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Valbenazine is a highly selective vesicular monoamine transporter 2 (VMAT2) inhibitor approved for treatment of tardive dyskinesia. To address the ongoing need for improved symptomatic treatments for individuals with Huntington's disease, valbenazine was evaluated for the treatment of chorea associated with Huntington's disease. KINECT-HD (NCT04102579) was a phase 3, randomised, double-blind, placebo-controlled trial, performed in 46 Huntington Study Group sites in the USA and Canada. The study included adults with genetically confirmed Huntington's disease and chorea (Unified Huntington's Disease Rating Scale [UHDRS] Total Maximal Chorea [TMC] score of 8 or higher) who were randomly assigned (1:1) via an interactive web response system (with no stratification or minimisation) to oral placebo or valbenazine (≤80 mg, as tolerated) for 12 weeks of double-blinded treatment. The primary endpoint was a least-squares mean change in UHDRS TMC score from the screening and baseline period (based on the average of screening and baseline values for each participant) to the maintenance period (based on the average of week 10 and 12 values for each participant) in the full-analysis set using a mixed-effects model for repeated measures. Safety assessments included treatment-emergent adverse events, vital signs, electrocardiograms, laboratory tests, clinical tests for parkinsonism, and psychiatric assessments. The double-blind placebo-controlled period of KINECT-HD has been completed, and an open-label extension period is ongoing. KINECT-HD was performed from Nov 13, 2019, to Oct 26, 2021. Of 128 randomly assigned participants, 125 were included in the full-analysis set (64 assigned to valbenazine, 61 assigned to placebo) and 127 were included in the safety-analysis set (64 assigned to valbenazine, 63 assigned to placebo). The full-analysis set included 68 women and 57 men. Least-squares mean changes from the screening and baseline period to the maintenance period in the UHDRS TMC score were –4·6 for valbenazine and –1·4 for placebo (least-squares mean difference –3·2, 95% CI –4·4 to –2·0; p<0·0001). The most commonly reported treatment-emergent adverse event was somnolence (ten [16%] with valbenazine, two [3%] with placebo). Serious treatment-emergent adverse events were reported in two participants in the placebo group (colon cancer and psychosis) and one participant in the valbenazine group (angioedema because of allergic reaction to shellfish). No clinically important ch anges in vital signs, electrocardiograms, or laboratory tests were found. No suicidal behaviour or worsening of suicidal ideation was reported in participants treated with valbenazine. In individuals with Huntington's disease, valbenazine resulted in improvement in chorea compared with placebo and was well tolerated. Continued research is needed to confirm the long-term safety and effectiveness of this medication throughout the disease course in individuals with Huntington's disease-related chorea. Neurocrine Biosciences.

SRX246 is a vasopressin (AVP) 1a receptor antagonist that crosses the blood-brain barrier. It reduced impulsive aggression, fear, depression and anxiety in animal models, blocked the actions of intranasal AVP on aggression/fear circuits in an experimental medicine fMRI study and demonstrated excellent safety in Phase 1 multiple-ascending dose clinical trials. The present study was a 3-arm, multicenter, randomized, placebo-controlled, double-blind, 12-week, dose escalation study of SRX246 in early symptomatic Huntington’s disease (HD) patients with irritability. Our goal was to determine whether SRX246 was safe and well tolerated in these HD patients given its potential use for the treatment of problematic neuropsychiatric symptoms. Participants were randomized to receive placebo or to escalate to 120 mg twice daily or 160 mg twice daily doses of SRX246. Assessments included standard safety tests, the Unified Huntington’s Disease Rating Scale (UHDRS), and exploratory measures of problem behaviors. The groups had comparable demographics, features of HD and baseline irritability. Eighty-two out of 106 subjects randomized completed the trial on their assigned dose of drug. One-sided exact-method confidence interval tests were used to reject the null hypothesis of inferior tolerability or safety for each dose group vs. placebo. Apathy and suicidality were not affected by SRX246. Most adverse events in the active arms were considered unlikely to be related to SRX246. The compound was safe and well tolerated in HD patients and can be moved forward as a candidate to treat irritability and aggression.

Your headline, \"Margate mosque's faithful reeling after imam's arrest,\" made me hopeful that for once the \"faithful\" would be speaking up, out and against the leaders of a religious movement...

The federal government rejects more insurance claims than any big, bad \"corporation.\" President Obama spouted off last year about \"inability to pay for medical bills\" being the major cause of bankruptcies.

Didn't Mr. Obama say the following regarding Sen. John McCain: \"Your health care benefits will get taxed for the first time in history\"? Mr. O's plan will do the same thing.

America: Are we outraged yet? In the midst of the financial crisis, Congress votes itself a raise.

The purpose of this experimental study was to learn whether self-modeling would be effective in altering attitudes. Results from such a study would also contribute to knowledge of the effectiveness of Albert Bandura's social cognitive learning theory as applied to the modeling of attitudes. This study was conducted in a high school setting with 34 10th-grade students randomly selected from nine English classes. The treatment and control groups were each composed of 17 students, all of whom were administered the Study Attitudes survey, a subscale of Brown and Holtzman's Survey of Study Habits and Attitudes, and observed using a behavior checklist of 17 behaviors taken from the attitude survey. All the subjects were then exposed to a videotaping process in several of their classes. The videotapes of the treatment group were edited to produce two, 2-2.5 minute videotapes of the student performing positive, in-school behaviors which were noted with a dubbed voice interjected six times on each tape. The treatment group viewed their tapes 10 times over a four-week period. After the treatment period, all subjects were again observed for the checklist behaviors and readministered the attitude survey. An analysis of variance was performed on each of the dependent variables: Study Attitude scores and behavior checklist scores. No significant differences were found between pre- and posttests or between the treatment group and the control group on either of the dependent variables. The results of the data analysis were not sufficient to confirm or refute the effectiveness of the self-modeling technique or social cognitive learning theory in the changing of attitudes. Recommendations based on this study include the conducting of additional research on the modeling of attitudes to increase positive affect, the self-modeling of a range of attitudes with subjects of varying ages and numbers, and, most emphatically, the conducting of experimental research that will further define and evaluate students' attitudes toward school.

Sen John McCain voted yes. Both Sen. Hillary Clinton and Sen. Barack Obama were no votes. They were obviously too busy to be thinking of you...

Regarding the article \"The Last Political Machine\" [Aug. 21!: I am appalled by the salaries listed. These politicians are not the solution to our problems. They are our problems. How on Earth do they sleep at night?

In Anthony Man's article regarding Rep. Allen West's district, West said, \"I like beating the odds. If you go back and if you study history, Alexander the Great never had odds better than 1:3 against him and he never lost a battle.\" What doesn't surprise me is the left's attempt to follow President [Barack Obama]'s insistence that the fault of our woes lies with everything and everyone but him. Did he not run on hope and change? How many are hopeful or content with the change he has brought about? Stifling business growth, health care \"reform\" (gotten your 2012 health benefits statement yet?) and the appointment of more \"czars\" all wreaking havoc on the economy. Wasn't he also the one who talked about transparency? \"I will allow five days of public comment before I sign any bills.\" \"I'll put the health care negotiations on C-SPAN.\"