Patient Global Impression Of Change Research Articles

Objective wearable measures and subjective questionnaires for predicting response to neurostimulation in people with chronic pain

BackgroundNeurostimulation is an effective therapy for treating and management of refractory chronic pain. However, the complex nature of pain and infrequent in-clinic visits, determining subject’s long-term response to the therapy remains difficult. Frequent measurement of pain in this population can help with early diagnosis, disease progression monitoring, and evaluating long-term therapeutic efficacy. This paper compares the utilization of the common subjective patient-reported outcomes with objective measures captured through a wearable device for predicting the response to neurostimulation therapy.MethodData is from the ongoing international prospective post-market REALITY clinical study, which collects long-term patient-reported outcomes from 557 subjects implanted by Spinal Cord Stimulator (SCS) or Dorsal Root Ganglia (DRG) neurostimulators. The REALITY sub-study was designed for collecting additional wearables data on a subset of 20 participants implanted with SCS devices for up to six months post implantation. We first implemented a combination of dimensionality reduction algorithms and correlation analyses to explore the mathematical relationships between objective wearable data and subjective patient-reported outcomes. We then developed machine learning models to predict therapy outcome based on the subject’s response to the numerical rating scale (NRS) or patient global impression of change (PGIC).ResultsPrincipal component analysis showed that psychological aspects of pain were associated with heart rate variability, while movement-related measures were strongly associated with patient-reported outcomes related to physical function and social role participation. Our machine learning models using objective wearable data predicted PGIC and NRS outcomes with high accuracy without subjective data. The prediction accuracy was higher for PGIC compared with the NRS using subjective-only measures primarily driven by the patient satisfaction feature. Similarly, the PGIC questions reflect an overall change since the study onset and could be a better predictor of long-term neurostimulation therapy outcome.ConclusionsThe significance of this study is to introduce a novel use of wearable data collected from a subset of patients to capture multi-dimensional aspects of pain and compare the prediction power with the subjective data from a larger data set. The discovery of pain digital biomarkers could result in a better understanding of the patient’s response to therapy and their general well-being.

493-P: SCS for the Treatment of Painful DPN—Consistent Outcomes from Multiple RCTs

Pain associated with diabetic peripheral neuropathy (DPN) is treated medically with gabapentin/pregabalin, tricyclic antidepressants, and serotonin-norepinephrine reuptake inhibitors1 which are often not satisfactory long-term. Spinal Cord Stimulation (SCS) is an effective alternative per 3 randomized controlled trials (RCTs)2,3,4. We reviewed and compared 3 published RCTs2,3,4 comparing SCS to conventional treatments for painful DPN in subjects with mostly type 2 diabetes (Table 1). Study outcome measures included a composite primary endpoint where patients could be identified as treatment responders by reduction in pain diary scores or Patient Global Impression of Change, ≥50% reduction in VAS measurement for pain, and a compound primary endpoint of ≥50% reduction in pain score and no neurologic decline. EQ5D questionnaires were used to assess Quality of Life. The difference in treatment success between SCS and control for the primary endpoint in the Intention-to-Treat populations ranged from 52 - 58%. Improvement in EQ5D index scores at 6 months ranged from 0.124 - 0.380. The similarity of outcomes in 3 RCTs2,3,4 demonstrate that SCS is an effective treatment modality for DPN pain compared with conventional medical approaches. Patients from 1 study4 have been followed-up to 18 months8 and patients in another2 up to 10 years9 with similar outcomes, demonstrating long-term benefits of SCS for patients with painful DPN. Disclosure B.W.Bode: Advisory Panel; Ascensia Diabetes Care, MannKind Corporation, Medtronic, Novo Nordisk, Zealand Pharma A/S, Research Support; Abbott Diabetes, Abvance Therapeutics, Better Therapeutics, Inc, Dexcom, Inc., Diasome, Dompé, Insulet Corporation, Lilly Diabetes, Medtronic, Novo Nordisk, Sanvita Medical, Senseonics, Provention Bio, Inc., REMD Biotherapeutics, ViaCyte, Inc., Xeris Pharmaceuticals, Inc., vTv Therapeutics, Speaker's Bureau; Abbott Diabetes, American Diabetes Association, Boehringer Ingelheim and Eli Lilly Alliance, Insulet Corporation, Lilly Diabetes, MannKind Corporation, Novo Nordisk, Sanofi, Xeris Pharmaceuticals, Inc., Stock/Shareholder; Glytec, LLC. G.Grunberger: Advisory Panel; CeQur SA, Nevro Corp., LifeScan Diabetes Institute, Speaker's Bureau; Eli Lilly and Company, Novo Nordisk. M.Fishman: Consultant; Abbott, Biotronik, Medtronic, Nevro Corp., Other Relationship; Medtronic, Abbott, Research Support; Abbott, Boston Scientific Corporation, Medtronic, Nalu, SGX Medical, Thermaquil, Biotronik, Stock/Shareholder; Celeri Health, Thermaquil. M.Murphy: Consultant; Medtronic, Relievant. R.A.Vigersky: Employee; Medtronic. L.Johanek: Employee; Medtronic. M.Larue: Employee; Medtronic. Funding Medtronic

#5821 CLINICALLY MEANINGFUL IMPROVEMENT IN QUALITY OF LIFE ACCOMPANIES ITCH RELIEF IN PATIENTS WITH CHRONIC KIDNEY DISEASE ASSOCIATED PRURITUS

Abstract Background and Aims The impairing effect of chronic kidney disease-associated pruritus (CKD-aP) on the quality of life (QoL) of patients undergoing haemodialysis (HD) is well-established. The aim of this post-hoc analysis was to assess the impact of itch relief on QoL, as measured by the 5-D itch scale, in patients with CKD-aP enrolled in the Phase 3 KALM-1 and -2 clinical trials. This study also aimed to confirm the use of ≥5-point reduction in 5-D itch scale total score as a threshold for clinically meaningful improvement in itch-related QoL, by comparing to notable improvement on the Patients’ Global Impression of Change (PGI-C) scale. Method Data were pooled from 851 patients with moderate-to-severe CKD-aP undergoing HD in the KALM-1 and -2 trials testing difelikefalin vs placebo. Sustained responders were defined as patients who achieved a ≥3-point improvement in the weekly mean 24-hour Worst Itching Intensity Numerical Rating Scale [WI-NRS] score at Week 12 of the study, whereas non-sustained responders were defined as patients that reported a ≥3-point improvement in any week of the study but not at Week 12. Improvements in QoL, as measured by the mean change in 5-D itch scale total score from baseline to Week 12, were compared in sustained responders vs non-sustained responders. Data were analysed by ANCOVA multiple imputation, with a missing-at-random assumption. The mean change in 5-D itch scale total score was analysed in relation to patients’ reporting on the five categories of the PGI-C scale. Results In pooled analysis, 305 patients undergoing HD with CKD-aP qualified as sustained responders, whereas 128 patients were non-responders. Reduction in 5-D itch scale total score over 12 weeks was significantly higher in sustained responders compared with non-sustained responders (least squares [LS] mean ±standard error; –7.1±0.2 vs –4.0±0.3, LS mean difference –3.0±0.3, p<0.001) (Figure 1). Greater reductions in 5-D itch scale total score were observed in patients reporting more substantial improvements in PGI-C. Specifically, patients reporting much, or very much, improvement in PGI-C scored ≥5-point reduction on the 5-D itch scale (mean ±standard error; –5.3±0.2 and –8.2±0.3, respectively) (Figure 2). Conclusion This study observed a greater improvement in QoL, as measured by the 5-D itch scale total score, in patients with CKD-aP who reported a clinically meaningful reduction in itch, as measured by WI-NRS, at Week 12. These results also support the use of ≥5-point reduction in the 5-D itch scale total score as a threshold for clinically meaningful improvement in the QoL of patients with CKD-aP. As only sustained responders exceeded this threshold, these data suggest that continued treatment of itch may be necessary to maximally improve QoL in these patients.

Effectiveness of Integrative Korean Medicine Treatment in Patients with Traffic-Accident-Induced Acute Low Back Pain and Mild Adult Scoliosis.

We investigated the effectiveness of integrative Korean medicine treatment in patients with pre-existing scoliosis who received inpatient care for traffic-accident-induced acute LBP. We selected 674 patients diagnosed with scoliosis between 1 January 2015, and 30 June 2021, using lumbar spine (L-spine) imaging, across four Korean medicine hospitals in Korea for a retrospective chart review and sent them a questionnaire-based follow-up survey. The primary outcome was a numeric rating scale (NRS) score of LBP. The secondary outcomes were the Oswestry Disability Index (ODI), 5-level EuroQol 5-dimension (EQ-5D-5L), and patient global impression of change (PGIC) scores. In total, 101 patients responded to the follow-up survey. NRS scores decreased from 4.86 (4.71-5.02) to 3.53 (3.17-3.90) from admission to discharge, subsequently decreasing to 3.01 (2.64-3.38) (p < 0.001) at the last follow-up. Similarly, ODI scores decreased from 35.96 (33.08-38.85) to 22.73 (20.23-25.24) and 14.21 (11.74-16.67) (p < 0.001), respectively. Approximately 87.1% of patients were satisfied with their inpatient care. There were no significant differences in the degree of improvement according to the severity of scoliosis. Integrative Korean medicine treatment can improve pain, lumbar dysfunction, and quality of life in patients with traffic-accident-induced acute low back pain and pre-existing mild scoliosis.

Effectiveness and Safety of Intra-arterial Imipenem/Cilastatin Sodium Infusion for Patients with Hand Osteoarthritis–Related Interphalangeal Joint Pain

PurposeTo evaluate the effectiveness and safety of intra-arterial imipenem/cilastatin sodium (IPM/CS) infusion for painful interphalangeal joint osteoarthritis (OA). Materials and MethodsFifty-eight patients with interphalangeal joint OA who underwent intra-arterial IPM/CS infusion were retrospectively evaluated. Intra-arterial infusions were performed via percutaneous wrist arterial access. The Numerical Rating Scale (NRS), Functional Index for Hand Osteoarthritis (FIHOA), and Patient Global Impression of Change (PGIC) scale scores were assessed at intervals of 1, 3, 6, 12, and 18 months. Clinical success was evaluated based on PGIC. ResultsAll patients were followed up for at least 6 months after treatment. Of them, 30 and 6 patients were followed up for 12 and 18 months, respectively. No severe or life-threatening adverse events were encountered. The mean NRS score was 6.0 ± 1.4 at baseline, which significantly decreased to 2.8 ± 1.4, 2.2 ± 1.9, and 2.4 ± 1.9 at 1, 3, and 6 months after treatment, respectively (all P < .001). The mean NRS scores were 2.8 ± 1.7 and 2.9 ± 1.9 at 12 and 18 months, respectively, in the remaining patients. The mean FIHOA score significantly decreased from 9.8 ± 5.0 at the baseline to 4.1 ± 3.5 at 3 months (P < .001). The mean FIHOA score was 4.5 ± 3.3 at 12 months in the remaining 30 patients. The clinical success rates based on PGIC at 1, 3, 6, 12, and 18 months were 62.1%, 77.6%, 70.7%, 63.4%, and 50.0%, respectively. ConclusionsIntra-arterial IPM/CS infusion is a potential treatment option for interphalangeal joint OA refractory to medical management.

Outcome after microvascular decompression for trigeminal neuralgia in a single center—relation to sex and severity of neurovascular conflict

BackgroundTrigeminal neuralgia (TN), a severe type of facial pain, is mainly caused by a neurovascular conflict (NVC). The severity of the NVC seems associated with the outcome following microvascular decompression (MVD) surgery. This study aimed to investigate the outcome after MVD and whether it is affected by NVC severity and sex.MethodsTN patients (n = 109) were followed for 5 to 10 years after MVD. Barrow Neurology Index (BNI), Patients Global Impression of Change (PGIC), complications, and time to relapse were evaluated. The NVC severity was retrospectively reviewed from presurgical MRI. Demographic and clinical factors and NVC severity were analyzed for potential association with outcome after MVD.ResultsThe success rate (BNI ≤ 2) was 80% after 5 to 10 years follow-up for TN patients with severe NVC (grade 2–3) and 56% for TN patients with mild NVC (grade 0–1, P = 0.003). No sex difference was observed in outcome for patients with both mild (P = 0.924) and severe NVC (P = 0.883) respectively. Three patients (2.8%) during the hospital stay, and two patients (1.8%) at 6 weeks, experienced a complication requiring invasive treatment. At long-term 52/109 patients (47.7%) reported some type of persistent adverse event, of which the majority were mild and required no treatment.ConclusionsMVD offers an 80% probability of long-term pain relief in TN patients with severe NVC, with low frequency of serious complications. NVC severity significantly affects outcome after MVD, while no sex differences in outcome were found. In consistency with previous work, the results stress the importance of adequate neuroradiological assessment of the NVC for preoperative patient selection.

Cannabis-based medicines and medical cannabis for adults with cancer pain.

Cannabis-based medicines and medical cannabis for adults with cancer pain.

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.

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: 219975 Application of Wearable Data in Predicting Chronic Pain Patient's Response to Spinal Cord Stimulation

Spinal cord stimulation (SCS) is widely used to provide pain relief and improve the quality of life for people with chronic pain [2]. Response to SCS therapy is usually evaluated in the clinical setting by patient-reported outcome measures including numerical rating system (NRS) and patient global impression of change (PGIC). Objective measures collected from wearable sensors can complement these measures and provide a better understanding of patient’s chronic pain. In this work, we aim to utilize objective data such as physical activity, and heart rate collected through a wearable sensor (Apple Watch) to predict patient’s response to spinal cord stimulation.

Consistency of pacritinib for spleen and symptom reduction in patients with myelofibrosis regardless of cytopenias.

7068 Background: In patients with myelofibrosis (MF), JAK inhibitor therapy can improve both splenomegaly and disease symptoms. Unfortunately, dosing – and thus efficacy – of available current JAK1/2 inhibitors is frequently limited in patients with cytopenic MF due to drug-induced exacerbation of cytopenias. Pacritinib is a novel JAK1-sparing inhibitor of JAK2/IRAK1/ACVR1 that has been studied at full dose in patients with MF regardless of cytopenias. Here, we present data on spleen and symptom benefit in pacritinib-treated patients across the cytopenic spectrum, stratified by both baseline platelet (PLT) count and hemoglobin (HB) level. Methods: Evaluable patients treated with pacritinib in the PERSIST-1 and PERSIST-2 studies were analyzed, stratified by baseline PLT (&lt;100, ≥100x109/L) and HB (&lt;8, 8 to &lt;10, ≥10 g/dL). Groups were analyzed for depth of spleen volume response (SVR), modified total symptom score (TSS) response, patient global impression of change (PGIC), and dose intensity. Results: Of 276 patients evaluable for spleen response, median age was 67 years, 51.5% had grade 3 fibrosis, 70% had primary MF, and 16% had prior JAK2 inhibitor exposure. Median dose intensity was &gt;99.7% for the duration of the study across PLT and HB subgroups. Overall, 80% of patients had ≥10% SVR (SVR-10), 75.5% had TSS-10, and 78% reported that their symptoms were improved at week 24. Week 24 spleen reduction occurred consistently across PLT and HB strata, with 84-93% and 86-90% of patients respectively (Table). SVR-35 occurred in 23-25% of patients across PLT strata and in 21-28% of patients across HB strata. Symptom response was also consistent across strata, though TSS-50 occurred at highest rates (62.5%) in patients with HB &lt;8 g/dL. There was no diminution in symptom burden reduction in patients with thrombocytopenia (Table). Across all subgroups, at least three-quarters of patients reported symptoms were “improved” at week 24. Conclusions: Pacritinib demonstrates consistent efficacy for spleen and symptom response in patients with MF regardless of blood counts. This consistent effect may be related to pacritinib’s unique kinome profile and its ability to be delivered at full dose in patients regardless of cytopenias. Clinical trial information: NCT01773187 , NCT02055781 . [Table: see text]

Systemic Lupus, Metabolic Syndrome, Cardiac Disease, and Peripheral Artery Disease

Systemic Lupus, Metabolic Syndrome, Cardiac Disease, and Peripheral Artery Disease

A Retrospective Review of Real-world Outcomes Following 60-day Peripheral Nerve Stimulation for the Treatment of Chronic Pain

BACKGROUND: Real-world data can provide important insights into treatment effectiveness in routine clinical practice. Studies have demonstrated that in multiple different pain indications temporary (60-day) percutaneous peripheral nerve stimulation (PNS) treatment can produce significant relief, but few real-world studies have been published. The present study is the first real-world, retrospective review of a large database depicting outcomes at the end of a 60-day PNS treatment period. OBJECTIVES: Evaluate outcomes during a 60-day PNS treatment in routine clinical practice. STUDY DESIGN: Secondary retrospective review. METHODS: Anonymized records of 6,160 patients who were implanted with a SPRINT PNS System from August 2019 through August 2022 were retrospectively reviewed from a national real-world database. The percentage of patients with ? 50% pain relief and/or improvement in quality of life was evaluated and stratified by nerve target. Additional outcomes included average and worst pain score, patient-reported percentage of pain relief, and patient global impression of change. RESULTS: Overall, 71% of patients (4,348/6,160) were responders with &gt;= 50% pain relief and/or improvement in quality of life; pain relief among responders averaged 63%. The responder rate was largely consistent across nerve targets throughout the back and trunk, upper and lower extremities, and posterior head and neck. LIMITATIONS: This study was limited by its retrospective nature and reliance on a device manufacturer’s database. Additionally, detailed demographic information and measures for pain medication usage and physical function were not assessed. CONCLUSIONS: This retrospective analysis supports recent prospective studies demonstrating that 60-day percutaneous PNS can provide significant relief across a wide range of nerve targets. These data serve an important role in complementing the findings of published prospective clinical trials. KEY WORDS: Peripheral nerve stimulation, neuromodulation, 60-day PNS, nonopiod, real-world evidence

0592 Efficacy of Lower-Sodium Oxybate by Baseline Sleep Inertia in a Phase 3 Clinical Study in Patients With Idiopathic Hypersomnia

Abstract Introduction Idiopathic hypersomnia is a debilitating neurologic sleep disorder. Sleep inertia (difficulty awakening) is a common symptom that can significantly impair functioning and quality of life. This post hoc analysis evaluated response to lower-sodium oxybate (LXB; Xywav®) by baseline sleep inertia in a phase 3 trial (NCT03533114). Methods Eligible participants began LXB treatment with an open-label treatment titration and optimization period (10–14 weeks), followed by a 2-week stable-dose period (SDP). Participants were randomized to placebo or continued LXB treatment during a 2-week, double-blind, randomized withdrawal period (DBRWP). Using the visual analog scale for sleep inertia (VAS-SI), participants rated their difficulty awakening during baseline, SDP, and DBRWP on a 100-mm line with anchors at 0 (very easy) and 100 (very difficult). VAS-SI terciles comprised score segments of &amp;lt; 44 (group A), ≥44 to &amp;lt; 70 (group B), and ≥70 (group C). Efficacy assessments included the Epworth Sleepiness Scale (ESS), Idiopathic Hypersomnia Severity Scale (IHSS), Clinical Global Impression of Severity (CGIs), and Patient Global Impression of Change (PGIc). Results Participants (A, n=34; B, n=33; C, n=32) were a mean (SD) 40.7 (13.5) years of age and primarily female (74%). At baseline, participants with the highest VAS-SI scores had numerically higher mean (SD) ESS (A=16.0 [3.1], B=15.6 [2.6], C=17.1 [2.4]) and IHSS (A=26.7 [7.7], B=34.5 [5.9], C=36.3 [5.5]) scores. Participants with the highest baseline sleep inertia were more frequently rated severely ill on the CGIs (A=17.6%, B=12.1%, C=34.4%). Baseline total sleep time trended higher with increasing VAS-SI scores. From baseline to end of SDP, mean (SD) scores decreased (improved) on the ESS (A=−9.9 [5.1], B=−9.8 [3.5], C=−10.0 [5.1]) and IHSS (A=−14.1 [9.9], B=−19.0 [9.0], C=−18.1 [9.9]), regardless of baseline sleep inertia; nearly all (99%) participants reported improvement on the PGIc. Mean (SD) VAS-SI scores decreased by 9.3 (11.9), 31.5 (14.8), and 42.8 (22.9) in groups A, B, and C, respectively, at end of SDP. Spearman correlation coefficients for VAS-SI and IHSS items assessing sleep inertia were moderate (≥0.3) to strong (≥0.6). Conclusion Participants with higher baseline sleep inertia generally had greater baseline disease burden. LXB treatment was efficacious across subgroups regardless of baseline sleep inertia. Support (if any) Jazz Pharmaceuticals.

0591 Effectiveness and Optimization of Lower-Sodium Oxybate in Participants With Narcolepsy Switching From Sodium Oxybate (SEGUE)

Abstract Introduction Lower-sodium oxybate (LXB, Xywav®) contains 92% less sodium than higher-sodium oxybate (SXB, Xyrem®) and is approved for treating cataplexy or excessive daytime sleepiness in patients with narcolepsy (≥7 years of age) and idiopathic hypersomnia in adults. The SEGUE study examines the safety, tolerability, effectiveness, and treatment optimization in participants with narcolepsy transitioning from SXB to LXB. Methods Eligible participants in this multicenter, open-label study were adults with narcolepsy type 1 or 2 who were on a stable dose (maximum 9 g/night; no single dose &amp;gt;6 g) and regimen (once, twice, or thrice nightly) of SXB. After 2 weeks on a stable SXB dose/regimen (baseline period), participants switched to the same dose/regimen of LXB (intervention period; 6 weeks). If needed, LXB dose/regimen was titrated to optimize efficacy/tolerability. Assessments included the Patient Global Impression of Change (PGIc), a forced preference questionnaire (FPQ), an ease of switching medication scale (EOSMS), and the Epworth Sleepiness Scale (ESS); all collected at end of treatment or early discontinuation. Results Of 60 participants who entered the intervention period, a majority were female (62%) and White (88%); mean (SD) age was 43.9 (15.33) years. Starting and ending (end of treatment or early discontinuation) median total nightly doses of LXB were 8.5 g and 9.0 g, respectively. In terms of regimen, most took LXB twice nightly (93% at both time points). Fifty-six participants completed the transition period; mean (SD) time to stable dose was 2.5 (4.82) days, and median (range) number of changes in dose/regimen was 0.0 (0, 1). At end of treatment or early discontinuation, most participants reported improvement (very much/much/minimal; 45%) or no change (48%) in narcolepsy symptoms on the PGIc, preferred LXB over SXB on the FPQ (79%), and reported the transition to LXB was easy, extremely easy, or not difficult at all on the EOSMS (93%). Mean (SD) change from baseline on the ESS (n=55) was −0.7 (2.31). Conclusion Most participants with narcolepsy switched from SXB to LXB with minimal modifications of dose/regimen and reported the transition process was easy. Effectiveness of oxybate treatment (ESS) was maintained after transition, and most preferred LXB over SXB. Support (if any) Jazz Pharmaceuticals.

Effect of voxelotor on cardiopulmonary testing in youths with sickle cell anemia in a pilot study.

Individuals with sickle cell anemia (SCA) exhibit decreased exercise capacity. Anemia limits oxygen-carrying capacity and affects cardiopulmonary fitness. The drug voxelotor raises hemoglobin in SCA. We hypothesized that voxelotor improves exercise capacity in youths with SCA. In a single-center, open-label, single-arm, longitudinal interventional pilot study (NCT04581356), SCA patients aged 12 and older, stably maintained on hydroxyurea, were treated with 1500mg voxelotor daily, and performed cardiopulmonary exercise testing before (CPET#1) and after voxelotor (CPET#2). A modified Bruce Protocol was performed on a motorized treadmill, and breath-by-breath gas exchange data were collected. Peak oxygen consumption (peak VO2 ), anaerobic threshold, O2 pulse, VE/VCO2 slope, and time exercised were compared for each participant. The primary endpoint was change in peak VO2 . Hematologic parameters were measured before each CPET. Patient Global Impression of Change (PGIC) and Clinician Global Impression of Change (CGIC) surveys were collected. Ten hemoglobin SS patients aged 12-24 completed the study. All demonstrated expected hemoglobin rise, with average +1.6g/dL (p=.003) and P50 left shift of average -11mmHg (p<.0001) with decreased oxygen off-loading at low pO2 . The change in % predicted peak VO2 from CPET#1 to CPET#2 ranged from -12.8% to +11.3%, with significant improvement of more than 5% in one subject, more than 5% decrease in five subjects, and insignificant change of less than 5% in four subjects. All 10 CGIC and seven of 10 PGIC responses were positive. In a plot study of 10 youths with SCA, voxelotor treatment did not improve peak VO2 in 9 out of 10 patients.

0560 Solriamfetol for Excessive Sleepiness in Narcolepsy and Obstructive Sleep Apnea: Effect Sizes and Numbers Needed to Treat or Harm

Abstract Introduction Solriamfetol (Sunosi®), a dopamine/norepinephrine reuptake inhibitor that has been shown to activate TAAR1, is approved (US and EU) to treat excessive daytime sleepiness (EDS) in adults with narcolepsy (75-150mg/day) or obstructive sleep apnea (OSA) (37.5-150mg/day). Effect size, number needed to treat (NNT) and number needed to harm (NNH) are statistical representations of efficacy and tolerability that clinicians may find helpful in guiding treatment decisions. This analysis characterized these statistical parameters from two registrational studies. Methods We conducted a post-hoc analysis of data from two phase 3 studies in adults with excessive daytime sleepiness associated with narcolepsy (TONES 2) or OSA (TONES 3). Effect size compared to placebo, NNT, and NNH were calculated based on previously published endpoints, post-hoc analyses, and adverse events. Results On the Maintenance of Wakefulness Test, effect size compared to placebo (Cohen’s d) was 0.29, 0.82, and 1.13 for 75mg, 150mg, and 300mg doses of solriamfetol in TONES 2 and 0.46, 0.89, 1.08, and 1.28 for 37.5mg, 75mg, 150mg, and 300mg in TONES 3. On the Epworth Sleepiness Scale (ESS), d was 0.47, 0.80, and 1.02 for 75mg, 150mg, and 300mg in TONES 2, and 0.42, 0.37, 0.99, and 1.04 for 37.5mg, 75mg, 150mg, and 300mg doses in TONES 3. NNT for patients achieving an ESS ≤10 was 7, 5, and 3 for 75mg, 150mg, and 300mg doses in TONES 2 and 8, 6, 4, and 3 for 37.5mg, 75mg, 150mg, and 300mg doses in TONES 3. On the Patient Global Impression of Change (PGIc), NNT was 4, 3, and 3 for 75mg,150mg, and 300mg doses in TONES 2 and 16, 5, 3, and 3 for 37.5, 75mg, 150mg, and 300mg in TONES 3. Similar NNT were found for the Clinician Global Impression of Change as for the PGIc. In both TONES 2 and TONES 3, NNH pooled across doses for adverse events occurring in ≥5% of patients and greater than placebo were all &amp;gt;10, with the exception of headache in TONES 2 (NNH=6). Conclusion This post-hoc analysis demonstrates favorable effect size, NNT, and NNH values for solriamfetol in the treatment of EDS associated with narcolepsy and OSA. Support (if any) Axsome Therapeutics

Peripheral Nerve Stimulation With a High-Frequency Electromagnetic Coupled Powered Implanted Receiver at the Posterior Tibial Nerve for the Treatment of Chronic Pain in the Foot

IntroductionPeripheral neuropathy has several causes, with diabetes being the most common. Conservative management may fail to control pain. Our study aimed at evaluating the use of peripheral nerve stimulation of the posterior tibial nerve for treating peripheral neuropathy. Materials and MethodsThis was an observational study of 15 patients who received peripheral nerve stimulation at the posterior tibial nerve to treat peripheral neuropathy. Outcomes measured were improvement of pain scores and Patient Global Impression of Change (PGIC) at 12 months compared with before the implant. ResultsMean pain scores with the verbal rating scale were 3 ± 1.8 at >12 months compared with 8.6 ± 1.2 at baseline, a reduction of 65% (p < 0.001). Median satisfaction with the PGIC at >12 months was 7 of 7, with most subjects reporting a 6 (better) or a 7 (a great deal better). ConclusionPeripheral nerve stimulation of the posterior tibial nerve can be a safe and effective modality for treating chronic pain symptoms related to peripheral neuropathy of the foot.

Antidepressants for pain management in adults with chronic pain: a network meta-analysis.

Antidepressants for pain management in adults with chronic pain: a network meta-analysis.

The short-term false positives after sacral neuromodulation therapy: Who, how many and why? A prospective descriptive single centre study

Aim:I. To describe the number of false positive cases (FP), their characteristics and reason of occurrence in sacral neuromodulation therapy (SNM). Methods:A multidisciplinary prospective single-centre study was conducted between March 2018 and December 2021 with a follow-up of 12 months. Patients with therapy-resistant pelvic organ dysfunctions, scheduled for a 2-staged SNM procedure at the Urology (UD) and Colorectal Surgery Department (CRD), were included. All patients completed bowel and bladder diaries at baseline and during the test phase. Patient global impression of change (PGIC) and satisfaction scores concerning urological (US) and bowel symptoms (BS) were surveyed at baseline, at 1, 6 and 12 months after implantation. Patient characteristics and diary outcomes between FP and true positive cases (TP) were compared using non-parametric statistical tests. SPSS 27.0 was used. Clinical trial registration: NCT05313984. Results:The FP ratio at one month follow-up was 16% (11/68), with a FP ratio of 13% (N=6/48) and 25% (N=5/20) for the urology patients and colorectal surgery patients, respectively. There were no significant differences in demographic characteristics between the FP and TP group (p > 0,05), however there is a trend towards FP having worse baseline symptoms than TP. The FP group had a significant lower baseline and test phase 24 h diuresis (p < 0,05), without having a significant different intake than the TP group. Conclusion:At one month after full implantation of a sacral neuromodulator, 16% of the patients showed loss of subjective success. These FP could not be predicted from demographic characteristics, most likely due to the small study population. Although not significant, FP seem to have worse symptoms at baseline than TP, with a significant lower diuresis regardless of fluid intake.