Global Impressions-Improvement Scale Research Articles

Effect of Pessary vs Surgery on Patient-Reported Improvement in Patients With Symptomatic Pelvic Organ Prolapse

Pelvic organ prolapse is a prevalent condition among women that negatively affects their quality of life. With increasing life expectancy, the global need for cost-effective care for women with pelvic organ prolapse will continue to increase. To investigate whether treatment with a pessary is noninferior to surgery among patients with symptomatic pelvic organ prolapse. The PEOPLE project was a noninferiority randomized clinical trial conducted in 21 participating hospitals in the Netherlands. A total of 1605 women with symptomatic stage 2 or greater pelvic organ prolapse were requested to participate between March 2015 through November 2019; 440 gave informed consent. Final 24-month follow-up ended at June 30, 2022. Two hundred eighteen participants were randomized to receive pessary treatment and 222 to surgery. The primary outcome was subjective patient-reported improvement at 24 months, measured with the Patient Global Impression of Improvement scale, a 7-point Likert scale ranging from very much better to very much worse. This scale was dichotomized as successful, defined as much better or very much better, vs nonsuccessful treatment. The noninferiority margin was set at 10 percentage points risk difference. Data of crossover between therapies and adverse events were captured. Among 440 patients who were randomized (mean [SD] age, 64.7 [9.29] years), 173 (79.3%) in the pessary group and 162 (73.3%) in the surgery group completed the trial at 24 months. In the population, analyzed as randomized, subjective improvement was reported by 132 of 173 (76.3%) in the pessary group vs 132 of 162 (81.5%) in the surgery group (risk difference, -6.1% [1-sided 95% CI, -12.7 to ∞]; P value for noninferiority, .16). The per-protocol analysis showed a similar result for subjective improvement with 52 of 74 (70.3%) in the pessary group vs 125 of 150 (83.3%) in the surgery group (risk difference, -13.1% [1-sided 95% CI, -23.0 to ∞]; P value for noninferiority, .69). Crossover from pessary to surgery occurred among 118 of 218 (54.1%) participants. The most common adverse event among pessary users was discomfort (42.7%) vs urinary tract infection (9%) following surgery. Among patients with symptomatic pelvic organ prolapse, an initial strategy of pessary therapy, compared with surgery, did not meet criteria for noninferiority with regard to patient-reported improvement at 24 months. Interpretation is limited by loss to follow-up and the large amount of participant crossover from pessary therapy to surgery. Netherlands Trial Register Identifier: NTR4883.

A preliminary study of comprehensive behavioral intervention for tics in Chinese children with chronic tic disorder or Tourette syndrome.

To investigate the adaptability of Comprehensive Behavioral Intervention for Tics (CBIT) for a Chinese population, and evaluate the efficacy of combined CBIT and pharmacotherapy (CBIT + PT) compared to CBIT or pharmacotherapy (PT) alone for reducing tics and for improving the quality of life (QoL) in a sample of Chinese children with chronic tic disorders (CTD) and Tourette syndrome (TS). In this 10-week randomized controlled pilot trial, 37 outpatients aged between 6 and 16 years affected by TS and CTD were randomly assigned to receive CBIT (n = 22) or PT alone (n = 15). Considering the feasibility, the patients allocated to the CBIT treatment group could further choose whether to simultaneously take medicine voluntarily, resulting in a CBIT alone group (n = 12) and a CBIT + PT group (n = 10). At baseline, no significant difference was found between the three groups in the demographic and clinical characteristics (p > 0.05). All three groups showed a significant reduction in tic severity after treatment assessed by the Yale Global Tic Severity Scale (YGTSS) severity score [F (2,33) = 35.05, p < 0.001, η p 2 = 0.51], the score of the Clinical Global Impression scale for Improvement (CGI-I) [F (1,34) = 13.87, p = 0.001, η p 2 = 0.29], and YGTSS impairment score [F (2,33) = 31.71, p < 0.001, η p 2 = 0.48]. Significant interactions were found between the time-point and group in emotional functioning [F (2,29) = 4.39, p = 0.02, η p 2 = 0.23], psychosocial functioning [F (2,29) = 5.93, p = 0.007, η p 2 = 0.29], and total QoL score [F (1,34) = 3.72, p = 0.04, η p 2 = 0.20] of Pediatric Quality of Life Inventory (PedsQL 4.0) for children suggesting a significantly larger improvement in emotional functioning, psychosocial functioning, and total QoL score of the life quality in the CBIT group for children self-report. PedsQL for proxy report only showed a significant main effect of time-point in physical functioning [F (1,33) = 8.35, p = 0.01, η p 2 = 0.2], emotional functioning [F (1,33) = 10.75, p = 0.002, η p 2 = 0.25], psychosocial functioning [F (1,34) = 11.38, p = 0.002, η p 2 = 0.26], and total Qol score [F (1,34) = 13.21, p = 0.001, η p 2 = 0.29]. CBIT is probably effective in reducing tic severity in Chinese children with tic disorders. CBIT + PT may not be superior to CBIT alone in reducing tic severity and improving quality of life. CBIT alone showed advantages in improving quality of life over CBIT + PT and PT alone. CBIT might be an appropriate treatment option for patients with tic disorder in Chinese mainland.

Effect of fenfluramine on seizures and comorbidities in SCN8A-developmental and epileptic encephalopathy: A case series.

SCN8A‐developmental and epileptic encephalopathy is caused by pathogenic variants in the SCN8A gene encoding the Nav1.6 sodium channel, and is characterized by intractable multivariate seizures and developmental regression. Fenfluramine is a repurposed drug with proven antiseizure efficacy in Dravet syndrome and Lennox–Gastaut syndrome. The effect of fenfluramine treatment was assessed in a retrospective series of three patients with intractable SCN8A epilepsy and severe neurodevelopmental comorbidity (n = 2 females; age 2.8–13 years; 8–16 prior failed antiseizure medications [ASM]; treatment duration: 0.75–4.2 years). In the 6 months prior to receiving fenfluramine, patients experienced multiple seizure types, including generalized tonic–clonic, focal and myoclonic seizures, and status epilepticus. Overall seizure reduction was 60%–90% in the last 3, 6, and 12 months of fenfluramine treatment. Clinically meaningful improvement was noted in ≥1 non‐seizure comorbidity per patient after fenfluramine, as assessed by physician‐ratings of ≥“Much Improved” on the Clinical Global Impression of Improvement scale. Improvements included ambulation in a previously non‐ambulant patient and better attention, sleep, and language. One patient showed mild irritability which resolved; no other treatment‐related adverse events were reported. There were no reports of valvular heart disease or pulmonary arterial hypertension. Fenfluramine may be a promising ASM for randomized clinical trials in SCN8A‐related disorders.

Minimal clinically important difference of the King’s Parkinson’s disease Pain Scale

Objective Pain is a common and debilitating symptom of Parkinson's disease (PD) and has no specific treatment. King's Parkinson's disease Pain Scale (KPPS) is the only specific scale for pain measurement in PD with established psychometric properties. The minimal clinically important difference (MCID) of KPPS, an important parameter for the design and interpretation of therapeutic interventions, has not yet been measured. The aim of our study was to assess the MCID of KPPS. Methods Two hundred and seven PD patients were evaluated by KPPS before and after receiving the intervention. The Clinical Global Impression of Improvement Scale was used as an anchor, and a Receiver Operating Characteristic (ROC) curve was used to determine the optimal MCID cut-off point for KPPS. The distribution-based approach applied one-third standard deviation (SD), 0.5 SD, and one standard error of measurement (SEM) of the total score of KPPS to determine the MCID. Results The MCID achieved from the ROC curve was 3 points (sensitivity: 74.4%; specificity: 81.9%). For the distribution-based method, the MCIDs corresponding to 0.3 SD, 0.5 SD, and one SEM were 5.65, 9.41, and 2.54 points, respectively. Conclusion KPPS is a valid scale for measuring pain in PD with demonstrable MCID. IMPLICATIONS FOR REHABILITATION The King's Parkinson's disease Pain Scale (KPPS) is a valid scale for measuring pain in patients with Parkinson's disease (PD) with demonstrable minimal clinically important difference (MCID). The MCID obtained in the current study will assist clinicians and researchers when interpreting KPPS change score to determine clinically meaningful changes of pain in both PD progression and response to interventions.

Findings from a pilot open-label trial of N-acetylcysteine for the treatment of pediatric mania and hypomania

BackgroundPediatric bipolar disorder is a highly prevalent and morbid disorder and is considered a prevalent public health concern. Currently approved treatments often pose the risk of serious side effects. Therefore, this study assessed the efficacy and tolerability of N-acetylcysteine (NAC), in children and adolescents with bipolar spectrum disorder.MethodsWe conducted a 12-week open-label trial of NAC for treatment of mania and hypomania in children and adolescents ages 5–17 with bipolar spectrum disorder including participants with full and subthreshold manic symptoms, accepting those with and without mixed states with co-occurring depression, and Young Mania Rating Scale scores ≥ 20 and < 40. Symptoms of mania and depression were assessed using the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HDRS), Children’s Depression Rating Scale (CDRS), and Clinical Global Impression (CGI) Severity (CGI-S) and Improvement (CGI-I) scales for mania and depression.ResultsThis study had a high drop-out rate with only 53% completing all 12 weeks. There was a significant reduction in YMRS, HDRS, and CDRS mean scores from baseline to endpoint. Of the 24 exposed participants, 54% had an anti-manic response measured by a reduction in YMRS ≥ 30% and 46% had a CGI-I mania score ≤ 2 at endpoint. Additionally, 62% of participants had an anti-depressive response measured by a reduction in HDRS ≥ 30%, 31% had an anti-depressive response measured by a reduction in CDRS ≥ 30%, and 38% had a CGI-I depression score ≤ 2 at endpoint.ConclusionsThese pilot open-label findings in a small sample provide preliminary data supporting the tolerability and safety of NAC in a pediatric population. The findings of this pilot scale study indicating improvement in mania and depression are promising, but require replication with a monotherapy randomized placebo controlled clinical trial and larger sample.Trial RegistrationClinicalTrials.gov Identifier: NCT02357290. First Registration 06/02/2015.

Efficacy and Safety of Fenfluramine for the Treatment of Seizures Associated With Lennox-Gastaut Syndrome

New treatment options are needed for patients with Lennox-Gastaut syndrome (LGS), a profoundly impairing, treatment-resistant, developmental and epileptic encephalopathy. To evaluate the efficacy and safety of fenfluramine in patients with LGS. This multicenter, double-blind, placebo-controlled, parallel-group randomized clinical trial was conducted from November 27, 2017, to October 25, 2019, and had a 20-week trial duration. Patients were enrolled at 65 study sites in North America, Europe, and Australia. Included patients were aged 2 to 35 years with confirmed diagnosis of LGS and experienced 2 or more drop seizures per week during the 4-week baseline. Using a modified intent-to-treat method, data analysis was performed from November 27, 2017, to October 25, 2019. The database lock date was January 30, 2020, and the date of final report was September 11, 2021. Patients were randomized to receive either a 0.7-mg/kg/d or 0.2-mg/kg/d (maximum 26 mg/d) dose of fenfluramine or placebo. After titration (2-week period), patients were taking their randomized dose for 12 additional weeks. Primary efficacy end point was percentage change from baseline in drop seizure frequency in patients who received 0.7 mg/kg/d of fenfluramine vs placebo. A total of 263 patients (median [range] age, 13 [2-35] years; 146 male patients [56%]) were randomized to the 0.7-mg/kg/d fenfluramine group (n = 87), 0.2-mg/kg/d fenfluramine group (n = 89), or placebo group (n = 87). The median percentage reduction in frequency of drop seizures was 26.5 percentage points in the 0.7-mg/kg/d fenfluramine group, 14.2 percentage points in the 0.2-mg/kg/d fenfluramine group, and 7.6 percentage points in the placebo group. The trial met its primary efficacy end point: patients in the 0.7-mg/kg/d fenfluramine group achieved a -19.9 percentage points (95% CI, -31.0 to -8.7 percentage points; P = .001) estimated median difference in drop seizures from baseline vs placebo. More patients in the 0.7-mg/kg/d fenfluramine group achieved a 50% or greater response (22 of 87 [25%]; P = .02) vs placebo (9 of 87 [10%]). Site investigators and caregivers gave a much improved or very much improved rating on the Clinical Global Impression of Improvement scale to more patients in the 0.7-mg/kg/d fenfluramine group than patients in the placebo group (21 [26%] vs 5 [6%]; P = .001). The seizure subtype that appeared most responsive to fenfluramine was generalized tonic-clonic seizure (120 of 263 [46%]), with a decrease in frequency of 45.7% in the 0.7-mg/kg/d fenfluramine group and 58.2% in the 0.2-mg/kg/d fenfluramine group compared with an increase of 3.7% in the placebo group. Most common treatment-emergent adverse events included decreased appetite (59 [22%]), somnolence (33 [13%]), and fatigue (33 [13%]). No cases of valvular heart disease or pulmonary arterial hypertension were observed. Results of this trial showed that, in patients with LGS, fenfluramine compared with placebo provided a significantly greater reduction in drop seizures and may be a particularly advantageous choice in patients who experience generalized tonic-clonic seizures. ClinicalTrials.gov Identifier: NCT03355209.

DILATATION OF IATROGENIC VAGINAL STENOSIS WITH AN ABSORBABLE OXIDIZED REGENERATED CELLULOSE

OBJECTIVE: Iatrogenic vaginal stenosis adversely affects the sexual life of couples. The definitive treatment of this condition is possible by redilatation of vagina. This study aims to investigate the outcomes of vaginal dilatation procedure performed using an absorbable oxidized regenerated cellulose.MATERIAL AND METHODS: 29 patients who could not have intercourse due to Iatrogenic vaginal stenosis underwent vagina enlargement surgery using an absorbable oxidized regenerated cellulose in the period of April 2014 to August 2020. The results were analysed with the help of the standard ‘Patient Global Impression of Improvement Scale (PGI-I) which evaluates patient satisfaction in particular.RESULTS: The mean follow-up period was 16 monts (14 - 24 months). No major perioperative complication was detected except from perianal hemotoma treated with antibiotics and drainage in a case. At 6th month follow up visit, 27 patients reported pain free sexual intercourse. Two patients needed re-dilatation 4 and 6 months later respectively.Based on the scores of patients as “much better ‘’and ‘’very much better” on the PGI-I scale, satisfaction rate was 93% at 6th month follow up visit.CONCLUSIONS: Vaginal dilatation surgery with absorbable oxidized regenerated cellulose seems to be a safe and effective procedure with positive anatomical and functional results. However, many comparative studies a

Randomised controlled trials of mood stabilisers for people with autism spectrum disorder: systematic review and meta-analysis.

Despite the widespread use of psychotropic medications in people with autism spectrum disorder (ASD), there is limited evidence to suggest that psychotropic medications including mood stabilisers are effective in individuals with ASD. To carry out a systematic review and meta-analysis of randomised controlled trials (RCTs) that assessed the effectiveness of mood stabilisers in people with ASD. We searched the following databases: Cochrane Library, MEDLINE, Embase, CINAHL, PsycINFO, ERIC, DARE, and ClinicalTrials.gov. In addition, we hand-searched 12 relevant journals. We used the Cochrane Risk of Bias and Jadad scores to assess the quality of included RCTs. We carried out a meta-analysis using a random-effects model. We included eight RCTs (four on valproate, two on levetiracetam, and one each on lamotrigine and topiramate) that included a total of 310 people with ASD, primarily children. Outcomes were based on core and associated ASD symptoms including irritability and aggression but not bipolar disorder. Only two small studies (25%) from the same group showed definite superiority over placebo and one over psychoeducation alone. Meta-analysis of pooled data on the Aberrant Behaviour Checklist-irritability, Clinical Global Impression Scale-improvement, and Overt Aggression Scale (OAS)/OAS-modified did not show any significant inter-group difference. The rates of adverse effects did not show any significant inter-group difference. Given the methodological flaws in the included studies and the contradictory findings, it is difficult to draw any definitive conclusion about the effectiveness of mood stabilisers to treat either ASD core symptoms or associated behaviours. Robust large-scale RCTs are needed in the future to address this issue.PROSPERO registration: CRD42021255467 on 18 May 2021.

Subcortical volumetric alterations as potential predictors of methylphenidate treatment response in youth with attention-deficit/hyperactivity disorder.

Background:Patients with attention-deficit/hyperactivity disorder (ADHD) show structural alterations in the subcortical and dopaminergic regions of the brain. Methylphenidate is a first-line treatment for ADHD, and it is known to affect the subcortical and dopaminergic systems. The degree of pretreatment structural alterations in patients with ADHD may be an important factor in predicting methylphenidate treatment outcomes. The present study examined whether pretreatment volumetric alterations in the subcortical and dopaminergic regions predicted treatment response in youth with ADHD.Methods:This study included 67 youth with ADHD and 25 healthy controls. Youth with ADHD received 8 weeks of methylphenidate treatment. They completed baseline (pretreatment) T1-weighted structural MRI scans and underwent clinical assessments before and after methylphenidate treatment. The healthy controls also completed baseline structural MRI scans. We assessed volumetric alterations using relative volumes (volume of each region of interest/intracranial volume).Results:Among 67 youth with ADHD, 44 were treatment responders and 23 were nonresponders based on post-treatment scores on the Clinical Global Impression Scale–Improvement. Nonresponders had larger volumes in the bilateral amygdala and right thalamus than responders. Nonresponders also had larger volumes in amygdalar subregions (i.e., the bilateral lateral nucleus and right basal nucleus) and hippocampal subregions (i.e., the right hippocampal head and right molecular layer) relative to responders.Limitations:We did not collect post-treatment structural T1-weighted images, so volumetric changes related to methylphenidate treatment in youth with ADHD were undetermined.Conclusion:These findings suggest that pretreatment volumetric alterations in subcortical regions may serve as biomarkers for predicting methylphenidate treatment response in youth with ADHD.

Comparison of the Effectiveness of Three Different Acupuncture Methods for TMD-Related Pain: A Randomized Clinical Study.

Purpose This study aimed to compare the effectiveness of three acupuncture methods for temporomandibular disorders- (TMDs-) related pain. Materials and Methods Different locations of pain, according to DC/TMD clinical assessment, were considered: temporomandibular joint (TMJ), masticatory muscles, head, and neck. Sixty patients were assigned randomly to one of three treatment groups (20 patients in each): group BA received body acupuncture, group EA received electroacupuncture, and group CA received acupuncture + cupping. The groups were compared in terms of pain (verbal numeric scale), pain-related disability (Brief Inventory Pain, BPI), and impression of the treatment's effectiveness (Patients' Global Impression of Improvement Scale, PGI-I). These were recorded before sessions of acupuncture treatment (T0), after 8 sessions of acupuncture treatment (T1), and after 4 weeks of follow-up after treatment (T2). The between-group and within-group differences in the data were analyzed statistically. The baseline characteristics were similar in all groups (p > 0.05). Results Significant improvements were noted in all types of pain compared to baseline values in all groups (all p < 0.05). No significant differences were noted in the improvement of TMDs-related pain according to the different acupuncture techniques (all p > 0.05). All acupuncture methods used resulted to be significantly effective in improving the pain-related interference in the patient's common activities and quality of life. EA resulted to be significantly more effective than BA and CA in improving the interference of pain with patients' mood (p=0.015) and quality of sleep (p=0.014). Conclusion BA, EA, and CA are all effective acupuncture methods in reducing pain and pain interference with common activities and quality of life in patients affected by TMD.

6.32 Assessing the Effect of Youth Involvement in Adverse Event Reporting during a Clinical Trial of Cannabidiol for Youth WITH AUTISM SPECTRUM DISORDER with Complex Verbal Language

Clinical trials in youth with autism spectrum disorder (ASD) have typically neglected the voices of the youth themselves. Besides raising ethical questions, this may also affect the quality of the data obtained. We examined differences in adverse event (AE) reporting between parents and parent-child dyads in an open trial of cannabidiol (CBD). We hypothesized that including youth with ASD in AE reporting would increase the number of total and related AEs independently of response. Twelve youth (ages 7-14 years) with ASD (verbally fluent, IQ ≥ 80) completed a 6-week, Phase 2 open trial of 98% CBD (Epidiolex [V], 100 mg/mL) at 3 or 6 mg/kg/day; target N = 30. An individualized target symptom domain was identified at baseline by clinician consensus from informant report, rating scales, and clinical observation. Responders were defined by Clinical Global Impression Scale–Improvement (CGI-I) ≤ 2 in their target symptom domain. AEs were assessed by phone with parents (weeks 1, 3, 5) and via the UKU (Udvalg for Kliniske Under-sogelser) Side Effects Rating Scale administered by clinicians to dyads (weeks 2, 4, 6). Clinician consensus determined the relatedness of AEs to treatment. Disease-related events (DREs) were considered adverse if the severity or frequency increased. In this interim analysis, we identified response to treatment and AEs, contrasted AE rates (parents vs dyads), and examined the relationship between treatment response and AE profile. All 12 initial participants completed the trial; 4 responded (33%). Clinical Global Impression Scale–Severity (CGI–S) improved significantly from pre- (M = 4.83; SD = 0.39) to posttreatment (M = 3.92; SD = 0.90) (t11 = 3.53; p < 0.004). The most frequent AEs were tiredness (n = 5) and increased emotionality (n = 3). Of 47 total AEs, all were mild and 39 were first reported by dyads. Of 14 related AEs, 9 were first reported by dyads. One DRE occurred: increased severity of restricted, repetitive behaviors. The number of AEs reported by dyads (M = 3.25; SD = 3.14) compared to parents alone (M = 0.67; SD = 0.89) was significantly higher (t11 = 2.18; p = 0.017). Responders and nonresponders did not differ significantly in the number of total or related AEs. This interim analysis suggests that including the input of children with ASD in AE reporting captures a fuller profile of total and related AEs without compromising the study integrity or results.

Efficacy of combination therapy of mid-urethral sling and low-dose Abobotulinumtoxin-A injection in mixed urinary incontinence.

To determine the outcome of combined transobturator tape sling (TOT) and low dose intradetrusor injection of Abobotulinumtoxin-A (Abobot-A, Dysport®) in women with mixed urinary incontinence (MUI). This randomized, active comparator-controlled, parallel-group, two-part clinical trial was conducted on women who had positive Valsalva leak point pressure (VLPP) + detrusor overactivity (DO), cough-associated DO. In Part 1, 20 women with MUI who had a failure of medical and behavioral therapies to cure MUI, randomized in two groups receiving TOT surgery alone, or in combination with Dysport® injection (n = 10 in each group), and then Part 2 was initiated as a prospective open-label on 40 more patients. We performed cystoscopy and injected 300 U of Dysport®in 20-30 intradetrusor injection sites in each patient. The patient's symptoms in both groups decreased significantly after treatment. The symptoms were improved significantly in the combination therapy group according to the International Consultation on Incontinence Questionnaire-overactive bladder (ICIQ-OAB) questionnaire (p < .001), and International Consultation on Incontinence Questionnaire-urinary Incontinence-short form (ICIQ-UI-SF) (p = .041) in comparing with the TOT group. In Part 2, the mean score was 17.10 (4.75) for ICIQ-UI-SF and 9.22 (2.89) for ICIQ-OAB before the treatment. Twelve weeks after the intervention, the median (interquartile range: IQR) of ICIQ-OAB symptoms (2.0 [3.0]; p < .001) and ICIQ-UI-SF decreased, too (1. 0 [2.0]; p < .001). Considering improvement using Patient Global Impression of Improvement scale, 46 (92.0%) stated that they had significant subjective improvement of their symptoms. Combination therapy was accompanied with a promising effect in the patients with MUI according to the results of standardized questionnaires. However, further studies with controlled arms are recommended.

The Use of Platelet-rich Plasma as a Novel Nonsurgical Treatment of the Female Stress Urinary Incontinence: A Prospective Pilot Study

The aim of the study was to evaluate the efficacy and safety of platelet-rich plasma (PRP) for the treatment of stress urinary incontinence (SUI). This was a prospective observational pilot study conducted in a tertiary referral unit, enrolling women with SUI booked for SUI surgery. A total of 20 consecutive women met the inclusion criteria and attended all follow-ups. All participants underwent 2 PRP injections into the lower one third of the anterior vaginal wall at 4- to 6-week intervals. At baseline, they underwent urodynamic studies, a 1-hour pad test, and completed the International Consultation on Incontinence Questionnaire-Female Lower Urinary Tract Symptoms and King's Health Questionnaire. At follow-up visits (1, 3, and 6 months), patients underwent the 1-hour pad test and completed the King's Health Questionnaire, International Consultation on Incontinence Questionnaire-Female Lower Urinary Tract Symptoms, and Patient Global Impression Scale of Improvement. Primary outcome was to evaluate posttreatment SUI. Secondary outcomes included assessment of patient-reported questionnaires, assessment of urine loss (1-hour pad test), and the level of discomfort during injections (visual analog scale score). Statistical analysis was performed before PRP and 1, 3, and 6 months after the last treatment. A significant improvement in SUI symptoms was observed 3 months after treatment with a further improvement at 6 months. A mean reduction of 50.2% in urine loss was observed in the 1-hour pad test. At the 6-month follow-up, 80.0% of women reported to be at least improved. No adverse effects were observed. Platelet-rich plasma injections were both effective and safe at least in the short term and could be offered as an alternative outpatient procedure for the treatment of SUI. However, these encouraging findings warrant further investigation with randomized controlled trials.

The impact of preoperative pelvic pain on outcomes after vaginal reconstructive surgery

Pelvic pain is a debilitating condition that is common among women with pelvic floor disorders. Limited information is known about the impact of preoperative pelvic pain on outcomes after vaginal reconstructive surgery. This study aimed to compare the outcomes after vaginal reconstructive surgery between women with and without preoperative pelvic pain. Baseline and postoperative data were analyzed from the "Outcomes Following Vaginal Prolapse Repair and Midurethral Sling trial." The multicenter trial involved women with anterior prolapse without symptoms of stress incontinence randomized to receive either a midurethral sling or sham incisions during a vaginal reconstructive surgery. Participants completed the visual analog scale adapted for suprapubic pain and Pelvic Floor Distress Inventory at baseline, 3 months, and 12 months. Preoperative pelvic pain was defined as a response of "5" or greater on pain on the visual analog scale or answering "moderately" or "quite a bit" on the Pelvic Floor Distress Inventory question, "Do you usually experience pain in the lower abdomen or genital area?" Outcomes and complication rates were compared between women with and without pelvic pain. The "Outcomes Following Vaginal Prolapse Repair and Midurethral Sling trial" participants included 112 women with pelvic pain (58 had a midurethral sling and 54 had sham incisions) and 212 women without pelvic pain (105 had a midurethral sling and 107 had sham incisions). Women who had a midurethral sling and pelvic pain were younger than women without pelvic pain (60.3±12.1 vs 65.1±8.6; P=.004). Women who had sham incisions and pelvic pain were more likely of Hispanic ethnicity than women without pelvic pain (27.8% vs 9.4%; P=.002). Patient improvement based on the Patient Global Impression of Improvement scale did not differ between arms. Women with pelvic pain had greater improvement on the visual analog scale pain scores after a surgical procedure at 3 months (-3.1±2.9 vs-0.4±1.6; P<.001) and at 12 months (-3.4±3.0 vs-0.6±1.6; P<.001) than women without pain, although their pain scores remained higher than those without preoperative pelvic pain at all time points (P<.001 for all). Similar improvements were found on the Pelvic Floor Distress Inventory and Pelvic Floor Impact Questionnaire. The differences observed were not affected by whether women were in the midurethral sling or sham arm of the trial. Postoperative urinary tract infection and incomplete bladder emptying did not differ between the groups. Women with preoperative pelvic pain experienced significant improvements in pain and pelvic floor symptoms with vaginal reconstructive surgery and had similar subjective improvement postoperatively compared with women without preoperative pelvic pain. Reassuringly, the performance of a midurethral sling did not have an impact on the results.

A French survey on the lockdown consequences of COVID-19 pandemic in Parkinson's disease. The ERCOPARK study

BackgroundIn 2020 the coronavirus disease 19 (COVID-19) pandemic imposed a total and sudden lockdown. We aimed to investigate the consequences of the first COVID-19 lockdown (mid-March – mid-April 2020) on motor and non-motor symptoms (NMS) in a cohort of French people with Parkinson's disease (PwP). MethodsPwP were enrolled either by an on-line survey sent from the national France Parkinson association (FP) to reach the French community of PwP or as part of outpatients' telemedicine visits followed by an hospital-based Parkinson Expert Center (PEC). All patients were evaluated using the same standardized questionnaire assessing motor and NMS (including a list of most disabling, new or worsened symptoms and Patient's Global Impression-Improvement scales [PGI-I]) psycho-social queries and quality of life. Results2653 PwP were included: 441 (16.6%) in the PEC group and 2122 (83.4%) in the community-based group. Physiotherapy was interrupted among 88.6% of the patients. 40.9% referred a clinical modification of their symptoms. Based on the questionnaire, pain (9.3%), rigidity (9.1%) and tremor (8.5%) were the three most frequently new or worsened reported symptoms. Based on the PGI-I, the motor symptoms were the most affected domain, followed by pain and psychic state. PwP in community-based group tended to have more frequent worsening for motor symptoms, motor complications, pain and confusion than those of the PEC group. ConclusionsThe first COVID-19 lockdown had a negative impact on motor and NMS of PwP. Efforts should be allocated to avoid interruption of care, including physiotherapy and physical activities and implement telemedicine. .

Oral and Palmitate Paliperidone Long-Acting Injectable Formulations' Use in Schizophrenia Spectrum Disorders: A Retrospective Cohort Study from the First Episode Psychosis Intervention Program (CRUPEP).

BackgroundLong-acting injectable antipsychotics (LAIs) may be a suitable therapeutic option for those patients in earlier stages of psychosis to avoid relapses and disease progression. Despite that, there is a lack of evidence in the literature regarding the use of LAIs in this profile of patients.MethodsThis is a retrospective cohort analysis to assess the efficacy, tolerability, and pattern of use of palmitate paliperidone long-acting injectable (PPLAI) formulations (1- and 3-month doses) compared to oral paliperidone/risperidone in patients with a nonaffective first episode of psychosis (FEP) over 12 months of follow-up. Relevant sociodemographic and clinical information were assessed, as well as main clinical scales: Positive and Negative Syndrome Scale, Personal and Social Performance Scale, and Clinical Global Impression Scale Improvement and Severity measures.ResultsThe study included 48 patients, 16 per arm, who were aged 20–50 years and had an FEP. Significant improvements were registered for all treatment groups. Despite that, patients receiving PPLAI 1- and 3-month formulations obtained greater improvements than those in the oral group in the main domains assessed (P < .001). We found no statistically significant differences in hospitalizations between groups. Side effects were presented in 24% of patients. A trend towards reducing antipsychotic doses was observed in 43.8% of patients to achieve the minimum effective dose and avoid the occurrence of side effects.ConclusionsTo our knowledge, this is the first study assessing the use of palmitate paliperidone long-acting formulations versus oral risperidone or paliperidone in FEP. Treatment with PPLAI formulations seems to be an effective therapeutic choice at earlier stages of the disease.

Long-term effects of zonisamide in adult patients with intellectual disability.

This study aimed to evaluate the tolerability and efficacy of zonisamide (ZNS) in adult patients with drug-resistant epilepsy and intellectual disability (ID) at our epilepsy centre. By conducting a monocentric, open-label observational study based on standardized seizure records we retrospectively assessed 87 patients (39 female, mean age 40.6±13.6, range 18-75years) with ID and drug-resistant epilepsy. Evaluation, including calculation of retention rate, was performed for the intervals 3-6, 9-12 and 21-24months after ZNS initiation. The Clinical Global Impressions Scale-Improvement (CGI-I) was used to detect qualitative changes in seizure severity and clinical status. Via regression analysis and the generalized estimating equations approach, we examined changes in body weight and impact of patient age also considering associations with other patient characteristics. The retention rate after 24months was 60%. 28% discontinued ZNS therapy due to increasing seizure frequency, lack of efficacy or adverse events (AEs). Sedation (38%), language impairment (19%), challenging behaviour (10%), mild rash (10%) and dizziness (10%) were the commonest AEs. The responder rate was 40%, eight patients (9%) became seizure free. We found CGI-I to be dose-dependent. Regarding changes in body weight, we observed no difference between patients continuing or withdrawing ZNS therapy and responders or non-responders. Though, we identified older age as a significant risk factor for weight loss. Zonisamide may provide a safe and efficient therapeutic option for patients with ID and drug-resistant epilepsy. However, weight status should be carefully monitored, especially in elderly patients.

Effectiveness of Mobilization of the Talus and Distal Fibula in the Management of Acute Lateral Ankle Sprain.

Distal fibular mobilization with movement (MWM), with and without a posterior gliding fibular tape, and anteroposterior mobilization of the talus (MOB) are widely used to treat acute lateral ankle sprains. The purpose of this study was to investigate the short-term and long-term relative effectiveness of these techniques. In this double-blind randomized controlled trial, 45 amateur soccer players with acute (<72hours) lateral ankle sprain were randomly allocated to 6 sessions (3/wk within the first 2weeks) of either MWM, MWM with tape (MWMtape), or MOB. All participants also received general advice, transcutaneous electrical nerve stimulation, edema draining massage, and a program of proprioception exercises. Participant ratings of function on the Foot and Ankle Ability Measure and Patient Global Impression of Improvement Scale were the primary outcomes measured over 52weeks. Secondary outcomes were ankle pain, pressure pain threshold, range of motion, volume, and strength. MWM and MWMtape were equally effective and participants demonstrated greater function on the Foot and Ankle Ability Measure at 12 and 52weeks when compared with those receiving MOB; however, the latter demonstrated superior function at 2weeks. No differences between groups were observed for Patient Global Impression of Improvement Scale or any of the secondary outcomes. There are limited differences in the short term among techniques, with the exception of better sport function with MOB. Over the longer term, the distal fibular MWM is most effective to achieve activities of daily living and sport function when added to usual physical therapy care. The addition of a posterior gliding fibular tape provides no additional benefit. Distal fibular mobilization with movement may be the most appropriate choice of treatment for acute lateral ankle sprain to achieve long-term activities of daily living and sport function. In the short term, anteroposterior mobilization of the talus offers greater improvement in sport function. The use of fibular tape provides no added benefit as an adjunct to a treatment that includes distal fibular mobilization with movement.

Stimulant treatment effectiveness, safety and risk for psychosis in individuals with 22q11.2 deletion syndrome.

This study aimed to retrospectively evaluate an association between stimulant treatment for attention-deficit/hyperactivity disorder (ADHD) in individuals with 22q11.2DS and the development of psychotic disorders, to evaluate long-term effectiveness and safety of stimulant treatment in individuals with 22q11.2DS compared to individuals with idiopathic ADHD, and to explore effects of catechol-O-methyltransferase (COMT) genotype on 22q11.2DS response to stimulants and risk of side effects. Rates of stimulant use and methylphenidate equivalent exposure were compared among individuals with 22q11.2DS, between 51 with psychotic disorders and a control group of 57 22q11.2DS without psychotic disorders, from Tel Aviv and Geneva. In addition, 44 individuals with 22q11.2DS and ADHD from Tel Aviv who initiated stimulants before age 18years were compared to a control group of 35 age- and sex-matched controls with idiopathic ADHD, for treatment effectiveness (Clinical Global Impression Scale-Improvement), and rates of side effects. Stimulant use history and methylphenidate equivalent exposure did not differ among individuals with 22q11.2DS, between those with and without psychotic disorders. The long-term retrospective follow-up (5.3 ± 4.1years) of stimulant-treated individuals with 22q11.2DS showed a higher rate of significant clinical improvement of ADHD symptoms, compared to idiopathic ADHD individuals (p = 0.013), and similar side effect rates. There was no effect of the COMT genotype on response to stimulants or on any side effects. This preliminary long-term retrospective analysis suggests that stimulant treatment in 22q11.2DS is apparently safe in terms of psychosis conversion and rates of side effects, and that it is effective in alleviating ADHD symptoms.

Clinical Outcomes of a Multidisciplinary Female Chronic Pelvic Pain Program

The aim of this study was to describe patient-reported longitudinal outcomes in a multidisciplinary female chronic pelvic pain (CPP) program. We conducted a retrospective cohort study for women cared for in a tertiary, multidisciplinary, female (CPP) program between 2012 and 2017. Patient demographics were collected from electronic medical records. Patients completed the numerical rating scale for pain, Pain Disability Index (PDI), and Patient Global Impression of Improvement scale at each visit. Mixed-effects models were used to assess change in patient responses over time. Patients (N = 317) with a mean age of 44.3 years (SD, 14.6) and median duration of symptoms of 3 years (interquartile range, 1.0-7.0) were assessed in this analysis. The primary diagnosis was pelvic floor myofascial pain (67%). On multivariable analysis, numerical rating scale scores decreased by -0.11 point [95% confidence interval (CI), -0.20 to -0.01] every 3 months (P = 0.03). On multivariable analysis, total PDI score decreased by -0.88 point (95% CI, -1.43 to -0.33) (P = 0.003), and PDI sexual subscores decreased by -0.29 point (95% CI, -0.44 to -0.14) (P < 0.001) every 3 months. A higher (worse) Patient Global Impression of Improvement score was associated with a higher (worse) PDI score at follow-up (odds ratio, 1.04; 95% CI, 1.01-1.07; P = 0.01). Patients in a multidisciplinary CPP program demonstrated improvement over time in pain disability that was associated with an overall global impression of improvement.