Placebo-controlled Crossover Clinical Trial Research Articles

The efficacy of cetirizine hydrochloride on the pruritus of cats with atopic dermatitis: a randomized, double‐blind, placebo‐controlled, crossover study

Various antihistamines have been used in the management of feline atopic dermatitis, with variable reported benefit. To date, there have been no randomized, double-blind, placebo-controlled, crossover clinical trials on the use of this drug class in cats. To evaluate the clinical efficacy of cetirizine hydrochloride for the control of pruritus and dermatitis in cats diagnosed with atopic dermatitis. In this randomized, double-blind, placebo-controlled crossover clinical trial, 21 client-owned cats diagnosed with mild to moderate nonseasonal atopic dermatitis were randomly assigned to two groups. Cats in each group received either 1 mg/kg cetirizine hydrochloride or placebo once daily per os for 28 days followed by a 14 day wash-out period. Treatments were then crossed over, and cats received placebo or cetirizine hydrochloride for another 28 days. Owners marked a pruritus severity scale before inclusion in the study and weekly throughout the entire study period. Lesions were scored by the clinician using a Canine Atopic Dermatitis Extent and Severity Index (CADESI)-03 modified for the cat before enrolment and at day 28 of each treatment. Nineteen cats completed the study. There were no statistically significant differences between treatment with cetirizine hydrochloride and placebo for modified CADESI-03 or pruritus scores. This study suggests that cetirizine hydrochloride cannot be recommended for the management of feline atopic dermatitis.

Mirtazapine as an appetite stimulant and anti-emetic in cats with chronic kidney disease: A masked placebo-controlled crossover clinical trial

Cats with chronic kidney disease (CKD) often experience inappetence and vomiting and might benefit from the administration of mirtazapine, a medication with appetite stimulant and anti-nausea properties. The aim of this placebo-controlled, double-masked crossover clinical trial was to evaluate the effects of mirtazapine on bodyweight, appetite and vomiting in cats with CKD. Eleven cats with stable CKD were randomized to receive 1.88mg mirtazapine or placebo orally every other day for 3weeks. After a 4day washout period, each cat crossed over to the alternate treatment for 3weeks. Physical examinations and serum biochemistry profiles were performed before and after each treatment period and owners kept daily logs of appetite, activity, behavior, and vomiting episodes.Compared to placebo, mirtazapine administration resulted in a statistically significant increase in appetite (P=0.02) and activity (P=0.02) and a statistically significant decrease in vomiting (P=0.047), as determined by Wilcoxon matched pairs analysis. Cats treated with mirtazapine also gained significant bodyweight compared with placebo-treated cats (P=0.002) as determined by linear mixed model analysis. Median weight gain during mirtazapine administration was 0.18kg (range 0–0.45kg). Median weight loss during placebo administration was 0.07kg (range 0–0.34kg). Mirtazapine is an effective appetite stimulant and anti-emetic for cats with CKD and could be a useful adjunct to the nutritional management of these cases.

Role of Probiotics in Short Bowel Syndrome in Infants and Children—A Systematic Review

Short bowel syndrome (SBS) is a cause of significant morbidity and mortality in children. Probiotics, due to their beneficial effects on the gastrointestinal tract (e.g., improving gut barrier function, motility, facilitation of intestinal adaptation and decreasing pathogen load and inflammation) may have a therapeutic role in the management of SBS. To conduct a systematic review of the current evidence for the effects of probiotic supplementation in children with SBS, the standard Cochrane methodology for systematic reviews was used. The databases, Pubmed, Embase, ACTR, CENTRAL, and the international trial registry, and reference lists of articles were searched for randomised (RCT) or quasi-randomised controlled trials reporting on the use of probiotics in SBS. Our search revealed no RCTs on the use of probiotics in children with SBS. We found one small cross-over RCT (placebo controlled crossover clinical trial), one case control study and nine case reports on the use of probiotics in children with SBS. In the crossover RCT, there was no consistent effect on intestinal permeability (primary outcome) after supplementation with Lactobacillus rhamnosus (LGG) in nine children with SBS. The case control study (four cases: four controls) reported a trend for increase in height and weight velocity and improvement in non-clinical outcomes, such as gut flora, lymphocyte count and serum prealbumin. Five of the nine case reports showed that children (n = 12) with SBS were benefited (e.g., cessation of diarrhoea, improved faecal flora, weight gain and weaning from parenteral nutrition) by probiotic supplementation. The remaining four reported on the adverse effects, such as Lactobacillus sepsis (n = 3) and D-lactic acidosis (n = 2). There is insufficient evidence on the effects of probiotics in children with SBS. The safety and efficacy of probiotic supplementation in this high-risk cohort needs to be evaluated in large definitive trials.

Red Grape Seed Extract Improves Lipid Profiles and Decreases Oxidized Low-Density Lipoprotein in Patients with Mild Hyperlipidemia

Hyperlipidemia can lead to atherosclerosis by lipoprotein deposition inside the vessel wall and oxidative stress induction that leads to the formation of atherosclerotic plaque. Oxidized low-density lipoprotein particles (Ox-LDL) have a key role in the pathogenesis of atherosclerosis. The lipid-lowering properties and antioxidants of the grape seed can be beneficial in atherosclerosis prevention. We conducted a randomized double-blind placebo-controlled crossover clinical trial. Fifty-two mildly hyperlipidemic individuals were divided into two groups that received either 200 mg/day of the red grape seed extract (RGSE) or placebo for 8 weeks. After an 8-week washout period, the groups were crossed over for another 8 weeks. Lipid profiles and Ox-LDL were measured at the beginning and the end of each phase. RGSE consumption reduced total cholesterol (-10.68±26.76 mg/dL, P=.015), LDL cholesterol (-9.66±23.92 mg/dL, P=.014), and Ox-LDL (-5.47±12.12 mg/dL, P=.008). While triglyceride and very low-density lipoprotein cholesterol were decreased and high-density lipoprotein cholesterol was increased by RGSE, the changes were not statistically significant. RGSE consumption decreases Ox-LDL and has beneficial effects on lipid profile-consequently decreasing the risk of atherosclerosis and cardiovascular disorders-in mild hyperlipidemic individuals.

Homeopathy for mental fatigue: lessons from a randomized, triple blind, placebo-controlled cross-over clinical trial

BackgroundDifficulty in controlling attention can lead to mental fatigue in the healthy population. We identified one trial reporting a benefit in patients’ attention using a homeopathic formula preparation. One component of the preparation was potassium phosphate, widely available off the shelf as Kali phos 6x for cognitive problems. The aim of this exploratory trial was to assess the effectiveness of Kali phos 6x for attention problems associated with mental fatigue.MethodsWe recruited student and staff volunteers (University of York) with self-reported mental fatigue, excluding any using homeopathy or prescribed stimulants, or with a diagnosis of chronic fatigue syndrome. In a triple blind, cross-over, placebo-controlled clinical trial, 86 volunteers were randomized to receive Kali phos 6x or identical placebo 10 minutes before taking a psychological test of attention (Stroop Colour-Word Test). One week later they were crossed over and took the other preparation before repeating the test.ResultsWe found no evidence of a treatment effect in a comparison of Kali phos 6x with placebo (Kali phos minus placebo = −1.1 (95% CI −3.0 to 0.9, P = 0.3) Stroop score units, Cohen effect size = −0.17) even when allowing for a weak period effect with accuracy scores in the second period being higher than those in the first (P = 0.05). We observed a ceiling effect in the Stroop test which undermined our ability to interpret this result.ConclusionsKali phos 6x was not found to be effective in reducing mental fatigue. A ceiling effect in our primary outcome measure meant that we could not rule out a type II error. Thorough piloting of an adequate outcome measure could have led to an unequivocal result.Current Controlled TrialsISRCTN16521161

Cross-conditional entropy and coherence analysis of pharmaco-EEG changes induced by alprazolam

Quantitative analysis of electroencephalographic signals (EEG) and their interpretation constitute a helpful tool in the assessment of the bioavailability of psychoactive drugs in the brain. Furthermore, psychotropic drug groups have typical signatures which relate biochemical mechanisms with specific EEG changes. To analyze the pharmacological effect of a dose of alprazolam on the connectivity of the brain during wakefulness by means of linear and nonlinear approaches. EEG signals were recorded after alprazolam administration in a placebo-controlled crossover clinical trial. Nonlinear couplings assessed by means of corrected cross-conditional entropy were compared to linear couplings measured with the classical magnitude squared coherence. Linear variables evidenced a statistically significant drug-induced decrease, whereas nonlinear variables showed significant increases. All changes were highly correlated to drug plasma concentrations. The spatial distribution of the observed connectivity changes clearly differed from a previous study: changes before and after the maximum drug effect were mainly observed over the anterior half of the scalp. Additionally, a new variable with very low computational cost was defined to evaluate nonlinear coupling. This is particularly interesting when all pairs of EEG channels are assessed as in this study. Results showed that alprazolam induced changes in terms of uncoupling between regions of the scalp, with opposite trends depending on the variables: decrease in linear ones and increase in nonlinear features. Maps provided consistent information about the way brain changed in terms of connectivity being definitely necessary to evaluate separately linear and nonlinear interactions.

Double blind placebo controlled crossover clinical trial of sildenafil citrate in patients with diabetes mellitus and erectile dysfunction

The Journal of the Ceylon College of Physicians (JCCP) is a peer-reviewed, open access journal published bi-annually by the Ceylon College of Physicians (CCP) in the last week of June and December.The objective of the Journal is to promote good clinical practice and influence policy making across the medical world through publication of original research and peer reviewed articles on current issues and to foster responsible and balanced debate on issues that affect medicine and health care in Sri Lanka. Contributions to the JCCP reflect its national and multidisciplinary readership and include current thinking across a range of medical specialties.

Effect of fruit and vegetable concentrates on endothelial function in metabolic syndrome: A randomized controlled trial

Background and ObjectiveDehydrated fruit and vegetable concentrates provide an accessible form of phytonutrient supplementation that may offer cardioprotective effects. This study assessed the effects of two blends of encapsulated juice powder concentrates (with and without added berry powders) on endothelial function in persons with metabolic syndrome, a risk factor for type 2 diabetes and cardiovascular disease.MethodsRandomized, double blind, placebo controlled crossover clinical trial with three treatment arms. 64 adults with metabolic syndrome were enrolled and received 8-week sequences of each blend of the concentrates and placebo. The primary outcome measure was change in endothelial function (assessed as flow-mediated dilatation of the brachial artery) 2 hr after consuming a 75 g glucose load, after 8-weeks of daily consumption (sustained) or 2 hr after consumption of a single dose (acute). Secondary outcome measures included plasma glucose, serum insulin, serum lipids, and body weight.ResultsNo significant between-group differences in endothelial function with daily treatment for 8 weeks were seen. No other significant treatment effects were discerned in glucose, insulin, lipids, and weight.ConclusionEncapsulated fruit and vegetable juice powder concentrates did not alter insulin or glucose measures in this sample of adults with metabolic syndrome.Trial Registrationclinicaltrials.gov NCT01224743

Serum IGF-1 Concentrations Change With Soy and Seaweed Supplements in Healthy Postmenopausal American Women

Insulin-like growth factor 1 (IGF-1) is an anabolic hormone important for growth and development. However, high-circulating serum concentrations in adults are associated with increased risk of postmenopausal breast cancer. Nutritional status and specific foods influence serum IGF-1 concentrations. Breast cancer incidence is typically low in Asian countries where soy is commonly consumed. Paradoxically, soy supplement trials in American women have reported significant increases in IGF-1. Seaweed also is consumed regularly in Asian countries where breast cancer risk is low. We investigated the possibility that seaweed could modify soy-associated increases in IGF-1 in American women. Thirty healthy postmenopausal women (mean age 58 yr) participated in this 14-wk double-blinded, randomized, placebo-controlled crossover clinical trial. Participants consumed 5 g/day placebo or seaweed (Alaria esculenta) in capsules for 7 wk. During the 7th wk, a high-soy protein isolate powder was added (2 mg/kg body weight aglycone equivalent isoflavones). Overnight fasting blood samples were collected after each intervention period. Soy significantly increased serum IGF-1 concentrations compared to the placebo (21.2 nmol/L for soy vs. 16.9 nmol/L for placebo; P = 0.0001). The combination of seaweed and soy significantly reduced this increase by about 40% (21.2 nmol/L for soy alone vs. 19.4 nmol/L; P = 0.01). Concurrent seaweed and soy consumption may be important in modifying the effect of soy on IGF-1 serum concentrations.

Evaluating the effect of zingiber officinalis on nausea and vomiting in patients receiving Cisplatin based regimens.

Ginger, the rhizome of Zingiber officinalis, has long been used as herbal medicine for its antiemetic effect. For evaluating the effect of zingiber officinalis on nausea and vomiting (N and V) in patients receiving cisplatin based regimens, a randomized double-blind placebo-controlled cross-over clinical trial was carried out in patients receiving cisplatin in combination with other chemotherapeutic agents. The patients were randomly assigned to receive ginger capsules (rhizome of zingiber officinalis) or placebo in their first cycle of the study. All patients received standard antiemetics for chemotherapy induced nausea and vomiting (CINV). The patients were crossed-over to receive ginger or placebo in their next cycle of chemotherapy. Among 36 eligible patients who received both cycles of treatment, there were no difference in prevalence, severity, and duration of both acute and delayed N and V. Addition of ginger to the standard antiemetic regimen has shown no advantage in reducing acute and delayed N and V in patients with cisplatin-based regimen in this study.

N-Acetylcarnosine Lubricant Eyedrops Possess All-In-One Universal Antioxidant Protective Effects of L-Carnosine in Aqueous and Lipid Membrane Environments, Aldehyde Scavenging, and Transglycation Activities Inherent to Cataracts: A Clinical Study of the New Vision-Saving Drug N-Acetylcarnosine Eyedrop Therapy in a Database Population of Over 50,500 Patients

The antioxidant activity of L-carnosine (beta-alanyl-L-histidine, bioactivated in ocular tissues) versus N-acetylcarnosine (N-acetyl-beta-alanyl-L-histidine, ocular-targeted small dipeptide molecules) was studied in aqueous solution and in a lipid environment, employing liposomes as a model of lipid membranes. Reactive oxygen species (ROS) were generated by an iron/ascorbate promoter system for induction of lipid peroxidation (LPO). L-carnosine, which is stabilized from enzymatic hydrolysis, operates as a universal aldehyde and ROS scavenger in both aqueous and lipid environments and is effective at preventing ROS-induced damage to biomolecules. Second-generation carnosine analogs bearing the histidyl-hydrazide moiety were synthesized and tested versus L-carnosine for their ability to reverse the glycation process, also known as the Maillard reaction, and reverse the stable intermolecular cross-links, monitored in the glucose-ethylamine Schiff base model, ultimately resulting in the formation of the advanced glycation end products (AGEs) from nonenzymatic glycation, accumulating in numerous body tissues and fluids. The obtained data demonstrate the transglycation properties of the ophthalmically stabilized L-carnosine and L-carnosine histidyl-hydrazide derivatives tested and can be used to decrease or predict the occurrence of long-term complications of AGE formation and improve therapeutically the quality of vision and length of life for diabetes mellitus patients and survivors with early aging. Scientists at Innovative Vision Products, Inc. (IVP), developed lubricant eyedrops designed as a sustained-release 1% N-acetylcarnosine prodrug of L-carnosine. The eyedrops contain a mucoadhesive cellulose-based compound combined with corneal absorption promoters and glycerine in a drug-delivery system. Anti-aging therapeutics with the ophthalmic drug eyedrop formula including N-acetylcarnosine showed efficacy in the nonsurgical treatment of age-related cataracts for enrolled participants in the prospective, randomized, double-masked, placebo-controlled crossover clinical trial after controlling for age, gender, and daily activities. In a cohort in excess of 50,500 various patients seeking cutting-edge medical care, the N-acetylcarnosine topical eyedrops target therapy was demonstrated to have significant efficacy, safety, and good tolerability for the prevention and treatment of visual impairment in this older population with relatively stable patterns of causes for blindness and visual impairment. Overall, accumulated study data demonstrate that the IVP-designed new vision-saving drugs, including N-acetylcarnosine eyedrops, promote health vision and prevent vision disability from senile cataracts, primary open-angle glaucoma, age-related macular degeneration, diabetic retinopathy, and aging. N-acetylcarnosine eyedrop therapy is the crown jewel of the anti-aging medical movement and revolutionizes early detection, treatment, and rejuvenation of aging-related eye-disabling disorders. N-acetylcarnosine, as an innovative medical science tool and component of the home medicine and alternative medicine approaches, has the potential to alleviate visual impairment and its associated social, economic, and political woes for an aging population.

Metformin Does Not Improve the Reproductive or Metabolic Profile in Women With Polycystic Ovary Syndrome (PCOS)

To determine whether metformin, when given to women with polycystic ovary syndrome (PCOS), promotes folliculogenesis by prompting a drop in free sex steroids resulting in a compensatory follicle stimulating hormone (FSH) rise, we conducted a randomized, double-blind, placebo-controlled crossover clinical trial. Eight mid-reproductive age PCOS participants with mean obese body mass index (BMI) and normal glucose tolerance received 8 weeks of metformin, given in a step-up fashion to a maximum dose of 2000 mg daily or placebo with daily urine sampling, 4-6 weeks washout, and crossover to the remaining arm for 8 weeks. To confirm the effects of metformin on glucose and other metabolic markers, a hyperinsulinemic, euglycemic 3-dose clamp (physiologic: 30 mU/m(2) per minute, high: 400 mU/m(2) per minute) followed each treatment. Urinary FSH, luteinizing hormone (LH), or pregnanediol glucuronide (Pdg) did not differ by treatment. Glucose disposal, endogenous glucose production, BMI, ovulation rates, serum sex steroids, free fatty acids, and lipids did not significantly differ by treatment, despite good evidence for compliance with the protocol. During the clamp, high-dose insulin administration was associated with an acute drop in serum LH. We conclude that short-term, high-dose metformin exerts minimal effects on both metabolic markers and reproductive hormones in a small sample of overall morbidly obese women.

Contact-free Infrared Thermography for Assessing Effects during Acupuncture: A Randomized, Single-blinded, Placebo-controlled Crossover Clinical Trial

Although evidence of its effects is tentative, acupuncture has long been used in the treatment of multiple maladies. So far, it has not been possible to discriminate the effects of the venue from specific results of needling itself, thus physicians merely depend on patients' statements. The authors investigated the efficacy of infrared thermography in distinguishing response to true acupuncture as compared to nonacupoint cutaneous and muscular needling (sham or minimal acupuncture), as well as without manipulation. Thermographic imaging was performed in 50 healthy volunteers randomly assigned to four groups: Acupuncture of Hegu (LI 4), needling of a cutaneous and a muscular point where no acupuncture point has been described yet, and without manipulation. In a crossover protocol, each proband completed all four arms of the protocol in a random order. Infrared thermograms were gathered at defined points in each group. A significant increase in surface temperature occurred within 2 min after needling the acupuncture point Hegu (from 30.1 +/- 2.7 degrees C [SD] to 31.2 +/- 3.0 degrees C and to 31.9 +/- 2.5 degrees C after 10 min, P < 0.001), whereas needling of the cutaneous and muscular point, as well as without any manipulation resulted in a decrease of temperature in the monitored area. Contact-free infrared thermographic imaging is a reliable and easy-to-handle tool to distinguish between needling at Hegu and needling of a nonacupoint ("sham" acupuncture).

A randomized double blind crossover placebo-controlled clinical trial to assess the effects of a mouthwash containing chlorine dioxide on oral malodor

BackgroundPrevious research has shown the oxidizing properties and microbiological efficacies of chlorine dioxide (ClO2), however, its clinical efficacies on oral malodor have been evaluated only with organoleptic measurements (OM) or sulphide monitors. No clinical studies have investigated the inhibitory effects of ClO2 on volatile sulfur compounds (VSCs) using gas chromatography (GC). The aim of this study was to assess the inhibitory effects of a mouthwash containing ClO2 on morning oral malodor using OM and GC.MethodsA randomized, double blind, crossover, placebo-controlled clinical trial was conducted among 15 healthy male volunteers, who were divided into 2 groups. In the first test phase, the group 1 subjects (N = 8) were instructed to rinse with the experimental mouthwash containing ClO2, and those in group 2 (N = 7) to rinse with the placebo mouthwash without ClO2. In the second test, phase after a one week washout period, each group used the opposite mouthwash.Oral malodor was evaluated before rinsing, right after rinsing and every 30 minutes up to 4 hours with OM, and concentrations of hydrogen sulfide (H2S), methyl mercaptan (CH3SH) and dimethyl sulfide ((CH3)2S), the main VSCs of human oral malodor, were evaluated with GC.ResultsThe baseline oral condition in the subjects in the 2 groups did not differ significantly. The mouthwash containing ClO2 improved morning bad breath according to OM and reduced concentrations of H2S, CH3SH and (CH3)2S according to GC up to 4 hours after rinsing. OM scores with ClO2 were significantly lower than those without ClO2 at all examination times. Significant reductions in the concentrations of the three kinds of VSCs measured by GC were also evident at all examination times. The concentrations of the three gases with ClO2 were significantly lower than those without ClO2 at most examination times.ConclusionIn this explorative study, ClO2 mouthwash was effective at reducing morning malodor for 4 hours when used by healthy subjects.Trial registrationClinicalTrials.gov NCT00655772

Intestinal Permeability and Effects of Lactobacillus rhamnosus Therapy in Children With Short Bowel Syndrome

The present study was conducted to investigate the effects of Lactobacillus rhamnosus (also known as LGG) on intestinal permeability (IP) in children with short bowel syndrome (SBS). In a double-blind, placebo-controlled crossover clinical trial, baseline IP (ie, lactulose-to-mannitol ratio) was measured in subjects with SBS and healthy control subjects. Subjects with SBS received LGG or placebo for 4 weeks, followed by a 3-week washout before therapy was crossed over for another 4 weeks. IP, quantitative fecal cultures for Lactobacillus species (in colony-forming units [cfu] per gram of stool) and hydrogen breath test (HBT) were performed during LGG and placebo phases of therapy. Twenty-one children (SBS, n = 9; control, n = 12) with a median age of 4.5 years (range 1.6-16.4 years) enrolled. Baseline IP measurements were similar in patients with SBS and control subjects: 0.08 +/- 0.06 (mean +/- SD) versus 0.07 +/- 0.05 (P = 1.0). IP was correlated with age in control subjects (r = -0.83, P = 0.001) but not among patients with SBS (r = -0.55, P = 0.16). Fecal colonization with Lactobacillus species did not differ during LGG versus placebo therapy (median 1.4 x 10(9) cfu/g [range 4.0 x 10(5) to 4.0 x 10(9) cfu/g] vs 6.0 x 10(9) cfu/g [1.0 x 10(3) to 1.0 x 10(10) cfu/g], respectively; P = 0.83). LGG therapy had no consistent effects on IP (P = 0.58) or its relationship with age (r = -0.40, P = 0.29), and was associated with conversion to positive HBT results in 1 subject. In this sample of children with SBS, the IP was within normal limits but did not correlate with age. LGG therapy had no consistent effects on IP. These findings do not support empiric LGG therapy to enhance IP in children with SBS.

No Relation between Therapeutic Response to Methylphenidate and its Cardiovascular Side Effects in Children with Attention-Deficit/Hyperactivity Disorder

ObjectiveThe aim of this study was to examine the relation between therapeutic response to methylphenidate (MPH) and its associated short term cardiovascular side effects (Systolic Blood Pressure-SBP, Diastolic Blood Pressure-DBP and Heart Rate-HR changes) in children with ADHD, based on the hypothesis that these parameters share common underlying mechanisms.MethodA double-blind placebo-controlled crossover clinical trial of children 6 to 12 years old diagnosed with ADHD was done. The children were given one week of 0.5 mg/kg MPH and one week of placebo (divided into two equal doses, given twice every day). On the morning of the third day of each week, Blood Pressure (BP) and HR were recorded immediately before (at time 0) and after (at time 10 and 45 minutes) administration of MPH. Children were grouped into 4 categories according to their therapeutic response (large, moderate, mild or no response) to MPH. A mixed model analysis of variance was performed to determine whether response groups were different with regard to cardiovascular side effects.ResultsAll variables were comparable among the four groups 10 min after treatment with MPH and with placebo. Small but significant (p &lt; 0.001) increases were seen in SBP (3.65 mm of Hg) and DBP (3.99 mm of Hg) 45 minutes after administration of MPH. A small but significant decrease in HR (3.3 beats per minute) was observed 45 min after administration of placebo. No significant differences in SBP, DBP and HR were found between response groups.ConclusionsMPH causes a small but significant change in BP at 45 minutes after administration. No changes in HR were observed with MPH at 45 minutes. Responders to MPH treatment do not differ from non-responders in occurrence of BP and HR changes, at least within 45 minutes after administration and with the MPH dosage used in the study.

Randomized Controlled Trial to Evaluate Transdermal Testosterone in Female Cancer Survivors With Decreased Libido; North Central Cancer Treatment Group Protocol N02C3

Decreased libido is one of several changes in sexual function that are often experienced by female cancer patients. Transdermal testosterone therapy has been associated with increased libido among estrogen-replete women who report low libido. In a phase III randomized, placebo-controlled crossover clinical trial, we evaluated whether transdermal testosterone would increase sexual desire in female cancer survivors. Postmenopausal women with a history of cancer and no current evidence of disease were eligible if they reported a decrease in sexual desire and had a sexual partner. Eligible women were randomly assigned to receive 2% testosterone in Vanicream for a testosterone dose of 10 mg daily or placebo Vanicream for 4 weeks and were then crossed over to the opposite treatment for an additional 4 weeks. The primary endpoint was sexual desire or libido, as measured using the desire subscales of the Changes in Sexual Functioning Questionnaire, as assessed at baseline and at the end of 4 and 8 weeks of treatment. Serum levels of bioavailable testosterone were measured at the same times. All statistical tests were two-sided. We enrolled 150 women. Women who were on active testosterone cream had higher serum levels of bioavailable testosterone than women on placebo (mean change from baseline, testosterone versus placebo, week 4, 11.57% versus 0%, difference = 11.57%, 95% confidence interval [CI] = 8.49% to 14.65%; week 8, 10.21% versus 0.28%, difference = 9.92%, 95% CI = 5.42% to 14.42%; P<.001 for all). However, the average intrapatient libido change from baseline to weeks 4 and 8 was similar on both arms. Increased testosterone level did not translate into improved libido, possibly because women on this study were estrogen depleted.

A neurophysiological study of the detrimental effects of alprazolam on human action monitoring

In order to adapt their behavior to different unexpected situations, humans need to be able to monitor their performance and detect and correct errors. Benzodiazepines have long been shown to impair performance in humans, but the performance-related neurophysiological processes targeted by these drugs remain largely unknown. In the present article, we assessed the impact of alprazolam administration on relevant aspects of action monitoring, i.e., the monitoring of response conflict and the detection and correction of errors by means of neurophysiological measures. Multichannel event-related brain potentials (ERPs) were recorded to assess the impact of the benzodiazepine alprazolam (0.25 mg and 1.00 mg) on action monitoring and motor preparation in a group of twelve healthy male volunteers who participated in a double-blind cross-over placebo-controlled clinical trial involving a letter flanker task. Error detection was evaluated using the error-related negativity (ERN); response conflict on correct trials was measured by means of the N2 amplitude difference between congruent and incongruent trials; motor preparation was assessed by means of the lateralized readiness potentials (LRPs); and post-error adjustments were assessed by measuring post-error slowing in reaction time. Alprazolam significantly reduced the amplitude of the ERN and the number of corrective responses and increased reaction time and LRP latencies. The drug had no effect on amplitude differences in the N2 component between congruent and incongruent trials or on post-error slowing. Thus, alprazolam was shown to affect brain correlates of error detection (ERN) and motor preparation (LRPs), while it did not disturb conflict monitoring on correct trials (N2) or post-error adjustments of behavior.

Local Anesthesia of the Sole of the Foot Alters Lower Limb Kinematics and Kinetics During Running

1649 PURPOSE: The purpose of this study was to investigate whether local anesthesia of the sole of the foot would alter lower limb kinematics, kinetics and perceptions of comfort during running. METHODS: The study was conducted as a randomised double blind placebo controlled crossover clinical trial (n = 10). Either a topical anaesthetic cream (EMLA™, lignocaine and prilocaine 25 mg/g) or placebo (CON) was applied after which subjects rested in sitting for 60 minutes and then performed 10 running trials in the Motion Analysis Laboratory to determine their kinetics and lower limb kinematics during running. Thereafter, they were required to run 840 metres on an indoor tartan track and rate their perceived comfort (Scale 0–10) during the run. RESULTS: The step length (m) (EMLA: 0.68 ± 0.065, CON: 0.718 ± 0.081: p = 0.0036) and stride length (m) (EMLA: 1.375 ± 0.146, CON: 1.43 ± 0.18: p = 0.026) in the laboratory and mean velocity (m/sec) (EMLA: 3.87 ± 0.358, CON: 4.07 ± 0.317: p = 0.0036) on the indoor track decreased significantly following EMLA™. Peak horizontal propulsive force (BW) was significantly reduced during the EMLA trial compared with the CON trial (EMLA: 0.162 ± 0.044 BW, CON: 0.177 ± 0.049 BW: p = 0.043). There was a significant increase (p = 0.0053) in dorsiflexion of the ankle at heelstrike (Ahs) during the EMLA trial (degrees) (EMLA: −3.23 ± 4.19, CON: 0.233 ± 4.9) compared with CON. There was also a significant increase of dorsiflexion of the ankle at the time of peak knee extension (Asw) (degrees) (EMLA: −4.113 ± 4.55, CON: −1.59 ± 4.55: p = 0.0078) and at the time of peak knee flexion in the stance phase (Ast) (degrees) (EMLA: −9.69 ± 5.43, CON: −7.2 ± 6.3: p = 0.028) during the EMLA trial compared with CON. CONCLUSION: The application of a topical local anesthetic cream to the sole of the foot reduced self-selected running speed and altered selected kinetic and kinematic variables during running. Sensory input from cutaneous afferents in the foot alters gait mainly by changing running speed.

Local Anesthesia of the Sole of the Foot Alters Lower Limb Kinematics and Kinetics During Running

1649 PURPOSE: The purpose of this study was to investigate whether local anesthesia of the sole of the foot would alter lower limb kinematics, kinetics and perceptions of comfort during running. METHODS: The study was conducted as a randomised double blind placebo controlled crossover clinical trial (n = 10). Either a topical anaesthetic cream (EMLA™, lignocaine and prilocaine 25 mg/g) or placebo (CON) was applied after which subjects rested in sitting for 60 minutes and then performed 10 running trials in the Motion Analysis Laboratory to determine their kinetics and lower limb kinematics during running. Thereafter, they were required to run 840 metres on an indoor tartan track and rate their perceived comfort (Scale 0–10) during the run. RESULTS: The step length (m) (EMLA: 0.68 ± 0.065, CON: 0.718 ± 0.081: p = 0.0036) and stride length (m) (EMLA: 1.375 ± 0.146, CON: 1.43 ± 0.18: p = 0.026) in the laboratory and mean velocity (m/sec) (EMLA: 3.87 ± 0.358, CON: 4.07 ± 0.317: p = 0.0036) on the indoor track decreased significantly following EMLA™. Peak horizontal propulsive force (BW) was significantly reduced during the EMLA trial compared with the CON trial (EMLA: 0.162 ± 0.044 BW, CON: 0.177 ± 0.049 BW: p = 0.043). There was a significant increase (p = 0.0053) in dorsiflexion of the ankle at heelstrike (Ahs) during the EMLA trial (degrees) (EMLA: −3.23 ± 4.19, CON: 0.233 ± 4.9) compared with CON. There was also a significant increase of dorsiflexion of the ankle at the time of peak knee extension (Asw) (degrees) (EMLA: −4.113 ± 4.55, CON: −1.59 ± 4.55: p = 0.0078) and at the time of peak knee flexion in the stance phase (Ast) (degrees) (EMLA: −9.69 ± 5.43, CON: −7.2 ± 6.3: p = 0.028) during the EMLA trial compared with CON. CONCLUSION: The application of a topical local anesthetic cream to the sole of the foot reduced self-selected running speed and altered selected kinetic and kinematic variables during running. Sensory input from cutaneous afferents in the foot alters gait mainly by changing running speed.