo of treatment, seven patients tolerized (no detectable IgG antibody), and 59% had ⩾4-fold reductions in antibody titers. As of 30 mo into the extension trial, three patients were withdrawn from the study because of positive serum IgE or skin tests; however, all have been rechallenged successfully at the time of this report. Thus, enzyme replacement therapy for 30–36 mo with agalsidase beta resulted in continuously decreased plasma GL-3 levels, sustained endothelial GL-3 clearance, stable kidney function, and a favorable safety profile. PMID:15154115

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.

Contested Issues of Efficacy and Safety between Transnational Formulation Regimes of Tibetan Medicines in China and Europe

PubMed Central

Schrempf, Mona

2016-01-01

Tibetan medicines are key material objects for medical treatment and have become part of a global trend of ‘pharmaceuticalisation’, playing increasingly important political and socio-economic roles in an ‘alternative modernity’. As I argue in this paper, they also have become key ‘sites of contestation’ between different epistemic values and styles of practice related to efficacy and safety that are reproduced in and through specific formulation regimes. Based on my multisited ethnography of production, prescription, and use practices of Tibetan medicines in China and Europe, this paper conceptualises three distinct formulation regimes, offering a heuristic model for transnational comparison—a classical, an industrialised or reformulated, and a polyherbal regime. The first two are the major orientations while the polyherbal is a conjoint hybrid with either the classical or the industrialised formulation regime. Globalised national drug safety regulations legalise and confer legitimacy to industrialised Tibetan formulas that follow biomedically defined efficacy, safety, and disease categories, while classical formulas produced by private physicians or small-scale cottage pharmacies are increasingly marginalised as producing ‘unsafe’ and at times illegal medicines, and need to find new ways for adapting and circulating their formulas. PMID:27885323