Clinical Global Impression Of Change Scores Research Articles

Analysis of feeding and eating disorders in 191 children according to psychiatric or gastroenterological recruitment: The PEDIAFED cohort study.

The DSM-5 classification introduced new Feeding and Eating Disorders (FED) diagnostic categories, notably Avoidant and Restrictive Food Intake Disorder (ARFID), which, like other FED, can present psychiatric and gastrointestinal symptoms. However, paediatric clinical research that focuses on children below the age of 12years remains scarce. The aim of this study was first to investigate the clinical features of FED in a cohort of children, second to compare them according to their recruitment (gastroenterology or psychiatry unit). This non-interventional retrospective cohort study analysed 191 patients in a French paediatric tertiary care centre (gastroenterology n=100, psychiatry n=91). The main outcome variables were clinical data (type of FED, BMI, nutritional support, chronic diseases, psychiatric comorbidities, sensory, sleep, language disorders, gastrointestinal complaints, adverse life events, family history). The outcome was defined by a Clinical Global Impression of Change-score. FED diagnoses were ARFID (n=100), Unspecified FED (UFED, n=57), anorexia nervosa (AN, n=33) and one pica/rumination. Mean follow-up was 3.28years (SD 1.91). ARFID was associated with selective and sensory disorders (p<0.001); they had more anxiety disorders than patients with UFED (p<0.001). Patients with UFED had more chewing difficulties, language disorder (p<0.001), and more FED related to chronic disease (p<0.05) than patients with ARFID and AN. Patients with AN were female, underweight, referred exclusively to the psychiatrist, and had more depression than patients with ARFID and UFED (p<0.001). The gastroenterology cohort included more UFED, while the psychiatry cohort included more psychiatric comorbidities (p<0.001). A worse clinical outcome was associated with ARFID, a younger age at onset (p<0.001), selective/sensory disorders and nutritional support (p<0.05). ARFID and UFED children were diagnosed either by gastroenterologists or psychiatrists. Due to frequently associated somatic and psychiatric comorbidities, children with FED should benefit from a multidisciplinary assessment and care.

Effect of Aerobic Exercise with and without Strengthening Exercises on Neuropathic Symptoms in People with Diabetic Peripheral Neuropathy

Background: The incidence of peripheral neuropathy among chronic diabetic patients is escalating, with a notable rise observed in Pakistan. This trend has been partly attributed to the predominant reliance on pharmacotherapy, while the role of physical exercise in management remains underutilized. Aerobic exercise is widely recommended in clinical guidelines for the treatment and prevention of diabetic complications, and it is hypothesized that the addition of strength training could yield even more benefits. Objective: This study aimed to evaluate the effects of combined aerobic and strength training exercises on neuropathic symptoms in patients with diabetic peripheral neuropathy. Methods: In this randomized clinical trial, 40 patients with diabetic peripheral neuropathy were equally divided into two groups: Group A underwent a combined regimen of aerobic and strength training exercises, whereas Group B engaged in aerobic exercises alone. The effectiveness of these interventions was assessed using the Michigan Neuropathy Screening Instrument (MNSI), Numeric Pain Rating Scale (NPRS), and Clinical Global Impression of Change (CGIC). Data were analyzed using SPSS version 20.0, employing independent t-tests, repeated measures ANOVA, and descriptive statistics for in-depth analysis. Results: Group A demonstrated a significant reduction in MNSI scores with a mean difference of 1.700 and a p-value &lt; 0.001, indicating a substantial improvement in neuropathic symptoms compared to Group B. While both groups showed significant improvements in NPRS and CGIC scores, the differences were not statistically significant, with p-values of 0.599 and 0.330, respectively, and mean differences of 0.1500 and 0.2500 for NPRS and CGIC. The overall statistical analysis revealed a high significance level (p &lt; 0.001) within both groups in all measured outcomes, suggesting considerable improvements post-intervention. Conclusion: The addition of strength training to aerobic exercises significantly enhances the reduction of neuropathic symptoms in diabetic patients. However, for pain relief and overall clinical improvement, both treatment approaches—combined aerobic and strength training or aerobic exercise alone—were equally effective.

Intranasal Carbetocin Reduces Hyperphagia and Anxiety and Distress Behaviors in Prader-Willi Syndrome: Results From the CARE-PWS Randomized, Double-Blind, Placebo-Controlled Study

Prader-Willi syndrome (PWS) is a complex genetic disorder associated with multiple neuroendocrine abnormalities, including significantly decreased hypothalamic oxytocin levels, resulting in symptoms of severe hyperphagia (an unrelenting false sense of starvation) and multiple severe neuropsychiatric and behavioral issues. CARE-PWS, a multi-center, randomized, double-blind, placebo-controlled phase 3 study, has evaluated the efficacy, safety and tolerability of intranasal carbetocin, a selective oxytocin receptor agonist, in participants with PWS. Eligible participants aged 7 through 18 with genetically confirmed PWS were randomized in equal proportions to three treatment arms for the 8-week placebo-controlled period of the study: carbetocin 9.6 mg, carbetocin 3.2 mg, or a matching placebo, administered by nasal spray three times a day with meals. The primary endpoint assessed changes from baseline to week 8 in Hyperphagia Questionnaire for Clinical Trials (HQ-CT) or Children’s Yale-Brown Obsessive Compulsive Scale (CY-BOCS) scores for the carbetocin 9.6 mg arm vs placebo, and the first secondary endpoint assessed changes from baseline to week 8 in HQ-CT or CY-BOCS scores for the carbetocin 3.2 mg arm vs placebo. Additional secondary endpoints included changes from baseline to week 8 in PWS Anxiety and Distress Questionnaire (PADQ) scores, and Clinical Global Impression of Change (CGI-C) scores evaluating the overall change in severity of PWS symptoms at week 8. Due to COVID-19, enrollment was closed early with 119 evaluable participants for the primary analysis. In the carbetocin 9.6 mg arm, trends toward numerically greater improvements in HQ-CT and CGI-C scores relative to placebo were observed but did not reach statistical significance; however, the carbetocin 3.2 mg arm demonstrated a significant improvement in HQ-CT scores (LS mean improvement vs placebo -3.14 points, p=0.016). In the 3.2 mg arm, additional consistent evidence of improvements versus placebo was seen in multiple secondary endpoints, including CGI-C (p=0.027) and PADQ (p=0.027). Numeric trends toward improvement in CY-BOCS scores were observed in each dose arm, but did not reach statistical significance versus placebo. During the subsequent long-term follow-up period of the study, both carbetocin arms have experienced continued numeric improvements from baseline across multiple endpoints. Intranasal carbetocin was generally well-tolerated; the most frequently reported adverse event was flushing, which was generally mild and transient. In conclusion, results of the CARE-PWS study support that intranasal carbetocin appears to be safe and well tolerated, and reduces hyperphagia and anxiety and distress behaviors in PWS.

Topline Results of the CARE-PWS Phase 3 Study: Intranasal Carbetocin Improves Hyperphagia and Anxiety and Distress Symptoms in Prader-Willi Syndrome (PWS)

Prader-Willi syndrome (PWS) is a complex genetic disorder associated with multiple neuroendocrine abnormalities including significantly decreased hypothalamic oxytocin levels, resulting in symptoms of severe hyperphagia (an unrelenting false sense of starvation) and multiple severe neuropsychiatric and behavioral issues. CARE-PWS, a multi-center, randomized, double-blind, placebo-controlled phase 3 study, has evaluated the efficacy, safety, and tolerability of intranasal carbetocin, a selective oxytocin receptor agonist, in participants with PWS.Eligible participants aged 7 through 18 with genetically confirmed PWS were randomized in equal proportions to three treatment arms for the 8-week placebo-controlled period of the study: carbetocin 9.6 mg, carbetocin 3.2 mg, or a matching placebo, administered by nasal spray three times a day with meals. The primary endpoint assessed changes from baseline to week 8 in Hyperphagia Questionnaire for Clinical Trials (HQ-CT) or Children’s Yale-Brown Obsessive Compulsive Scale (CY-BOCS) scores for the carbetocin 9.6 mg arm vs placebo, and the first secondary endpoint assessed changes from baseline to week 8 in HQ-CT or CY-BOCS scores for the carbetocin 3.2 mg arm vs placebo. Additional secondary endpoints included changes from baseline to week 8 in PWS Anxiety and Distress Questionnaire (PADQ) scores, and Clinical Global Impression of Change (CGI-C) scores evaluating the overall change in severity of PWS symptoms at week 8.Due to COVID-19, enrollment was closed early with 119 evaluable participants for the primary analysis. In the carbetocin 9.6 mg arm, trends toward numerically greater improvements in HQ-CT and CGI-C scores relative to placebo were observed but did not reach statistical significance; however, the carbetocin 3.2 mg arm demonstrated a significant improvement in HQ-CT scores (LS mean improvement vs placebo -3.14 points, p=0.016). In the 3.2 mg arm, additional consistent evidence of improvements versus placebo was seen in multiple secondary endpoints, including CGI-C (p=0.027) and PADQ (p=0.027). Numeric trends toward improvement in CY-BOCS scores were observed in each dose arm, but did not reach statistical significance versus placebo. During the subsequent long-term follow-up period of the study, both carbetocin arms have experienced continued numeric improvements from baseline across multiple endpoints. Intranasal carbetocin was generally well-tolerated; the most frequently reported adverse event was flushing, which was generally mild and transient.In conclusion, results of the CARE-PWS study support that intranasal carbetocin appears to be safe and well tolerated, and reduces hyperphagia and anxiety and distress behaviors in PWS.

Improvement in the Clinical Global Impression of Change with Voxelotor in Patients with Sickle Cell Disease in the Phase 3 HOPE Trial

Background: Patients with sickle cell disease (SCD) experience varied salient symptoms that impact their health-related quality of life, which incorporates illness severity, their level of distress and other aspects of impairment, and the impact of the illness on functional status. SCD symptoms may begin at an early age, and their severity varies over time and between patients. Although detection of changes in patients' self-assessed symptoms may be obfuscated by their lifelong symptoms, treating physicians with SCD expertise may be able to detect changes in a patient's status given their experience in treating the diverse symptoms across multiple patients. We evaluated the longitudinal impact of voxelotor (Oxbryta®) in the HOPE study using the single-item Clinical Global Impression of Change (CGI-C), a validated clinician-reported outcome analogous to the commonly used Patient Global Impression of Change (PGI-C), which provides expert clinical impressions that transcend symptom checklists. Methods: In the randomized, placebo-controlled, double-blinded HOPE study, participants with SCD aged 12 to 65 years were randomized to receive voxelotor (1500 mg or 900 mg dose administered orally, once daily) or placebo. Study participants had a hemoglobin (Hb) level 5.5 to 10.5 g/dL at enrollment and 1 to 10 vaso-occlusive crises in the past 12 months at screening. Clinicians were blinded to treatment assignment and to all central laboratory measures (eg, hematological parameters) throughout the 72-week study period. Clinicians rated the CGI-C at 24 and 72 weeks from baseline. CGI-C ratings used a 7-point scale ("very much improved," "moderately improved," "minimally improved," "no change," "minimally worse," "moderately worse," and "very much worse"). CGI-C outcomes were stratified by baseline Hb levels and baseline markers of hemolysis to identify measures predictive of assessment outcomes. Results: Trends of improvement from baseline in overall clinical status with voxelotor 1500 mg, as assessed by CGI-C scores, were observed as early as week 24. At week 72, patients receiving voxelotor 1500 mg were more often rated by the clinician as "very much improved" or "moderately improved" (74%; 39 of 53) compared with those who received placebo (47%; 24 of 51) (P&amp;lt;0.01, Figure 1). CGI-C score improvement was consistently greater in participants treated with voxelotor compared with placebo regardless of baseline Hb. Greater proportions of participants were rated "very much improved" or "moderately improved" with voxelotor 1500 mg than placebo regardless of baseline hemolysis markers (indirect bilirubin, percentage reticulocytes, absolute reticulocyte count). Conclusions: Treatment with voxelotor 1500 mg resulted in improved clinician-reported patient outcomes, as assessed using the CGI-C. Greater proportions of participants were rated "very much improved" or "moderately improved" regardless of baseline Hb levels and baseline markers of hemolysis. The CGI provides an overall clinician-determined summary measure that takes all available information into account, including the patient's history, psychosocial circumstances, symptoms, and behavior, as well as the impact of symptoms on the patient's ability to function. Therefore, a tool that provides a holistic assessment of a patient's well-being may be complementary in capturing changes in a patient's status, considering the substantial interpatient and intrapatient variability in SCD symptomatology. CGI-C assessments are being included in ongoing studies of voxelotor. Disclosures Smith: Emmaeus Pharmaceuticals, Inc.: Consultancy; Novartis, Inc.: Consultancy, Other: Investigator, Research Funding; Global Blood Therapeutics, Inc.: Consultancy, Research Funding; Shire, Inc.: Other: Investigator, Research Funding; NHLBI: Research Funding; Patient-Centered Outcomes Research Institute: Other: Investigator, Research Funding; Health Resources and Services Administration: Other: Investigator, Research Funding; Incyte: Other: Investigator; Pfizer: Consultancy; Ironwood: Consultancy; Novo Nordisk: Consultancy; Imara: Research Funding; Shire: Research Funding; GlycoMimetics, Inc.: Consultancy. Hankins:American Society of Pediatric Hematology/Oncology: Honoraria; UptoDate: Consultancy; Novartis: Research Funding; MJH Life Sciences: Consultancy, Patents &amp; Royalties; LINKS Incorporate Foundation: Research Funding; National Heart, Lung, and Blood Institute: Honoraria, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding. Abboud:Novartis: Consultancy, Honoraria, Research Funding; Global Blood Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Crispr Therapeutics: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Other: Travel support; Eli Lilly: Research Funding; Modus Pharmaceuticals: Research Funding. Cong:Global Blood Therapeutics: Current Employment, Current equity holder in publicly-traded company. Sorof:Global Blood Therapeutics: Current Employment, Current equity holder in publicly-traded company. Gray:Global Blood Therapeutics: Current Employment, Current equity holder in publicly-traded company. Hoppe:Global Blood Therapeutics: Current Employment, Current equity holder in publicly-traded company. Telfer:Global Blood Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Terumo: Honoraria; Pfizer: Membership on an entity's Board of Directors or advisory committees; Bluebird Bio: Honoraria, Research Funding; ApoPharma: Membership on an entity's Board of Directors or advisory committees.

Safety and Efficacy of RimabotulinumtoxinB for Treatment of Sialorrhea in Adults

RimabotulinumtoxinB (RIMA) may be preferable as an anti-sialorrhea treatment compared with current oral anticholinergic drugs in people with neurological disorders. To assess the safety, efficacy, and tolerability of RIMA injections for the treatment of sialorrhea in adults. This randomized, parallel, double-blind, placebo-controlled clinical trial of RIMA 2500 U and 3500 U was conducted from November 14, 2013, to January 23, 2017. A total of 249 adult patients with troublesome sialorrhea secondary to any disorder or cause were screened. Of them, 13 refused further participation in the study or were lost to follow-up and 49 did not fulfill the criteria for participation; 187 were ultimately enrolled. Patients had to have a minimum unstimulated salivary flow rate (USFR) of 0.2 g/min and a minimum Drooling Frequency and Severity Scale score of 4. Patients were randomized 1:1:1 to RIMA, 2500 U (n = 63); RIMA, 3500 U (n = 64); or placebo (n = 60). Primary outcomes were the change in USFR from baseline to week 4 and the Clinical Global Impression of Change (CGI-C) at week 4. The CGI-C scores were recorded on a 7-point scale ranging from very much improved to very much worse. Adverse events were recorded throughout the trial period. Of 187 patients enrolled (147 men [78.6%]; mean [SD] age, 63.9 [13.3] years), 122 patients had Parkinson disease (65.2%), 13 (7.0%) were stroke survivors, 12 had amyotrophic lateral sclerosis (6.4%), 6 had medication-induced sialorrhea (3.2%), 4 had adult cerebral palsy (2.1%), and 30 had sialorrhea owing to other causes (16.0%). A total of 176 completed the study. Treatment with both doses of RIMA significantly reduced USFR at week 4 vs placebo (mean treatment difference, -0.30 g/min [95% CI, -0.39 to -0.21] for both doses vs placebo, P < .001). The CGI-C scores were statistically significantly improved at week 4 for both treatment groups vs placebo (-1.21 [95% CI, -1.56 to -0.87] for 2500 U, -1.14 [95% CI, -1.49 to -0.80] for 3500 U, both P < .001). Treatment benefits were seen as early as 1 week after injection and were maintained over the treatment cycle of approximately 13 weeks. The RIMA injections were well tolerated compared with placebo. The most common adverse events were self-limited mild to moderate dry mouth, dysphagia, and dental caries. Treatment with RIMA (2500 U and 3500 U) in adults was well tolerated and reduced sialorrhea, with the onset of the effect at 1 week after the injection. These data support the clinical use of RIMA in the management of sialorrhea in adults. ClinicalTrials.gov Identifier: NCT01994109.

Comparison of the treatment efficacies of paroxetine, fluoxetine and dapoxetine in low socioeconomic status patients with lifelong premature ejaculation.

IntroductionTo assess the treatment efficacies of paroxetine, fluoxetine and dapoxetine in patients with lifelong premature ejaculation (PE).Material and methodsOne hundred and seventy male patients with lifelong PE were included in our study. Premature ejaculation profile (PEP) and Intravaginal ejaculation latency times (IELT) were recorded. Paroxetine 20 mg/d was given in Group 1 (n = 64), fluoxetine 20 mg/d was given in Group 2 (n = 47) and dapoxetine 30 mg on demand (at least two times/week) was given in Group 3 (n = 59) patients. After 1 month of treatment, the patients' IELT, PEP and patient reported clinical global impression of change (CGIC) were completed.ResultsThe mean age was 36 ±9.2 years. There was no difference between the groups' age, PEP and IELT before treatment (p >0.05). PEP and IELT improved in all three groups (p <0.001). The changes in the 1st and 3rd questions of PEP was significantly higher in group 1 than in the other groups (pPEP-1 = 0.042, pPEP-3 = 0.001). The changes in the 2nd and 4th questions of PEP were similar between groups (pPEP-2 = 0.444, pPEP-4 = 0.442). In group 1 and 3 IELT changes were better than group 2 (pIIEL1-3 = 0.297, pIIEL1-2 = 0.017, pIIEL2-3 = 0.100). There was no difference between CGIC scores (p = 0.087). The treatment was terminated by 8 patients in Group 1 and 9 patients in Group 2 because of side effects.ConclusionsWhile paroxetine treatment seemed to be better than the other medications, dapoxetine 30 mg treatment has less side effects than the two others and its' on demand usage makes it more prominent than the others.

Trial of Prazosin for Post-Traumatic Stress Disorder in Military Veterans

BackgroundIn randomized trials, prazosin, an α1-adrenoreceptor antagonist, has been effective in alleviating nightmares associated with post-traumatic stress disorder (PTSD) in military veterans.MethodsWe recruited veterans from 13 Department of Veterans Affairs medical centers who had chronic PTSD and reported frequent nightmares. Participants were randomly assigned to receive prazosin or placebo for 26 weeks; the drug or placebo was administered in escalating divided doses over the course of 5 weeks to a daily maximum of 20 mg in men and 12 mg in women. After week 10, participants continued to receive prazosin or placebo in a double-blind fashion for an additional 16 weeks. The three primary outcome measures were the change in score from baseline to 10 weeks on the Clinician-Administered PTSD Scale (CAPS) item B2 (“recurrent distressing dreams”; scores range from 0 to 8, with higher scores indicating more frequent and more distressing dreams); the change in score from baseline to 10 weeks on the Pittsburgh Sleep Quality Index (PSQI; scores range from 0 to 21, with higher scores indicating worse sleep quality); and the Clinical Global Impression of Change (CGIC) score at 10 weeks (scores range from 1 to 7, with lower scores indicating greater improvement and a score of 4 indicating no change).ResultsA total of 304 participants underwent randomization; 152 were assigned to prazosin, and 152 to placebo. At 10 weeks, there were no significant differences between the prazosin group and the placebo group in the mean change from baseline in the CAPS item B2 score (between-group difference, 0.2; 95% confidence interval [CI], −0.3 to 0.8; P=0.38), in the mean change in PSQI score (between-group difference, 0.1; 95% CI, −0.9 to 1.1; P=0.80), or in the CGIC score (between-group difference, 0; 95% CI, −0.3 to 0.3; P=0.96). There were no significant differences in these measures at 26 weeks (a secondary outcome) or in other secondary outcomes. At 10 weeks, the mean difference between the prazosin group and the placebo group in the change from baseline in supine systolic blood pressure was a decrease of 6.7 mm Hg. The adverse event of new or worsening suicidal ideation occurred in 8% of the participants assigned to prazosin versus 15% of those assigned to placebo.ConclusionsIn this trial involving military veterans who had chronic PTSD, prazosin did not alleviate distressing dreams or improve sleep quality. (Funded by the Department of Veterans Affairs Cooperative Studies Program; PACT ClinicalTrials.gov number, NCT00532493.)

Correlation of Changes in Patient-Reported Quality of Life With Physician-Rated Global Impression of Change in Patients With Narcolepsy Participating in a Clinical Trial of Sodium Oxybate: A Post Hoc Analysis

IntroductionNarcolepsy patients report lower health-related quality of life (HRQoL) than the general population, as measured by the Short Form-36 Health Survey (SF-36). This analysis evaluated whether changes in SF-36 correlated with physician-rated Clinical Global Impression of Change (CGI-C).MethodsData were from 209 of 228 narcolepsy patients participating in an 8-week clinical trial of sodium oxybate. Changes from baseline for SF-36 subscales (Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional, and Mental Health) and the summary scores were evaluated for correlation with CGI-C overall and by treatment group. Correlations were calculated using the Pearson product-moment correlation coefficient (r).ResultsCorrelations described an inverse relationship in scores, but a direct relationship in improvement; lower CGI-C scores (i.e., better) were associated with higher SF-36 subscale scores (i.e., improved HRQoL). Moderate and significant correlations were observed for Vitality (r = −0.464; P < 0.0001) and Role Physical (r = −0.310; P < 0.0001) subscales, but weak correlations were observed with other subscales including summary scores. Correlations were stronger at higher sodium oxybate doses for most SF-36 subscales.ConclusionSome aspects of HRQoL, measured by the SF-36, may be associated with narcolepsy. In particular, Vitality (indicative of energy and tiredness) and Role Physical (impact of physical function on daily roles) moderately correlated with overall change in status observed by clinicians. However, lack of strong correlations between SF-36 and CGI-C indicates differences in patient and clinician perspectives of disease, and suggest a need for broader assessment of the impact of narcolepsy and its treatment on patients.FundingJazz Pharmaceuticals.

Treatment of Alzheimer's Disease with Repetitive Transcranial Magnetic Stimulation Combined with Cognitive Training: A Prospective, Randomized, Double-Blind, Placebo-Controlled Study.

Background and PurposeRepetitive transcranial magnetic stimulation (rTMS) has been examined as a potential treatment for many neurological disorders. High-frequency rTMS in particular improves cognitive functions such as verbal fluency and memory. This study explored the effect of rTMS combined with cognitive training (rTMS-COG) on patients with Alzheimer's disease (AD).MethodsA prospective, randomized, double-blind, placebo-controlled study was performed with 27 AD patients (18 and 8 in the treatment and sham groups, respectively, and 1 drop-out). The participants were categorized into mild [Mini-Mental State Examination (MMSE) score=21-26] and moderate (MMSE score=18-20) AD groups. The rTMS protocols were configured for six cortical areas (both dorsolateral prefrontal and parietal somatosensory associated cortices and Broca's and Wernicke's areas; 10 Hz, 90-110% intensity, and 5 days/week for 6 weeks). Neuropsychological assessments were performed using the AD Assessment Scale-cognitive subscale (ADAS-cog), Clinical Global Impression of Change (CGIC), and MMSE before, immediately after, and 6 weeks after the end of rTMS-COG treatment.ResultsData from 26 AD patients were analyzed in this study. There was no significant interactive effect of time between the groups. The ADAS-cog score in the treatment group was significantly improved compared to the sham group (4.28 and 5.39 in the treatment group vs. 1.75 and 2.88 in the sham group at immediately and 6 weeks after treatment, respectively). The MMSE and CGIC scores were also improved in the treatment group. Based on subgroup analysis, the effect of rTMS-COG was superior for the mild group compared to the total patients, especially in the domains of memory and language.ConclusionsThe present results suggest that rTMS-COG represents a useful adjuvant therapy with cholinesterase inhibitors, particularly during the mild stage of AD. The effect of rTMS-COG was remarkable in the memory and language domains, which are severely affected by AD.

Efficacy of once-daily extended-release topiramate (USL255): A subgroup analysis based on the level of treatment resistance

Results from a previously conducted global phase III study (PREVAIL; NCT01142193) demonstrate the safety and efficacy of once-daily USL255, Qudexy™ XR (topiramate) extended-release capsules, as adjunctive treatment of drug-resistant partial-onset seizures (POSs). In this study, we report a post hoc analysis of PREVAIL data according to patient level of treatment resistance (based upon the number of concomitant antiepileptic drugs [AEDs] and lifetime AEDs) at baseline, with patients defined as either having “highly” drug-resistant seizures (≥2 concurrent AEDs and ≥4 lifetime AEDs) or having “less” drug-resistant seizures (1 concurrent AED or <4 lifetime AEDs) at baseline. For each subgroup, median percent reduction in POS frequency (primary endpoint), responder rate, Clinical Global Impression of Change (CGI-C), and Quality of Life in Epilepsy — Problems (QOLIE-31-P) survey were assessed. Of 249 PREVAIL patients, 115 were classified as having highly drug-resistant seizures (USL255: n=52, placebo: n=63), and 134 were classified as having less drug-resistant seizures (USL255: n=72, placebo: n=62) at baseline. For the primary endpoint, USL255 resulted in significantly better seizure outcomes compared with placebo regardless of drug-resistant status (P=.004 and P=.040 for “highly” and “less”, respectively). Responder rate was also significantly improved in patients with highly drug-resistant group (P=.023). The CGI-C scores indicated significant improvement in both subgroups (P=.003 and P=.013 for “highly” and “less”, respectively). On the QOLIE-31-P, a significant improvement on the seizure worry subscale for the group with less drug-resistant seizures was noted in USL255-treated patients compared with placebo-treated patients (P=.003); the overall score and all other subscales were not significantly different for both subgroups. We conclude that USL255 led to significant improvements across multiple outcomes compared with placebo, including in those classified as having highly drug-resistant seizures to prior treatment, making it a valuable treatment option for patients with epilepsy.

An improved dosage regimen of sertraline hydrochloride in the treatment for premature ejaculation: an 8-week, single-blind, randomized controlled study followed by a 4-week, open-label extension study

This study aimed at evaluating the safety and efficacy of an improved dosage regimen of sertraline in patients with premature ejaculation (PE) and to examine whether the premature ejaculation diagnostic tool (PEDT) can be used as a measure of treatment response in these patients. A total of 218 PE patients were randomized into control (n=61) and treatment (n=157) groups to receive mycelium of cordyceps sinensis C4 and sertraline 50mg daily for 8weeks, respectively. Following this blinded stage, sixty-three patients chose to take sertraline 100mg daily for an additional 4-week period, and 80 other patients continued treatment with sertraline 50mg. Main outcome measures include intravaginal ejaculatory latency time (IELT), PEDT score and Clinical Global Impression of Change (CGIC) score. At weeks 4 and 8, mean IELT of patients who subsequently chose to take 100mg of sertraline was significantly lower than that of patients who continued taking 50mg of sertraline, although the IELT value was comparable between the two groups of patients at baseline. However, with an additional 4-week treatment, the mean IELT increased significantly more in the 100-mg group than in the 50-mg continuation group. Similar results were also obtained in the analyses of the PEDT and CGIC scores. Both regimens were well tolerated, and relapse rate did not differ significantly between the two groups. These findings suggest that PE patients not responding to an 8-week treatment with sertraline 50mg can benefit from an additional 4-week treatment with sertraline 100mg and that the PEDT may be a valid measure of treatment response in PE patients.

Repetitive transcranial magnetic stimulation combined with cognitive training is a safe and effective modality for the treatment of Alzheimer’s disease: a randomized, double-blind study

Cortical excitability can be modulated using repetitive transcranial magnetic stimulation (rTMS). Previously, we showed that rTMS combined with cognitive training (rTMS-COG) has positive results in Alzheimer's disease (AD). The goal of this randomized double-blind, controlled study was to examine the safety and efficacy of rTMS-COG in AD. Fifteen AD patients received 1-h daily rTMS-COG or sham treatment (seven treated, eight placebo), five sessions/week for 6weeks, followed by biweekly sessions for 3months. The primary outcome was improvement of the cognitive score. The secondary outcome included improvement in the Clinical Global Impression of Change (CGIC) and Neuropsychiatric Inventory (NPI). There was an improvement in the average ADAS-cog score of 3.76 points after 6weeks in the treatment group compared to 0.47 in the placebo group and 3.52 points after 4.5months of treatment, compared to worsening of 0.38 in the placebo (P=0.04 and P=0.05, respectively). There was also an improvement in the average CGIC score of 3.57 (after 6weeks) and 3.67 points (after 4.5months), compared to 4.25 and 4.29 in the placebo group (mild worsening) (P=0.05 and P=0.05, respectively). NPI improved non-significantly. In summary, the NeuroAD system offers a novel, safe and effective therapy for improving cognitive function in AD.

Efficacy and Safety of Switching from Oral Cholinesterase Inhibitors to the Rivastigmine Transdermal Patch in Patients with Probable Alzheimer's Disease

Background and PurposeThe goal of this study was to estimate the efficacy and safety of the rivastigmine transdermal patch in patients with probable Alzheimer's disease (AD) who cannot tolerate or do not respond to oral cholinesterase inhibitors (ChEIs).MethodsA 24-week, prospective, open-label, single-arm, multicenter study was conducted from June 2009 to June 2010 in patients with probable AD. The enrolled patients had either a poor response or a decline in global function after treatment with oral ChEIs, or they were not able to tolerate treatment with oral ChEIs due to adverse events such as nausea or vomiting. A poor response was defined as a decrease of at least 2 points on the Korean version of the Mini-Mental State Examination (K-MMSE) within the previous 6 months (the decline in global function was determined by the investigator or caregiver). The efficacy of treatment was assessed using a follow-up Clinical Global Impression of Change (CGIC) assessment and K-MMSE conducted after 24 weeks, and safety was measured by the occurrence of adverse events and patient disposition.ResultsIn total, 164 patients aged 74.7±7.52 years (mean±SD) and with 5.12±3.64 years of education were included. The study was completed by 70% of the patients (n=116), with 12.2% discontinuing due to adverse events. The most frequently reported adverse events (11%) were skin lesions, such as erythema or itching, followed by gastrointestinal problems (1.2%). Either an improvement or no decline in CGIC scores was reported for 82% of the patients.ConclusionsThe immediate switching of patients from an oral ChEI to the rivastigmine transdermal patch without a washout period was safe and well tolerated by the probable-AD patients in this study.

Memantine in patients with Parkinson's disease dementia or dementia with Lewy bodies: a double-blind, placebo-controlled, multicentre trial

Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are common forms of dementia that substantially affect quality of life. Currently, the only treatment licensed for PDD is rivastigmine, and there are no licensed treatments for DLB. We aimed to test the safety and efficacy of the N-methyl D-aspartate (NMDA) receptor antagonist memantine in patients with PDD or DLB. We did a parallel-group, 24-week, randomised controlled study of memantine (20 mg per day) versus placebo at four psychiatric and neurological outpatient clinics in Norway, Sweden, and the UK during 2005-08. Patients were included if they fulfilled the UK Parkinson's Disease Society Brain Bank clinical diagnostic criteria for Parkinson's disease (PD) and developed dementia according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM IV) criteria at least 1 year after the onset of motor symptoms (PDD) or met the revised consensus operationalised criteria for DLB. Patients were assigned to a computer-generated randomisation list. All physicians who had contact with patients were masked to treatment allocation. The primary outcome measure was clinical global impression of change (CGIC), which ranged from 1 to 7 points, and a low score means a better outcome. Analysis was by intention to treat based on the last observation carried forward. This trial is registered, number ISRCTN89624516. 72 patients with PDD or DLB were randomly assigned and started treatment: 34 with memantine and 38 with placebo. 56 (78%) completed the study. All withdrawals were owing to adverse events, but the proportion of withdrawals was similar in both groups. At week 24 the patients in the memantine group had better CGIC scores than those taking placebo (mean difference 0.7, 95% CI 0.04-1.39; p=0.03). With the exception of improved speed on attentional tasks in the memantine group (a quick test of cognition [AQT] form: difference 12.4, 95% CI 6.0-30.9; p=0.004), there were no significant differences between the groups in secondary outcome measures. Patients with DLB or PDD might benefit from treatment with memantine, which was well tolerated. Large-scale studies are now required to confirm our preliminary findings. The Western Norway Regional Health Authority; H Lundbeck A/S.

Objective Versus Subjective Assessment of Methylphenidate Response

Subjective improvement-assessment in attention deficit/hyperactivity disorder (ADHD), following a single dose of methylphenidate (MPH) was compared to performance on the Test-of-Variables-of-Attention (TOVA). Self-perception was assessed with the clinical-global-impression-of-change (CGI-C). Participants included 165 ADHD subjects (M:F ratio 67%:33%) aged 5-18 (11.09 +/- 3.43) years. TOVA was administered before and after MPH challenge (0.3 mg/kg). Self-perception CGI-C scores were compared to the TOVA scores. An inverse correlation was found only between CGI-C and the TOVA-Commission-scores (r = -0.326, p < 0.001). We thus conclude that subjective reports are too unreliable to be used in order to assess MPH benefit in ADHD pediatric populations.

Quetiapine treatment for behavioural and psychological symptoms of dementia in Alzheimer's disease patients: a 6‐week, double‐blind, placebo‐controlled study

Treating elderly patients with Alzheimer's disease (AD) and behavioral and psychological symptoms of dementia (BPSD) is challenging due to the increased risk of iatrogenic movement disorders with old neuroleptics and the seemingly increasing risk of cardiovascular events with newer atypical agents. Quetiapine is an atypical antipsychotic agent that warrants further investigation. To assess tolerability, safety, and clinical benefit of quetiapine in AD patients with BPSD. AD patients with BPSD participated in a 6-week randomized, double-blind, placebo-controlled trial. Quetiapine was increased on the basis of clinical response and tolerability. Primary efficacy assessments included the Neuropsychiatric Inventory (NPI) and Clinical Global Impression of Change (CGI-C). Secondary efficacy measures included the Mini-Mental State Examination (MMSE), the Simpson-Angus Scale (SAS) and the Abnormal Involuntary Movement Scale (AIMS). Forty patients (26 women), mean age 82.2 (SD 6.4) years were enrolled, 27 completed treatment. Median dose of quetiapine was 200 mg/day. Significant NPI total scores reductions (79% for placebo and 68.5% for quetiapine) were observed. The CGI-C score decreased significantly in the quetiapine group (p = 0.009 at 6 weeks) and did not change significantly in the placebo group (p = 0.48). The MMSE, AIMS, SAS scores and adverse events did not differ significantly between the two arms. Quetiapine did not significantly improve psychosis scores. It did not cause cognitive and motor deterioration. These results might possibly be due to small sample size.

Rater-blinded, Prospective Comparison

To compare the safety and efficacy of quetiapine versus clozapine for the treatment of psychosis in patients with Parkinson's disease (PD). Twenty-seven patients with PD and recent-onset psychosis were randomly allocated to 2 arms of 22 weeks' treatment with quetiapine or clozapine after 2 weeks of adjustment of antiparkinsonian medications. Assessment was done by a blinded neuropsychologist using the Clinical Global Impression of Change (CGIC) questionnaire and the Neuropsychiatric Inventory (NPI). Mixed-effect models were used to compare CGIC and Neuropsychological Inventory scores over time between the 2 groups. Both drugs were equally effective based on the CGIC. Clozapine had a trend over quetiapine in controlling the frequency of hallucinations (P = 0.097) and a significant advantage in reducing delusions (P = 0.011). However, one patient in the clozapine arm developed leukopenia. None of the drugs worsened parkinsonism. Clozapine and quetiapine are effective atypical neuroleptics for the treatment of psychotic symptoms in PD. Clozapine had greater efficacy in reducing hallucinations and delusions frequency, but its use is associated with an increased risk of leukopenia.

Tetrabenazine Treatment in Movement Disorders

Tetrabenazine (TBZ) is a catecholamine depletor used for the treatment of a variety of movement disorders. The purpose of this study was to assess the efficacy of TBZ in a retrospective chart review in 3 tertiary care movement disorders centers over long-term treatment. Of 150 patients to whom TBZ was prescribed, 118 were followed up and assessed using the Clinical Global Impression of Change (CGIC), (-3 to +3), a composite grade from a patient and caregiver scale over variable periods. The patients had a variety of hyperkinetic movement disorders including dystonia (generalized and focal: axial, Meige syndrome, torticollis, blepharospasm, bruxism), Huntington disease (HD) or other choreas, tardive dyskinesia (TD) or akathisia, and Tourette syndrome. Mean patient age was 48.8 +/- 18.7 years; 48 were men (40.7%) with a mean disease duration of 93 months. The mean follow-up time was 22 months and the mean TBZ dose was 76.2 +/- 22.5 mg/d (median 75 mg, range 25-175 mg/d). The mean CGIC score was +1 (mild improvement). The group of patients who scored +3 on the CGIC (very good improvement) represented 18.6% (n = 22) of all patients. They had HD or other types of chorea 7.6% (n = 9), facial dystonia/dyskinesia (n = 7, 5.9%), 1 with TD, 2 with trunk dystonia, 2 with Tourette syndrome, and 1 with tardive akathisia. This group had the longest treatment duration and received a mean TBZ dose of 70.5 mg/d (median 75 mg/d) for a mean of 25.4 +/- 21.3 months. The report concludes that TBZ is a moderately effective treatment of a large variety of hyperkinetic movement disorders, with excellent effects in a subgroup with chorea and facial dystonia/dyskinesias.

Quantifying behavioral disturbance in Alzheimer's disease patients

In the course of a four-month study of interventions for behavioral disturbances in Alzheimer's disease (AD) patients, the following assessment instruments were examined for validity: the clinical global impression of change (CGIC), Cohen-Mansfield agitation inventory (CMAI); CERAD behavioral rating scale for dementia (BRSD), revised memory and behavioral problems checklist (RMBPC) and the agitated behavior in dementia scale (ABID). The four specific behavioral/agitation scales had excellent cross-sectional and longitudinal correlations with each other, suggesting high validity, but changes as indicated by CGIC scores did not correlate well with change scores on the other instruments. We conclude that specific behavioral instruments are preferable to the more general CGIC for detecting and quantifying behavioral disturbances in AD patients.