Global Impression Of Change Scores Research Articles

Efficacy of Dapoxetine in the Treatment of Patients With Lifelong Premature Ejaculation as an Alternative to Sertraline Therapy.

IntroductionBefore dapoxetine was approved for the treatment of lifelong premature ejaculation (LPE) in China, daily dosing with off-label sertraline was common.AimTo investigate the efficacy of dapoxetine in the treatment of patients with LPE as an alternative to sertraline therapy.MethodsThis prospective study included LPE patients who previously attempted treatment with sertraline and who agree to receive dapoxetine therapy in our hospital from January 2020 to March 2021. Patients who received any PE therapy in the two months prior to the dapoxetine therapy were excluded. All patients received dapoxetine 30 mg (taken 1–3 hours before sexual intercourse) for 12 weeks, and they were not taking sertraline during the trial.Main Outcome MeasureData on their intravaginal ejaculatory latency time and premature ejaculation profile were recorded before and after the dapoxetine treatment. Clinical Global Impression of Change scores and data on Treatment-Emergent adverse events were collected after treatment.ResultsA total of 144 patients with LPE completed this study; including 64 patients who reported that previous sertraline treatment was satisfactory (group A) and 80 patients for whom previous sertraline therapy was unsatisfactory in treating PE (group B). Both groups experienced significantly increased intravaginal ejaculatory latency time. Dapoxetine therapy was reported satisfactory by 67.5% of patients with LPE in whom sertraline therapy unsatisfactory according to their Clinical Global Impression of Change score, which was not different from those who reported this result in group A (62.5%). Similar outcomes were also reported for premature ejaculation profile and treatment-emergent adverse events.Conclusion: Although both dapoxetine and sertraline are selective serotonin re-uptake inhibitors, dapoxetine therapy is satisfactory in 67.5% of patients with LPE in whom sertraline treatment unsatisfactory, and the effect of dapoxetine was independent of the effect of sertraline.Liu G, Yin Y, Zhang L. et al., Efficacy of Dapoxetine in the Treatment of Patients With Lifelong Premature Ejaculation as an Alternative to Sertraline Therapy. Sex Med 2021;10:100473.

Association between 5-HTTLPR and STin2 VNTR polymorphisms in the serotonin transporter gene and clinical response of a selective serotonin reuptake inhibitor (dapoxetine) in lifelong premature ejaculation

Association between 5-HTTLPR and STin2 VNTR polymorphisms in the serotonin transporter gene and clinical response of a selective serotonin reuptake inhibitor (dapoxetine) in lifelong premature ejaculation

Stress and Pain Before, During and After the First Wave of the COVID-19 Pandemic: An Exploratory Longitudinal Mixed Methods Study.

Aims: This study explores the association between subjective feeling of stress and pain experience in the context of the COVID-19 pandemic with a focus on characteristics known to trigger a physiological stress response [sense of low control, threat to ego, unpredictability and novelty (STUN)].Methods: This exploratory longitudinal convergent mixed methods design consisted of online questionnaires over three time points (before, during and after the 1st wave of the COVID-19 pandemic) (N = 49) and qualitative interviews (N = 27) during the 1st wave of the pandemic on distinct samples of individuals living with chronic pain (CP). Both types of data sources were mixed upon integration using joint display.Results: Mean pain intensity scores remained stable across time points, while pain unpleasantness and pain interference scores significantly improved. Global impression of change scores measured during the first wave of the pandemic do not entirely concord with pain scores evolution. Two thirds of participants reported a global deterioration of their pain condition at the beginning of the pandemic. Stress and pain catastrophizing before the pandemic were associated with pain scores throughout the pandemic; while most specific measures of stress due to the novel, uncontrollable, unpredictable and threatening nature of the pandemic were not. Qualitative data demonstrated that the deterioration reported in pain status reflected additional dimensions, including spatial expansion of the painful area, reduced access to treatments and challenges in adapting pain management strategies.Conclusions: Helping individuals to negotiate stressful aspects of the pandemic might help offset the negative impacts of stress on pain status in this context or other important life events.

Validating an instrument for direct patient reporting of chemotherapy toxicity among South African cancer patients.

172 Background: In the USA, use of patient-reported outcome (PRO) instruments for monitoring treatment toxicity has been associated with improved patient quality of life (QoL) and clinical outcomes. No similar PRO tools exist for the African cancer patients. We aimed to validate the Patient Reported Symptoms – South Africa (PRS-SA) survey, a novel PRO tool designed to measure subjective stress and symptoms in South African (SA) cancer patients receiving chemotherapy. Methods: We enrolled patients receiving chemotherapy at the oncology clinic at Charlotte Maxeke Hospital, Johannesburg. At 3 separate visits, participants completed the PRS-SA survey, which allowed reporting of stress on a numerical ranking scale (range 0-10) and severity of 11 common chemotherapy-related symptoms (i.e., pain, fatigue, fever, dyspnea, cough, mucositis, nausea, vomiting, diarrhea, constipation, and neuropathy) using lay language descriptions corresponding to Common Terminology Criteria for Adverse Events grades. They simultaneously completed the EORTC Core Quality of Life Questionnaire (QLQ-C30), the Global Impression of Change (GIC) questionnaire, and the Hospital Anxiety and Depression Scale (HADS). All instruments were offered in English and isiZulu. We constructed a receiver operator characteristics (ROC) curve for stress scale values and a total HADS score ≥15, representing clinical depression/anxiety. We evaluated construct validity for each symptom item by comparing symptom severity to the simultaneous QLQ-C30 summary score (Pearson correlation tests) and ECOG performance status (PS) (Mann-Whitney U tests). We assessed symptom item responsiveness by comparing change in severity across visits to change in QLQ-C30 summary score and comparing standardized mean symptom scores in those reporting negative, no, or positive change on the GIC using a Jockheere-Terpstra trend test. Results: Overall, 196 participants completed instruments at visit 1, 173 at visit 2, and 150 at visit 3. Area under the ROC curve for stress score was 0.76, and a score of 4 had 82% sensitivity and 55% specificity for clinical depression/anxiety. All symptom items showed construct validity by association with QLQ-C30 score (all p-values < 0.0001), and all but mucositis showed validity by association with ECOG PS (highest p = 0.03). All but cough showed responsiveness to change in QLQ-C30 score (highest p = 0.045), and the standardized mean in symptom scores demonstrated a trend across negative, neutral, and positive GIC scores (p = 0.03). Conclusions: In SA cancer patients, the PRS-SA’s stress scale behaves similarly to the distress thermometer in other populations, and the symptom items demonstrated construct validity and responsiveness. Further research should address implementation of the PRS-SA in the clinical setting for monitoring cancer treatment-related toxicity and its impact of patients’ QoL and outcomes.

Efficacy and Tolerability of Oral Compared with Sublingual Ketamine Lozenges as Rescue Analgesics in Adults for Acute Pain: The OSKet Trial.

Ketamine is an N-methyl-D-aspartate receptor (NMDA) antagonist used widely as an intravenous analgesic for treatment of acute pain. Its use as oral and sublingual analgesics is not well studied. This study aims to compare the clinical efficacy and tolerability of oral (PO) versus sublingual (SL) ketamine lozenges in adult patients with moderate-to-severe breakthrough pain. The study had a randomized, double-blind crossover design in 23 inpatients requiring ketamine as rescue analgesics when pain scores exceeded 4/10 on the Numerical Rating Scales. Each participant received either SL 50 mg ketamine lozenge and PO placebo lozenge or SL placebo lozenge and PO 50 mg ketamine lozenge in two treatment periods with a minimum 24-h washout. Pain scores and adverse effects were documented half hourly for the first 2 h, then one hourly for the next 2 h after treatment. The time to first effect and time to meaningful pain relief were recorded. Patients reported their satisfaction and a global impression of change (GIC) at the end of each treatment period. Data were analysed using random effects regression models. Sixteen subjects completed both days, 7 completed 1 day. Time to first effect was 13.1 min PO versus 6.6 min SL (p = 0.069), time to meaningful pain relief was 29.4 min PO versus 10.8 min SL (p = 0.02). Pain scores were not significantly different at all time points post-treatment. Satisfaction and GIC scores were similar for both groups. Overall, adverse events occurred more often with SL administration (p = 0.02). Sublingual administration of ketamine led to a faster onset of pain relief (but also a higher adverse event rate), but in all other aspects treatment with ketamine given sublingually and orally produced similar analgesic effects. ACTRN12621000240842, 08/03/2021, retrospectively registered.

Flexible vs. standard subthalamic stimulation in Parkinson disease: A double-blind proof-of-concept cross-over trial

BackgroundDeep brain stimulation (DBS) of the subthalamus (STN) is effective for the treatment of cardinal motor signs of Parkinson disease (PD). Structures around the STN can suppress dyskinesia and tremor (zona incerta) and improve gait and balance (substantia nigra pars reticulata). ObjectiveIs the newer 8-contact linear lead connected to a ‘flexible’ DBS system superior to standard 4-contact stimulation in PD patients receiving STN DBS? MethodsAfter 3 months of open label programming, 10 patients were randomized to standard or flexible stimulation before crossing over to the other arm (3 months each period). Patients and assessors were blinded. ResultsA trend to improvement in Patient Global Impression of Change scores was seen with standard to flexible stimulation and worsening from flexible to standard stimulation (mean ± SD: 0.7 ± 1.2 and −0.4 ± 1.5 respectively, p = 0.152). There was a significant reduction in the number of troublesome symptoms reported prior to DBS (2.6 ± 3.3 per patient), more so with flexible stimulation (0.4 ± 0.6 vs. 1.5 ± 1.6 with standard stimulation, p = 0.001 and p = 0.034). There was no significant difference between the flexible and standard stimulation groups. ConclusionFurther studies confirming that flexible stimulation is superior to standard DBS are warranted.

Gabapentin enhances the antinociceptive effect of intrathecal morphine in refractory cancer pain patients.

Morphine infusion through Intrathecal Drug Delivery System (IDDS) is widely used to relieve refractory cancer pain. However, continuous escalation of morphine dose caused by opioid tolerance and/or progress of cancer was commonly observed. Combining morphine with medications of different analgesic mechanisms is applied to blunt the rate of morphine increase. The purpose of this study was to determine the analgesic efficacy and safety of combining gabapentin with morphine after IDDS implantation. This study compared patients that received IDDS implantation from January 1, 2017 to November 10, 2018 in our institute. Key outcomes included change in mean pain score, dose of morphine used in patients, percentage of patients with 30% and 50% reduction in mean pain score, Patient Global Impression of Change scores, breakthrough pain characters and side effects. 34 patients in the combination group (morphine + gabapentin) and 40 patients in the monotherapy group(morphine)were analyzed. The results showed that both therapy groups achieved similar analgesic efficacy, demonstrated by Numerical rating scale (2.42 ± 0.88 vs 2.57 ± 0.85; Combination vs Monotherapy), PGIC and responder status. Mean daily dose of morphine was significantly lower in combination group compared to monotherapy group (3.54 ± 1.29mg vs 4.64 ± 1.28mg, P = 0.007). More patients experienced dizziness and somnolence after receiving combination therapy compared to morphine-alone treatment although no statistical significance was found (P = 0.49). Addition of gabapentin achieved similar analgesic efficacy with lower dose of morphine compared to morphine alone accompanying with higher incidence of dizziness and somnolence.

An Internally Validated Nomogram for Predicting the Likelihood of Improvement of Clinical Global Impression in Patients With Lifelong Premature Ejaculation Treated With Dapoxetine

BackgroundAlthough the introduction of dapoxetine has ushered in a new era in the treatment of premature ejaculation, many patients with lifelong premature ejaculation (LPE) exhibit an unimproved clinical global impression even after treatment with dapoxetine. AimTo investigate independent predictors of the improvement of Clinical Global Impression (iCGI) in patients with LPE treated with dapoxetine and develop a nomogram to predict a patient's likelihood of achieving iCGI. MethodsData of 243 patients with LPE diagnosed at Xijing Hospital (Xi'an, China) and Northwest Women's and Children's Hospital (Xi'an, China) from January 2019 to May 2020 were analyzed. Independent predictors of iCGI were identified, and a nomogram was developed using R software based on a multivariate logistic regression model. The predictive accuracy of the nomogram was measured using the area under the receiver operating characteristic curve. The nomogram was calibrated by comparing predictions with observations. Main Outcome MeasuresThe primary outcome was the patient-rated Clinical Global Impression of Change scale score after a 4-week course of dapoxetine treatment, which was collected via an online questionnaire. A Clinical Global Impression of Change score of ≥1 was defined as iCGI in this study. ResultsPatients with LPE with at least a bachelor's degree, a self-reported intravaginal ejaculation latency time of >1 minute, and an International Index of Erectile Function question 5 score of ≥3 were independent factors associated with achieving iCGI, whereas a Premature Ejaculation Diagnostic Tool question 1 score of ≥2 was an independent factor negatively associated with achieving iCGI. The predictive accuracy of the nomogram, which was developed by integrating all variables with independent predictive significance, was 0.710 (95% confidence interval: 0.702–0.718). In addition, the calibration plot demonstrated excellent agreement between predictions and observations. Clinical ImplicationsIf the predictive performance of our nomogram is further proven in multiple external validations, it can be used to select suitable patients for dapoxetine treatment, thereby reducing the number of patients discontinuing treatment. Strengths & LimitationsThis study developed the first nomogram for predicting the likelihood of achieving iCGI in patients with LPE treated with dapoxetine. However, our nomogram was not externally validated using independent cohorts from other institutions. ConclusionThis study identified several independent predictors of iCGI in patients with LPE treated with dapoxetine. An effective nomogram was developed to predict their likelihood of achieving iCGI. External validations using data of Western patients with LPE are required to test the broader applicability of this Chinese patient-based tool.Hou G, Gao M, Zhang L, et al. An Internally Validated Nomogram for Predicting the Likelihood of Improvement of Clinical Global Impression in Patients With Lifelong Premature Ejaculation Treated With Dapoxetine. J Sex Med 2020;17:2341–2350.

Cannabidiol in conjunction with clobazam: analysis of four randomized controlled trials.

ObjectivesTo assess the efficacy and safety profile of add‐on cannabidiol (CBD) in patients with Lennox–Gastaut syndrome (LGS) and Dravet syndrome (DS) on clobazam and in the overall population of four randomized, controlled phase 3 trials.MethodsPatients received plant‐derived, highly purified CBD medicine (Epidiolex® in the USA; Epidyolex® in Europe; 100 mg/ml oral solution) at a dose of 10 or 20 mg/kg/day, or placebo for 14 weeks. A subgroup analysis of patients on clobazam and meta‐analysis by syndrome were conducted. The primary endpoint was percentage reduction in primary seizure type during the treatment period.Results396 patients with LGS (49% on clobazam) and 318 patients with DS (64% on clobazam) were included. CBD treatment resulted in a reduction in primary seizure frequency vs placebo in the overall population (treatment ratio [95% confidence interval]: LGS, 0.70 [0.62‐0.80]; DS, 0.71 [0.60‐0.83]) and in patients receiving clobazam (LGS, 0.56 [0.47‐0.67]; DS, 0.63 [0.52‐0.77]). The antiseizure efficacy of CBD was also demonstrated across other endpoints vs placebo (≥50% responder rate, total seizure frequency, number of seizure‐free days, and Subject/Caregiver Global Impression of Change scores) in the overall populations and in patients receiving clobazam. There were higher incidences of somnolence and sedation in patients on CBD and clobazam. Most incidences of elevated transaminases occurred in patients on concomitant valproate and, to a lesser extent, clobazam.ConclusionsAdd‐on CBD was effective in reducing seizures in the overall populations and in conjunction with clobazam. Somnolence and sedation occurred more frequently in patients on CBD and clobazam.

Meniscal tear outcome Study (METRO Study): a study protocol for a multicentre prospective cohort study exploring the factors which affect outcomes in patients with a meniscal tear

IntroductionThis study is designed to explore the baseline characteristics of patients under 55 years of age with a meniscal tear, and to describe the relationship between the baseline characteristics and...

Does patients’ perception of Improvement following a pain management programme, match reported minimally clinically important differences?

Purpose: Clinical outcomes for patients attending a pain management programme were evaluated to determine whether patients who rated an improvement on a Global Impression of Change Score, achieved mean changes in BPI that were consistent with’acceptable’ change, and to determine mean changes on other outcomes in this population. It is suggested that a mean change of 2.09 in pain interference, as measured by the Brief Pain Inventory (BPI), could be considered acceptable to patients. Currently data is unavailable for changes in pain acceptance.

Dose-Ranging Effect of Adjunctive Oral Cannabidiol vs Placebo on Convulsive Seizure Frequency in Dravet Syndrome

Clinical evidence supports effectiveness of cannabidiol for treatment-resistant seizures in Dravet syndrome, but this trial is the first to evaluate the 10-mg/kg/d dose. To evaluate the efficacy and safety of a pharmaceutical formulation of cannabidiol, 10 and 20 mg/kg/d, vs placebo for adjunctive treatment of convulsive seizures in patients with Dravet syndrome. This double-blind, placebo-controlled, randomized clinical trial (GWPCARE2) recruited patients from April 13, 2015, to November 10, 2017, with follow-up completed on April 9, 2018. Of 285 patients screened from 38 centers in the United States, Spain, Poland, the Netherlands, Australia, and Israel, 86 were excluded, and 199 were randomized. Patients were aged 2 to 18 years with a confirmed diagnosis of Dravet syndrome and at least 4 convulsive seizures during the 4-week baseline period while receiving at least 1 antiepileptic drug. Data were analyzed from November 16 (date of unblinding) to December 13 (date of final outputs), 2018, based on intention to treat and per protocol. Patients received cannabidiol oral solution at a dose of 10 or 20 mg/kg per day (CBD10 and CBD20 groups, respectively) or matched placebo in 2 equally divided doses for 14 weeks. All patients, caregivers, investigators, and individuals assessing data were blinded to group assignment. The primary outcome was change from baseline in convulsive seizure frequency during the treatment period. Secondary outcomes included change in all seizure frequency, proportion with at least a 50% reduction in convulsive seizure activity, and change in Caregiver Global Impression of Change score. Of 198 eligible patients (mean [SD] age, 9.3 [4.4] years; 104 female [52.5%]), 66 were randomized to the CBD10 group, 67 to the CBD20 group, and 65 to the placebo group, and 190 completed treatment. The percentage reduction from baseline in convulsive seizure frequency was 48.7% for CBD10 group and 45.7% for the CBD20 group vs 26.9% for the placebo group; the percentage reduction from placebo was 29.8% (95% CI, 8.4%-46.2%; P = .01) for CBD10 group and 25.7% (95% CI, 2.9%-43.2%; P = .03) for the CBD20 group. The most common adverse events were decreased appetite, diarrhea, somnolence, pyrexia, and fatigue. Five patients in the CBD20 group discontinued owing to adverse events. Elevated liver transaminase levels occurred more frequently in the CBD20 (n = 13) than the CBD10 (n = 3) group, with all affected patients given concomitant valproate sodium. Adjunctive cannabidiol at doses of 10 and 20 mg/kg/d led to similar clinically relevant reductions in convulsive seizure frequency with a better safety and tolerability profile for the 10-mg/kg/d dose in children with treatment-resistant Dravet syndrome. Dose increases of cannabidiol to greater than 10 mg/kg/d should be tailored to individual efficacy and safety. ClinicalTrials.gov Identifier: NCT02224703.

Prolotherapy injections and physiotherapy used singly and in combination for lateral epicondylalgia: a single-blinded randomised clinical trial

BackgroundLateral epicondylalgia (tennis elbow) is a common, debilitating and often treatment-resistant condition. Two treatments thought to address the pathology of lateral epicondylalgia are hypertonic glucose plus lignocaine injections (prolotherapy) and a physiotherapist guided manual therapy/exercise program (physiotherapy). This trial aimed to compare the short- and long-term clinical effectiveness, cost effectiveness, and safety of prolotherapy used singly and in combination with physiotherapy.MethodsUsing a single-blinded randomised clinical trial design, 120 participants with lateral epicondylalgia of at least 6 weeks’ duration were randomly assigned to prolotherapy (4 sessions, monthly intervals), physiotherapy (weekly for 4 sessions) or combined (prolotherapy+physiotherapy). The Patient-Rated Tennis Elbow Evaluation (PRTEE) and participant global impression of change scores were assessed by blinded evaluators at baseline, 6, 12, 26 and 52 weeks. Success rate was defined as the percentage of participants indicating elbow condition was either ‘much improved’ or ‘completely recovered.’ Analysis was by intention-to-treat.ResultsEighty-eight percent completed the 12-month assessment. At 52 weeks, there were substantial, significant improvements compared with baseline status for all outcomes and groups, but no significant differences between groups. The physiotherapy group exhibited greater reductions in PRTEE at 12 weeks than the prolotherapy group (p = 0.014).ConclusionThere were no significant differences amongst the Physiotherapy, Prolotherapy and Combined groups in PRTEE and global impression of change measures over the course of the 12-month trial.Trial registrationACTRN12612000993897.

Evaluating the impact of gabapentinoids on sleep health in patients with chronic neuropathic pain: a systematic review and meta-analysis.

Chronic neuropathic pain (NP) is debilitating and impacts sleep health and quality of life. Treatment with gabapentinoids (GBs) has been shown to reduce pain, but its effects on sleep health have not been systematically evaluated. The objective of this systematic review and meta-analysis was to assess the relationship between GB therapy dose and duration on sleep quality, daytime somnolence, and intensity of pain in patients with NP. Subgroup comparisons were planned for high- vs low-dose GBs, where 300 mg per day or more of pregabalin was used to classify high-dose therapy. Trial data were segregated by duration less than 6 weeks and 6 weeks or greater. Twenty randomized controlled trials were included. Primary outcome measures included pain-related sleep interference and incidence of daytime somnolence. Secondary outcomes included daily pain scores (numerical rating scale 0-10) and patient global impression of change. Significant improvement in sleep quality was observed after 6 weeks of GB treatment when compared with placebo (standardized mean difference 0.39, 95% confidence interval 0.32-0.46 P < 0.001). Increased daytime somnolence was observed among all GB-treated groups when compared with placebo. Treated patients were also more likely to report improvement of patient global impression of change scores. Pain scores decreased significantly in patients both after 6 weeks of treatment (P < 0.001) and in trials less than 6 weeks (P = 0.017) when compared with placebo. Our data demonstrate that GBs have a positive impact on sleep health, quality of life, and pain in patients with NP syndromes. However, these benefits come at the expense of daytime somnolence.

Long-Term Assessment of a Prospective Cohort of Patients Undergoing Laparoscopic Sacrocolpopexy.

To report long-term outcomes after laparoscopic sacrocolpopexy. We conducted a prospective descriptive cohort study on 331 consecutive patients who underwent laparoscopic sacrocolpopexy for symptomatic prolapse (Pelvic Organ Prolapse Quantification [POP-Q] system stage 2 or greater) at one center, with minimum 1.5 years of follow-up by April 30, 2014. Primary outcome measures were Patient Global Impression of Change score and failure at the apex (C≥-1 cm; POP-Q stage 2 or greater). Secondary outcomes were anatomical failure in other compartments, duration of follow-up, occurrence and time point of complications, reinterventions, and functional outcomes by response to a standardized 24-question interview on prolapse and bladder, bowel, and sexual function. Assessment was by an experienced clinician not involved in patient management. The follow-up rate was 84.6% (280/331); 185 of 331 (55.9%) patients were both physically examined and interviewed, and 95 of 331 (25.7%) were interviewed only. The median age at interview was 72 years (interquartile range 13 years), with a follow-up period of 85.5 months (interquartile range 46 months). Approximately 83% (231/280) reported improvement; 5.7% (16/280) were unchanged, 5.7% (16/280) felt slightly worse, and 6.8% (17/280) reported clear deterioration. Anatomical failure at point-C was 8.6% (16/185); anterior (22.2%, 41/185) and posterior (28.6%, 53/185) prolapse were more common than apical prolapse. Of those with level-I anatomical cure, 10.1% (17/185) felt worse; half of them (9/17) because of prolapse in another compartment. The others had urinary problems (41.2%, 7/17), obstructive defecation (11.8%, 2/17), or dyspareunia (11.8%, 2/17). Conversely, the majority of patients with recurrence at the vault (62.5%, 10/16) self-reported to be improved. The reoperation rate was 17.8% (48/270), including 19 (7.0%) for graft-related complications and nine (3.3%) for prolapse. More than four out of five patients (82.5%) felt improved 86 months after laparoscopic sacrocolpopexy. Of those not improved, two thirds had recurrent prolapse; however, typically mid-vaginal. The other third reported urinary or bowel problems or dyspareunia. Reintervention for prolapse was 3.3%. The most common reasons for reoperation were graft-related complications (7.0%) and urinary incontinence (6.7%).

Abnormal involuntary movement scale in tardive dyskinesia: Minimal clinically important difference.

BackgroundA minimal clinically important difference has not been established for the Abnormal Involuntary Movement Scale in patients with tardive dyskinesia. Valbenazine is a vesicular monoamine transporter 2 inhibitor approved for the treatment of tardive dyskinesia in adults. Efficacy in randomized, double‐blind, placebo‐controlled trials was defined as the change from baseline in Abnormal Involuntary Movement Scale total score (sum of items 1‐7).ObjectivesTo estimate an minimal clinically important difference for the Abnormal Involuntary Movement Scale using valbenazine trial data and an anchor‐based method.MethodsData were pooled from three 6‐week double‐blind, placebo‐controlled trials: KINECT (NCT01688037), KINECT 2 (NCT01733121), and KINECT 3 (NCT02274558). Valbenazine doses were pooled for analyses as follows: “low dose,” which includes 40 or 50 mg/day; and “high dose,” which includes 75 or 80 mg/day. Mean changes from baseline in Abnormal Involuntary Movement Scale total score were analyzed in all participants (valbenazine‐ and placebo‐treated) with a Clinical Global Impression of Change‐Tardive Dyskinesia or Patient Global Impression of Change score of 1 (very much improved) to 3 (minimally improved).ResultsThe least squares mean improvement from baseline to week 6 in Abnormal Involuntary Movement Scale total score was significantly greater with valbenazine (low dose: –2.4; high dose: –3.2; both, P < 0.001) versus placebo (–0.7). An minimal clinically important difference of 2 points was estimated based on least squares mean changes in Abnormal Involuntary Movement Scale total score in participants with a Clinical Global Impression of Change‐Tardive Dyskinesia score ≤3 at week 6 (mean change: –2.2; median change: –2) or Patient Global Impression of Change score ≤3 at week 6 (mean change: –2.0; median change: –2).ConclusionsResults from an anchor‐based method indicate that a 2‐point decrease in Abnormal Involuntary Movement Scale total score may be considered clinically important. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

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.

Efficacy and safety of burosumab in children aged 1–4 years with X-linked hypophosphataemia: a multicentre, open-label, phase 2 trial

Children with X-linked hypophosphataemia have high concentrations of circulating phosphatonin fibroblast growth factor 23 (FGF23), which causes renal phosphate wasting and hypophosphataemia, rickets, skeletal deformities, and growth impairment. Burosumab, a human monoclonal antibody against FGF23, improves phosphate homoeostasis and rickets in children aged 5-12 years with X-linked hypophosphataemia. We aimed to assess the safety and efficacy of burosumab in younger children with X-linked hypophosphataemia. In this open-label, phase 2 trial at three hospitals in the USA, children (aged 1-4 years) with X-linked hypophosphataemia received burosumab (0·8 mg/kg) via subcutaneous injection every 2 weeks for 64 weeks. The dose was increased to 1·2 mg/kg if two consecutive pre-dose serum phosphorus concentrations were below 1·03 mmol/L (3·2 mg/dL), serum phosphorus had increased by less than 0·16 mmol/L (<0·5 mg/dL) from baseline, and a dose of burosumab had not been missed. Participants could continue to receive burosumab for up to an additional 96 weeks during the extension period. Key inclusion criteria were age 1-4 years at the time of informed consent; fasting serum phosphorus concentration of less than 0·97 mmol/L (3·0 mg/dL); serum creatinine 8·8-35·4 μmol/L (0·1-0·4 mg/dL); radiographic evidence of rickets (at least five participants were required to have a Thacher Rickets Severity Score of ≥1·5 at the knee); and a confirmed PHEX mutation or a variant of unknown significance in the patient or direct relative also affected with X-linked hypophosphataemia. Conventional therapy was stopped upon enrolment. The coprimary endpoints were safety and change from baseline to week 40 in fasting serum phosphorus concentrations. Changes in rickets severity from baseline to weeks 40 and 64 (assessed radiographically using Thacher Rickets Severity Score and an adaptation of the Radiographic Global Impression of Change), and recumbent length or standing height, were key secondary outcomes. This trial is registered with ClinicalTrials.gov, number NCT02750618, and is ongoing. Between May 16, 2016, and June 10, 2016, we enrolled 13 children with X-linked hypophosphataemia. All 13 children completed 64 weeks of treatment and were included in the efficacy and safety analysis; none exceeded 70 weeks of treatment at the time of analysis. Serum phosphorus least squares mean increase from baseline to week 40 of treatment was 0·31 mmol/L (SE 0·04; 95% CI 0·24-0·39; 0·96 mg/dL [SE 0·12]; p<0·0001). All patients had at least one adverse event. 14 treatment-related adverse events, mostly injection site reactions, occurred in five children. One serious adverse event considered unrelated to treatment (tooth abscess) occurred in a child with a history of tooth abscess. All other adverse events were mild to moderate, except a severe food allergy considered unrelated to treatment. No instances of nephrocalcinosis or noteworthy changes in the results of a standard safety chemistry panel emerged. Total Thacher Rickets Severity Score decreased by a least squares mean of -1·7 (SE 0·1; p<0·0001) from baseline to week 40 and by -2·0 (SE 0·1; p<0·0001) by week 64. The Radiographic Global Impression of Change score also indicated significant improvement, with a least squares mean score of +2·3 (SE 0·1) at week 40 and +2·2 (0·1) at week 64 (both p<0·0001). Mean length or standing height Z score was maintained from baseline to week 64. Burosumab had a favourable safety profile, increased serum phosphorus, and improved rickets and prevented early declines in growth in children aged 1-4 years with X-linked hypophosphataemia. These findings could substantially alter the treatment of young children with X-linked hypophosphataemia. Ultragenyx Pharmaceutical and Kyowa Kirin International.

A Multicenter Study on Neuropathic Pain in China: Characteristics and the Efficacy of Pregabalin

Background: This clinical study aims to analyse the characteristics of neuropathic pain patients across country nationwide and evaluate the efficacy and tolerability of pregabalin for the treatment of neuropathic pain. The GABA analogue, pregabalin, is being studied to try to establish standardized management of neuropathic pain as it is commonly used in postherpetic neuralgia in China.Methods: Patients with neuropathic pain from 17 hospitals were included for four weeks. The demographics and baseline characteristics of patients were analyzed. The primary outcome was the difference in the pain intensity scores in the numerical rating scale from baseline to follow-up visits. Secondary outcomes included the differing visual analogue scale (VAS) of the short-form McGill Pain Questionnaire, sleep quality, anxiety and depression scores, and side effects during four weeks of follow-up.Results: As 355 patients completed the 4-week follow up, various types of neuropathic pain intensity scores significantly decreased at the first week of treatment and improved through the course of the study. Meanwhile; the difference in the percentage change in patient global impression of change scores, mean sleep interference scores, anxiety and depression scores are all significantly higher after 4-week treatment. Most of the side effects went away during treatment as patients adjust to the medicine.Conclusions: The data demonstrated that pregabalin was effective and well tolerated in Chinese patients with neuropathic pains. This study also analyzed the distribution features of neuropathic pain in a general population and established standardized management of neuropathic pain in China.

Spinal Instrumentation Rescue with Cement Augmentation.

Altered biomechanics or bone fragility or both contribute to spine instrumentation failure. Although revision surgery is frequently required, minimally invasive alternatives may be feasible. We report the largest to-date series of percutaneous fluoroscopically guided vertebral cement augmentation procedures to address feasibility, safety, results and a variety of spinal instrumentation failure conditions. A consecutive series of 31 fluoroscopically guided vertebral augmentation procedures in 29 patients were performed to address screw loosening (42 screws), cage subsidence (7 cages), and fracture within (12 cases) or adjacent to (11 cases) the instrumented segment. Instrumentation failure was deemed clinically relevant when resulting in pain or jeopardizing spinal biomechanical stability. The main study end point was the rate of revision surgery avoidance; feasibility and safety were assessed by prospective recording of periprocedural technical and clinical complications; and clinical effect was measured at 1 month with the Patient Global Impression of Change score. All except 1 procedure was technically feasible. No periprocedural complications occurred. Clinical and radiologic follow-up was available in 28 patients (median, 16 months) and 30 procedures. Revision surgery was avoided in 23/28 (82%) patients, and a global clinical benefit (Patient Global Impression of Change, 5-7) was reported in 26/30 (87%) cases at 1-month follow-up, while no substantial change (Patient Global Impression of Change, 4) was reported in 3/30 (10%), and worsening status (Patient Global Impression of Change, 3), in 1/30 (3%). Our experience supports the feasibility of percutaneous vertebral augmentation in the treatment of several clinically relevant spinal instrumentation failure conditions, with excellent safety and efficacy profiles, both in avoidance of revision surgery and for pain palliation.