Placebo-controlled Parallel-group Trial Research Articles

Zoledronic Acid Treatment After Acute Spinal Cord Injury: Results of a Randomized, Placebo-Controlled Pilot Trial

ObjectiveTo determine the effect of intravenous zoledronic acid 5 mg on the extent and course of bone loss after spinal cord injury (SCI). DesignDouble-blind, randomized, placebo-controlled parallel-group trial. SettingAcute in-patient, tertiary-care rehabilitation hospital. ParticipantsConvenience sample of 17 in-patients with SCI <12 weeks before randomization; American Spinal Injury Association Impairment scale A, B, or C and medically stable. Twelve patients were evaluated at the primary endpoint at 6 months. MethodsPatients meeting study criteria were randomly assigned to zoledronic acid 5 mg or matching placebo. Dual x-ray absorptiometry scan and serum for bone markers (type 1 procollagen amino-terminal propeptide, bone-specific alkaline phosphatase, collagen type 1 cross-linked C-telopeptide) were obtained at baseline and after 3 months, 6 months, and the every 6 months for up to 2 years. Main Outcome MeasuresThe primary endpoint was change in bone mineral density (BMD) at the total hip after 6 months; secondary endpoints were changes in BMD at other skeletal sites and changes in levels of serum bone markers. ResultsThe group treated with zoledronic acid had a smaller decrease in BMD at 6 months at the total hip than the placebo group (right: −2.2 ± 3.4% versus −8.6 ± 3.5%, respectively, P = .03; left: −3.7 ± 1.0% versus −12.3 ± 6.9%, P = .03). Differences in BMD at the femoral neck were similar (right: −5.1 ± 6.5% versus −20.0 ± 6.4%, P = .01; left: −1.1 ± 3.5% versus −11.1 ± 7.4%, P = .02) with larger bone loss and smaller between group differences at the knee. Zoledronic acid resulted in a decrease in serum levels of both formation and resorption markers. ConclusionsZoledronic acid is effective at mitigating bone loss after SCI. Duration of efficacy and activity at different skeletal sites may differ from that observed in able-bodied individuals and needs further study.

Evaluating the efficacy of memantine on improving cognitive functions in epileptic patients receiving anti-epileptic drugs: A double-blind placebo-controlled clinical trial (Phase IIIb pilot study).

Objectives:People with epilepsy have greater cognitive and behavioral dysfunction than the general population. There is no specific treatment available for cognitive impairment of these patients. We aimed to evaluate the effects of memantine, an N-methyl-D-aspartate-type glutamate receptor noncompetitive antagonist, on improving cognition and memory functions in epileptic patients with cognitive and memory impairment, who received anti-epileptic drugs (AEDs).Methods:We did a randomized, double-blind, placebo-controlled parallel group trial, in SRM Medical College Hospital and Research Centre, Kattankulathur, Kancheepuram, Tamil Nadu, India between April 2013 and September 2013. Fifty-nine epileptic patients taking AEDs with subjective memory complaints were recruited and randomized to either Group 1 to receive 16 weeks of once-daily memantine, (5 mg for first 8 weeks, followed by memantine 10 mg for next 8 weeks) or Group 2 to receive once daily placebo. This trial is registered with Clinical Trial Registry of India CTRI/2013/04/003573.Results:Of 59 randomized patients, 55 patients completed the study (26 memantine and 29 placebo). Memantine group showed statistically significant improvement in total mini mental state examination score from baseline (P = 0.765) to 16th week (P < 0.001) in comparison with the placebo. The Weshler's Memory Scale total score in memantine group improved significantly after 8 weeks (P = 0.002) compared with baseline (P = 0.873) and highly significant at the end of 16th week (P < 0.001). The self-rated quality of life and memory in memantine group also significantly improved at the study end.Conclusion:We conclude that once-daily memantine (10 mg) treatment significantly improved cognition, memory and quality of life in epileptic patients with mild to moderate cognitive impairment and was found to have a favorable safety profile.

Effects of Resistant Glucan Mixture on Bowel Movement in Female Volunteers.

Resistant glucan (RG) is a water-soluble polysaccharide resistant to hydrolysis by digestive enzymes in the human gastrointestinal system. RG mixture (RGM) contains more than 75% RG as dietary fiber and other saccharides. The effects of ingestion of 3.3, 6.6, and 13.2 g/d of RGM (containing of 2.5, 5.0, and 10.0 g/d RG as dietary fiber) on the fecal properties and the frequency of defecation were investigated in 60 female volunteers with constipation. The study was designed as a randomized, single-blinded, and placebo-controlled parallel-group trial. Each subject consumed RGM or a placebo (digestible maltodextrin) for 2 wk. Questionnaire data on the effects on bowel movement were analyzed according to defecation days, defecation frequency, fecal volume, fecal shapes, fecal color, fecal odor, and fecal excretory feeling. The results showed significant increases in defecation frequency (p<0.05), defecation days (p<0.05), and fecal volume (p<0.05) during the 13.2 g/d RGM ingestion period. The effects of RGM on defecation days and frequency showed a dose-dependent increase (p<0.05). These results suggested that the intake of RGM increased defecation days, defecation frequency, and fecal volume. In the gastrointestinal tract, RGM is useful as a water-soluble dietary fiber for the improvement of bowel movements.

Atorvastatin for treating spontaneous subarachnoid hemorrhage: study protocol for a randomized double-blind placebo-controlled trial

Background: Animal studies have confirmed that statins have neuroprotective effects during and following a subarachnoid hemorrhage; however, the therapeutic effect of statins in humans remains controversial. The interpretation of data currently available on the clinical application of statins to spontaneous subarachnoid hemorrhage is limited by the small sample sizes used in the studies, making it difficult to draw valid conclusions regarding the multiple neuroprotective effects of statins. Thus, we propose to perform a randomized double-blind placebo-controlled parallel-group clinical trial to determine the effects of atorvastatin on spontaneous subarachnoid hemorrhage, apoptosis-related factors, and serum inflammatory factors in cerebrospinal fluid and to observe its neuroprotective effect mediated by relieving vasospasm. Methods/Design: This is a randomized parallel-group placebo-controlled double-blind clinical trial. This trial will recruit 300 patients with spontaneous subarachnoid hemorrhage from the Department of Neurosurgery, 101 st Hospital of PLA (Wuxi Taihu Hospital). These patients will be equally and randomly assigned to atorvastatin (40 mg/day) and placebo control groups. Outcomes will be evaluated at baseline, 3, 5, and 14 days after hemorrhage, and 6 months after discharge. The primary outcomes will be the results of computed tomography (CT) angiography combined with CT perfusion imaging and conventional CT. The secondary outcomes will be cerebrospinal fluid analysis, blood testing (tumor necrosis factor α, vascular endothelial growth factor, interleukin-6, and C-reactive protein levels), and the Hunt-Hess classification, the results of transcranial Doppler ultrasonography, and the scores on the Glasgow Coma Scale, the Glasgow Outcome Scale, and the National Institutes of Health Stroke Scale. Discussion: The results of this trial will provide data on the clinical application and neuroregenerative effect of atorvastatin in the acute stage of spontaneous subarachnoid hemorrhage. Trial registration: This trial was registered with the Chinese Clinical Trial Registry (ChiCTR-IPR-14005395) on 18 May 2014.

No effects of atorvastatin (10 mg/d or 80 mg/d) on nitric oxide, prostacyclin, thromboxane and oxidative stress in type 2 diabetes mellitus patients of the DALI study

The present study describes the effects of atorvastatin on whole body synthesis of nitric oxide (NO), prostacyclin (PGI2), and thromboxane A2 (TxA2), on oxidative stress and nitrite/nitrate-related renal carbonic anhydrase (CA) activity in patients with type 2 diabetes mellitus (T2DM). A double-blind, randomized, placebo-controlled parallel-group trial (the DALI study group) on 217 patients with T2DM and dyslipidemia was performed. Urinary samples were collected before and after administration of a standard dose (10mg/d, n=73), a maximal dose atorvastatin (80mg/d, n=72) or placebo (n=72) for 30 weeks. Urinary nitrite and nitrate were measured to assess whole body NO synthesis. The urinary molar ratio of nitrate to nitrite (UNOxR) served as a measure of renal CA activity. Free radical- and cyclooxygenase (COX)-catalyzed lipid peroxidation was estimated by measuring urinary 8-iso-prostaglandin F2α (8-iso-PGF2α). In subgroups, systemic PGI2 and TxA2 synthesis was assessed by measuring their major urinary metabolites 2,3-dinor-6-keto-prostaglandin F1α and 2,3-dinor-thromboxane B2, respectively. All biochemical parameters were measured by GC–MS and GC–MS/MS methods. T2DM patients had elevated levels of nitrate, nitrite, UNOxR, and 8-iso-PGF2α compared to healthy non-diabetic and normolipidemic subjects. Thirty-week treatment with atorvastatin (10 or 80mg/d) did not significantly alter NO, PGI2, TxA2 and 8-iso-PGF2α synthesis and did not improve the renal reabsorption of nitrite which is considered an important reservoir of NO. Our study suggests that atorvastatin (10 or 80mg/d) does not provide cardiovascular benefit beyond its cholesterol lowering effect in patients with T2DM.

The Cannabinoid Use in Progressive Inflammatory brain Disease (CUPID) trial: a randomised double-blind placebo-controlled parallel-group multicentre trial and economic evaluation of cannabinoids to slow progression in multiple sclerosis.

The Cannabinoid Use in Progressive Inflammatory brain Disease (CUPID) trial aimed to determine whether or not oral Δ(9)-tetrahydrocannabinol (Δ(9)-THC) slowed the course of progressive multiple sclerosis (MS); evaluate safety of cannabinoid administration; and, improve methods for testing treatments in progressive MS. There were three objectives in the CUPID study: (1) to evaluate whether or not Δ(9)-THC could slow the course of progressive MS; (2) to assess the long-term safety of Δ(9)-THC; and (3) to explore newer ways of conducting clinical trials in progressive MS. The CUPID trial was a randomised, double-blind, placebo-controlled, parallel-group, multicentre trial. Patients were randomised in a 2 : 1 ratio to Δ(9)-THC or placebo. Randomisation was balanced according to Expanded Disability Status Scale (EDSS) score, study site and disease type. Analyses were by intention to treat, following a pre-specified statistical analysis plan. A cranial magnetic resonance imaging (MRI) substudy, Rasch measurement theory (RMT) analyses and an economic evaluation were undertaken. Twenty-seven UK sites. Adults aged 18-65 years with primary or secondary progressive MS, 1-year evidence of disease progression and baseline EDSS 4.0-6.5. Oral Δ(9)-THC (maximum 28 mg/day) or matching placebo. Three and 6 months, and then 6-monthly up to 36 or 42 months. Primary outcomes were time to EDSS progression, and change in Multiple Sclerosis Impact Scale-29 version 2 (MSIS-29v2) 20-point physical subscale (MSIS-29phys) score. Various secondary patient- and clinician-reported outcomes and MRI outcomes were assessed. RMT analyses examined performance of MS-specific rating scales as measurement instruments and tested for a symptomatic or disease-modifying treatment effect. Economic evaluation estimated mean incremental costs and quality-adjusted life-years (QALYs). Effectiveness - recruitment targets were achieved. Of the 498 randomised patients (332 to active and 166 to placebo), 493 (329 active and 164 placebo) were analysed. no significant treatment effect; hazard ratio EDSS score progression (active : placebo) 0.92 [95% confidence interval (CI) 0.68 to 1.23]; and estimated between-group difference in MSIS-29phys score (active-placebo) -0.9 points (95% CI -2.0 to 0.2 points). Secondary clinical and MRI outcomes: no significant treatment effects. Safety - at least one serious adverse event: 35% and 28% of active and placebo patients, respectively. RMT analyses - scale evaluation: MSIS-29 version 2, MS Walking Scale-12 version 2 and MS Spasticity Scale-88 were robust measurement instruments. There was no clear symptomatic or disease-modifying treatment effect. Economic evaluation - estimated mean incremental cost to NHS over usual care, over 3 years £27,443.20 per patient. No between-group difference in QALYs. The CUPID trial failed to demonstrate a significant treatment effect in primary or secondary outcomes. There were no major safety concerns, but unwanted side effects seemed to affect compliance. Participants were more disabled than in previous studies and deteriorated less than expected, possibly reducing our ability to detect treatment effects. RMT analyses supported performance of MS-specific rating scales as measures, enabled group- and individual person-level examination of treatment effects, but did not influence study inferences. The intervention had significant additional costs with no improvement in health outcomes; therefore, it was dominated by usual care and not cost-effective. Future work should focus on determining further factors to predict clinical deterioration, to inform the development of new studies, and modifying treatments in order to minimise side effects and improve study compliance. The absence of disease-modifying treatments in progressive MS warrants further studies of the cannabinoid pathway in potential neuroprotection. Current Controlled Trials ISRCTN62942668. The National Institute for Health Research Health Technology Assessment programme, the Medical Research Council Efficacy and Mechanism Evaluation programme, Multiple Sclerosis Society and Multiple Sclerosis Trust. The report will be published in full in Health Technology Assessment; Vol. 19, No. 12. See the NIHR Journals Library website for further project information.

Low-dose dexamethasone as a treatment for women with heavy menstrual bleeding: protocol for response-adaptive randomised placebo-controlled dose-finding parallel group trial (DexFEM)

IntroductionHeavy menstrual bleeding (HMB) diminishes individual quality-of-life and poses substantial societal burden. In HMB endometrium, inactivation of cortisol (by enzyme 11β hydroxysteroid dehydrogenase type 2 (11βHSD2)), may cause local endometrial...

Transcranial Magnetic Stimulation as a Treatment for Tinnitus

Objectives: This presentation describes a Phase II clinical trial that was conducted to assess transcranial magnetic stimulation (TMS) as a treatment for chronic tinnitus. (1) Interpret the results of this clinical trial. (2) Describe the issues that need to be addressed before TMS can be implemented clinically as a treatment for tinnitus. Methods: This is a randomized, subject and clinician/observer blind, placebo-controlled parallel-group clinical trial of repetitive TMS (rTMS) for chronic tinnitus that was conducted from January 2011 to December 2014 at Portland VA Medical Center. 60 subjects (average age 61.2 years) who experienced chronic tinnitus for 1 year or longer were randomly assigned to receive either active rTMS treatment or placebo treatment to either the left or right side of the head. Subjects received 2000 pulses of 1 Hz rTMS therapy daily on 10 consecutive work days. The primary outcome measure is the Tinnitus Functional Index (TFI), a 25-item questionnaire that assesses tinnitus severity. Independent variables: Beck Depression Inventory score; State Anxiety Inventory score. Preliminary analysis: Change in TFI score from baseline at 6 post-treatment time points. Results: Fifteen of 30 subjects in the active rTMS group exhibited significant improvement in TFI score that persisted for 6 months posttreatment. Seven of 30 subjects in the placebo rTMS group exhibited significant improvement in TFI score. Conclusions: While rTMS demonstrates potential as a treatment option for tinnitus patients, additional clinical trials should be conducted to confirm the efficacy of this method.

Study protocol of Prednisone in episodic Cluster Headache (PredCH): a randomized, double-blind, placebo-controlled parallel group trial to evaluate the efficacy and safety of oral prednisone as an add-on therapy in the prophylactic treatment of episodic cluster headache with verapamil

BackgroundEpisodic cluster headache (ECH) is a primary headache disorder that severely impairs patient’s quality of life. First-line therapy in the initiation of a prophylactic treatment is verapamil. Due to its delayed onset of efficacy and the necessary slow titration of dosage for tolerability reasons prednisone is frequently added by clinicians to the initial prophylactic treatment of a cluster episode. This treatment strategy is thought to effectively reduce the number and intensity of cluster attacks in the beginning of a cluster episode (before verapamil is effective). This study will assess the efficacy and safety of oral prednisone as an add-on therapy to verapamil and compare it to a monotherapy with verapamil in the initial prophylactic treatment of a cluster episode.Methods and designPredCH is a prospective, randomized, double-blind, placebo-controlled trial with parallel study arms. Eligible patients with episodic cluster headache will be randomized to a treatment intervention with prednisone or a placebo arm. The multi-center trial will be conducted in eight German headache clinics that specialize in the treatment of ECH.DiscussionPredCH is designed to assess whether oral prednisone added to first-line agent verapamil helps reduce the number and intensity of cluster attacks in the beginning of a cluster episode as compared to monotherapy with verapamil.Trial registrationGerman Clinical Trials Register DRKS00004716

Assessment of the health-related quality of life impact of Euflexxa® (1% sodium hyaluronate) using the short form (SF)-36 data collected in a randomized clinical trial

s / Osteoarthritis and Cartilage 21 (2013) S63–S312 S246 465 ASSESSMENT OF THE HEALTH-RELATED QUALITY OF LIFE IMPACT OF EUFLEXXA (1% SODIUM HYALURONATE) USING THE SHORT FORM (SF)-36 DATA COLLECTED IN A RANDOMIZED CLINICAL TRIAL H.T. Hatoum y, J.E. Rosen z, A.L. Fierlinger x, S.-J. Lin k, R.D. Altman {. yCtr. for Pharmacoeconomic Res., Univ. of IL, Chicago, IL, USA; zDept. of Orthopaedics & Rehabilitation, NY Hosp. Queens, Queens, NY, USA; x Ferring Pharmaceuticals Inc., Parsippany, NJ, USA; kUniv. of Illinois at Chicago, Coll. of Pharmacy, Chicago, IL, USA; {Univ. of California, Los Angeles, Los Angeles, CA, USA Purpose: Viscosupplementation with intra-articular (IA) injection of hyaluronic acid (HA) is used to help relieve knee pain in patients with osteoarthritis (OA), but littledata isavailable forpatient reportedoutcomes of IA-HA therapy. The FLEXX trial, a 26-week, double-blind, randomized, parallel-group placebo-controlled trial assessed the efficacy and safety of bioengineered 1% sodium hyaluronate (IA-BioHA) vs saline (IA-SA) for OA knee pain, and was followed by a 26-week open-label Extension Study to evaluate the safety of IA-BioHA reinjection. Here we investigate healthrelated quality of life (HRQoL) measures using the SF-36 in patients with OA of the knee enrolled in the FLEXX Trial and Extension Study. Methods: SF-36 scores were collected at baseline, week 26, and week 52 of the Flexx Trial and Extension Study. Correlations between the SF36 scores and the clinical outcomes of the 50-foot walk test (100 mm visual analog scale), Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) scores, and the OMERACT-OARSI responder index were also investigated. Results: Baseline SF-36 scores for patients indicated significant physical limitations relative to the US population (aged 55-64 years) as well as norms for an OA population. Both the IA-BioHA and IA-SA treatment groups experienced significant improvements over baseline in SF-36 domains measuring physical ability at weeks 12 and 26 posttreatment. Improvements in the form of effect size at week 26 were: 0.49 vs 0.35 in physical functioning (PF), 0.39 vs 0.27 in role physical (RP), 0.39 vs 0.31 in bodily pain (BP), and 0.54 vs 0.32 in physical component summary (PCS) scores in the IA-BioHA and IA-SA groups, respectively. Patients treated with IA-BioHA experienced statistically significant improvement over the IA-SA group at week 26 in PCS (P<0.05) after controlling for other covariates. Changes in several physical domains of the SF-36 significantly correlated with changes in the other outcome measures, with the highest correlation between the WOMAC disability subscale and the PCS (r1⁄4-0.58, P<0.001). At the end of the FLEXX Trial therewere 169 responders and 85 non-responders in the IA-BioHA group per OARSI criteria. Compared to non-responders, responders experienced improvement in all SF-36 scores, with statistically significant differences for PF, RP, BP, social functioning, role-emotional and PCS (P1⁄4<0.05). Several physical function domains of the SF-36 were found to discriminate treatment response: i,e., changes between the SF-36 scores at week 26 continued to improve through week 52, with a significantly lower bodily pain domain (P1⁄40.014) in patients who received IA-BioHA in both the FLEXX Trial and the Extension Study. Conclusions: Patients treated with IA-BioHA in the FLEXX Trial experienced significantly greater improvement in physical functioning as measuredby the SF-36PCS score compared topatients treatedwith IA-SA. Also, IA-BioHA resulted in clinically meaningful differences in reducing patients’physical disability. Patientswhoreceiveda repeatedcourseof IABioHA treatment afterweek 26 experienced further improvement in their physical ability with a significant reduction in bodily pain. 466 OSTEOARTHRITIS OF THE KNEE AT 6-YEAR FOLLOW-UP AND THEIR PROGNOSTIC FACTORS IN ADULTS WITH NON-TRAUMATIC KNEE COMPLAINTS IN GENERAL PRACTICE M. Kastelein, G. van de Zande, J. Verhaar, B. Koes, P. Luijsterburg, S. Bierma-Zeinstra. Erasmus MC, Erasmus Univ. Med. Ctr., Rotterdam, The

Retrospective Subgroup Analysis to Assess the Efficacy and Safety of Pancrelipase/Pancreatin (CREON®) in Patients with Exocrine Pancreatic Insufficiency (EPI) and a Medical History of Diabetes Mellitus

Purpose: To perform a retrospective exploratory post-hoc subgroup analysis to assess the efficacy and safety of CREON® in patients with exocrine pancreatic insufficiency (EPI) and medical history of diabetes mellitus (DM). Methods: This was an analysis of S245.3.124 (NCT00414908), a phase-III, multi-center, double-blind, randomized, placebo-controlled parallel-group trial. Patients with confirmed EPI due to chronic pancreatitis (CP) or pancreatic surgery (PS) were randomized to receive pancrelipase (PL) delayed-release (CREON®), 12,000 lipase units capsules (72,000 lipase units per meal, 36,000 per snack) or placebo. Fifty-two patients completed the 1-week double-blind period (24 PL, 28 placebo). DM was present in 34/52 (65.4%) participants (16 PL, 18 placebo). The primary endpoint was the change in coefficient of fat absorption (CFA) from baseline to end of randomized period. Secondary endpoints included safety parameters. Data was analyzed using non-parametric analysis of covariance. Results: The mean change in CFA from baseline was significantly greater in the PL+ DM group compared to placebo + DM (35.2 ± 18.6 vs. 6.92 ± 12.5, p<.0001). No significant difference was observed in the number of subjects with at least one treatment-emergent adverse event (TEAE) in the PL+ DM group compared to placebo + DM (29.4% vs. 26.3%). The efficacy and safety results in the PL+ no DM group (n=8) compared to placebo + no DM (n=10) were consistent with the findings for the two DM groups: change in CFA from baseline (24.2 ± 17.8 vs. 11.8 ± 12.4, p=.0046), number of subjects with at least one TEAE (0.0% vs. 10.0%). The efficacy and safety results in the PL+ DM group were also consistent with the overall trial results (change in CFA from baseline 32.1 ± 18.5% vs. 8.8 ± 12.5%, p<0.0001, number of subjects with at least one TEAE (20.0% vs. 20.7%). Conclusion: PL (CREON®) was effective in treating fat maldigestion with a TEAE rate similar to that of placebo in patients with EPI due to CP or PS with or without medical history of DM. Disclosure: Dr. Whitcomb has served as a consultant to Abbott; Dr. Bodhani, Dr. Fuldeore, Dr. Sander-Struckmeier, Dr. Beckmann and Dr. Pollack are employees and shareholders of Abbott.

Effect of escitalopram on insomnia symptoms and subjective sleep quality in healthy perimenopausal and postmenopausal women with hot flashes

The aim of this study was to determine the effect of escitalopram on insomnia symptoms and subjective sleep quality in healthy perimenopausal and postmenopausal women with hot flashes.A randomized, blinded, multicenter, placebo-controlled parallel-group 8-week trial with 205 women (95 African American, 102 white, 8 other) was conducted between July 2009 and June 2010. The participants received escitalopram (10-20 mg/d) or placebo. Insomnia symptoms (Insomnia Severity Index [ISI]) and subjective sleep quality (Pittsburgh Sleep Quality Index [PSQI]) at weeks 4 and 8 were the prespecified secondary outcomes. A total of 199 women (97%) provided ISI data, and 194 (95%) women provided PSQI data at follow-up.At baseline, mean hot flash frequency was 9.78 per day (SD, 5.60), mean ISI was 11.4 (SD, 6.3), and mean PSQI was 8.0 (SD, 3.7). Treatment with escitalopram reduced ISI at week 8 (mean difference, -2.00; 95% CI, -3.43 to -0.57; P < 0.001 overall treatment effect), with mean differences of -4.73 (95% CI, -5.72 to -3.75) in the escitalopram group and -2.73 (95% CI, -3.78 to -1.69) in the placebo group. The reduction in PSQI was greater in the escitalopram than in the placebo group at week 8 (mean difference, -1.31; 95% CI, -2.14 to -0.49; P < 0.001 overall treatment effect). Clinical improvement in insomnia symptoms and subjective sleep quality (≥50% decreases in ISI and PSQI from baseline) was observed more frequently in the escitalopram group than in the placebo group (ISI, 50.0% vs 35.4%, P = 0.04; PSQI, 29.6% vs 19.2%, P = 0.09).Among healthy perimenopausal and postmenopausal women with hot flashes, escitalopram at 10 to 20 mg/day compared with placebo reduced insomnia symptoms and improved subjective sleep quality at 8 weeks of follow-up.

Pain relief in laparoscopic tubal ligation using intraperitoneal lignocaine: a double masked randomized controlled trial

The intraperitoneal route of analgesia has been studied over the years for effective perioperative pain relief during minimally invasive surgery, but there were conflicting reports of the use of intraperitoneal analgesic administration and moreover there was no consensus regarding the dose and type of drugs used. We report a randomized trial to assess the safety and effectiveness of intraperitoneal lignocaine as an intraoperative and postoperative analgesic in laparoscopic tubal ligation. This is a double masked, randomized parallel group placebo-controlled trial of women seeking laparoscopic sterilization under local anaesthesia at a university hospital. The intervention group and placebo group received 20 ml of 0.5% lignocaine and 20 ml of isotonic saline intraperitoneally respectively. Allocation concealment was done by fixed block randomization. The participating women, the surgeon, anaesthetist, technician and the doctor who assessed the pain score were masked to the type of intervention. Intraoperative and postoperative pain was assessed by visual analogue pain scale and the scores are expressed as mean difference (95% confidence interval) between groups. Our trial is registered with the Clinical Trials Registry, India (http://www.ctri.nic.in/, CTRI/2009/091/000072). Out of 200 women recruited, 196 were available for final analysis with 98 women in each arm. The mean difference in the intraoperative pain score at the time of tubal ligation was 3.5 cm (95% CI 2.91-4.09). The mean difference in the postoperative pain scores at half an hour was 2.9 (95% CI 2.50-3.44), 1h was 2.5 (95% CI 2.08-3.00) and 3h was 1.2 (95% CI 0.75-1.76). There was no case of adverse reaction to lignocaine. Our findings show that intraperitoneal instillation of lignocaine is a safe and effective method for perioperative pain relief during laparoscopic tubal occlusion performed under conscious sedation.

Improvement Effect of Resistant Maltodextrin in Humans with Metabolic Syndrome by Continuous Administration

Resistant maltodextrin (RMD) is a soluble dietary fiber ingredient whose physiological functions are well recognized in Foods for Specified Health Use (FOSHU) for maintaining healthy intestinal regularity, blood glucose levels, and serum lipids. However, its efficacy on combined health risks--metabolic syndrome--was not studied yet. In this study the efficacy of RMD on humans with metabolic syndrome was investigated. A randomized double-blind placebo-controlled parallel-group trial was conducted. Thirty subjects with metabolic syndrome were randomly allocated into 2 groups and took either tea containing 9 g of RMD (treatment group) or placebo tea at three mealtimes daily for 12 wk. Blood was collected and body fat was scanned periodically. In the RMD treatment group, waist circumference, visceral fat area, fasting blood glucose, HOMA-R and serum triacylglycerol (TG) were significantly decreased compared to baseline, and significant time-by-treatment interaction was observed for waist circumference, visceral fat area, HOMA-R and serum TG (p=0.044, p=0.012, p=0.032, and p=0.049, respectively). The change ratio of visceral fat area showed negative statistical correlation with the baseline value (p=0.033), suggesting that efficacy of RMD was emphasized in the subjects having a larger visceral fat area. After the 12-wk RMD treatment, the total number of metabolic syndrome risk factors decreased to 20 from 32 with 2 subjects having no risks, while that of the placebo group decreased to 25 from 32. These findings suggest that continuous ingestion of RMD may improve the risk factors of metabolic syndrome by reducing visceral fat and improving glucose and lipid metabolism.

Effect of Niacin on Erectile Function in Men Suffering Erectile Dysfunction and Dyslipidemia

Dyslipidemia is closely related to erectile dysfunction (ED). Evidence has shown that the lipid-lowering agent, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor (statins), can improve erectile function. However, information about the potential role of another class of lipid-lowering agent, niacin, is unknown. To assess the effect of niacin alone on erectile function in patients suffering from both ED and dyslipidemia. A single center prospective randomized placebo-controlled parallel-group trial was conducted. One hundred sixty male patients with ED and dyslipidemia were randomized in a one-to-one ratio to receive up to 1,500 mg oral niacin daily or placebo for 12 weeks. The primary outcome measure was the improvement in erectile function as assessed by question 3 and question 4 of the International Index of Erectile Function (IIEF Q3 and Q4). Secondary outcome measurements included the total IIEF score, IIEF-erectile function domain, and Sexual Health Inventory for Men (SHIM) score. From the overall analysis, the niacin group showed a significant increase in both IIEF-Q3 scores (0.53 ± 1.18, P < 0.001) and IIEF-Q4 scores (0.35 ± 1.17, P = 0.013) compared with baseline values. The placebo group also showed a significant increase in IIEF-Q3 scores (0.30 ± 1.16, P = 0.040) but not IIEF-Q4 scores (0.24 ± 1.13, P = 0.084). However, when patients were stratified according to the baseline severity of ED, the patients with moderate and severe ED who received niacin showed a significant improvement in IIEF-Q3 scores (0.56 ± 0.96 [P = 0.037] and 1.03 ± 1.20 [P < 0.001], respectively) and IIEF-Q4 scores (0.56 ± 1.03 [P = 0.048] and 0.84 ± 1.05 [P < 0.001], respectively] compared with baseline values, but not for the placebo group. The improvement in IIEF-EF domain score for severe and moderate ED patients in the niacin group were 5.28 ± 5.94 (P < 0.001) and 3.31 ± 4.54 (P = 0.014) and in the placebo group were 2.65 ± 5.63 (P < 0.041) and 2.74 ± 5.59 (P = 0.027), respectively. There was no significant improvement in erectile function for patients with mild and mild-to-moderate ED for both groups. For patients not receiving statins treatment, there was a significant improvement in IIEF-Q3 scores (0.47 ± 1.16 [P = 0.004]) for the niacin group, but not for the placebo group. Niacin alone can improve the erectile function in patients suffering from moderate to severe ED and dyslipidemia.

Parallel-Group Placebo-Controlled Trial of Testosterone Gel in Men With Major Depressive Disorder Displaying an Incomplete Response to Standard Antidepressant Treatment

Parallel-Group Placebo-Controlled Trial of Testosterone Gel in Men With Major Depressive Disorder Displaying an Incomplete Response to Standard Antidepressant Treatment

Parallel-Group Placebo-Controlled Trial of Testosterone Gel in Men With Major Depressive Disorder Displaying an Incomplete Response to Standard Antidepressant Treatment

Parallel-Group Placebo-Controlled Trial of Testosterone Gel in Men With Major Depressive Disorder Displaying an Incomplete Response to Standard Antidepressant Treatment

Short-term effects of l-citrulline supplementation on arterial stiffness in middle-aged men

BackgroundNitric oxide (NO) plays a key role in the maintenance of vascular tone, contributing to the functional regulation of arterial stiffness. Although oral l-citrulline could become the effective precursor of l-arginine (substrate for endothelial NO synthase) via the l-citrulline/ l-arginine pathway, little is known about the efficacy of l-citrulline application on arterial stiffness. ObjectiveWe examined the short-term effects of l-citrulline supplementation on arterial stiffness in humans. MethodsIn a double-blind, randomized, placebo-controlled parallel-group trial, 15 healthy male subjects (age: 58.3±4.4years) with brachial–ankle pulse wave velocity (baPWV; index of arterial stiffness >1400cm/sec) were given 5.6g/day of l-citrulline (n=8) or placebo (n=7) for 7days. baPWV and various clinical parameters were measured before (baseline) and after oral supplementation of l-citrulline or placebo. ResultsCompared with the placebo group, baPWV was significantly reduced in the l-citrulline group (p<0.01). No significant differences in blood pressure (BP) were found between the two groups, and no correlation was observed between BP and baPWV. The serum nitrogen oxide (NOx, the sum of nitrite plus nitrate) and NO metabolic products were significantly increased only in the l-citrulline group (p<0.05). Plasma citrulline, arginine and the ratio of arginine/asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase (arginine/ADMA ratio) were significantly increased in the l-citrulline group compared with the placebo group (p<0.05, p<0.01, p<0.05, respectively). Moreover, there was a correlation between the increase of plasma arginine and the reduction of baPWV (r=-0.553, p<0.05). ConclusionThese findings suggest that short-term l-citrulline supplementation may functionally improve arterial stiffness, independent of blood pressure, in humans.

Dianicline, a Novel 4 2 Nicotinic Acetylcholine Receptor Partial Agonist, for Smoking Cessation: A Randomized Placebo-Controlled Clinical Trial

Dianicline is a α4β2 nicotinic acetylcholine receptor partial agonist, a class of drugs that includes varenicline and cytisine. Varenicline is efficacious for smoking cessation, while cytisine has not been studied systematically. The efficacy of dianicline has not been previously tested in an adequately powered study. In a randomized, double-blind, parallel group placebo-controlled trial, 602 generally healthy cigarette smokers were assigned to dianicline (n = 300) or placebo (n = 302) for 7 weeks followed by a 19-week off drug follow-up period. Exhaled carbon monoxide and cotinine-confirmed continuous abstinence rates for Weeks 4-7 were 24.0% for dianicline versus 20.5% for placebo (odds ratio 1.22; 95% CI, 0.83-1.80; p = .307). For Weeks 4-26, the abstinence rates were 16.7% for dianicline versus 13.9% for placebo (odds ratio 1.24; 95% CI, 0.79-1.93; p = .366). Craving for a cigarettes was reduced by dianicline compared with placebo after 7 weeks (p = .0175). Nicotine withdrawal symptoms measured by the Hughes and Hatsukami Minnesota Withdrawal Scale were lower for dianicline compared with placebo in the first 3 weeks of treatment during which time quit rates were also higher in the dianicline-treated group. Dianicline did not increase cigarette smoking abstinence rates beyond the initial phase of treatment. However, self-reported craving and nicotine withdrawal symptoms were reduced.

Anesthesia Literature Review

Anesthesia Literature Review