Clinical Global Impression Of Change Research Articles

Ameliorative Effects Of N-Acetylcysteine As Adjunct Therapy On Symptoms Of Painful Diabetic Neuropathy.

PurposePainful diabetic neuropathy (PDN) is a variant of diabetic peripheral neuropathy which is highly prevalent and distressing in diabetic patients. Despite its high burden, the optimal treatment of PDN has remained a clinical challenge. To explain the emergence and maintenance of PDN, increasing attention has been focused on dimensions of inflammation and oxidative toxic stress (OTS). Accordingly, the aim of this study was to investigate the effects of oral N-acetylcysteine (NAC), an agent with known anti-oxidant and anti-inflammatory effects, as an adjunct therapy in patients suffering from PDN.Patients and methods113 eligible patients with type 2 diabetes suffering from PDN were randomly assigned to either the pregabalin + placebo or pregabalin + NAC group for 8 weeks (pregabalin at a dose of 150 mg per day, NAC and matched placebo at doses of 600 mg twice a day). Mean pain score was evaluated at baseline, week 1, 2, 4, 6, and 8 of the study based on the mean 24 hr average pain score, using an 11-point numeric rating scale (NRS). As secondary efficacy measures, mean sleep interference score (SIS) resulting from PDN, responder rates, Patient Global Impression of Change (PGIC), Clinical Global Impression of Change (CGIC), and safety were also assessed. Additionally, serum levels of total antioxidant capacity (TAC), total thiol groups (TTG), catalase activity (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), nitric oxide (NO), and malondialdehyde (MDA) were assessed at baseline and at the end of the study.ResultsNinety patients completed the eight-week course of the study. The decrease in mean pain scores and mean sleep interference score in pregabalin + NAC group was greater in comparison with pregabalin + placebo group (p value<0.001 in both conditions). Moreover, more responders (defined as ≥50% reduction in mean pain score from baseline to end-point) were observed in the pregabalin + NAC group, in comparison with pregabalin + placebo group (72.1% vs 46.8%). More improvement in PGIC and CGIC from baseline to the end of the study was reported in pregabalin + NAC group. Oral NAC had minimal adverse effects and was well tolerated in almost all patients. Furthermore, in respect to OTS biomarkers, adjuvant NAC significantly decreased serum level of MDA and significantly increased serum levels of SOD, GPx, TAC, and TTG.ConclusionThe pattern of results suggests that compared to placebo and over a time period of 8 weeks, adjuvant NAC is more efficacious in improving neuropathic pain associated with diabetic neuropathy than placebo. Ameliorative effects of NAC on OTS biomarkers demonstrated that NAC may alleviate painful symptoms of diabetic neuropathy, at least in part by its antioxidant effects.

Escitalopram for agitation in Alzheimer's disease (S-CitAD): Methods and design of an investigator-initiated, randomized, controlled, multicenter clinical trial

IntroductionAlzheimer's disease (AD) is a disabling, common cause of dementia, and agitation is one of the most common and distressing symptoms for patients with AD. Escitalopram for agitation in Alzheimer's disease (S-CitAD) tests a novel, clinically derived therapeutic approach to treat agitation in patients with AD. MethodsS-CitAD is a NIH-funded, investigator-initiated, randomized, multicenter clinical trial. Participants receive a structured psychosocial intervention (PSI) as standard of care. Participants without sufficient response to PSI are randomized to receive 15 mg escitalopram/day or a matching placebo in addition to PSI. Primary outcome is the Modified Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (mADCS-CGIC). DiscussionS-CitAD will provide information about a practical, immediately available approach to treating agitation in patients with AD. S-CitAD may become a model of how to evaluate and predict treatment response in patients with AD and agitation as a neuropsychiatric symptom (ClinicalTrials.gov Identifier: NCT03108846).

Efficacy of opicapone in Parkinson’s disease patients with ‘early’ motor fluctuations: Patient and clinical global impression of change from the BIPARK-I double-blind experience

Efficacy of opicapone in Parkinson’s disease patients with ‘early’ motor fluctuations: Patient and clinical global impression of change from the BIPARK-I double-blind experience

Deep brain stimulation for orthostatic tremor: A single-center case series.

Orthostatic tremor (OT) is a high-frequency weight-bearing tremor of the legs and trunk associated with progressive disability and is often refractory to medications. Case reports suggest that thalamic deep brain stimulation (DBS) is effective. We report 5 female patients with medication-refractory OT who underwent bilateral thalamic DBS at the Mayo Clinic and assess factors associated with a successful DBS outcome. Demographic, clinical, electrophysiology, and DBS data were abstracted. Outcomes were change in tremor-onset latency, standing time, standing ADLs, and patient and clinician global impression of change (PGIC; CGIC). All 5 patients had improved standing time (72 vs 408 seconds, p ≤ 0.001) and improved standing ADLs after surgery, without change in tremor-onset latency (16 vs 75 seconds, p = 0.14). Maximal benefit was reached up to 3 years after surgery and sustained for up to 6 years. CGIC was "much improved" in all; PGIC was "much improved" in 4 and "minimally improved" in 1. There were no major complications. Postoperative electrophysiology (n = 1) showed lower tremor amplitude and slower tremor ramp-up on vs off stimulation. Bilateral thalamic DBS improved OT symptoms with benefit lasting up to 6 years. A modest increase in standing time of several minutes was associated with meaningful improvement in standing ADLs. Microlesional effect and bilateral stimulation are likely favorable features, while baseline standing time of several minutes may be unfavorable. These findings may inform clinician and patient counseling and require confirmation in larger studies.

Minimal clinically important change in patients with cervical dystonia: Results from the CD PROBE study

ObjectiveTo determine the minimal clinically important change (MCIC) on Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) scores using data from Cervical Dystonia Patient Registry for Observation of OnabotulinumtoxinA Efficacy (CD PROBE), which captured real-world practices and outcomes. MethodsChanges in the baseline TWSTRS scores (point and percentage changes) were compared to changes in the Patient and Clinician Global Impression of Change (PGIC and CGIC) ratings. Using logistic regression, the discrimination of the model was determined. ResultsAmong the 479 patients who completed all TWSTRS assessments, the mean TWSTRS Total score significantly decreased from baseline (39.2) to the final visit (27.1) (P < .0001). TWSTRS Total score point changes that compared with PGIC assessments “very much improved,” “much improved” or better, and “minimally improved” or better were −11, −9, and −8, respectively, and were similar to previously published changes (ie, a decrease of ≥10 points). TWSTRS Total score data met indicators of good cutoffs for discrimination of the model including ≥70% percentage of outcomes correctly classified when compared with PGIC ratings. The TWSTRS Total score mapped to PGIC and CGIC ratings better than any TWSTRS subscale score. ConclusionsThe MCIC for improvement was ≥8 points based on mean TWSTRS Total scores in patients with cervical dystonia when compared against the patient-based evaluation of benefit (PGIC).

The Oxytocin Antagonist Cligosiban Prolongs Intravaginal Ejaculatory Latency and Improves Patient-Reported Outcomes in Men with Lifelong Premature Ejaculation: Results of a Randomized, Double-Blind, Placebo-Controlled Proof-of-Concept Trial (PEPIX)

IntroductionCligosiban is an orally administered oxytocin receptor antagonist being developed to treat premature ejaculation (PE). AimTo determine the safety and efficacy of cligosiban capsules (dose range 400–800 mg) to improve intravaginal ejaculation latency time (IELT) and patient-reported outcomes in men with severe lifelong PE. MethodsPatients recorded details of at least 4 sexual intercourse events during a 4-week run-in period, after which they underwent baseline assessments. Patients were eligible for the study if they rated their control of ejaculation as poor/very poor and their stopwatch-assessed IELT was ≤1 minute in ≥75% of intercourse attempts. Eligible patients were randomized to an 8-week treatment period with double-blind cligosiban or placebo (to be taken 1 to 6 hours prior to sexual activity). The starting dose was 400 mg (not more than 1 dose per day) which could be increased to 800 mg after 2 and/or 4 weeks of treatment. Assessments were conducted at 2, 4, and 8 weeks. Main Outcome MeasureEfficacy measures were comprised of IELT, self-rating of ejaculation control and ejaculation-related distress (recorded in an electronic diary after each intercourse attempt), premature ejaculation profile, and the Clinical Global Impression of Change. ResultsThe mean ratio of fold change from baseline in IELT to the last 4 weeks of treatment (cligosiban/placebo) was 1.9 compared to a baseline of 1.0 (P = .0079). The mean increase in IELT from baseline to the last 4 weeks of treatment was 61.0 seconds for cligosiban, which was significantly different from (and 3.6-fold greater than) the mean increase of 16.4 seconds for placebo (P = .0086). Statistically significant improvements in ejaculation control and ejaculation-related personal distress scores were also observed for cligosiban compared to little or no change with placebo. Cligosiban was generally well tolerated, with no serious or severe adverse events or other safety parameters. Clinical ImplicationsThis proof-of-concept study demonstrated the potential for cligosiban, an oxytocin antagonist, to successfully treat symptoms of severe lifelong PE. Strengths and LimitationsThis was a Phase II, randomized, double-blind, placebo-controlled study that was adequately powered to detect a clinically meaningful difference in change in IELT between cligosiban and placebo. Larger studies will be needed to confirm these findings, determine the optimal dose of cligosiban and assess efficacy in men with acquired PE. ConclusionsCligosiban was well tolerated, and resulted in significant benefits in both objective and subjective measures of ejaculatory control in men with lifelong PE and therefore offers significant potential as an on-demand, orally administered agent for the treatment of PE.McMahon C, Althof S, Rosen R, et al. The Oxytocin Antagonist Cligosiban Prolongs Intravaginal Ejaculatory Latency and Improves Patient-Reported Outcomes in Men with Lifelong Premature Ejaculation: Results of a Randomized, Double-Blind, Placebo-Controlled Proof-of-Concept Trial (PEPIX). J Sex Med 2019; 16:1178–1187.

The Oxytocin Antagonist Cligosiban Fails to Prolong Intravaginal Ejaculatory Latency in Men with Lifelong Premature Ejaculation: Results of a Randomized, Double-Blind, Placebo-Controlled Phase IIb trial (PEDRIX)

IntroductionCligosiban is an orally administered, centrally penetrant oxytocin receptor antagonist being developed to treat premature ejaculation (PE). AimTo determine the efficacy of 3 dose levels of cligosiban caplets to prolong intravaginal ejaculation latency time (IELT) and improve patient-reported outcomes in men with lifelong PE. MethodsPatients recorded details of at least 4 sexual intercourse events during a 4-week run-in period, after which they underwent baseline assessments. Patients were eligible for the study if their stopwatch-assessed IELT was ≤1 minute in ≥75% of intercourse attempts and if they met other diagnostic criteria for lifelong PE. Eligible patients (target 220 evaluable) were randomized to double-blind cligosiban 400, 800, or 1200 mg or matching placebo caplets (to be taken 1 to 6 hours prior to sexual activity). Assessments were conducted at 2, 4, and 8 weeks. Main Outcome MeasureEfficacy measures were comprised of IELT, self-rating of ejaculation control and ejaculation-related distress (recorded in an electronic diary after each intercourse attempt), premature ejaculation profile, Patient’s Global Impression of Severity, and the Clinical Global Impression of Change. ResultsThere were no clinically or statistically significant differences between cligosiban (at any dose level) and placebo for the primary endpoint (change in geometric IELT) or any of the secondary endpoints. Cligosiban was well tolerated with a side-effect profile similar to placebo. Clinical ImplicationsThis Phase IIb study failed to demonstrate the potential for cligosiban, an oxytocin antagonist, to successfully treat symptoms of severe lifelong PE at doses up to 1200 mg. Strengths and LimitationsThis was a Phase IIb, randomized, double-blind, placebo-controlled study that was adequately powered but failed to detect a clinically meaningful or statistical difference in change in IELT between cligosiban at 3 dose levels and placebo. This is in contrast to a similarly designed proof-of-concept study where cligosiban was flexibly dosed at doses up to 800 mg and did demonstrate clinically meaningful and statistically significant changes in efficacy parameters. The reasons for this disparity are not known. ConclusionsCligosiban was well tolerated but failed to demonstrate efficacy for the treatment of men with lifelong PE at doses up to 1200 mg.Althof S, Osterloh IH, Muirhead GJ, et al. The Oxytocin Antagonist Cligosiban Fails to Prolong Intravaginal Ejaculatory Latency in Men with Lifelong Premature Ejaculation: Results of a Randomized, Double-Blind, Placebo-Controlled Phase IIb trial (PEDRIX). J Sex Med 2019; 16:1188–1198.

Long-term effects on body functions, activity and participation of hemiplegic patients in equino varus foot deformity surgical correction followed by immediate rehabilitation. A prospective observational study

ABSTRACTBackground: Functional surgery is an effective approach in the treatment of the rigid equinovarus foot deformity (EVFD). This must be associated with early rehabilitation treatments (ERTs) to prevent muscle rearrangements due to immobilization.Objectives: To assess the effects of EVFD surgical correction in adult stroke patients, when assessed according to the ICF domains.Methods: Variables from 24 adult chronic stroke survivors with EVFD surgical correction followed by ERT, age 55 ± 13 years, affected side 12L/12R, time from lesion 5 ± 4 years were analyzed. Body function domain: pain (NPRS), walking speed, clinical global impression of change (cGIC). Activity domain: Rivermead Mobility Index (RMI), FAC, and 6 min walking test (6MWT). Participation domain: Walking Handicap Scale (WHS). Patients were assessed before (T0), one (T1), three (T2) and twelve (T3) months after surgery by a single assessor.Results: All variables but the 6MWT significantly improved (Wilcoxon test, p < .05) at T1 or T2 and this remained until the 12-months mark. Since T1, all patients reached and maintained a supervised independent walking (FAC≥3) and all those wearing an AFO stopped using it. The median cGCI was “much improved” at T1, with a “further minimal improvement” at T3. This was not associated with the improvement measured by both FAC, and WHS (Chi-square test, p = .20 and p = .36, respectively).Conclusions: Functional surgery combined with ERT is effective in improving the patients’ condition according to all ICF domains. Both subjective and objective assessments have to be used when assessing these patients.

Determinants of Early Response to Low-Intensity Extracorporeal Shockwaves for the Treatment of Vasculogenic Erectile Dysfunction: An Open-Label, Prospective Study

The aim of this study was to expand existing literature on the effects of cardiovascular risk factors on the outcome of low-intensity extracorporeal shockwaves therapy (LIESWT), and to evaluate the role of hormone concentrations. Twenty patients with long-standing, PDE5i-resistant, vasculogenic erectile dysfunction (VED) were treated with six weekly sessions of LIESWT (9000 pulses). After a three-week break, four poor responders underwent another six weekly sessions. Rigidity score (RS) questionnaire was administered at baseline (T0), last session (T1), and three months after LIESWT (T2), while the Improvement component of the Clinical Global Impression of Change (CGIC-I) and the International Index of Erectile Function-5 (IIEF-5) questionnaires were administered at T1 and T2, and at T0 and T2, respectively. At T0 serum luteinizing hormone (LH), testosterone, sex hormone binding globulin (SHBG), calculated free testosterone, and prolactin levels were also recorded. At T1 and T2, 12/20 (60%) and 11/20 (55%) patients reached a RS ≥ 3; 16/20 (80%) and 13/20 (65%) improved their erections variably. Testosterone levels correlated positively with CGIC-I at T1. Patients < 65 years and those nonhypercholesterolemic had higher RS at T1 and T2. Age correlated negatively with RS at T1 and T2. At T0, diabetic patients had lower IIEF-5 scores, but those with RS ≥ 3 at T1 had higher IIEF-5 compared to those with RS < 3. Also, diabetes duration correlated inversely with IIEF-5 at T0. At T2, IIEF-5 improved significantly by an average of 2.8-points. We confirm safety and effectiveness of LIESWT for the treatment of VED. Age ≥ 65 years, diabetes, and hypercholesterolemia influence early and negatively the outcome of LIESWT.

Optimal Muscle Selection for OnabotulinumtoxinA Injections in Poststroke Lower-Limb Spasticity: A Randomized Trial.

The aim of the study was to identify optimal muscle selection patterns for onabotulinumtoxinA treatment of poststroke lower-limb spasticity. Adults with poststroke lower-limb spasticity (ankle Modified Ashworth Scale ≥3) were randomized to onabotulinumtoxinA (300 U, mandatory ankle plantar flexors; ≤100 U, optional lower-limb muscles) or placebo. Post hoc analysis assessed the impact of muscle selection patterns on ankle Modified Ashworth Scale and physician-assessed Clinical Global Impression of Change based on change from baseline to average of weeks 4/6 versus placebo. Among 468 patients randomized, onabotulinumtoxinA improved ankle Modified Ashworth Scale (-0.81 vs -0.61, P = 0.01) and Clinical Global Impression of Change (0.86 vs 0.65, P = 0.012) versus placebo. Injection of mandatory muscles alone was not sufficient in improving ankle Modified Ashworth Scale (P = 0.255) or Clinical Global Impression of Change (P = 0.576) versus placebo but was adequate 24 mos or less after stroke (Modified Ashworth Scale, -1.13 vs -0.62, P = 0.019; Clinical Global Impression of Change, 1.24 vs 0.68, P = 0.006). Additional injections into toe muscles (flexor digitorum longus, flexor hallucis longus) improved ankle Modified Ashworth Scale (-0.98 vs -0.52, P = 0.002) and Clinical Global Impression of Change (0.80 vs 0.38, P = 0.023) versus placebo regardless of time since stroke. OnabotulinumtoxinA was well tolerated, with no new safety findings. Post hoc analyses suggested additional injections of onabotulinumtoxinA into toe flexors improved ankle Modified Ashworth Scale and Clinical Global Impression of Change scores versus mandatory muscles alone overall and with treatment initiation more than 24 mos after stroke.

PND32 EVALUATION OF GLOBAL IMPROVEMENT AND LIFETIME COSTS OF TREATING TARDIVE DYSKINESIA SHOWS TREATMENT WITH VALBENAZINE DOMINATES DEUTETRABENAZINE

To evaluate the cost-effectiveness of tardive dyskinesia (TD) treatment using a model that assessed global improvement after 1 year, as well as the effects of TD on managing underlying psychiatric diseases and overall survival. A discretely integrated condition event model was developed to assess cost-effectiveness of TD treatment in a synthetic patient population derived from the distributions of the characteristics of the KINECT 3 (NCT02274558) trial participants. Clinical inputs included response data from relevant studies (KINECT 3 extension, KINECT 4 [NCT02405091], AIM-TD [NCT02291861], ARM-TD [NCT02195700]). Other inputs were taken from the published literature or other public sources. Patients received valbenazine or deutetrabenazine for 48 weeks and treatment response was assessed periodically using the Clinical Global Impression of Change –Tardive Dyskinesia (CGI-TD) scale, with response defined as a score ≤2 (“much improved” or “very much improved”). Participants achieving response at a given visit experienced improved utility until their next assessment. Those not responding after one year of treatment discontinued. Responders at 1 year were assumed to maintain response indefinitely and remained on treatment until death. The model evaluated treatment response, life years, quality-adjusted life years (QALYs), psychiatric condition relapses, time employed, and costs. Patients treated with valbenazine or deutetrabenazine had better response to treatment, increased survival, improved quality of life, decreased disease management costs, and more time employed compared with no treatment. Compared with no treatment, valbenazine cost $198,243 per QALY; however, valbenazine dominated deutetrabenazine, with higher response rates at 1 year (79% vs. 66%), more QALYs gained (10.2 vs. 9.7 years), and lower lifetime costs ($748,053 vs. $828,298). Treatment of TD with valbenazine or deutetrabenazine was associated with higher response rates. Over a lifetime horizon, valbenazine was associated with better clinical and economic outcomes than deutetrabenazine.

A proposed definition of remission from chronic pain, based on retrospective evaluation of 24-month outcomes with spinal cord stimulation

ABSTRACTObjective: In the treatment of chronic diseases, remission is commonly used as a meaningful treatment goal, synonymous with the absence of significant clinical signs and symptoms of a disease, but not representing a cure. The objective of this paper is to propose a definition for remission for use as an outcome to evaluate the long-term efficacy of therapies for chronic pain.Methods: Data from a randomized clinical trial (NCT01609972) testing the efficacy of spinal cord stimulation in low back and leg pain subjects was used to evaluate the association between pain and functional outcomes and identify the cut-off value to predict remission. Available data over 24-month assessment period included visual analog score (VAS), disability (Oswestry Disability Index [ODI]), patient and clinician global impression of change (PGIC and CGIC), and patient satisfaction. Cluster analysis, Pearson’s correlation coefficients, sensitivity, and specificity analyses were used to evaluate its utility in predicting higher patient functionality and satisfaction.Results: Though the term remission has been used in the chronic pain field, a consistent definition has not been previously established. Based on the analysis of the clinical data, we propose that a sustained (≥6 months) pain score of ≤3.0 cm out of 10 cm on VAS be defined as remission. Applying this definition to the clinical trial data: subjects in remission at 24 months versus non-remitters were significantly more likely to be in the highest functional category of minimally disabled according to the ODI (31.5 vs. 8.2%, respectively, p = 0.001), and be ‘very satisfied’ (75.7 vs 22.6%, respectively, p < 0.001).Conclusions: The validity of the proposed definition of remission is supported by the persistence of remission in this study group, and its correspondence with patient satisfaction, and reduced disability. Further evaluation of the definition using clinical data from other long-term studies is needed.Trial registration: ClinicalTrials.gov identifier: NCT01609972.

Effect of premature ejaculation desensitisation therapy combined with dapoxetine hydrochloride on the treatment of primary premature ejaculation.

To evaluate the overall treatment benefits of premature ejaculation desensitisation therapy combined with 30mg dapoxetine hydrochloride treatment on patients with primary premature ejaculation (PPE). Ninety-nine PPE patients were randomly divided into two groups at the ratio of 2:1. Sixty-six PPE patients received premature ejaculation desensitisation therapy accomplished by Weili Automatic Semen Collection-Penis Erection Detection and Analysis workstation (WLJY-2008) combined with 30mg dapoxetine hydrochloride treatment (DTCD group), and another 33 patients received 30mg dapoxetine hydrochloride-only treatment (DO group). Intravaginal ejaculation latency time (IELT) and premature ejaculation profile (PEP) were recorded before and during the treatment, and clinical global impression of change (CGIC) in PPE was recorded at the fourth week and the end of the treatment and the items. In both groups were significantly improved (p<0.0001) in IELT, PEP and CGIC for premature ejaculation compared with baseline, and DTCD treatment showed a more significant improvement on PPE patients in the items compared with DO treatment (p<0.05). Thus, premature ejaculation desensitisation combined with dapoxetine therapy may be a better choice for improving premature ejaculation with PPE.

Pharmacological Management of Dementia with Lewy Bodies.

Dementia with Lewy bodies (DLB) is a complex disease that involves a variety of cognitive, behavioral and neurological symptoms, including progressive memory loss, visual hallucinations, parkinsonism, cognitive fluctuations and rapid eye movement sleep behavior disorder (RBD). These symptoms may appear in varying combinations and levels of severity in each patient who is seen in the clinic, making diagnosis and treatment a challenge. DLB is the third most common of all the neurodegenerative diseases behind both Alzheimer’s disease and Parkinson’s disease (PD). The median age of onset for DLB (76.3 years) is younger than that seen in PD dementia (81.4 years). New pathological studies have shown that most DLB patients have variable amounts of Alzheimer’s changes in their brains, explaining the wide variability in this disease’s clinical presentation and clinical course. This review discusses the three cholinesterase inhibitors that have been shown to be effective in managing the cognitive and behavioral symptoms of DLB: rivastigmine, galantamine and donepezil. Memantine is able to improve clinical global impression of change in those with mild to moderate DLB. Levodopa can treat the parkinsonism of some DLB patients, but the dose is often limited due to the fact that it can cause agitation or worsening of visual hallucinations. A recent phase 2 clinical trial showed the benefit of zonisamide when it is added as an adjunct to levodopa for treating DLB parkinsonism. While atypical antipsychotic drugs may not always be helpful as monotherapy in managing the agitation associated with DLB, low doses of valproic acid can be effective when added as an adjunct to drugs like quetiapine. Pimavanserin may prove to be a useful treatment for psychosis in DLB patients, but like other antipsychotic drugs that are used in dementia patients, there is a small increased risk of mortality. RBD, which is a common core clinical feature of DLB, can be managed with either melatonin or clonazepam. Two agents targeting alpha-synuclein (NPT200-11 and ambroxol) currently hold promise as disease-modifying therapies for DLB, but they are yet to be tested in clinical trials. An agent (E2027) that offers hope of neuroprotection by increasing central cyclic guanosine monophosphate (cGMP) levels is currently being examined in clinical trials in DLB patients.

The Effect of a Multicomponent Intervention on Quality of Life in Residents of Nursing Homes: A Randomized Controlled Trial (COSMOS)

ObjectivesTo investigate if the multicomponent intervention of the COSMOS trial, combining communication, systematic pain management, medication review, and activities, improved quality of life (QoL) in nursing home patients with complex needs. DesignMulticenter, cluster-randomized, single-blinded, controlled trial. SettingThirty-three nursing homes with 67 units (clusters) from 8 Norwegian municipalities. ParticipantsSeven hundred twenty-three patients with and without dementia (≥65 years) were cluster randomized to usual care or intervention in which health care staff received standardized education and on-site training for 4 months with follow-up at month 9. MeasurementsPrimary outcome was change in QoL as measured by QUALIDEM (QoL dementia scale); QUALID (QoL late-stage dementia scale), and EQ-VAS (European QoL–visual analog scale) from baseline to month 4. Secondary outcomes were activities of daily living (ADL), total medication, staff distress, and clinical global impressions of change (CGIC). ResultsDuring the active intervention, all 3 QoL measures worsened, 2 significantly (QUALID P = .04; QUALIDEM P = .002). However, follow-up analysis from month 4 to 9 showed an intervention effect for EQ-VAS (P = .003) and QUALIDEM total score (P = .01; care relationship P = .02; positive affect P = .04, social relations P = .01). The secondary outcomes of ADL function, reduction of medication (including psychotropics) and staff distress, improved significantly from baseline to month 4. Intervention effects were also demonstrated for CGIC at month 4 (P = .023) and 9 (P = .009), mainly because of deterioration in the control group. Conclusion and implicationsTemporarily, the QoL decreased in the intervention group, leading to our hypothesis that health care staff may be overwhelmed by the work-intensive COSMOS intervention period. However, the decrease reversed significantly during follow-up, indicating a potential learning effect. Further, the intervention group improved in ADL function and received less medication, and staff reported less distress and judged COSMOS as able to bring about clinically relevant change. This suggests that nonpharmacologic multicomponent interventions require long follow-up to ensure uptake and beneficial effects.

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.

A 24-week double-blind placebo-controlled study of the efficacy and safety of the AMPA modulator S47445 in patients with mild to moderate Alzheimer's disease and depressive symptoms

IntroductionS47445 is a novel positive allosteric modulator of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors that may emerge as a favorable candidate for the symptomatic treatment of cognitive and depressive disorders in patients suffering from Alzheimer's disease (AD) of mild to moderate severity and with depressive symptoms. MethodsFor this double-blind, placebo-controlled 24-week phase II trial, 520 outpatients aged between 55 and 85 years, with probable AD at mild to moderate stages (a Mini-Mental State Examination score of 24-15 inclusive) and exhibiting depressive symptoms (Cornell Scale for Depression in Dementia [CSDD] ≥ 8) were recruited in twelve countries and randomized to 3 doses of S47445 (5-15-50 mg) or placebo. The primary end point was the change from baseline in the 11-item Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) total score at week 24. Secondary measures included the Disability Assessment for Dementia, Mini-Mental State Examination, ADAS-Cog 13-item, CSDD, Clinical Global Impression of Change (Alzheimer's Disease Cooperative Study-CGIC), Neuropsychiatric Inventory (NPI), and safety criteria. ResultsBaseline characteristics were comparable between the 4 groups. After 24 weeks, no statistically significant treatment difference was demonstrated between S47445 (5, 15 or 50 mg/d) and placebo on cognition (ADAS-Cog), function (Disability Assessment for Dementia), or depressive symptoms (CSDD). An improvement on neuropsychiatric symptoms assessed by NPI was evidenced at the lower dose 5 mg/d (Δ -2.55, P = .023, post hoc analysis) compared to placebo. CSDD and total NPI scores improved in all groups including placebo. There were no specific and/or unexpected safety signals observed with any of the S47445 doses. DiscussionS47445 administered for 24 weeks was safe and well tolerated by patients with mild to moderate AD; the compound did not show significant benefits over placebo on cognition, function, or depressive symptoms.

Association between Neuropsychiatric Improvement and Neurocognitive Change in Alzheimer's Disease: Analysis of the CATIE-AD Study.

To assess associations between improvements in neuropsychiatric symptoms (NPS) and neurocognitive change in patients with Alzheimer's disease (AD) during treatment using the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer Disease (CATIE-AD) dataset. AD outpatients with NPS who needed pharmacological treatment (n = 421) were followed up with antipsychotics, citalopram, or placebo for up to 36 weeks (mean±SD = 252±52 days). The study aim was to investigate associations between improvement in each NPS evaluating scale (by Clinical Global Impression of Change [CGI-C], Neuropsychiatric Inventory [NPI], or Brief Psychiatric Scale [BPRS]) at endpoint (week 36 or early termination [ET], n = 340) and neurocognitive change (change score in the Mini-Mental State Examination [MMSE] between endpoint and baseline during the treatment). Multiple logistic regression analyses were performed on the associations between each NPS improvement and neurocognitive change as well as socio-clinico-demographic variables of interest. At endpoint, NPS improvement rates were 76.1%, 70.8%, and 58.1% in CGI-C, NPI, and BPRS, respectively, while MMSE score change was -2.3±3.8. NPS improvement was significantly related to more severe psychotic symptoms at baseline and preserved levels of neurocognition (smaller MMSE score change) among several variables. Our findings suggested that neurocognitive preservation may be associated with attaining optimal benefits from any treatment against NPSs in a longitudinal treatment course of patients with AD.

Safinamide in the management of patients with Parkinson's disease not stabilized on levodopa: a review of the current clinical evidence.

Safinamide (Xadago®) is a novel medication with both dopaminergic and non-dopaminergic effects, approved first by the European Commission and more recently by the US Food and Drug Administration (FDA) as an adjunctive treatment to carbidopa/levodopa in patients with mid- to late-stage Parkinson’s disease (PD) and motor fluctuations. It works through multiple mechanisms, namely as a reversible selective monoamine oxidase-B inhibitor and through modulation of glutamate release. Safinamide is extensively metabolized via oxidation to several inactive metabolites that are excreted primarily through the urine. Several large Phase III clinical trials of patients with advanced PD with motor fluctuations have shown that safinamide, administered orally at doses of 50–100 mg daily, increased ON time with no or non-troublesome dyskinesia, decreased daily OFF time, improved overall motor function (as measured by Unified Parkinson’s Disease Rating Scale [UPDRS] part III total score), and quality of life (as measured by Clinical Global Impression-Change and 39-item Parkinson’s Disease Questionnaire). In large clinical trials of patients with early PD on a single dopamine agonist, safinamide administered orally at a dose of 100 mg daily improved overall motor function as measured by UPDRS part III total score; however, some of the results reported were exploratory. Safinamide is generally well-tolerated and safe, with few to no treatment-related adverse events. Safinamide does not cause new or worsening dyskinesia and may be able to reduce this symptom in patients reporting it at baseline. Evidence suggests that safinamide is a good option for add-on therapy to carbidopa/levodopa in patients with advanced PD with motor complications, but there is still insufficient evidence to recommend it as monotherapy or add-on therapy in patients with early PD.

Acupuncture as Adjuvant Therapy for the Management of Cervical Dystonia.

Objectives: There are no curative treatments for cervical dystonia (CD), therefore conventional management is aimed at pain relief and muscle relaxation. Many patients with CD use complementary and integrative medicine interventions to manage symptoms, yet there are limited data on the use of acupuncture for CD. The aim of the current study was to determine the feasibility, safety, and efficacy of adjuvant acupuncture. Materials and Methods: A pilot open-label study was conducted on acupuncture treatments as add-on therapy to botulinum-toxin injection sessions (3 months apart) in 5 subjects with chronic idiopathic CD. Six 1-hour acupuncture sessions were administered every other week over the 3-month period between consecutive botulinum-toxin sessions. Data from exploratory efficacy endpoints-including a visual analogue scale for pain, the Clinician Global Impression of Change, the Patient Global Impression of Change, the Toronto Western Spasmodic Torticollis Rating Scale, and the Short Form-36) Health Survey-were collected. Results: Five subjects completed the study with only 1 acupuncture session missed by 1 subject, thereby meeting the study's predetermined adherence goal. All participants reported improvement from acupuncture. Only minor adverse events were reported, with self-resolved discomfort in 1 subject and self-resolved minor bruising in 2 subjects. Conclusions: Acupuncture is feasible and safe as an adjunct treatment for chronic CD, and might be associated with subjective symptomatic benefits.