Patient Global Impression Of Change Scores Research Articles

A - 32 The Patient Global Impression of Change—a Powerful Complimentary Tool for Assessing Improvement in Concussion Patients

Abstract Objective The purpose of this study was to determine the extent to which patient’s perspective of symptom improvement, as indexed by the Patient Global Impression of Change (PGIC) survey, is associated with symptom improvement on common measures of neurobehavioral and mental health symptoms following concussion. Methods Data were from 474 US active duty service members in interdisciplinary treatment programs for TBI. PGIC rating (range = 1–7) was evaluated for compatibility in assessing improvement in or clinically-elevated neurobehavioral (using Neurobehavioral Symptom Inventory, NSI) and mental health (using Post-traumatic Stress Disorder Checklist, DSM-5, PCL-5 and Patient Health Questionnaire, PHQ-8) symptoms. Results Higher PGIC scores were related to a higher prevalence of a clinically-relevant decrease in NSI, PCL-5 or PHQ-8 scores. Participants with a PGIC rating of 3+ (vs. < 3) were about 2.2 (CI = 1.4–3.5), 1.6 (CI = 1.1–1.3), and 2.7 (CI = 1.4–5.1) times more likely to report a clinically-relevant decrease in NSI, PCL-5 and PHQ-8 symptoms, respectively. Conclusion PGIC may help providers incorporate patients’ perspectives on symptom improvement achieved during rehabilitation. An approach combining PGIC with surveys such as NSI, PCL-5 and PHQ-8 may provide a more comprehensive understanding of symptom improvement and realistic view of expectations for what would be deemed recovery to pre-injury symptom levels.

Pelvic Floor Physical Therapy is Self-Reported as a Minimally Effective, and Sometimes Harmful, Treatment for Pudendal Neuralgia: A Cross-Sectional Study

Objectives: Pudendal neuralgia (PN) is a sexual pain disorder characterized as pain of the genital and/or perineal regions, and despite the lack of clinical evidence supporting its use, pelvic floor physical therapy (PFPT) is a recommended treatment for PN. Methods: An online anonymous cross-sectional survey was administered to participants through convenience sampling conducted on May 19 to September 19, 2023 to understand the self-reported efficacy of PFPT as a treatment for PN. Participants’ measures included sociodemographics, Patient Global Impression of Change (PGIC), and satisfaction scores. Results: The average self-reported PGIC score among participants was 4.6 ± 1.3 (n = 144), indicating no to minimal improvement in symptoms. Most participants (66%) scored 4 or 5, suggesting no change to minimal improvement. Twelve percent of participants scored 3 or lower, indicating worsening of symptoms, and only 22% scored 6 or 7, indicating much or very much improvement of symptoms. Participants who only participated in PFPT (n = 24) had a lower PGIC score of 4.4 ± 1.3. For self-reported satisfaction with PFPT as a treatment for PN, participants self-reported a score of 4.9 ± 3.0, indicating slight dissatisfaction. For those who experienced symptom improvement, the median number of sessions before noticing improvement was five sessions. Conclusion: Based on self-reported results, PFPT is a minimally effective, and sometimes harmful, treatment for PN. Patients should receive greater transparency regarding the lack of efficacy of PFPT and its potential harm.

LeFort Colpocleisis: Unmet Expectations about Correction of Urinary Symptoms Are Related to Disappointment and Regret

ABSTRACT Introduction and Hypothesis: The aims of this study were to define long-term anatomic outcome, satisfaction rate, and reasons for disappointment and regret in a group of patients with advanced pelvic organ prolapse who underwent LeFort colpocleisis (LFC). Materials and Methods: This was a retrospective, single-center, cohort study including consecutive patients who underwent LFC from 2007 to 2021. All patients had surgery involving vaginal hysterectomy and anti-incontinence procedure where clinically indicated. All patients were examined 3 months after surgery. A cross-sectional telephone survey was performed in 2022 using the Patient Global Impression of Severity (PGI-S), Patient Global Impression of Improvement (PGI-I), and Patient Global Impression of Change (PGI-C) questionnaires, as well as the Decision Regret Scale. Student’s t-test, Fisher’s Chi-square test, and univariable logistic regression analysis were carried out. Results: One hundred and forty-one patients (mean age 74.95 ± 6.25 years) were included. The mean preoperative POP Quantification C/D point was +6 (±2.7). In 86 (60.99%) patients, a hysterectomy and in 56 (39.71%), a mid-urethral synthetic sling was performed. At 3-month follow-up, there was one prolapse recurrence (0.71%) and no case of regret of sexual function loss. In the long term, 28 patients died, and 69 patients were interviewed through telephone (follow-up 61.65 months). The mean PGI-S, PGI-I, and PGI-C scores were 1.42 (±0.81), 1.93 (±1.45), and 5.91 (±1.69) respectively, and no patient declared regret about vaginal intercourse loss. Preoperative and postoperative persistent or de novo mixed UI appeared to be related to decreased satisfaction and regret post-LFC (P = 0.0021). Conclusion: LFC is a valuable, easy-to-perform technique with long-lasting results and decreased postoperative anti-incontinence rates. However, de novo or persistent urinary incontinence appears to be related to decreased satisfaction rates.

(133) SELF-REPORTED EFFICACY OF PELVIC FLOOR PHYSICAL THERAPY AS A TREATMENT FOR PUDENDAL NEURALGIA: A CROSS-SECTIONAL STUDY

Abstract Introduction Pudendal neuralgia (PN) is a devastating sexual pain disorder characterized as pain of the genital and/or perineal regions and is often due to injury, irritation, or entrapment of the pudendal nerve. Pelvic floor physical therapy (PFPT) is a recommended treatment for PN despite the lack of clinical evidence supporting its use. Objective We aimed to understand the efficacy of PFPT for treating PN by evaluating self-reported efficacy from PN patients. Methods An online survey was conducted on PN patients who had participated in PFPT as a treatment for PN. Participants were asked to evaluate the efficacy of PFPT specifically regarding its effects on PN symptoms using a seven-point Patient Global Impression of Change (PGIC) scale: 1=very much worse, 2=much worse, 3=minimally worse, 4=no change, 5=minimally improved, 6=much improved, 7=very much improved. If lasting symptom improvement was achieved, participants were asked how many sessions before they first noticed an improvement in symptoms. Results The average PGIC score among participants was 4.6 ± 1.3 (n=144), indicating no to minimal improvement in symptoms. Twelve percent of participants scored 3 or lower, indicating worsening of symptoms, and only 22% scored 6 or 7, indicating much or very much improvement of symptoms. For those who had symptom improvement, 14.6% of participants reported improvement after only one PFPT session, and five was the median number of sessions before first noticing improvement. Conclusions PFPT is a minimally effective, and sometimes harmful, treatment for pudendal neuralgia. Better transparency should be provided to patients regarding PFPT’s lack of efficacy and potential harm for treating PN symptoms. Disclosure No.

The Patient Global Impression of Change as a complementary tool to account for neurobehavioral and mental health symptom improvement for patients with concussion

Purpose The purpose of this study was to determine the extent to which patient’s perspective of symptom improvement, as indexed by the Patient Global Impression of Change (PGIC) survey, is associated with symptom improvement on common measures of neurobehavioral and mental health symptoms following concussion. Materials and methods Data were from 449 US active duty service members receiving treatment in interdisciplinary programs for their concussion. PGIC rating (range = 1–7) was evaluated for compatibility in assessing improvement in or clinically-elevated neurobehavioral (using Neurobehavioral Symptom Inventory [NSI]) and mental health (using Post-traumatic Stress Disorder Checklist, DSM-5 [PCL-5] and Patient Health Questionnaire [PHQ-8]) symptoms. Results Higher PGIC scores were related to a higher prevalence of clinically-relevant decrease in NSI, PCL-5 or PHQ-8 scores. Participants with a PGIC rating of 3+ (vs.<3) were about 2.2 (CI = 1.4–3.5), 1.6 (CI = 1.1–1.3), and 2.7 (CI = 1.4–5.1) times more likely to report clinically-relevant decrease in NSI, PCL-5 and PHQ-8 symptoms, respectively. Conclusion PGIC may help providers incorporate patients’ perspectives on symptom improvement achieved during rehabilitation. An approach combining PGIC with surveys such as NSI, PCL-5 and PHQ-8 may provide a more comprehensive understanding of symptom improvement and realistic view of expectations for what would be deemed recovery to pre-injury symptom levels.

A clinical audit in a UK-based acupuncture private practice: assessing patient demographics, outcomes and experience.

The aim of this clinical audit was to assess patient demographics, outcomes and experience with care in patients who received acupuncture in a private practice setting in the United Kingdom. Demographic and clinical data were extracted from patients' records over a 7-year period. The Measure Yourself Medical Outcomes Profile (MYMOP) questionnaire and an adapted Patient Global Impression of Change (PGIC) scale were used routinely to monitor patient outcomes over an 18-month period. Finally, a retrospective questionnaire was used to assess patient beliefs regarding treatment effectiveness, adverse events and overall experience with care. Patients not providing consent or known to be deceased were excluded. Data were collected for 306 patients presenting with 376 separate health complaints, 58% of which were musculoskeletal. Follow-up outcomes (MYMOP scores (n = 51) and PGIC scale responses (n = 50)) showed a clinically significant improvement compared to baseline for the majority of health complaints (93% of PGIC scores were 'improved' and 79% MYMOP demonstrated > 1 point change). Total mean MYMOP severity scores were reduced by almost 50% (p < 0.001) after 1-4 weeks, and this was sustained in the medium-to-long term. There was a strong negative correlation (r = -0.767, p < 0.001) between the MYMOP and PGIC scores. A total of 118 health complaints were reported by 85/255 patients who responded to a retrospective questionnaire. Over 84% of patients believed that the treatments they received were 'effective' at addressing their health complaints. Seven minor adverse events were reported and four patients experienced negative treatment outcomes. Although musculoskeletal conditions were the most common, this audit found that patients sought treatment for a wide range of predominantly chronic health complaints, for many of which there is a currently a lack of quality evidence to support the use of acupuncture. Overall, the small sample of patients who responded to outcome questionnaires reported clinically meaningful and sustained improvements.

Effectiveness and safety of hominis placental pharmacopuncture for chronic temporomandibular disorder: A multi-center randomized controlled trial

BackgroundHominis placental (HPP) extract has been approved by the Ministry of Food and Drug Safety in Korea for treating chronic liver diseases and postmenopausal syndrome. However, its efficacy and safety for treating chronic temporomandibular disorder (TMD) remains unclear. We aimed to assess the effectiveness and safety of HPP for treating chronic TMD compared with physical therapy (PT). MethodsThis study is a 2-arm parallel, multi-center, randomized controlled trial. We enrolled 82 chronic TMD patients from 2 Korean medicine hospitals between December 2019 and January 2021. We included patients with chronic TMD and randomly assigned them to undergo HPP or PT. The primary outcome was the difference in the scores for temporomandibular joint (TMJ) pain at baseline and week 6. The secondary outcomes were the scores for TMJ pain and bothersomeness, TMJ range of motion, the Korean version of Beck's depression index-Ⅱ, jaw functional limitation scale (JFLS) score, patient global impression of change (PGIC) scores, EuroQoL 5-dimension 5-level score, and short form-12 health survey (SF-12) scores. ResultsCompared with PT, HPP showed significantly superior effects on TMJ pain and bothersomeness, protrusive movement pain, JFLS (verbal, emotional, and global), SF-12, and PGIC scores at week 6 (P < 0.05). Compared with the PT group, the HPP group showed a significantly higher recovery rate (≥50 % reduction in the scores for TMJ pain at the 24-week follow-up). ConclusionHPP was more effective than PT managing pain and improving function and quality of life. Our findings demonstrate the effectiveness and safety of HPP for TMD treatment. Trial registrationThis study has been registered at clinicalTrials.gov (NCT04087005), Clinical Research Information Service (CRIS) (KCT0004437), and Ministry of Food and Drug Safety (No. 31886).

Percutaneous delivery of liquid tetracycline using a thermal resurfacing drug delivery system for the treatment of festoons.

To examine the effects of percutaneous tetracycline delivery to the malar area using a thermomechanical device (Tixel) in patients suffering from festoons. This retrospective study included patients who underwent combination treatment with a thermomechanical device (Tixel) followed by application of topical tetracycline 1% at two private clinics between 2019 and 2023. Demographic and medical data, treatment parameters along with before and after treatment photographs were retrieved retrospectively. All patients were asked to answer a questionnaire, assessing self-reported pre and posttreatment disturbance, patient global impression of change (PGIC) score, overall satisfaction with treatment, and the onset and duration of treatment effect. Finally, three masked reviewers evaluated and graded the severity of before and after treatment photographs. Twenty healthy patients received the combination treatment. The mean age was 59.4 ± 8.2 years (range: 45-72 years), and 90.0% (n = 18) were female. The number of treatment sessions per patient ranged from 2 to 8, mean of 5.0 ± 1.9, performed at 5.4 ± 1.2-week intervals. The masked reviewers' grading scores demonstrated a significant improvement (2.81 ± 1.3 before vs. 1.6 ± 1.1 after, p < 0.001). The self-reported disturbance caused by the festoons improved significantly as well (4.7 ± 0.98 vs. 1.7 ± 1.1, p < 0.001). On the PGIC score, 85% (17/20) reported moderate (grade 5) to significant (grade 7) improvement of symptoms and life quality after treatment. Improvement onset was reported to occur 11.2 ± 6.6 days after the first treatment (range 2-30 days), and 90% (18/20) of the patients reported improvement lasting at least 4 months after completion of the second treatment. Topical tetracycline application following Tixel treatment induced significant improvement in patient with festoons.

512 - Dupilumab treatment improves satisfaction in patients with prurigo nodularis who did not achieve the multicomponent endpoint: analysis from LIBERTY-PN PRIME and PRIME2

Abstract Introduction Patients with prurigo nodularis (PN) often report high disease burden with substantial impact on quality of life. Patient Global Impression of Change (PGIC) and Severity (PGIS) are patient self-assessment measures that quantify their experience of disease during treatment. Dupilumab has recently been approved as the first systemic treatment for PN in the US and Europe. Objectives To evaluate patient-reported global impression of disease severity improvement in dupilumab-treated patients with PN during the LIBERTY-PN PRIME and PRIME 2 trials. Materials &amp; Methods PRIME and PRIME2 were randomized, double-blind, multicenter, parallel-group, 24-week, phase 3 trials in adults with PN with ≥20 nodules and severe itch, inadequately controlled with topical prescription therapies or for whom these are inadvisable. Patients received 300 mg dupilumab subcutaneously (600 mg loading dose; n = 153) or matched placebo (n = 158) every 2 weeks. In this analysis, data from the two studies were pooled. Patient satisfaction was assessed in the overall placebo group, overall dupilumab-treated group, and those treated with dupilumab who did not achieve the stringent multicomponent endpoint (n = 99) of ≥4-point improvement from baseline in Worst Itch Numerical Rating Scale (WI-NRS, range: 0–10) and an Investigator’s Global Assessment PN Stage (IGA PN-S, score range: 0–4) score 0 or 1 (clear or almost clear; ≤5 nodules) at Week (W) 24. Endpoints include proportion of patients achieving: PGIC (range: 0–6) scores of 0 or 1 (very much better or moderately better) at W12, and W24; and PGIS (range: 1–4) score of 1 or 2 (none or mild) at baseline, W12, and W24. Safety was also assessed. Results Baseline demographic and clinical characteristics were generally similar between groups. In the overall dupilumab and placebo groups, baseline mean (SD) WI-NRS scores were 8.6 (0.9) and 8.4 (1.1), respectively; 32.7% and 34.2% had an IGA PN-S score of 4 (remaining patients had IGA PN-S 3); and mean (SD) PGIS scores were 3.7 (0.5) and 3.7 (0.5) respectively. In dupilumab multicomponent endpoint non-responders, mean (SD) WI-NRS score was 8.6 (0.9). 35.4% and 64.6% had an IGA PN-S score of 4 and 3 respectively; and mean (SD) PGIS score was 3.7 (0.5). At W12, 68.0% vs 38.0% (P &amp;lt; 0.0001 vs placebo) of dupilumab-treated vs placebo-receiving patients achieved PGIC 0 or 1, while 55.6% of dupilumab multicomponent non-responders achieved this endpoint (P = 0.0099 vs placebo). At W24, this increased to 74.5% vs 32.9% (P &amp;lt; 0.0001 vs placebo) of dupilumab-treated vs placebo-receiving patients achieving PGIC 0 or 1, and 61.6% of multicomponent non-achievers (P &amp;lt; 0.0001 vs placebo). At W12, 51.6% vs 22.2% (P &amp;lt; 0.0001 vs placebo) of dupilumab-treated vs placebo-receiving patients achieved PGIS 1 or 2, while 40.4% of multicomponent non-responders achieved the endpoint (P = 0.0027 vs placebo). At W24, 61.4% vs 24.1% (P &amp;lt; 0.0001 vs placebo) of dupilumab-treated vs placebo-receiving patients achieved PGIS 1 or 2, while 44.4% of multicomponent non-responders achieved the endpoint (P = 0.0025 vs placebo). Safety findings were consistent with the known dupilumab safety profile. Conclusions While not all patients achieved the stringent multicomponent endpoint within the 24-week treatment period during PRIME and PRIME 2 trials, around half of the dupilumab-treated patients still reported significantly more improvement in disease severity and satisfaction with therapy. Overall safety was consistent with the known dupilumab safety profile.

Transcutaneous Electrical Nerve Stimulation Integrated into Pants for the Relief of Postoperative Pain in Hip Surgery Patients: A Randomized Trial.

The effect of transcutaneous electrical nerve stimulation (TENS) on pain and impression of change was assessed during a 2.5-hour intervention on the first postoperative days following hip surgery in a randomized, single-blinded, placebo-controlled trial involving 30 patients. Mixed-frequency TENS (2 Hz/80 Hz) was administered using specially designed pants integrating modular textile electrodes to facilitate stimulation both at rest and during activity. The treatment outcome was assessed by self-reported pain Numerical Rating Scale (NRS) and Patient Global Impression of Change (PGIC) scores at four time points. The ability to perform a 3-meter walk test and the use of analgesics were also evaluated. Group comparison and repeated-measure analysis were carried out using nonparametric statistics. The active TENS group exhibited significantly higher PGIC scores after 30 minutes, which persisted throughout the intervention (all p ≤ 0.001). A reduction in NRS appeared after one hour of active TENS, persisting throughout the intervention (all p ≤ 0.05). The median group differences in pain ratings were greater than the minimum clinically important difference, and the analysis of pain trajectories confirmed clinical significance at the individual level. Moreover, patients in the active TENS group were more likely able to perform a 3-meter walk test by the end of the intervention (p = 0.04). Analysis of the opioid-sparing effect of TENS was inconclusive (p = 0.066). No postoperative surgical complications or TENS-related side effects were observed during the study. Mixed-frequency TENS integrated in pants could potentially be an interesting addition to the arsenal of treatments for multimodal analgesia following hip surgery. This trial is registered with NCT05678101.

Assessment of Minimal Clinically Important Difference in Patient-Reported Myelofibrosis-Associated Symptoms Using an Anchor-Based Analysis Based on MANIFEST Arm 3 Data

Background Myelofibrosis (MF) is a life-threatening hematologic neoplasm that can arise as a primary condition or as a progression from polycythemia vera or essential thrombocythemia. The MF Symptom Assessment Form (MFSAF) v4.0 is a seven-item questionnaire that assesses symptom severity from the patients' (pts) perspective. Each item is rated on a scale from 0 (Absent) to 10 (Worst Imaginable). The MFSAF Total Symptom Score (TSS) ranges from 0 to 70, with higher scores indicating worse symptoms. A ≥50% reduction in TSS (TSS50) is a commonly used binary endpoint in clinical trials. However, the clinical meaningfulness of the dichotomization of response at 50% cutoff across the spectrum of responses remains uncertain. The relevance of considering TSS as a continuous endpoint in MF studies is assessed here to capture the full spectrum of symptom changes, enabling a potentially more accurate assessment of treatment effects. Pelabresib (CPI-0610) is an investigational oral small-molecule BET inhibitor, while the Janus kinase inhibitors (JAKis) ruxolitinib or fedratinib are the current standard of care for intermediate- or high-risk pts with MF.InArm 3 of the Phase 2 MANIFEST trial of JAKi treatment-naïve pts with MF treated with pelabresib and ruxolitinib, 56% achieved TSS50 response at Week (Wk) 24. Aims This anchor-based analysis aims to determine the minimal clinically important difference (MCID) of change in TSS as a continuous endpoint, based on data from JAKi treatment-naïve pts with MF treated with pelabresib and ruxolitinib, to better evaluate the incremental clinical benefit of treatment effects. Methods Data from Arm 3 of the MANIFEST Phase 2 study of treatment-naïve pts with MF treated with pelabresib combined with ruxolitinib were used (July 29, 2022 data cut). Anchor-based methods compare the change in a scale-based outcome measure with that of an established patient-reported outcome (PRO). These methods are commonly used to establish the MCID, defined as the smallest difference in score that pts consider beneficial. In this analysis, the Patient Global Impression of Change (PGIC), a seven-point scale reflecting overall improvement compared with baseline (BL), was used as the anchor PRO. On the PGIC, pts rated their change from ‘very much improved’ to ‘very much worse’ (Table 1). The relationship between TSS changes (percentage and absolute) at Wk 24 and PGIC categories was examined using correlation and graphical analyses. Linear and quantile regressions were applied to assess the impact of a one-point difference in PGIC score on TSS change at Wk 24, adjusting for BL TSS score. Only pts with available TSS and PGIC data at Wk 24 were included, with no imputation for missing values. Results In Arm 3 of the MANIFEST trial, 78 of 84 pts treated with pelabresib and ruxolitinib had complete TSS data and PGIC at Wk 24. At BL, mean TSS was 16.4 (SD=8.4), and median TSS was 15.5 (range 2.0-38.3). A -58.8% and -7.7 median percentage and absolute reduction in TSS at Wk 24 was observed, respectively. For PGIC at Wk 24 (Table 1), only six pts (7.7%) scored in the three worsening PGIC categories. Percentage and absolute changes in TSS, and the percentage TSS50 responders for each PGIC category are shown in Table 1. Linear regression demonstrated that a one-category increase in PGIC (indicating worsening) corresponded to an 11.89% increase (95% CI 3.12-20.65) in TSS (indicating worsening) at Wk 24. The quantile regression estimate for this relationship was 11.36% (3.53-19.19). For absolute change at Wk 24, a one-category increase in PGIC resulted in a 1.67 (range 0.74-2.60) increase in mean TSS, with a 1.87 (range 0.62-3.12) increase in median TSS. Conclusion Assuming a one-category change in the seven-category PGIC represents a clinically meaningful difference, the analyses suggest that the MCID in TSS for JAKi treatment-naïve pts with MF could be approximately 11-12% for percentage change from BL and approximately 1.5-2 points for absolute change from BL. These findings provide valuable guidance for assessing treatment outcomes and evaluating symptom improvements' clinical significance in this patient population. Further exploration of these findings requires larger data sets, which will be addressed in the forthcoming Phase 3 MANIFEST-2 study evaluating pelabresib and ruxolitinib versus placebo and ruxolitinib in JAKi treatment-naïve pts with MF.

Foot Surgery Using Resorbable Magnesium Screws

The use of bioabsorbable magnesium (Mg) screws is new in foot surgery. Their relative merit over conventional titanium screws has not yet been proven. This prospective case series study was conducted to compare the clinical and radiological outcomes of bioabsorbable Mg screws and titanium screws. A consecutive series of patients (n=60; 11 men and 49 women) underwent corrective hallux valgus surgery. The minimum follow-up period was 1 year. The assessment was based on a patient questionnaire, including the American Orthopedic Foot and Ankle Society(AOFAS) hallux valgus score, visual analog scale, patient's global impression of change (PGIC), and fifth metatarsus circumference (IF5C). The radiographic assessment included the intermetatarsal and hallux valgus angles, as well as time to osteotomy union and hardware failure. At 1 year, similar results were obtained radiographically. The healing of the osteotomies was significantly faster in the Mg group. Hardware failure was common in the Mg group (5/26) than in the TI group (0/34) but hardware removal was more common in the TI group (6/34) versus the MG group (0/26). IF5C increased by 8 ± 2 mm in the Mg group. The AOFAS and PGIC scores at 6 months were similar. Validated foot scores and radiographic analysis indicated that there was no detectable difference between the groups. The fast achievement of osteotomy union compensates for a high rate of hardware failure, resulting in patient satisfaction and avoiding reoperation for hardware removal.

P.016 Impact of eptinezumab on patient-reported outcomes in patients with prior preventive treatment failures

Background: In DELIVER, eptinezumab reduced migraine frequency and was well tolerated in patients with migraine and prior preventive treatment failures. This analysis evaluated changes in patient-reported outcomes (PROs). Methods: DELIVER (NCT04418765; phase 3b double-blind study) randomized adults with migraine and 2-4 prior preventive treatment failures to eptinezumab or placebo every 12 weeks. The assessed PROs included EuroQol 5-Dimensions 5-Levels visual analogue scale (EQ-5D-5L VAS); 6-item Headache Impact Test (HIT-6), Patient Global Impression of Change (PGIC), most bothersome symptom (MBS), and Migraine-Specific Quality of Life Questionnaire (MSQ, v2.1). Results: Patients received eptinezumab 100mg (n=299), 300mg (n=294), or placebo (n=298). Mean changes from baseline to Wk12 in EQ-5D-5L VAS scores were 2.0 (100mg, P=0.0007) and 4.4 (300mg, P&lt;0.0001) versus -3.1 (placebo), and were maintained or further improved to Wk24 (2.0, 5.2, -2.8, respectively). Mean baseline HIT-6 total scores were ~66.4, with mean changes of -6.9 (100mg, P&lt;0.0001) and -8.5 (300mg, P&lt;0.0001) versus -3.1 (placebo) at Wk12 that were further improved through Wk24 (-8.9 and -9.9 vs -3.9). PGIC, MBS, and MSQ domain scores showed greater improvement for eptinezumab than placebo. Conclusions: In adults with migraine and prior preventive treatment failures, eptinezumab robustly improved health-related quality of life and migraine-related burden over 24 weeks versus placebo.

ID: 215734 Correlation of Change in Pain Score and PGIC Following Spinal Cord Trials and Implants

Though Numerical Rating Scale (NRS) pain scores are often used to assess response to pain treatments, global ratings of improvement and satisfaction such as the Patient Global Impression of Change (PGIC) scale allow the participants to provide a composite report of their experience (Dworkin 2005). Previous research found a moderate correlation between PGIC and NRS scores (Perrot 2019). Other studies have found similar correlations between PGIC and other methods of assessment (Rampakakis et al, 2015). In this study, we determined the correlation between PGIC and change in pain scores following SCS implants and trials.

Sustained Treatment Response With Long-Term Valbenazine in Patients With Tardive Dyskinesia

AbstractBackgroundValbenazine is a once-daily VMAT2 inhibitor approved for the treatment of tardive dyskinesia (TD), a persistent and potentially disabling movement disorder associated with prolonged exposure to antipsychotics, antiemetics, and other dopamine receptor blocking agents. The efficacy, safety, and tolerability of valbenazine has been established in several phase 3 trials, including a long-term study (KINECT 4 [NCT02405091]) in which participants received open-label valbenazine (40 or 80 mg) for 48 weeks. Post hoc analyses of KINECT 4 data were conducted to assess patterns of treatment response.MethodsData from KINECT 4 treatment completers (participants who reached the Week 48 visit and had the longest duration of treatment) were analyzed post hoc. TD was assessed using the Abnormal Involuntary Movement Scale (AIMS) total score (sum of items 1–7, as rated by the study investigator), the Clinical Global Impression of Change-Tardive Dyskinesia (CGI-TD), and the Patient Global Impression of Change (PGIC). Analyses were conducted at Week 8 (first study visit after the valbenazine dose-optimization period) and Week 48 using the following definitions of response: ≥50% and ≥70% improvement from baseline in AIMS total score; rating of “much improved” or “very much improved” (score ≤2) on the CGI-TD and PGIC.ResultsOf the 167 participants who entered KINECT 4, 103 (62%) were treatment completers and included for analysis. Of these 103 participants, 39% and 86% met the ≥50% AIMS response threshold at Weeks 8 and 48, respectively. The percentages of participants who met the highly rigorous AIMS ≥70% response threshold at Weeks 8 and 48 were 17% and 52%, respectively. Of the 40 participants with AIMS ≥50% total score improvement at Week 8, 95% also met this threshold at Week 48 (“sustained response”). Of the 63 participants with &lt;50% AIMS improvement at Week 8, 81% achieved the ≥50% response threshold by end of treatment at Week 48. The proportion of participants meeting the threshold for CGI-TD response also increased over time, from 50% at Week 8 to 92% at Week 48. PGIC results were similar, with response rates of 53% and 88% at Weeks 8 and 48, respectively.ConclusionsPost hoc analyses of data from a 48-week, open-label study of once-daily valbenazine showed that the proportion of participants meeting rigorous treatment response thresholds increased over time. By the end of treatment at Week 48, &gt;80% of participants demonstrated robust improvements in TD, as assessed using the AIMS (≥50% improvement), CGI-TD (score ≤2), and PGIC (score ≤2).FundingNeurocrine Biosciences, Inc.

A prospective study of BurstDR™ spinal cord stimulation for non-operated discogenic low back pain.

Chronic discogenic low back pain (CD-LBP) is caused by degeneration of the disc due to trauma to the annulus or by unprovoked degeneration, resulting in chronic pain. Spinal cord stimulation (SCS) employing the BurstDR™ waveform has been shown to be an effective treatment in a variety of chronic pain conditions. The aim of this prospective case study was to determine the effect of BurstDR™ SCS on pain relief, disability, and patient satisfaction in a population with CD-LBP. Seventeen subjects with CD-LBP received a SCS trial with BurstDR™ stimulation. Patients with >50% pain relief after a trial period of 2 weeks were permanently implanted (n=15). Patients then rated LBP and leg pain using the numeric rating scale (NRS), Oswestry disability index (ODI), patient global impression of change (PGIC), EQ-5D quality of life, and painDETECT for neuropathic pain at baseline following trial, 3, 6, and 12 months after permanent implantation. Treatment with BurstDR™ SCS resulted in significant reduction of LBP as the NRS was reduced from 71.7 ± 7.3 at baseline to 42.5 ± 18.1 at 12 months. Average pain relief at 12 months was 42.5%. In patients with leg pain (n=8), pain was significantly reduced from 66.9 ± 8.2 to 11.7 ± 10.4 at 12 months. PainDETECT scores for neuropathic pain significantly reduced from 18.9 ± 4.8 at baseline, and 14.8 ± 3.2 at 12 months. Baseline ODI score significantly reduced from 41.2 ± 12.8 to 25.8 ± 8.6 at 12 months. PGIC scores remained low from 2.6 ± 1.6 at 3months, 2.5 ± 1.0 at 6months, and 2.5 ± 1.3 at 12 months. EQ-5D-5L rates remained constant from baseline 56.10 ± 23.9 to 68.6 ± 12.9 at 12 months. BurstDR™ SCS resulted in significant reduction of back pain, leg pain, and quality of life in patients with CD-LBP and decreased the level of disability and generated positive patient satisfaction scores.

Validation and Meaningful Change Thresholds for an Objective Cough Frequency Measurement in Chronic Cough

PurposeObjective cough frequency is used to assess efficacy of chronic cough (CC) treatments. The objective of this study was to explore the relationship between objective cough frequency and cough-specific patient-reported outcomes (PROs) and estimate a clinically meaningful change threshold (MCT) for objective cough frequency.MethodsData collected in a phase 2b study in participants with refractory or unexplained CC were used to investigate the relationship between 24-h cough frequency (measured using an ambulatory cough monitor) and cough-specific PROs (i.e., cough severity visual analog scale, cough severity diary, Leicester Cough Questionnaire). Convergent validity was assessed using Spearman ρ. An MCT for 24-h cough frequency was estimated using the patient global impression of change (PGIC) scale as an anchor.ResultsCorrelations between 24-h cough frequency and cough-specific PROs at baseline, Week 4, and Week 12 were significant (P < 0.0001) but low to moderate in strength (ρ = 0.30–0.58). Participants categorized as very much improved/much improved (i.e., PGIC of 1 or 2) or minimally improved (i.e., PGIC of 3) had mean 24-h cough frequency reductions of 55% and 30%, respectively. Receiver operating characteristic curve analysis suggested that a 24-h cough frequency reduction of 38% optimizes sensitivity and specificity for predicting a PGIC score of 1–3.ConclusionObjective 24-h cough frequency is significantly associated with cough-specific PROs, but cough frequency and PROs most likely capture distinct aspects of CC. A ≥ 30% reduction in 24-h cough frequency is a reasonable MCT to define treatment response in CC clinical trials.

Effects of Levodopa-Carbidopa Intestinal Gel Compared with Optimized Medical Treatment on Nonmotor Symptoms in Advanced Parkinson's Disease: INSIGHTS Study.

Nonmotor symptoms (NMS) are common in advanced Parkinson's disease (APD) and reduce health-related quality of life. The aim of the study was to evaluate levodopa-carbidopa intestinal gel (LCIG) versus optimized medical treatment (OMT) on NMS in APD. INSIGHTS was a phase 3b, open-label, randomized, multicenter study in patients with APD (LCIG or OMT, 26 weeks) (NCT02549092). Primary outcomes assessed were total NMS (NMS scale (NMSS) and PD sleep scale (PDSS-2)). Key secondary outcomes included the Unified PD Rating Scale (UPDRS) Part II, Clinical Global Impression of Change (CGI-C), and PD Questionnaire-8 (PDQ-8). Additional secondary measures of Patient Global Impression of Change (PGIC), King's PD Pain Scale (KPPS), and Parkinson Anxiety Scale (PAS) also were evaluated. Finally, safety was assessed. Out of 89 patients randomized, 87 were included in the analysis (LCIG, n = 43; OMT, n = 44). There were no significant differences in NMSS or PDSS-2 total score changes (baseline to Week 26) between LCIG and OMT; within-group changes were significant for NMSS (LCIG, p < 0.001; OMT, p = 0.005) and PDSS-2 (LCIG, p < 0.001; OMT, p < 0.001). Between-group treatment differences were nominally significant for UPDRS Part II (p = 0.006) and CGI-C (p < 0.001) at Week 26 in favor of LCIG; however, statistical significance could not be claimed in light of primary efficacy outcomes. PGIC (Week 26) and KPPS (Week 12) scores were nominally significantly reduced with LCIG versus OMT (p < 0.001; p < 0.05). There were no significant differences in PDQ-8 or PAS. Adverse events (AEs) were mostly mild to moderate; common serious AEs were pneumoperitoneum (n = 2) and stoma-site infection (n = 2) (LCIG). There were no significant differences between LCIG versus OMT in NMSS or PDSS-2; both LCIG and OMT groups significantly improved from baseline. AEs were consistent with the known safety profile.

Using artificial intelligence to analyze publicly available social media posts to understand patient perspectives toward specific treatments of alopecia areata

Although studies exist on the clinical efficacy of alopecia areata (AA) treatments, there are limited data on patient-perceived efficacy and satisfaction. Patients’ perception of efficacy may not always match providers’ perceived efficacy because clinicians’ ratings of successful outcomes, side effects, costs, etc1Mesinkovska N. King B. Mirmirani P. Ko J. Cassella J. Burden of illness in alopecia areata: a cross-sectional online survey study.J Investig Dermatol Symp Proc. 2020; 20: S62-S68Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar were not developed with patient input. Because of the psychosocial burden associated with AA,2Titeca G. Goudetsidis L. Francq B. et al.'The psychosocial burden of alopecia areata and androgenetica': a cross-sectional multicentre study among dermatological out-patients in 13 european countries.J Eur Acad Dermatol Venereol. 2020; 34: 406-411Crossref PubMed Scopus (31) Google Scholar many patients use social media to discuss their disease, offering perspectives into disease burden and treatment satisfaction.3Aldhouse N.V.J. Kitchen H. Knight S. et al.“‘You lose your hair, what’s the big deal?’ I was so embarrassed, I was so self-conscious, I was so depressed:” a qualitative interview study to understand the psychosocial burden of alopecia areata.J Patient Rep Outcomes. 2020; 4: 76Crossref PubMed Scopus (16) Google Scholar Our study analyzed 102,444 public social media posts from Facebook, Twitter, Reddit, and Instagram regarding AA treatment. Analysis aimed to determine patient-perceived efficacy of treatment and identify efficacious treatments associated with a negative emotional response. The treatments included were minoxidil, dexamethasone (oral), prednisone (oral), triamcinolone (injection), biotin, essential oils, JAK Inhibitors, and wig/hairpiece. The Brandwatch artificial intelligence-powered database identified posts related to AA treatments. Natural language processing provided a Patient Global Impression of Change (PGIC) score4Wyrwich K.W. Winnette R. Bender R. et al.Validation of the alopecia areata patient priority outcomes (aappo) questionnaire in adults and adolescents with alopecia areata.Dermatol Ther (Heidelb). 2022; 12: 149-166Crossref PubMed Scopus (2) Google Scholar following treatment for each post. Emolex identified underlying positive or negative emotion behind posts. PGIC scores and underlying emotion were compared between posts for each treatment using an independent samples Student t test. For all treatment modalities except dexamethasone, there were >75% positive PGIC score posts, indicating most reported some degree of improvement in AA. For dexamethasone, only 34.5% posts included a positive PGIC score, indicating most reported either no improvement or worsening of AA (Table I).Table IAlopecia areata social media posts from May 2008 to February 2020Drug/treatmentNumber of positive PGIC posts (%)Number of neutral PGIC posts (%)Number of negative PGIC posts (%)Total number of postsMinoxidil23,269 (85.2)789 (2.9)3255 (11.9)27,313Dexamethasone (oral)1919 (34.5)938 (16.9)2705 (48.6)5562Prednisone (oral)8104 (78.7)608 (5.9)1590 (15.4)10,302Triamcinolone (injection)86 (83.5)7 (6.8)10 (9.7)103Biotin28,606 (89.2)431 (1.3)3045 (9.5)32,082Essential oils6931 (92.2)263 (3.5)321 (4.3)7515JAK inhibitors674 (85.1)11 (1.4)107 (13.5)792Wigs/hairpiece16,041 (85.4)186 (1.0)2548 (13.6)18,775PGIC, Patient Global Impression of Change. Open table in a new tab PGIC, Patient Global Impression of Change. When comparing underlying emotion and PGIC scores, minoxidil, JAK inhibitors, and prednisone had significantly more posts with positive PGIC score and negative underlying emotion than posts with positive PGIC score and positive underlying emotion. This suggests that although >75% patients using these treatments noticed improvement in AA, a significant number still had underlying negative sentiments (Fig 1). Biotin and wigs/hairpieces were also associated with more underlying negative emotion in positive PGIC score posts, although this difference was not significant. For dexamethasone, even in the small proportion that reported a positive PGIC score, a significant number of patients indicated a negative underlying sentiment. For essential oils treatment and triamcinolone, more positive PGIC score posts had a positive underlying sentiment, suggesting that most patients using these treatments noticed improvement and were satisfied, although this was not statistically significant. In terms of limitations, our study involved only self-identified patients with AA without verification that posts were from clinically diagnosed patients with AA. Also, our findings may be biased toward populations that utilize social media and may not represent all patients with AA. “Essential oils” could include different ingredients and we were unable to standardize ingredients based on our methodology. Although the study’s purpose was to analyze “subjective” data in online patient perspectives, future studies could combine electronic medical records with patient posts to understand the gap between “objective” improvement and what makes a patient happy/satisfied with treatment. Further analysis of these data may reveal reasons associated with the satisfaction category. Our findings could assist providers in optimizing treatment regimen(s) for patients with AA and allow for consideration of patient preferences in choosing treatment(s). This could improve patient-centered care and patient satisfaction, creating a better patient-provider relationship. None disclosed.

Headache response after CT-guided fibrin glue occlusion of CSF-venous fistulas.

To assess headache response and patient perception of improvement after computed tomography (CT)-guided fibrin glue occlusion of cerebrospinal fluid-venous fistulas (CVFs) in a large sample size and with a long clinical follow-up. CVFs are an increasingly identified type of spinal leak in patients with spontaneous intracranial hypotension (SIH), and CT-guided fibrin glue occlusion has been introduced as a treatment option in a prior small series. Retrospective case series review of medical records from a single institution was performed for all patients with CVFs that were treated with CT-guided fibrin glue occlusion between August 2018 and April 2022 in an outpatient or inpatient setting. Pre- and posttreatment Headache Impact Tests (HIT-6) were administered to patients, and a change in scores was evaluated. In some patients, pretreatment HIT-6 tests were not obtained prior to the fibrin glue procedure, and the patient was asked to fill out the pretreatment test based on personal recall of their symptoms prior to treatment. Patients completed a Patient Global Impression of Change (PGIC) scale after treatment. Pre- and posttreatment brain imaging was compared using Bern SIH scores. Thirty-five patients (19 females, 16 males; mean age 60 years) with CVFs treated with CT-guided fibrin glue occlusion met the inclusion criteria. Mean pretreatment and posttreatment HIT-6 scores were 64.7 ± 10.2 and 43.4 ± 9.9 (p < 0.001), respectively. The posttreatment HIT-6 questionnaires were completed on average 10.3months after treatment, and 20 patients filled out the pretreatment HIT-6 form after their treatment. The mean PGIC score was 6.1 ± 1.3. Mean pretreatment and posttreatment Bern SIH scores were 5.9 ± 2.5 and 1.5 ± 1.5 (p < 0.001), respectively. We report a large series of patients who underwent CT-guided fibrin glue occlusion of CVFs. We showed that headache scores decreased after treatment, and the majority of patients had high PGIC scores. Posttreatment brain MRIs also showed improved Bern SIH scores.