Reductions in and relations between “craving” and drinking in a prospective, open-label trial of ondansetron in adolescents with alcohol dependence

Recently, we reported that ondansetron (a 5-HT₃ antagonist) as an adjunct to cognitive behavioral therapy (CBT) produced significant within-group decreases (improvement) in drinking in adolescents with alcohol dependence. We previously have hypothesized that the mechanism of ondansetron treatment response in adolescents with alcohol dependence should be similar to early onset adult alcoholics, wherein blockade of serotonin-3 receptors may decrease dopamine release and subsequent alcohol consumption and craving. We now suggest that one mechanism by which ondansetron diminishes drinking in adolescents with alcohol dependence is through a reduction in “craving” as measured by the Adolescent Obsessive–Compulsive Drinking Scale (A-OCDS). We conducted an 8-week, prospective, open-label study of ondansetron (4 μg/kg b.i.d.) in 12 adolescents (age 14–20 years) who had alcohol dependence. Results showed that “irresistibility” and total scores as measured by the A-OCDS were correlated significantly with drinking indices (drinks / day, percent days abstinent) at the end of treatment, and that “irresistibility” and total A-OCDS scores decreased significantly by the end of treatment. These preliminary results suggest that the A-OCDS can be useful as an outcome measure in clinical studies of adolescents with alcohol dependence.     

Subcutaneous tocilizumab in adults with severe and critical COVID-19: A prospective open-label uncontrolled multicenter trial

Potential therapeutic approaches in coronavirus disease 2019 (COVID-19) comprise antiviral and immunomodulatory agents; however, no immunomodulator drug has been approved. This multicenter, prospective, open-label, uncontrolled study aimed to assess the use of subcutaneous tocilizumab in adult patients with severe and critical COVID-19. Tocilizumab was added to the standard care of therapy at a dose of 324 mg (<100 kg bodyweight) or 486 mg (≥100 kg bodyweight). The study endpoints were all-cause mortality rate, changes in oxygen-support level, oxygen saturation, body temperature, respiratory rate, and laboratory variables during the study, and drug safety. Of 126 patients enrolled, 86 had severe and 40 had critical disease. Most patients were male (63.49%) and aged below 65 (78.57%). By day 14 of the study, 4.65% (4/86) of severe patients and 50.00% (20/40) of critical patients died. By the end, 6.98% (6/86) of severe patients and 60.00% (24/40) of critical patients died. Outcomes concerning three additional endpoints (oral temperature, oxygen saturation, and respiratory rate) were significantly improved as early as three days after tocilizumab administration in both groups of subjects, more considerably in severe patients. Significant improvement in the required level of oxygenation was reported in severe patients seven days after tocilizumab administration. No tocilizumab-related serious adverse event occurred in this study. Subcutaneous tocilizumab might improve some clinical parameters and reduce the risk of death in COVID-19 patients, particularly if used in the early stages of respiratory failure.     

Changes in schizophrenia-related hospitalization and ER use among patients receiving paliperidone palmitate: results from a clinical trial with a 52-week open-label extension (OLE)

Abstract

Background:

Schizophrenia affects ～1.1% of the United States population, resulting in substantial direct, indirect and societal costs.     

A clinical evaluation of risperidone in the treatment of schizophrenia: a 10-week, open-label, multicenter trial

The efficacy and safety of risperidone have previously been demonstrated in controlled clinical trials in hospitalized chronic schizophrenia patients who met strict research criteria. The present study was designed to evaluate the efficacy and safety of risperidone in a heterogeneous patient population. Patients were enrolled in the study if they had a diagnosis of schizophrenia (DSM-III-R) with or without acute exacerbation. Of the 945 patients from 158 psychiatric centers who entered this phase IV study, 558 completed the 10-week trial. During week 1, the dose of risperidone was titrated to 6 mg/day, maintained there for 1 week, and then adjusted over a 4-week period as clinically necessary; the dose was then fixed for the final 4-week period. The mean dose of risperidone at endpoint was 5.9 mg/day. Patients were evaluated at baseline and at weeks 2, 6, and 10, using Clinical Global Impression scale, Psychotic Symptoms Assessment scale, and Global Assessment of Functioning scale. Significant improvement in mean scores was found on each of these measures at endpoint. Comparable results were obtained at week 10 in treatment-resistant and non-treatment-resistant patients. Risperidone was generally well tolerated and the severity of extrapyramidal symptoms was significantly reduced at endpoint. Received: 17 April 1996/Final version: 31 December 1996     

The effect of topiramate on energy balance in obese men: a 6-month double-blind randomized placebo-controlled study with a 6-month open-label extension

Objective Topiramate (TPM) has been reported to reduce body weight beyond a placebo in the treatment of obese participants, but the effect of this agent on components of energy balance has not yet been established in humans. Thus, the aim of this study was to study the impact of TPM on food preferences, measures of satiety, food intake, resting metabolic rate (RMR), and 24-h energy expenditure. Methods The study design consisted of a 6-month, single-center, randomized, double-blind, parallel group, placebo-controlled trial with a 6-month open-label extension. The study included 68 sedentary men with abdominal obesity (waist circumference ≥100 cm), of between 25 and 55 years of age, with a dyslipidemic profile and a body mass index (BMI) ≥27 and ≤40 kg/m². Results Treatment with TPM produced significant changes in anthropometric variables and body composition compared with placebo. However, at the end of the 1-year study, the placebo/TPM group showed similar weight loss and reduction in body fatness compared with the TPM/TPM group. For instance, at the end of the 12-month intervention, mean percentage of body weight loss from baseline was about −5% in both groups (−4 kg fat loss). Topiramate treatment reduced energy intake, be it in the context of an ad libitum buffet-type meal or under free living conditions. The 24-h daily energy expenditure (DEE) assessed by whole-body indirect calorimetry adjusted for body weight and age was not altered by TPM treatment. Conclusion Topiramate treatment produced significantly greater weight loss than placebo and the majority of this loss was explained by a decrease in body fat stores. Most of the weight loss effect produced by TPM therapy was observed within a period of 6 months. Finally, TPM treatment had an impact on energy balance through a reduction in food intake that appears to have created an energy deficit of about 30,000–40,000 kcal compared with treatment with the placebo over 6 months.     

Venlafaxine versus mirtazapine in the treatment of undifferentiated somatoform disorder: a 12-week prospective, open-label, randomized, parallel-group trial

OBJECTIVE: We set out to compare the efficacy and tolerability of mirtazapine versus venlafaxine in patients with undifferentiated somatoform disorder (USD) using the Patient Health Questionnaire-15 (PHQ-15). METHODS: This was a 12-week prospective, open-label, randomized, parallel-group trial. The trial consisted of six visits that included baseline and weeks 1, 2, 4, 8 and 12. The primary effectiveness measure was the mean change in PHQ-15 total score from baseline to the end of treatment. Secondary effectiveness measures included the mean changes in total scores on the Beck Depression Inventory (BDI) and the 12-item General Health Questionnaire (GHQ) from baseline to the end of treatment. Ninety-five subjects were randomized to either mirtazapine (n = 50) or venlafaxine (n = 45); 71 subjects completed the study (mirtazapine: n = 39/50 [78%]; venlafaxine: n = 32/45 [71%]). RESULTS: The mean total score on the PHQ-15 decreased by 34.7% (-8.4, p < 0.0001) from baseline to endpoint in the mirtazapine group and by 26.6% (-6.1, p < 0.0001) in the venlafaxine group. A marginally significant between-group difference was observed for the mean change in total score on the PHQ-15 from baseline to endpoint (F = 4.126, p = 0.046). The mean total scores on the GHQ-12 and BDI from baseline to endpoint decreased by -4.9 (29.4%, p < 0.0001) and -13.5 (55.9%, p < 0.0001), respectively, in the mirtazapine group, and by -4.3 (26.2%, p = 0.001) and -9.02 (46.0%, p < 0.0001), respectively, in the venlafaxine group. No between-group difference was observed for the mean changes in total scores on the secondary effectiveness measures from baseline to endpoint. Both treatments were well tolerated. CONCLUSION: Our findings suggest that both mirtazapine and venlafaxine may be effective and well tolerated in the treatment of patients with USD. Double-blind, placebo-controlled and/or head-to-head comparison studies are required to allow definite conclusions to be drawn.     

Efficacy and safety of alogliptin added to insulin in Japanese patients with type 2 diabetes: a randomized,double-blind, 12-week,placebo-controlled trial followed by an open-label,long-term extension phase

Objective: To evaluate the efficacy and safety of alogliptin added to insulin in Japanese patients with type 2 diabetes mellitus (T2DM) who are poorly controlled with insulin and diet or exercise.

Study design: This was a randomized, double-blind, 12-week comparative trial of alogliptin and insulin versus placebo and insulin in 179 patients with T2DM followed by a 40-week, open-label phase in 169 patients on alogliptin and insulin.

Primary outcome measure: Change in glycated hemoglobin (HbA1c) from baseline to the end of double-blind phase (week 12).

Results: The change in HbA1c (least squares means) from baseline to week 12 was ?0.96% for the alogliptin and insulin group and ?0.29% for the placebo and insulin group. The point estimate (95% confidence interval) intergroup difference was ?0.66% ([?0.824%, ?0.503%]). In the alogliptin and insulin group, HbA1c started to decrease from week 2 onward and peaked by week 12. The proportions of patients who achieved HbA1c < 8.0, < 7.0 and < 6.0% at week 12 were significantly higher in alogliptin and insulin group (73.0, 23.3 and 1.1%) than in placebo and insulin group (25.0, 5.7 and 0%). Incidences of adverse effects were comparable between groups, with no relevant increases in hypoglycemia or weight gain seen.

Conclusions: Alogliptin 25 mg/day was effective and well tolerated when added to insulin in Japanese patients with inadequately controlled T2DM.     

Etoricoxib versus naproxen in patients with rheumatoid arthritis: a prospective,randomized, comparator-controlled 121-week trial

ABSTRACT

Background: Etoricoxib is a cyclooxygenase-2 (COX?2) selective inhibitor effective in the treatment of rheumatoid arthritis. An initial 12-week treatment study found that etoricoxib (90?mg once daily) was more effective than naproxen (500?mg twice daily) or placebo in treating rheumatoid arthritis. The present two-part extension of that study was performed to monitor tolerability and examine long-term efficacy of etoricoxib 90?mg or 120?mg compared with naproxen.

Methods: Patients completing the initial 12-week study and those discontinuing due to lack of efficacy, were eligible for the Extension Study Part I (12–52 weeks) and assigned (2?:?1?:?2 ratio) to receive etoricoxib (90?mg or 120?mg daily) or naproxen (500?mg twice daily); these patients remained on the same therapy for Extension Study Part II (52–121 weeks). Primary outcome measures included investigator and patient assessment of disease activity, and tender and swollen joint counts.

Results: Of 816 patients enrolled in the initial 12-week trial, 717 continued into the Extension Study Part I; 505 patients completed and 390 entered the Extension Study Part II, with 283 patients completing 121 weeks. Patients receiving etoricoxib (90?mg) or naproxen throughout the study experienced sustained efficacy in all outcomes, as did patients transitioning to etoricoxib (120?mg) following the initial 12-week trial. Patients transitioning from placebo to etoricoxib (90?mg) experienced rapid, sustained improvements in all outcome measures.

Conclusion: In conclusion, etoricoxib provided sustained efficacy throughout the 121-week study, with efficacy comparable to naproxen.     

Comparison of antiplatelet effect and safety of clopidogrel napadisilate with clopidogrel bisulfate in stroke patients: multicenter,randomized, open-label,phase 4, non-inferiority clinical trial

Objective:

Clopidogrel napadisilate has better chemical stability than clopidogrel bisulfate. Our trial’s objective was to compare the efficacy and safety of clopidogrel napadisilate with clopidogrel bisulfate in participants with ischemic stroke.

Research design and methods:

The study was a phase 4, 4 week, randomized, parallel-group, non-inferiority trial. Patients with ischemic stroke were randomized to receive either clopidogrel napadisilate 75?mg or clopidogrel bisulfate 75?mg. The primary study endpoint was change from baseline in P2Y12 percentage inhibition at week 4. The primary analysis was conducted in the per-protocol population. Non-inferiority was confirmed if the lower limit of the 95% confidence interval (CI) of the treatment difference was greater than or equal to ?9.0% points.

Results:

Sixty-one participants were randomly assigned clopidogrel napadisilate and 60 were randomly assigned clopidogrel bisulfate. Thirty-nine participants in the clopidogrel napadisilate group and 39 in the clopidogrel bisulfate group were analyzed for the primary endpoint. At 4 weeks, mean P2Y12 percentage inhibition had increased in both treatment groups. The estimated mean change from baseline was 22.3% with clopidogrel napadisilate and 21.4% with clopidogrel bisulfate; the estimated treatment difference of 0.9% (95% CI, ?8.6 to 10.4) confirmed the non-inferiority of clopidogrel napadisilate to clopidogrel bisulfate.

Conclusions:

Clopidogrel napadisilate was non-inferior to clopidogrel bisulfate as assessed by change in P2Y12 percentage inhibition. Rates of adverse events were similar between the two groups. Therefore, clopidogrel napadisilate is a useful alternative option for the dosing of ischemic stroke patient populations.     

Promising effects of tocilizumab in COVID-19: A non-controlled,prospective clinical trial

BackgroundThe clinical presentation of SARS-CoV-2 infection ranges from mild symptoms to severe complications, including acute respiratory distress syndrome. In this syndrome, inflammatory cytokines are released after activation of the inflammatory cascade, with the predominant role of interleukin (IL)-6. The aim of this study was to evaluate the effects of tocilizumab, as an IL-6 antagonist, in patients with severe or critical SARS-CoV-2 infection.MethodsIn this prospective clinical trial, 76 patients with severe or critical SARS-CoV-2 infection were evaluated for eligibility, and ultimately, 42 patients were included. Tocilizumab was administered at a dose of 400 mg as a single dose via intravenous infusion. Primary outcomes included changes in oxygenation support, need for invasive mechanical ventilation, and death. Secondary outcomes included radiological changes in the lungs, IL-6 plasma levels, C-reactive protein levels, and adverse drug reactions. The data were analyzed using SPSS software.ResultsOf the 42 included patients, 20 (48%) patients presented the severe infection stage and 22 (52%) were in the critical stage. The median age of patients was 56 years, and the median IL-6 level was 28.55 pg/mL. After tocilizumab administration, only 6 patients (14%) required invasive ventilation. Additionally, 35 patients (83.33%) showed clinical improvement. By day 28, a total of 7 patients died (6 patients in the critical stage and 1 patient in the severe stage). Neurological adverse effects were observed in 3 patients.ConclusionsBased on the current results, tocilizumab may be a promising agent for patients with severe or critical SARS-CoV-2 infection, if promptly initiated during the severe stage.     

Clinical profile of botulinum toxin A in patients with chronic headaches and cervical dystonia: a prospective, open-label, longitudinal study conducted in a naturalistic clinical practice setting

BACKGROUND AND OBJECTIVES: Some evidence for the efficacy of botulinum toxin A as a preventive treatment for chronic primary headaches has been reported in randomized, controlled clinical studies. This study investigated the clinical profile of botulinum toxin A in a naturalistic clinical practice setting in a population of patients with cervical dystonia associated with chronic headache and a history of migraine. METHODS: This was a prospective, open-label, longitudinal study. Following a prospective run-in period, eligible patients were given three sets of botulinum toxin A injections at 8- to 12-week intervals over a 16- to 24-week period and were monitored for 3 months after the final injections. Efficacy was assessed in terms of headache-related disability (using the Migraine Disability Assessment [MIDAS] questionnaire), pain and emotional function (using the Short Pain Inventory [SPI]), quality of life (QOL, using the Short-Form-36 [SF-36] questionnaire) and patient-assessed headache frequency and severity, and medication use and its effectiveness. Safety was assessed as adverse events. The primary endpoint was the change in MIDAS score from baseline following treatment with botulinum toxin A. RESULTS: Twenty-four patients took part in the study and 17 (71%) completed the study. There were significant improvements in headache-related disability (MIDAS score), pain and emotional function (SPI), QOL (SF-36), headache frequency and medication use following treatment with botulinum toxin A (p < 0.05 for all endpoints). An efficacy response occurred within 8 weeks of treatment initiation and was maintained throughout the study duration. Botulinum toxin A was generally well tolerated. CONCLUSIONS: This study demonstrated that botulinum toxin A is an effective and well tolerated preventive treatment for chronic headache in patients with cervical dystonia and a history of migraine. These results warrant further investigation in a large, randomized, controlled study.     

A prospective study of persistence in the prediction of smoking cessation outcome: Results from a randomized clinical trial

Research has had mixed success in identifying pretreatment variables which can be used to guide treatment and enhance outcome. A critical first step in the process is to identify variables that reliably predict outcome. Some recent studies, largely retrospective, have found mixed evidence on the relationship between task persistence and smoking outcome measures. In the present study, we use data from a randomized clinical trial (N = 241) to prospectively investigate the ability of persistence to predict outcome. Findings from multivariate analyses did not support our hypotheses: persistence did not predict outcome. We discuss these findings in relation to previous studies by focusing on theoretical and measurement issues related to the study of persistence in smoking cessation research. We conclude by recommending directions for future research, including conceptual clarification of the relationship between persistence and theoretically related constructs and investigations of variables that may moderate relationships between these constructs and cessation outcome.     

Efficacy and safety of saxagliptin in combination with insulin in Japanese patients with type 2 diabetes mellitus: a 16-week double-blind randomized controlled trial with a 36-week open-label extension

Background: We examined the efficacy and safety of saxagliptin as an add-on to insulin in Japanese patients with type 2 diabetes mellitus.

Research design and methods: We randomized 240 patients with type 2 diabetes mellitus on insulin monotherapy to 5-mg saxagliptin or placebo as add-on therapy for a 16-week, double-blind period. All patients received 5-mg saxagliptin and insulin for an additional 36 weeks (open-label extension). Change in hemoglobin A1c (HbA1c) at Week 16 was the main endpoint.

Results: At Week 16, the adjusted change in HbA1c from baseline increased by 0.51% with placebo and decreased by 0.40% with saxagliptin (difference ?0.92% [95% confidence interval ?1.07%, ?0.76%; p < 0.001]). In patients receiving saxagliptin, reductions in HbA1c at Week 16 were maintained to Week 52, while switching from placebo to saxagliptin resulted in a similar reduction in HbA1c. The incidence of hypoglycemia was not markedly increased with saxagliptin versus placebo in the double-blind period and did not increase substantially during the open-label extension period. The efficacy and safety of saxagliptin was similar between the elderly and non-elderly patient groups.

Conclusions: Adding saxagliptin to ongoing insulin therapy improved glycemic control and was well tolerated in Japanese patients with type 2 diabetes.     

甲硝唑凝胶治疗中、重度酒渣鼻随机双盲、安慰剂对照临床试验

目的 :评价 0 .75 %甲硝唑凝胶治疗中、重度酒渣鼻的临床疗效和安全性。方法 :采用随机、双盲、安慰剂对照方法 ;病人在皮损区域局部外用0 .75 %甲硝唑凝胶或安慰剂 ,每日 2次 ,疗程 12wk。结果 :可分析病例 6 2例 ,其中甲硝唑组 31例 ,安慰剂组 31例。治疗后炎性损害百分数 ,甲硝唑组与安慰剂组在wk 4时分别为 (2 9± 38) %vs (1±83) % (P >0 .0 5 ) ,wk 8时为 (49± 5 1) %vs (3±83) % (P <0 .0 5 ) ,wk 12时为 (5 6± 4 2 ) %vs (2 1± 4 8) % (P <0 .0 1)。wk 12时红斑消失甲硝唑组和安慰剂组分别为 8%和 4 % ,2组比较差异无显著意义 (P >0 .0 5 )。用药后局部刺激反应 ,甲硝唑组为 2 9% ,安慰剂组为 2 3% ,均为轻、中度 ,2组比较差异无显著意义 (P >0 .0 5 )。结论 :0 .75 %甲硝唑凝胶治疗中、重度酒渣鼻的疗效肯定 ,安全性高     

The effectiveness and safety of adjunctive aripiprazole in Taiwanese patients with antidepressant-refractory major depressive disorder: a prospective, open-label trial

There is currently no published clinical trial on the safety and effectiveness of aripiprazole in Taiwanese patients with treatment-refractory major depressive disorder. We were interested in determining the applicability of current recommended doses of aripiprazole as an adjunct to antidepressant therapy in this population. We conducted a prospective, open-label nonrandomized, 4-week flexibly dosed (2.5-5 mg/d) trial with aripiprazole augmentation in 9 Taiwanese patients who had a history of nonresponse to at least 2 adequate courses of antidepressant therapy with different types of antidepressants. The primary end point for clinical effectiveness was mean change in the 17-item Hamilton Rating Scale for Depression at the end of the 4-week trial. Secondary end points for clinical effectiveness included mean change in Beck Depression Inventory and Beck Anxiety Inventory scores. The Systematic Assessment of Treatment Emergent Events-General Inquiry was used to assess adverse effects. All patients completed the trial and responded to treatment; the remission rate was 77.8%. The mean daily dose of adjunctive aripiprazole was 4.2 mg. Common treatment-emergent adverse events included insomnia and sedation (33.3%) and akathisia (22.2%). We found high effectiveness despite a lower mean daily dose of adjunctive aripiprazole (4.2 mg) when compared with previously reported findings; however, we also observed a higher frequency of treatment-emergent adverse effects. Additional studies are required to ascertain whether there are ethnic differences in the pharmacokinetics and/or pharmacodynamics of aripiprazole in treatment-refractory depression.     

睡眠质量对全膝关节置换术后早期康复的影响: 一项前瞻、双盲、随机对照临床研究

目的 探讨睡眠质量对全膝关节置换术(TKA)后早期康复的影响。方法 选择安徽医科大学第一附属医院2017年3—9月符合纳入标准的行初次单侧TKA术的72例病人,对其进行前瞻性、随机化研究,按1∶2比例、随机数字表法分为试验组(24例)和对照组(48例),术后通过口服唑吡坦提高睡眠质量的24例为试验组,术后口服等剂量维生素B6(安慰剂)的48例为对照组,分别记录两组术后24 h及72 h静息状态时疼痛视觉模拟评分(visual analogue scale,VAS),术后3 d的总蛋白、白蛋白、血红蛋白值,术后住院天数,屈膝90°所需天数,术后3 d的SCL-90量表评分。结果 两组病人术前基线资料如年龄、性别、体质量指数、术前膝关节HSS评分等均差异无统计学意义(P>0.05),具有可比性。试验组术后24 h静息状态VAS评分[(3.50±0.59)分比(4.06±0.70)分]及72 h静息状态VAS评分[(2.00±0.42)分比(2.42±0.54)分]、术后住院天数[(6.25±1.15)d比(7.15±1.83)d]、屈膝90°所需天数[(2.83±0.70)d比(3.52±1.01)d]、术后3 d焦虑得分[(11.79±1.32)分比(13.04±1.75)分]及抑郁得分[(13.96±0.96)分比(16.58±2.13)分]均明显低于对照组(P<0.05),试验组术后3 d的总蛋白[(63.28±4.51)g/L比(55.19±4.65)g/L]、白蛋白[(37.79±2.57)g/L比(33.66±2.94)g/L]及血红蛋白值[(107±13.98)g/L比(95.83±14.06)g/L]均明显高于对照组(P<0.05)。结论 提高TKA术后睡眠质量,能加速病人康复。     

Ciprofloxacin in the treatment of chronic bacterial prostatitis: a prospective, non-comparative multicentre clinical trial with long-term follow-up. The German Prostatitis Study Group

The efficacy and safety of ciprofloxacin 500 mg bd for 28 days were assessed in 65 adult males with symptomatic bacterial prostatitis, from eight centres in Germany. Urine and prostatic secretions were obtained for culture. Clinical signs and symptoms were evaluated at 12-18 days during treatment, end of treatment (4-9 days post-treatment), and 1, 3, 6 and 9 months post-treatment. Safety was monitored during and at the end of treatment. E. coli was the most frequent pathogen causing infection (35/62) and Enterococcus faecalis the second most frequent (13/62). The combined bacteriological response by patient determined at return visits 4-9 days post and 1 month post-treatment, respectively, was eradication 48/54 (88.9%), persistence 3/54 (5.6%), eradication with recurrence 1/54 (1.9%) and eradication with reinfection 2/54 (3.7%). The clinical response at 1 month post-treatment was resolution 53/54 (98. 1%) and 1/54 (1.9%) failure. The rates for continued eradication in the extended follow-up were 32/39 (82.1%) after 3 months, 26/34 (76. 4%) after 6 months and 13/22 (59.1%) after 9 months. Nineteen patients experienced at least one adverse event. In two patients the trial was prematurely discontinued due to adverse events.