Patient Global Impression Of Change Research Articles

Short-Term Efficacy of Using a Novel Low-Volume Bone Marrow Aspiration Technique to Treat Knee Osteoarthritis: A Retrospective Cohort Study.

Intra-articular bone marrow concentrate (BMC) and aspirate (BMA) injections have been used with mixed results to treat osteoarthritis (OA). Given the various aspiration and concentration methods available for preparing bone marrow, more data are needed to identify the optimal bone marrow harvesting techniques to treat OA. This retrospective cohort study examined the effect of using low-volume BMAs harvested using the Marrow Cellution™ (MC) device on 160 patients (262 knees) suffering from pain due to knee OA, KL grades 2-4, that did not respond to conservative treatment. Changes in visual analog scores (VAS) for overall daily activity were examined over a six-month time frame in these patients (63.5 ± 0.97 years of age; 48.1% male). In addition, changes in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and Patient Global Impression of Change (PGIC scores) were examined over the same time frame in a smaller subset of patients (95 patients including 172 knees). There was a statistically significant improvement in VAS scores for overall daily activity 6 months postprocedure in the study population, 7.29 ± 0.27 vs. 3.76 ± 0.34 (p < 0.0001), as well as statistically significant improvements in WOMAC scores, 49.3 ± 4.27 vs. 66.3 ± 4.08 (p < 0.0001). On the individual level, 71% of the cases displayed VAS improvements and 61% of the cases displayed WOMAC improvements that exceeded levels previous studies determined to be the minimal clinically important difference (MCID) for knee OA treatments. The improvements in WOMAC scores were also seen in both the WOMAC pain subscore, 52.2 ± 4.39 vs. 72.2 ± 4.36 (p < 0.0001) and the WOMAC function subscore, 51.6 ± 4.67 vs. 69.0 ± 4.36 (p < 0.0001). In addition, the PGIC scores measuring patient satisfaction improved from 4.03 ± 0.26 at 6 weeks postprocedure to 4.65 ± 0.28 at 6 months postprocedure (p < 0.0001). Knee OA patients treated with MC BMA intra-articular injections exhibited significant reductions in VAS pain scores and significant improvements in WOMAC scores that exceeded the minimal clinically important difference thresholds. In addition, reductions in VAS pain scores and improvements in WOMAC scores correlated with higher PGIC 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.

The effect of continuous positive airway pressure (CPAP) on the quality of life in patients with multiple system atrophy.

To evaluate the effect of continuous positive airway pressure (CPAP) on the quality of life (QoL) in patients with multiple system atrophy (MSA) and their caregivers. We reviewed the electronic medical records of patients with MSA treated with CPAP (n = 15). After CPAP treatment, we checked the patient global impression of change (PGI-C) scale for sleep complaints and QoL for six patients who continued to use CPAP. QoL was alsoassessed forfive caregiversof these patients. A total of 15 patients (6 women) were included. The mean age was 63.6 ± 8.1years old and the mean disease duration was 4.9years. The mean duration of CPAP treatment was 22.1 ± 10.6months and the average compliance was 90%. Three patients died during CPAP treatment, and two patients discontinued CPAP after tracheostomy. For six patients who continued to use CPAP, sleep complaints minimally improved. Five patients reported an improved QoL, and all five caregivers reported improved caregivers' QoL. This study showed that the use of CPAP has a beneficial effect on sleep complaints and QoL of patients with MSA and their caregivers.

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.

A Prospective, Observational, Open-Label, Non-Randomized, Multicenter Study Measuring Functional Outcomes in a Novel Interspinous Fusion Device in Subjects with Low Back Pain: REFINE Study.

Lumbar degenerative disease and the accompanying pain and dysfunction affect a significant number of patients in the USA and around the world. As surgery and innovation are moving towards minimally invasive treatments, this study looks to explore interspinous fixation as a standalone posterior approach to treat lumbar degenerative disc disease in the presence of neurogenic claudication and spinal stenosis. This study was approved by an institutional review board (IRB) and is actively enrolling in a single-arm, multicenter, prospective, open-label fashion. Patients are followed with reporting at 3months, and 12months for primary endpoint analysis of efficacy and safety based on improved composite endpoints relative to baseline, with success defined as greater than 20mm back pain reduction in Visual Analog Scale 100mm (VAS) while standing or walking, greater than 20mmleg pain reduction in VAS while standing or walking, Zurich Claudication Questionnaire (ZCQ) improvement of 0.5 or greater in two or three domains, Oswestry Disability Index (ODI) improvement of a least 10points and no reoperations or revisions at the index level(s). Secondary endpoints included a multidimensional assessment in the Patient-Reported Outcomes Measurement Information System (PROMIS) 29 v2.1 and Patient Global Impression of Change (PGIC). In this interim 3-month analysis, 82% of patients reported they were improved from the procedure, while 65% of patients demonstrated clinical meaningful improvement in their pain and function, as defined by the VAS, ODI, and ZCQ. There was only one adverse event and no complications were identified at last clinic research follow-up visit. This interim analysis of the first 20% of the enrolled patients out to 3months was to determine safety of the procedure and report on adverse events, acknowledging the heterogeneity of surgical specialty. Further follow-up and greater numbers are needed as the study is ongoing. ClinicalTrials.gov identifier, NCT05504499.

MPN-141 Retrospective Comparison of Patient Outcomes on Pacritinib Versus Ruxolitinib in Patients With Myelofibrosis and Thrombocytopenia.

Pacritinib (PAC) is a JAK2/IRAK1 inhibitor for patients with myelofibrosis (MF) and thrombocytopenia. Unlike the JAK1/2 inhibitor ruxolitinib (RUX), which is used at lower doses in patients with thrombocytopenia, PAC has been studied at full dose regardless of platelet count. This analysis focused on PERSIST-2 patients with platelet counts ≤100 × 109/L who were randomized to PAC 200mg BID and patients who received RUX on best available therapy (BAT) prior to week 24. Endpoints included percent of patients with 35% spleen volume reduction (SVR), 50% modified total symptom score (mTSS) reduction (based on early satiety, abdominal discomfort, night sweats, itching, bone pain, and rib pain), and improvement in disease symptoms measured by Patient Global Impression of Change (PGIC). Safety analyses were based on all treated patients; efficacy analyses were based on the intention-to-treat population randomized at least 22 weeks prior to study end. The Fisher Exact test was used to describe differences in response. Logistic and Cox regression was used to adjust for differences in baseline characteristics. Safety analysis included 106 patients on PAC and 44 on RUX; efficacy analysis included 74 on PAC and 32 on RUX (median total daily dose 10 mg). Baseline characteristics were similar between groups, including median platelet count (55 vs 61 × 109/L) and percent receiving RBC transfusion (46% vs 43%). Patients treated with PAC vs RUX achieved higher rates of SVR (22% vs 3%, p=0.02) and numerically higher rates of mTSS response (35% vs 19%; p=0.11) and "much" or "very much" improved symptoms (35% vs 16%, p=0.06) at week 24. Among RUX patients with an available PGIC measure at week 24, 50% reported either no improvement or worsening symptoms, while 76% of PAC patients reported improvement. The adjusted hazard ratio on PAC vs RUX was 0.46 [95% CI: 0.15-1.43]. Bleeding occurred at similar rates (43% vs 41%) on PAC vs RUX. Fatal AEs occurred in 8% on PAC compared to 11% on RUX. PAC yielded higher response rates and a similar safety profile to lower-dose RUX in patients with MF who have moderate or severe thrombocytopenia. This study was supported by CTI BioPharma.

S1588 Pooled Efficacy Analysis of Tradipitant in Idiopathic and Diabetic Gastroparesis Study VP-VLY-686-3301 and VP-VLY-686-2301

Introduction: Tradipitant is a novel NK-1 receptor antagonist studied in diabetic and idiopathic gastroparesis for short-term relief of nausea. This report presents the pooled analysis from 2 multicenter, randomized, double-blind, placebo-controlled studies (VP-VLY-686-3301 and VP-VLY-686-2301) assessing the efficacy of tradipitant in relieving symptoms of gastroparesis. Methods: N=342 idiopathic and diabetic gastroparesis patients with delayed gastric emptying, moderate to severe nausea were included in the pooled ITT (Intent-to-Treat) population. Subjects were randomized to 85mg tradipitant twice a day (n=175) or placebo (n=167) and endpoints were assessed at Week 4. Nausea was assessed with the 5-point Gastroparesis Core Symptom Daily Diary (GCSDD). Overall gastroparesis symptom improvement was evaluated with the Patient Global Impression of Change (PGI-C) and Overall Patient Benefit (OPB) scales. Sensitivity analyses were performed to control for confounders. Results: In a pooled analysis of double-blind subjects in the ITT population of Study 1 and Study 2, tradipitant demonstrated a clinically meaningful and statistically significant improvement in average nausea at week 4 (-1.15 for tradipitant v. -0.85 for placebo, P=0.0138). Significant improvement was seen in the number of nausea free days (20.96% improvement for tradipitant v. 12.52% for placebo, P=0.0085). Tradipitant also showed improvement in other gastroparesis symptoms as measured by the GCSI total score (-0.99 for tradipitant v. -0.76 for placebo, P=0.0265). Responder rates for PGI-C were 79.3% on tradipitant versus 69% on placebo at week 4 (P value = 0.036). For the Overall Patient Benefit, more patients improved on tradipitant versus placebo with 85.3% v. 71.2% at week 4 (P= 0.002). Sensitivity analysis adjusting for drug compliance confirmed the PK population (tradipitant blood levels ≥ 140ng/mL) in the pooled data set (n=284). In the pooled PK Population, tradipitant significantly improved average nausea at week 4 with -1.38 for tradipitant v. -0.85 for placebo (P=0.0001). Conclusion: Pooling the data provided an opportunity to analyze a much larger data set, increase statistical power, and confirm results and subpopulations from the 2 separate studies. In the pooled analysis, we observed a clinically meaningful and significant effect on change of nausea severity at week 4. Improvements were also seen across core gastroparesis symptoms and overall measures of gastroparesis.

Efficacy and Safety of Lower-Sodium Oxybate in an Open-Label Titration Period of a Phase 3 Clinical Study in Adults with Idiopathic Hypersomnia.

PurposeTo report the efficacy and safety of lower-sodium oxybate (LXB; Xywav®) during the open-label titration and optimization period (OLT) and stable-dose period (SDP) in a clinical study for the treatment of idiopathic hypersomnia.Patients and MethodsData were collected during treatment titration and optimization in a phase 3 randomized withdrawal trial in adults (18–75 years of age) with idiopathic hypersomnia who took LXB treatment (once, twice, or thrice nightly, administered orally) in the OLT (10–14 weeks), followed by the 2-week, open-label SDP. Endpoints included the Epworth Sleepiness Scale (ESS), Idiopathic Hypersomnia Severity Scale (IHSS), Patient Global Impression of Change, Clinical Global Impression of Change, Functional Outcomes of Sleep Questionnaire (FOSQ)-10, and Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP).ResultsThe safety population included 154 participants; the modified intent-to-treat population comprised 115 participants. During open-label treatment, mean (SD) ESS scores improved (decreased) from 15.7 (3.8) at baseline to 6.1 (4.0) at end of SDP, and IHSS scores improved (decreased) from 31.6 (8.3) to 15.3 (8.5). Improvements were also observed during OLT in each individual IHSS item and in FOSQ-10 and WPAI:SHP scores. Thirty-five (22.7%) participants discontinued during OLT and SDP, 22 (14.3%) due to treatment-emergent adverse events (TEAEs) during OLT and SDP. The most frequent TEAEs in the first 4 weeks were nausea, headache, dizziness, and dry mouth; TEAE incidence decreased throughout OLT and SDP (weeks 1–4, n = 87 [56.5%]; weeks 13–16, n = 39 [31.7%]).ConclusionDuring open-label treatment with LXB, participants showed clinically meaningful improvements in idiopathic hypersomnia symptoms and in quality of life and functional measures. TEAE incidence declined over LXB titration and optimization.

Thread Embedding Acupuncture for Temporomandibular Disorder: Protocol for a Pilot Randomized Controlled Trial.

BackgroundTemporomandibular disorder (TMD) affects multiple tissues of the temporomandibular joint complex and manifests as orofacial pain and functional disturbance. While thread embedding acupuncture (TEA) is used for the treatment of TMD in clinical practice, sufficient clinical evidence is lacking. This pilot trial will explore the feasibility of a confirmatory randomized controlled trial (RCT) by considering the efficacy, safety, and cost-effectiveness of TEA to address pain, function, and quality of life in patients with TMD.MethodsThis randomized, assessor-blinded, controlled trial will include two parallel arms. Thirty patients with TMD and temporomandibular joint pain more severe than 40 mm on the 100-mm visual analog scale (VAS) and aged 19–70 years will be recruited and randomly allocated to either TEA or usual care groups. The TEA group will receive treatment at 14 predefined acupoints once weekly for 4 weeks. The usual care group will receive physical therapy consisting of transcutaneous electrical nerve stimulation and infrared therapy. The average VAS score over the last week for temporomandibular pain after four sessions will be assessed as the primary outcome. Furthermore, maximum pain VAS, vertical opening movement, Graded Chronic Pain version 2, Jaw Functional Limitation Scale 20, Patient Global Impression of Change, Korean version of Beck’s Depression Index, Short Form-12 Health Survey, EuroQol 5-Dimension 5-level, treatment expectation, rescue medication consumption, adverse events, and medical costs for economic evaluation will be measured and analyzed as secondary outcomes during four follow-up visits and after the termination of all sessions.ConclusionThe results of this trial will help evaluate the feasibility of a confirmatory RCT considering efficacy, safety, and cost-effectiveness and verify the effect size required to determine an appropriate sample size.Trial Registration NumberKCT0007421.

“FastSchool”: A single session of an interprofessional pain management program for chronic pain patients inspired by cognitive behavioral therapy

ObjectivesMultidisciplinary approaches to treating chronic pain have been proven effective. Currently, chronic pain patients face lengthy waitlists in pain medicine departments. To overcome this problem, we developed the “FastSchool” program to educate patients about pain management and treatment. In this study, we evaluated the benefit of a “FastSchool” session on pain and catastrophizing in chronic pain patients. MethodsIncluded patients had chronic non-cancer pain, no more than 2 visits to a pain medicine department. Patients attended a single 3-hour session, conducted by an interprofessional team. Four topics were addressed: chronic pain mechanisms, pharmacological therapies, physical activity, and the management of analgesics. Patients completed questionnaires at baseline and at 3 months post-session to assess pain interference, pain intensity, and catastrophizing. ResultsThe study population included 88 patients; 71 completed the follow-up questionnaires. Pain interference (p = 0.002), average pain intensity (p = 0.013), and catastrophizing (p < 0.001) decreased 3 months after FastSchool. At M3, 35 % of patients felt their pain had improved based on the Patient Global Impression of Change. ConclusionFastSchool, an innovative short-term educational program inspired by cognitive behavioral therapy, showed positive results in reducing pain impact. Practice implicationsImplementation of FastSchool in pain medicine departments would reduce waitlist times for non-pharmacological treatment.

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.

Study protocol: Effects of active versus passive recharge burst spinal cord stimulation on pain experience in persistent spinal pain syndrome type 2: a multicentre randomized trial (BURST-RAP study)

BackgroundSpinal cord stimulation (SCS) has shown to be an effective treatment for patients with persistent spinal pain syndrome type 2 (PSPS Type 2). The method used to deliver electrical charge in SCS is important. One such method is burst stimulation. Within burst stimulation, a recharge pattern is used to prevent buildup of charge in stimulated tissues. Two variations of burst waveforms are currently in use: one that employs active recharge and one that uses passive recharge. It has been suggested that differences exist between active and passive recharge paradigms related to both efficacy of pain relief and their underlying mechanism of action. Active recharge has been shown to activate both the medial spinal pathway, engaging cortical sensorimotor areas involved in location and intensity of pain, and lateral pathway, reaching brain areas involved with cognitive-emotional aspects of pain. Passive recharge has been suggested to act via modulation of thalamic neurons, which fire in a similar electrical pattern, and thereby modulate activity in various cortical areas including those related to motivational and emotional aspects of pain. The objective of this randomized clinical trial is to assess and compare the effect of active versus passive recharge Burst SCS on a wide spectrum of pain in PSPS Type 2 patients.MethodsThis multicentre randomized clinical trial will take place in 6 Dutch hospitals. PSPS Type 2 patients (n=94) will be randomized into a group receiving either active or passive recharge burst. Following a successful trial period, patients are permanently implanted. Patients complete the Pain Catastrophizing Scale (PCS) (primary outcome at 6 months), Numeric Pain Rating Scale (NRS), Patient Vigilance and Awareness Questionnaire (PVAQ), Hospital Anxiety and Depression Scale (HADS), Quality of Life (EQ-5D), Oswestery Disability Index (ODI), Patient Global Impression of Change (PGIC) and painDETECT questionnaires (secondary outcomes) at baseline, after trial, 1, 3, 6 and 12 months following implantation.DiscussionThe BURST-RAP trial protocol will shed light on possible clinical differences and effectivity of pain relief, including emotional-motivational aspects between active and passive burst SCS in PSPS Type 2 patients.Trial registrationClinicalTrials.gov registration: NCT05421273. Registered on 16 June 2022. Netherlands Trial Register NL9194. Registered on 23 January 2021.

Effectiveness and Safety of Pharmacopuncture Therapy for Chronic Low Back Pain: A Protocol for a Pragmatic Randomized Controlled Trial.

PurposeChronic low back pain (LBP) is a common musculoskeletal disorder that affects everyday life; moreover, it occasionally causes disability and increases medical expenditure. This pragmatic randomized clinical trial aims to investigate the effects of pharmacopuncture on chronic LBP by comparing the effectiveness of pharmacopuncture and physiotherapy strategies.Patients and MethodsIn this two-armed, parallel, multi-center randomized controlled study, the participants will randomly undergo 10 sessions of pharmacopuncture therapy or physiotherapy over five weeks based on the randomization outcomes. The primary outcome will be the numeric rating scale (NRS) score of LBP. The secondary outcomes will include the NRS score of radiating leg pain, visual analog scale (VAS) score of LBP and radiating leg pain, Oswestry disability index, the Korean version of the Roland–Morris disability questionnaire, patient global impression of change (PGIC), short Form-12 health survey version 2, and 5-level EuroQol-5 dimension (EQ-5D-5L).ConclusionThis protocol aims to examine the comparative effectiveness of pharmacopuncture, which is a widely used therapy in Korean medicine, with respect to the standard therapy through a pragmatic randomized controlled trial to present useful data to facilitate clinical or policy decision making.Trial RegistrationClinicaltrials.gov (NCT04833309); Clinical Research Information Service (KCT0006088).

33993 Oral difelikefalin improves itch and quality of life in subjects with itch-dominant atopic dermatitis: Subgroup analysis of a randomized, phase 2 study

Background: In atopic dermatitis (AD), pruritus and lesional severity are not well correlated. Patients with limited body surface area (BSA) involvement may have intense pruritus not fully addressed by available therapies. Itch-dominant AD impairs quality of life (QoL). We report efficacy of oral difelikefalin (DFK), a kappa-opioid receptor agonist, for pruritus, QoL, and sleep disturbance in subjects with BSA <10% receiving DFK 0.5 mg or placebo (PBO) for 12 weeks. Methods: Phase 2, randomized, PBO-controlled study (NCT04018027) in adults with AD (Investigator Global Assessment ≥2, BSA ≤30%) and moderate-to-severe pruritus (Itch Numerical Rating Scale [I-NRS] ≥5.0) inadequately controlled by topical therapy. Results: Subjects (DFK, n = 82; PBO, n = 79) had high disease burden (mean I-NRS, 7.7, 7.6, respectively; DLQI, 10.6, 12.0) despite limited Eczema Area and Severity Index (mean, 4.0, 3.7). At week 12, a significantly greater proportion of subjects receiving DFK achieved ≥4-point I-NRS improvement versus PBO (33% vs 19%; P < .05; OR = 2.1). Greater proportions of subjects receiving DFK achieved responses at week 12 on the Patient Global Impression of Change (“much improved” or “very much improved”: 50% vs 35%; OR = 1.8); Sleep NRS (≥3-point improvement: 57% vs 47%; OR = 1.5); and Dermatology Life Quality Index (≥4-point improvement: 62% vs 50%; OR = 1.6). Conclusion: Itch-dominant AD is associated with impaired QoL despite mild-to-moderate lesional severity, suggesting that itch reduction should be a primary treatment goal in these patients. DFK showed clinically meaningful improvements in itch intensity, sleep, and QoL and may address the unmet need for a safe, effective antipruritic treatment in itch-dominant AD.

Efficacy and Safety of Cheong-A-Won Gagambang (JCE003) on Knee Osteoarthritis: Randomized Controlled Pilot Trial

Background: The aim of this study was to evaluate the effectiveness and safety of Cheong-A-Won Gagambang (JCE003) treatment for degenerative knee osteoarthritis.Methods: This was a single-center, randomized, double-blind, placebo-controlled pilot clinical trial. There were 36 adults with degenerative knee osteoarthritis who were randomly allocated into JCE003 1,000 mg, JCE003 2,000 mg, or the placebo group (in a 1:1:1 ratio). The participants received 12 weeks of treatment and had scheduled tests every 6 weeks. The primary outcomes were measured using the Korean Western Ontario and McMaster Universities scale, and the secondary outcomes were measured using the visual analog scale, European quality of life-5-dimensions, patient global impression of change, C-reactive protein, and erythrocyte sedimentation rate. Changes between baseline scores and scores following study completion were analyzed.Results: There were 29 participants whose data were analyzed in this study. The change of Korean Western Ontario and McMaster Universities, visual analog scale, European quality of life-5-dimensions scores showed significant improvement in the JCE003 1,000 mg group. The change of patient global impression of change was significantly improved in the placebo group. There were 14 adverse events, but there was no clinically significant relationship with the intake of JCE003 compared with the placebo.Conclusion: Taking JCE003 may be effective at improving knee pain in patients with degenerative knee osteoarthritis and appears to be safe. Based on this study, the concentration and feasibility of the test group may be used when conducting a large-scale clinical trial of degenerative knee osteoarthritis in the future.

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.

A randomized, controlled trial on the effectiveness of a proprietary marine lipo-peptide formula vs omega-3 on cytokines profile, anxiety, and pain symptoms in patients with fibromyalgia

Objective: The aim of the present study in an RCT manner (physicians and patients) a novel lipo-peptide marine compound, LD-1227, on physical-, emotional- and functional-related symptomatic complaints in fibromyalgia patients as well as inflammatory cytokines profile and gene expression while using omega-3 as a control group.Methods: The following questionnaire-based or clinical evaluation-based parameters were evaluated: widespread pain index [WPI] patient global impression of change, total tender points [TTP], fibromyalgia impact questionnaire, Beck depression inventory, fatigue severity ratings, cognitive symptom severity, symptom severity score [SSS] and weekly pain intensity ratings. Additional biochemical and gene expression analysis of cytokines (IL6, TNF-α, IL-1β, MCP-1, IL-8, IL-13, IL-1α, and GM-CSF) was performed as well. Data were analyzed with either a paired t-test or the Wilcoxon signed rank test depending on the parametric or non-parametric distribution.Results: Comparing the data from before and after treatment for Group B indicated a statistically significant reduction (p=0.05) in TTP, WPI score, and SSS score. These data suggest a positive effect of a 3-month treatment with the LD-1227 but not omega-3 treatment on Fibromyalgia pain and related anxiety/depressive symptoms. Inspections of HRV and Cytokines found a statistically significant improvement after LD1227 treatment. Unlike the group supplemented with omega-3, the treatment with LD-1227 brought about a decrease in WPI and weekly pain intensity symptoms for the majority of participants. The pre-and post-treatment data for Group B indicated a statistically significant reduction (p=0.05) in TPC, WPI, and SSS scores. No adverse events were reported.Conclusion: These results provide the first indications that the LD-1227 treatment has a statistically significant effect on the recognized fibromyalgia diagnosis metrics of WPI, TTP, and SSS as well on inflammatory markers and parasympathetic balance.Keywords: fibromyalgia, marine compound, lipopeptide, cytokines, anxiety, pain, LD-1227.

Sutimlimab improves quality of life in patients with cold agglutinin disease: results of patient-reported outcomes from the CARDINAL study

Patients with cold agglutinin disease (CAD) experience fatigue and poor quality of life. However, previous CAD-related studies have not explored patient-reported outcomes such as the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue. Sutimlimab, a C1s complement inhibitor, has been shown to halt haemolysis in CAD. Here, we present 26-weeks’ patient-reported data from CARDINAL Part A (ClinicalTrials.gov, NCT03347396), which assessed efficacy and safety of sutimlimab in patients with CAD and recent history of transfusion. Aside from measuring changes in haemolytic markers, FACIT-Fatigue was measured at the treatment assessment timepoint (TAT; average of weeks 23, 25, and 26). Exploratory endpoints included the change in EuroQol 5-dimension 5-level questionnaire (EQ-5D-5L) and the 12-Item Short Form Health Survey (SF-12) at TAT, and Patient Global Impression of Change (PGIC), and Patient Global Impression of (fatigue) Severity (PGIS) at week 26. Mean (range) FACIT-Fatigue scores increased from 32.5 (14.0–47.0) at baseline (a score indicative of severe fatigue) to 44.3 (28.0–51.0) at TAT. Considerable improvements were reported for EQ-5D-5L at TAT, SF-12 scores at TAT, and PGIC and PGIS scores at week 26. Sutimlimab treatment resulted in sustained improvements in symptoms of fatigue and overall quality of life in patients with CAD. NCT03347396. Registered 20 November, 2017.

Solriamfetol treatment of excessive daytime sleepiness in participants with narcolepsy or obstructive sleep apnea with a history of depression

Given the high rate of depression associated with narcolepsy or obstructive sleep apnea (OSA), this analysis compared effects of solriamfetol treatment of excessive daytime sleepiness (EDS) in participants with/without a history of depression (DHx+/DHx-). This secondary analysis included data from two randomized, controlled trials in which participants were randomized to 12 weeks placebo or solriamfetol 37.5 (OSA only), 75, 150, or 300 mg/day. Efficacy/safety (combined solriamfetol doses) was summarized for DHx+/DHx-subgroups. 27.5% (65/236) with narcolepsy and 23.4% (111/474) with OSA were DHx+. In narcolepsy (DHx+ and DHx-), 40-min Maintenance of Wakefulness Test (MWT40) mean sleep latency increased (5.4 and 7.0 min), Epworth Sleepiness Scale (ESS) score decreased (3.8 and 3.5 points), and percentage of participants improved on Patient Global Impression of Change (PGI-C) was higher (31.7% and 39.4%) relative to placebo. In OSA (DHx+ and DHx-), MWT40 mean sleep latency increased (7.7 and 10.7 min), ESS decreased (3.5 and 3.7 points), and percentage of participants improved on PGI-C was higher (41.1% and 29.4%) relative to placebo. Common treatment-emergent adverse events (headache, decreased appetite, nausea, anxiety) were similar in DHx+/DHx-. This study suggests that safety and efficacy of solriamfetol for treating EDS in narcolepsy and OSA are not affected by depression history. Moreover, the findings emphasize the high prevalence of depression in people with sleep disorders and suggest that increased awareness of this association may have clinical significance.

226. Surgical treatment of refractory low back pain using implanted BurstDR spinal cord stimulation (SCS) in a cohort of patients without options for corrective surgery: findings and results from the DISTINCT study, a prospective randomized multi-center controlled trial

226. Surgical treatment of refractory low back pain using implanted BurstDR spinal cord stimulation (SCS) in a cohort of patients without options for corrective surgery: findings and results from the DISTINCT study, a prospective randomized multi-center controlled trial