Patient Global Impression Of Change Research Articles

The Downside of Botulinum Injections for Anterocollis: A Case Series and a Review of the Literature.

This is a case series and a review of the literature of therapeutic outcomes of botulinum toxin (BT) injections for anterocollis. Data collected included gender, age, age at onset, muscles targeted, and doses injected. Routine forms were filled out during each visit: Patient Global Impression of Change, Clinician Global Impression of Severity, Tsui scale. The effect duration and side effects (SEs) of the previous treatment were noted. We described 4 patients (3 men, 13 visits) with anterocollis, as primary postural abnormality of the neck, emphasizing the therapeutic response to BT injection. Mean age at onset was 75.3 ± 7.0 years, age at first injection was 80.7 ± 3.5 years. The mean total dose per treatment was 290.0 ± 95.6 units. Patient Global Impression of Change with any grade of favorable effect was reported in 27.3% of the treatments. In objective assessment, Global Impression of Severity and Tsui scores did not show a consistent tendency of improvement. Neck weakness was prevalent in 18.2% of the visits of the anterocollis group while no other SEs were noted. We found 15 articles describing experience with BT for anterocollis in 67 patients (19 in deep and 48 in superficial neck muscles). This case series describes the poor outcome of BT treatment for anterocollis, with low efficacy and bothersome SE. Levator scapulae injection for anterocollis is not effective and is highly associated with head drop and should perhaps be abandoned. Injection to the longus colli might give some benefit in non-responders.

Patient-centered results from a multicenter study of continuous peripheral nerve blocks and postamputation phantom and residual limb pain: secondary outcomes from a randomized, clinical trial

IntroductionWe previously reported that a 6-day continuous peripheral nerve block reduces established postamputation phantom pain. To provide patients and providers with the information to best inform treatment decisions, here we...

Short-Term Effects of Manual Therapy on Balance: A Multicenter, Randomized, Double-Blind Controlled Trial

ObjectiveThe purpose of this study was to analyze short-term changes in dynamic and static balance after a manual therapy protocol in healthy participants and analyze any repercussions on mood and perception of change after applying articulatory techniques. MethodsA single-blind, randomized, multicenter clinical trial was conducted. Participants were allocated to either a manual therapy group (MTG) (n = 101) or a control group (CG) without intervention (n = 99), and measures were taken before treatment, after the intervention, and 1 week after treatment. Assessments included the Star Excursion Balance Test, Unipedal Stance Test (UPST), Profile of Mood States (POMS), and Patient Global Impression of Change (PGIC) scale. ResultsTwo hundred healthy participants completed the study (mean age, 22 [SD = 2.67]). There was a statistically significant interaction between groups and time measurements in the right leg for anterior (P = .003), posteromedial (P < .001), and posterolateral (P = .001) directions in favor of the MTG, as well as in the left leg for anterior (P < .001), posteromedial (P < .001), and posterolateral (P = .012) directions. The analysis failed to show statistically significant interactions between any of the factors for the UPST and POMS (P > .05). The MTG showed a significant improvement compared to the CG after treatment (P = .003) and at 1-week follow-up (P < .001) on the PGIC scale. ConclusionThe results suggest the MT intervention was effective on dynamic balance in post-intervention in healthy participants, and some of the directions maintained the results at 1-week follow-up. Perception of change in post-treatment and 1-week follow-up also significantly improved. The protocol did not seem to produce changes in static balance and mood states. Positive changes after manual therapy were maintained in the short term.

Durable patient-reported outcomes following 60-day percutaneous peripheral nerve stimulation (PNS) of the medial branch nerves

BackgroundChronic low back pain (CLBP) is often associated with clinical evidence of central nervous system sensitization and finding a clear source of nociceptive input can be challenging. Conventional therapies targeting peripheral spinal pain structures can fail to address centrally-mediated, underlying causes of pain. Sixty-day percutaneous peripheral nerve stimulation (PNS) applied to the lumbar medial branch nerves is a non-surgical, non-opioid treatment that may restore the balance of peripheral inputs to the central nervous system and reverse maladaptive changes in central pain processing. As a minimally invasive, non-destructive treatment, percutaneous PNS was designed to be used earlier in the treatment continuum than radiofrequency ablation or permanently-implanted neurostimulation systems. ObjectiveThe objective of this clinical trial was to characterize the durability of responses to medial branch PNS in a prospective multicenter case series study of CLBP patients recalcitrant to multiple non-surgical treatments. DesignProspective, multicenter clinical trial. PopulationAdults with CLBP without radicular leg pain who had previously failed multiple types of conventional treatments. InterventionSixty-day percutaneous PNS applied to the lumbar medial branch nerves. MethodsPercutaneous PNS leads were implanted under image guidance (ultrasound and/or fluoroscopy) and treatment was applied for up to 60 days, after which the leads were removed. Participants were followed through 14 months (12 months after the 2-month PNS treatment). Prospectively-defined endpoints included assessments of pain intensity, disability, pain interference, health-related quality of life, depression, and patient global impression of change. ResultsTreatment of CLBP with 60-day percutaneous PNS treatment produced clinically meaningful improvements in average pain intensity, disability, and/or pain interference for a majority of participants through the entire 14 month follow up period without requiring permanent system implantation. The proportion of participants experiencing clinically meaningful improvement in at least one outcome (pain intensiy, disability, pain interference) with PNS was 91% after 2 months, 79% at 5 months, 73% at 8 months, 75% at 11 months, and 77% at 14 months. There were no serious or unanticipated study-related adverse events. ConclusionThis prospective multicenter clinical trial demonstrates the clinical utility of percutaneous PNS when applied to the medial branch nerves for the treatment of chronic low back pain recalcitrant to non-surgical treatments. Given the minimally invasive nature of percutaneous PNS and the significant benefits experienced by participants, percutaneous PNS provides a safe and effective first-line neuromodulation treatment for patients with CLBP that may obviate the need for neuroablative procedures or permanent neurostimulation system implantation.

Transvenous embolization of cerebrospinal fluid-venous fistulas: Independent validation and feasibility of upper-extremity approach and using dual-microcatheter and balloon pressure cooker technique

BackgroundTransvenous embolization is emerging as a promising treatment for cerebrospinal fluid-venous fistulas (CVF) associated with spontaneous intracranial hypotension (SIH).ObjectiveTo perform an independent validation of the efficacy and safety of the...

A Shoulder/Elbow Triage and Assessment model of care reduced a public orthopaedic shoulder/elbow clinic waitlist with high patient satisfaction.

Patients referred to public orthopaedic clinics can experience long waiting times before assessment. This study aims to evaluate the effectiveness of a collaborative Shoulder/Elbow Triage and Assessment (SHELTA) model of care involving orthopaedic surgeons and physiotherapists to reduce the waitlist and improve service and clinical outcomes for patients on an orthopaedic shoulder/elbow clinic waitlist. Patients on the waitlist were triaged by surgeons and physiotherapists and invited to an assessment by experienced physiotherapists. Patients were treated nonoperatively or transferred to orthopaedic management based on clinical discussion. The primary outcome was the number of patients on the waitlist. Secondary outcomes included adverse events, patient satisfaction, re-referral and conversion to surgery rates. Pain, function and patient global impression of change were recorded for participants managed nonoperatively. From July 2019 to December 2019, the waitlist reduced from 451 to 298 patients with no adverse events. Seventy-nine patients could not be contacted and 25 no longer required assessment, and were removed from the waitlist. Nonoperatively managed participants reported satisfaction with the service, a median score of 6 on a 7-point Patient Global Impression of Change scale, change in pain of -2.5/10 (95% CI -3.3, -1.7; P < 0.001) on a numerical pain rating scale, and change in function of -17.4/100 (95% CI: -24.1, -10.8; P< 0.001) on the QuickDASH, indicating improvement. The SHELTA model of care effectively reduced the number of patients on an orthopaedic shoulder/elbow clinic waitlist with good service and clinical outcomes.

Cross-cultural adaptation, validity, reliability and responsiveness of the Japanese version of the Victorian Institute of sports assessment for patellar tendinopathy (VISA-P-J)

BackgroundThis study aimed to translate, adapt, and test the psychometric properties of the Japanese version of the Victorian Institute of sports assessment for patellar tendinopathy (VISA-P-J).MethodsThis prospective cohort study registered 43 participants ≥ 18 years old with a history of painful symptoms in the inferior pole of the patella to the proximal patellar tendon lasting ≥ 1 month for patellar tendinopathy. Pain in daily life and during sports activities, symptom classification, and patient global impression of change were assessed at the baseline, 1 week, and 12 weeks. The psychometric properties, test–retest reliability, standard error of measurement, internal consistency criterion validity, construct validity, responsiveness, and interpretability, of the VISA-P-J were calculated according to the COSMIN.ResultsThe two-way random-effects, absolute agreement intraclass correlation coefficient for test–retest reliability of VISA-P-J was 0.87 (95% confidence interval: 0.78, 0.93), and the standard error of measurement of VISA-P-J was 0.89. The Cronbach's alpha for internal consistency of VISA-P-J was 0.81. A correlation between VISA-P-J and Roel’s classification, Visual Analog Scale for pain (VAS)-Active Daily Living, and VAS-Sports (r = − 0.52, r = − 0.66, r = − 0.86, p < 0.01, respectively) was observed for criterion validity. All hypotheses of the hypothesis-testing method to evaluate construct validity and responsiveness of VISA-P-J were substantiated. The minimal clinically important difference of VISA-P-J was 7 points.ConclusionWe demonstrated that the VISA-P-J was a reliable, valid, and responsive assessment method for individuals with chronic pain in the patellar tendon.

Treatment of Peripheral Neuropathy: Combination Therapy Using LED Light, Extracorporeal Shockwave Therapy, Platelet Rich Plasma, and an Oral Dietary Supplement

Objectives: Peripheral neuropathy (PN) is a significant contributor to disability in the elderly. It is also one of the most prevalent complications of type 2 diabetes, prediabetes and metabolic syndrome. PN is commonly associated with pain, numbness, tingling, burning, and cramping in the feet and legs. Current treatment options are limited to controlling pain, seizures and use of antidepressant medications. These treatments have undesirable side effects and don’t stop PN progression. Here we utilized a combination of individual-specific modalities to improve local circulation and relieve PN symptoms. Methods: We conducted an open-label, multicenter pilot trial with 34 subjects (19 males and 15 females ranging from 40 - 85 years of age). All of the participants were diagnosed with peripheral neuropathy and had bilateral symptoms in their feet, and many reported the same symptoms (pain, numbness, tingling, burning, and cramping) in their lower legs. The duration of symptoms ranged from four months to over six years. On Day 0, subjects were given a 90-day supply of the oral supplement with dosing instructions and a LED light therapy device. They also received three platelet-rich plasma (PRP) injections in their lower extremities. Subjects also received an extracorporeal shockwave therapy (ESWT) treatment for each foot and subsequently twice per week for the first six weeks, then once weekly for the duration of the study. Subjects filled out the Brief Pain Index (BPI) at weekly intervals. On Day 90, subjects completed the Patient Global Impression of Change (PGIC) survey. Results: There were significant responses to pain, as evidenced by BPI scores at weeks 8, 9, 10 and 11 (p = 0.02, 0.01, 0.02, and 0.003, respectively). Analysis of the final day PGIC survey showed a favorable outcome for 73% of participants (p = 0.003), with the majority reporting Very Much Improved. Conclusions: By utilizing a multi-modality treatment protocol that includes PRP, LED light therapy, ESWT and an oral dietary supplement, we observed significant reductions in BPI scores. Quality of life and their overall impression of change (PGIC) were significantly improved, and there were no significant side effects.

Surgical treatment of post-traumatic vertebral osteonecrosis including intravertebral expansive implants-clinical, functional and imaging outcomes and a center experience over 7 years.

The effective treatment of post-traumatic vertebral osteonecrosis continues to be an under discussion and controversial subject. Armed kyphoplasty with expansive intravertebral implants is an emerging procedure, which, in theory, allow for a more effective preservation of the restored vertebral height. The development of the indications for these recent devices has given rise to auspicious outcomes in vertebral non-union situations. The aim of this study is to evaluate the clinical, functional and imaging outcomes of the surgical treatment of situations of post-traumatic vertebral necrosis, following a therapeutic algorithm that includes armed kyphoplasty with intravertebral expansive implants and bridge pedicular stabilization, according to a predefined necrosis stage. We present a retrospective observational study, in which 35 patients took part, including a total of 35 cases of post-traumatic vertebral osteonecrosis submitted to surgical treatment over 7 years (between 2016 and 2023) at the same center according to a defined therapeutic algorithm. The cases were staged according to vertebral morphology (non-plana or plana) and mobility (mobile or immobile)-stages 1m (mobile necrotic vertebra non-plana), 1i (immobile necrotic vertebra non-plana), 2m (mobile necrotic vertebra plana), and 2i (immobile necrotic vertebra plana)-and the following surgeries were performed: armed kyphoplasty with intravertebral expansive implants filled with bone cement, associated or not to adjacent pedicle instrumentation; or bridge pedicle fixation of the adjacent levels. Clinical results [Patient Global Impression of Change (PGIC), Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI)] as well as imaging outcomes (restoration and preservation of the heights of the vertebral body) were studied. The mean follow-up time corresponded to 3.17 years (range, 1-7.5 years). Most of the clinical-functional and imaging parameters showed important improvements after surgical treatment, with few complications. A statistically significant greater degree of functional improvement was found in plana vertebrae when compared to non-plana, which reflects that the first are quite symptomatic and disabling at the beginning and improve a lot with surgical treatment. Significant indirect correlations were found between the time from the initial fracture to surgical intervention after diagnosis of vertebral necrosis and the anterior sagittal height in the immediate postoperative time and at the ending of the follow-up. Also, a significant direct correlation was identified between this time and the VAS for pain at the end of the follow-up and the PGIC scale in the same period. It was also found that patients with surgical complications had a statistically significantly longer time between the initial fracture and surgery for post-traumatic necrosis. We present the results of a surgical therapeutic algorithm that includes the use of recent expansive intravertebral implants at post-traumatic vertebral osteonecrosis, resulting in satisfactory clinical, functional and imaging results. This work shows a pioneering statistical demonstration of the clinical, functional and imaging importance of early detection of this condition (ideally in vertebrae non-plana morphology stages), so that there is still sufficient bone tissue in the vertebral body to permit the stabilization and restoration of its anatomy through a minimally invasive interior reconstruction, with percutaneous access and quicker convalescence, that is to say, armed kyphoplasty, avoiding the unwanted disease progression that will require more aggressive surgical solutions that doesn't allow anatomical restauration.

Med Check: Alzheimer’s Agitation, Idiopathic Hypersomnia, Depression, and More

Back to table of contents Previous article Next article Med CheckFull AccessMed Check: Alzheimer’s Agitation, Idiopathic Hypersomnia, Depression, and MoreTerri D’ArrigoTerri D’ArrigoSearch for more papers by this authorPublished Online:4 Jan 2023https://doi.org/10.1176/appi.pn.2023.01.1.5AXS-05 May Delay Relapse of Alzheimer’s AgitationAxsome Therapeutics’ investigational combination drug AXS-05 (45 mg dextromethorphan/105 mg bupropion) may delay relapse of agitation associated with Alzheimer’s disease, the company announced in November.In the phase 3 ACCORD trial, 108 patients with Alzheimer’s disease agitation who had already responded to AXS-05 in a previous, open-label trial either continued treatment with the drug or were switched to placebo for up to 26 weeks. Relapse was defined as a worsening of 10 points or more on the Cohen-Mansfield Agitation Inventory (CMAI) from the time the patients were randomized to either continued treatment or to placebo, a CMAI total score greater than when they entered the study, or hospitalization or other institutionalization because of agitation associated with Alzheimer’s disease.Patients who took AXS-05 had a 3.6-fold lower risk of relapse compared with those who took placebo. During the trial, 7.5% of patients who took the drug experienced a relapse of Alzheimer’s disease agitation, compared with 25.9% of those who took placebo. Serdexmethylphenidate Granted Orphan Drug Status for Idiopathic Hypersomnia The Food and Drug Administration (FDA) has granted orphan drug status to serdexmethylphenidate for the treatment of idiopathic hypersomnia, KemPharm Inc. announced in November. Serdexmethylphenidate is KemPharm’s prodrug of d-methylphenidate.The FDA may grant orphan drug status to investigational therapies that address rare medical diseases or conditions. If the drug later receives FDA approval for treating the disease or condition, the FDA may not approve any other applications to market the same drug for the same indication for seven years, except in limited circumstances.KemPharm will soon begin a phase 2 trial of serdexmethylphenidate in patients with idiopathic hypersomniaand a second trial in patients with narcolepsy.Serdexmethylphenidate is also an active ingredient in Corium’s Azstarys (serdexmethylphenidate and dexmethylphenidate), which the FDA approved in March of 2021 for treating symptoms of attention-deficit/hyperactivity disorder in patients aged 6 years and older. Spravato May Be More Effective Than Quetiapine XR for TRDAn open-label phase 3b trial suggests that Spravato (esketamine nasal spray) may have greater efficacy than quetiapine extended release (XR) for treating symptoms of treatment-resistant depression (TRD) in adults, Janssen Pharmaceutical Companies announced in November. Janssen is the manufacturer of Spravato.In the ESCAPE-TRD trial, 676 patients with TRD were randomized to receive either Spravato or quetiapine XR, both in combination with a continuing selective serotonin reuptake inhibitor or serotonin and norepinephrine reuptake inhibitor, for 32 weeks. At the eighth week, 21.7% of the patients who received Spravato experienced remission of their symptoms, compared with 14.1% of those who took quetiapine. At study’s end, symptoms abated in 55% of patients who took Spravato, compared with 37% of those who took quetiapine FDA to Review IPX203 for Parkinson’s DiseaseIn November, Amneal Pharmaceuticals Inc. announced that the FDA has accepted for review the company’s New Drug Application for IPX203 (carbidopa/levodopa extended release) for the treatment of Parkinson’s disease.In the phase 3 RISE-PD trial, 506 patients who were at least 40 years old when they were diagnosed with Parkinson’s disease were randomized to receive either IPX203 or immediate-release carbidopa/levodopa. All patients had motor fluctuations.The primary endpoint was change from baseline in the daily amount of “Good On” time, defined as the sum of “On” time without dyskinesia and “On” time with non-troublesome dyskinesia. At the twentieth week, those who took IPX203 had an average of roughly half an hour more of “Good On” time compared with those who took immediate-release carbidopa/levodopa.In addition, a study published in the May 2022 Neurology found that 29.7% of patients who took IPX203 were “much improved” or “very much improved,” as evidenced in their scores on the Patient Global Impression of Change, compared with 18.8% of those who took immediate-release carbidopa/levodopa. ■“A Phase 3 Trial of IPX203 vs CD-LD IR in Parkinson’s Disease Patients with Motor Fluctuations (RISE-PD)” ISSUES NewArchived

Arbaclofen extended-release tablets for spasticity in multiple sclerosis: open-label extension study.

Baclofen, a racemic γ-aminobutyric acid B receptor agonist, is commonly used for the management of multiple sclerosis-related spasticity but is associated with frequent dosing and poor tolerability. Arbaclofen, the active R-enantiomer of baclofen, exhibits 100- to 1000-fold greater specificity for the γ-aminobutyric acid B receptor compared with the S-enantiomer and ∼5-fold greater potency compared with racemic baclofen. Arbaclofen extended-release tablets allow a dosing interval of 12 h and have shown a favourable safety and efficacy profile in early clinical development. A 12-week, randomized, placebo-controlled Phase 3 trial in adults with multiple sclerosis-related spasticity demonstrated that arbaclofen extended-release 40 mg/day significantly reduced spasticity symptoms compared with placebo and was safe and well tolerated. The current study is an open-label extension of the Phase 3 trial designed to evaluate the long-term safety and efficacy of arbaclofen extended-release. In a 52-week, open-label, multicentre study, adults with a Total Numeric-transformed Modified Ashworth Scale score ≥2 in the most affected limb received oral arbaclofen extended-release titrated over 9 days up to 80 mg/day based on tolerability. The primary objective was assessment of arbaclofen extended-release safety and tolerability. Secondary objectives included an assessment of efficacy using the Total Numeric-transformed Modified Ashworth Scale-most affected limb, the Patient Global Impression of Change and Expanded Disability Status Scale. Of 323 patients enrolled, 218 (67.5%) completed 1 year of treatment. Most patients (74.0%) achieved an arbaclofen extended-release maintenance dose of 80 mg/day. At least one treatment-emergent adverse event was reported by 278 patients (86.1%). The most common adverse events were [n patients (%)]: urinary tract disorder [112 (34.7)], muscle weakness [77 (23.8)], asthenia [61 (18.9)], nausea [70 (21.7)], dizziness [52 (16.1)], somnolence [41 (12.7)], vomiting [29 (9.0)], headache [24 (7.4)] and gait disturbance [20 (6.2)]. Most adverse events were of mild-moderate severity. Twenty-eight serious adverse events were reported. One death occurred during the study, a myocardial infarction that was considered by investigators as unlikely to be related to treatment. Overall, 14.9% of patients discontinued due to adverse events, primarily muscle weakness, multiple sclerosis relapse, asthenia and nausea. Evidence of improvement in multiple sclerosis-related spasticity was observed across arbaclofen extended-release dosages. Arbaclofen extended-release treatment (up to 80 mg/day) was well tolerated and reduced symptoms of spasticity in adult patients with multiple sclerosis for 1 year. Clinical Trial Identifier: ClinicalTrials.gov, NCT03319732.

Role of Protopine and Nuciferine in the Management of Nocturia, Urgency, and Dysuria in Pre- and Postmenopausal Women: A Prospective Pilot Study

Objectives: Nocturia was commonly treated with drugs burdened with high costs and numerous side effects; in fact, more than 70% of patients drop out of long-term treatment. Protopine and nuciferine are two alkaloids that have different effects on the neurotransmitter receptors involved in the regulation mechanism of the onset of urinary stimuli. The aim of the study was to evaluate the efficacy in controlling primarily nocturia and secondarily urgency and dysuria after 3 months of treatment with combination therapy of protopine and nuciferine syrup. Design: This is a prospective cohort study in which all patients were diagnosed with overactive bladder syndrome (OAB) and the presence of the following symptoms: nocturia, urgency, and dysuria. Thirty patients were administered 10 mL/die (16.6 mg of nuciferine, 0.09 mg of protopine) of syrup for 3 months. Patients were evaluated at baseline (T₀) with the International Consultation on Incontinence Questionnaire (ICIQ), Visual Analogue Scale (VAS) for the evaluation of dysuria, Patient Perception of Intensity of Urgency Scale (PPIUS) and at 3 months (T₁) with the Patients’ Global Impression of Change (PGI-C) scale, PPIUS, VAS, and ICIQ. Participants: Women with diagnosis of OAB; the presence of nocturia, urgency, and dysuria symptoms agreeing to undergo treatment and compiling informed consent; and the absence of contraindications to the use of active ingredients were included in the study. Setting: Patients were recruited at T0 during the visit to the Uro-Gynecology clinic of the University of “Campus Bio-Medico” and visited again 3 months (T1) after the initiation of therapy. Methods: We explored survey data by descriptive statistics: in particular, continuous values (i.e., ICIQ) have been summarized by mean and standard deviation of discrete ordinal values (i.e., VAS, PPIUS, and bladder diary parameters at T₀ and T₁) by median, minimum, and maximum reported scores. Where we could assume normality in distribution, assessed by the Shapiro-Wilk test and the evaluation of the QQ plot, we compared the observation of T₀ and T1 with the paired Student’s t test; otherwise, we tested differences in distribution with the paired Mann-Whitney U test. Results: Thirty patients completed a 3-month therapy. The ICIQ and VAS questionnaires for the assessment of dysuria, both, reported an improvement in dysuria at T₁ (p < 0.001). The PPIUS questionnaire reported an improvement in urinary urgency at T₁ (p < 0.001). The PGI-C scale in T1 indicated an improvement in symptoms: 93% for nocturia, 70% for urinary urgency, and 63% for dysuria. Limitations: The weaknesses of this study are the small number of patients; as a pilot study, the study design was not randomized with a placebo and without blinding; and the short follow-up. Conclusions: Protopine and nuciferine can be an interesting alternative to primarily treat and reduce nocturia episodes, in addition to improving OAB-related urgency and dysuria.

A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Phase 2b Trial of P2X3 Receptor Antagonist Sivopixant for Refractory or Unexplained Chronic Cough

IntroductionTo determine the optimal dose of sivopixant, a highly selective P2X3 receptor antagonist, for refractory or unexplained chronic cough (RCC/UCC).MethodsIn this phase 2b, randomized, double-blind, placebo-controlled, parallel-group, multicenter trial, patients received sivopixant 50, 150, or 300 mg or placebo once daily for 4 weeks. The primary endpoint was a change from baseline in 24-h cough frequency (coughs/h) with sivopixant vs placebo.ResultsOverall, 390/406 randomized patients completed the study. Placebo-adjusted changes in hourly cough count over 24 h were 13.17% (P = 0.3532), − 1.77% (P = 0.8935), and − 12.47% (P = 0.3241) and in cough severity (visual analog scale) were 1.75 mm (P = 0.5854), − 1.21 mm (P = 0.7056), and − 6.55 mm (P = 0.0433) with sivopixant 50, 150, and 300 mg, respectively. Placebo-adjusted changes from baseline in Leicester Cough Questionnaire total scores were − 0.37 (P = 0.4207), − 0.07 (P = 0.8806), and 0.69 (P = 0.1473) with sivopixant 50, 150, and 300 mg, respectively. Additionally, 61.3%, 78.3%, 86.8%, and 71.4% of patients receiving sivopixant 50, 150, and 300 mg and placebo, respectively, reported any improvements in Patient Global Impression of Change. The incidence of treatment-emergent adverse events (TEAEs) was 25.7%, 32.0%, 49.0%, and 20.6% in sivopixant 50, 150, and 300 mg and placebo groups, respectively; all TEAEs in the sivopixant group were mild-to-moderate.ConclusionSivopixant did not demonstrate a statistically significant difference vs placebo in change from baseline in 24-h cough frequency. The dose of 300 mg has potential for RCC/UCC, showing the greatest improvements in cough frequency and patient-reported outcomes and dose-related mild to moderate reversible taste disturbance, although further trials are needed.Clinical Trial RegistrationClinicalTrials.gov identifier NCT04110054; registered September 26, 2019.

Utilisation du dronabinol dans le traitement des douleurs neuropathiques réfractaires : retour d’expérience des patients suivis dans un Centre d’évaluation et de traitement de la douleur

Dronabinol is a drug composed of synthetic delta-9-tetrahydrocannabinol. In France, dronabinol requires a named Temporary Utilisation Authorisation (TUA), for the treatment of refractory neuropathic pain. Few data currently exist concerning its efficacy and tolerance. We present our feedback on its use for chronic pain patients, the multidisciplinary supervision and the monitoring set up by the clinical pharmacist. This retrospective monocentric study presents Patients Global Impression of Change and tolerance data from patients treated with dronabinol in a pain center between October 2020 and July 2021. We present their satisfaction towards the care process. Nineteen patients were treated with dronabinol during the study period. - The clinical pharmacist issued 180 advices for patients and doctors. Patients reported a positive impact of the telephone follow-up carried out by the clinical pharmacist. - 75% (n=9/12) of patients who continued treatment for more than 3 months reported improvement in their health. - 74% (n=14/19) of patients had at least one adverse event, six patients needed to discontinue the treatment. Dronabinol represents an alternative that can improve the quality of life of some patients suffering from refractory neuropathic pain. Nevertheless, as with any medicine, its initiation requires a rigorous evaluation of the benefit-risk balance. The close collaboration between the physician and the clinical pharmacist allows a secure management patients and makes this complex drug circuit easer.

Sutimlimab provides clinically meaningful improvements in patient-reported outcomes in patients with cold agglutinin disease: Results from the randomised, placebo-controlled, Phase 3 CADENZA study.

Cold agglutinin disease (CAD) is a rare chronic autoimmune haemolytic anaemia, driven mainly by classical complement pathway activation, leading to profound fatigue and poor quality of life. In the Phase 3 CADENZA trial, sutimlimab-a C1s complement inhibitor-rapidly halted haemolysis, increased haemoglobin levels and improved fatigue versus placebo in patients with CAD without a recent history of transfusion. Patient-reported outcomes (PROs) included Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), 12-Item Short Form Health Survey (SF-12), EuroQol visual analogue scale (EQ-VAS), Patient Global Impression of Change (PGIC) and Patient Global Impression of (fatigue) Severity (PGIS). Sutimlimab resulted in significant rapid and meaningful improvements versus placebo in PROs. From Week 1, the FACIT-Fatigue mean score increased >5 points above baseline (considered a clinically important change [CIC]). Least-squares (LS) mean change in FACIT-Fatigue score from baseline to treatment assessment timepoint was 10.8 vs. 1.9 points (sutimlimab vs. placebo; p< 0.001). Improvements in physical (PCS) and mental (MCS) component scores of the SF-12 were also considered CICs (LS mean changes from baseline to Week 26: PCS 5.54 vs. 1.57 [p= 0.064]; MCS 5.65 vs. -0.48 [p= 0.065]). These findings demonstrate that in addition to improving haematologic parameters, sutimlimab treatment demonstrates significant patient-reported benefits. Study registered at www.clinicaltrials.gov: NCT03347422.

Exploring a New Cueing Device in People Who Experience Freezing of Gait: Acceptance of a Study Design.

Freezing of Gait (FoG) is a disabling symptom of Parkinson's Disease (PD) and is defined as a "brief episodic absence or marked reduction of forward progression of the feet despite the intention to walk." Compensatory strategies such as cueing and high frequency vibrotactile stimulation can reduce FoG severity and improve gait parameters. A new Sternal high frequency Vibrotactile Stimulation Device (SVSD) with cueing function has been developed, however the clinical effects of this device are yet to be fully investigated. The aim of this study was to investigate, if the proposed study design using a SVSD and gait analysis sensor insoles was acceptable for people with PD. This feasibility study was designed as a randomized cross-over study. Thirteen participants took part in a one off 60-minute data collection session. The acceptability of the study design was assessed with a mixed methods questionnaire considering each step of the study process. Secondary outcome measures were the feasibility of using the 10 Metre Walk Test (10MWT), the Freezing of Gait Score (FoG-Score), and Patient Global Impression of Change (PGI-C) with and without the SVSD. The participants scored all aspects of the study design as very satisfactory. In addition, all participants could perform the secondary outcome measures and were deemed feasible. Feedback from open ended questions provided ideas and considerations for adaptations of future clinical studies. The proposed study design was acceptable for people with PD. Implications. This study design, with small adaptations, can be used for larger studies to evaluate the effect of an SVSD on FoG in people with PD.

Stent-armed kyphoplasty in osteoporotic thoracolumbar fractures-clinical and functional results and a center experience over 10 years.

The optimal treatment of osteoporotic vertebral fractures is still a controversial and under discussion topic. Armed kyphoplasty with expansive intravertebral implants is an emerging procedure, which, in theory, it not only makes it possible to achieve instant analgesia, and to get stabilization gains of benefits of kyphoplasty and vertebroplasty, but also, allows for a more effective maintenance of the restored vertebral height. A retrospective observational study is presented, in which 30 patients participated, including a total of 33 osteoporotic thoracolumbar compression burst vertebral fractures with involvement of one or both vertebral platforms and of more than one fifth of the posterior wall. These individuals underwent armed kyphoplasty with VBS® stents (or stentoplasty) filled with bone cement over 10 years (between 2012 and 2022) at the same center. Clinical (visual analogue scale, Oswestry Disability Index and Patient Global Impression of Change) and imaging results (restoration and maintenance of vertebral body heights) achieved were investigated. The mean follow-up time was 4.5 years (range, 1-10 years). There was a statistically significant improvement in all clinical and functional parameters evaluated, as well as a statistically significant difference in the various vertebral body heights between preoperative and end of follow-up time [increase of 10.7-15.2-5.0 mm (anterior-median-posterior) in the sagittal plane and 6.7-11.6-9.7 mm (right-median-left) in the coronal plane]. There was a statistically significant direct correlation between vertebral heights in the coronal plane, and between the Beck index assessed at the end of the follow-up period and the improvement in functional disability. The percutaneous transpedicular posterior approach, the ability to anatomically restore the fractured vertebra and to maintain it in the medium-long term, as well as the reduced risk of adverse effects, make stent-armed kyphoplasty a very attractive treatment option for osteoporotic compressive thoracolumbar fractures. A clinical-morphological correlation was demonstrated regarding the surgical treatment of these fractures, it was found that a more effective morphological restoration of vertebral heights in both the sagittal and coronal planes is associated with superior satisfactory clinical functional parameters.

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.

Real-World Experience of Patients with Sickle Cell Disease Treated with Crizanlizumab: A Single Comprehensive Sickle Cell Center Retrospective Cohort Analysis

Background:Sickle cell disease (SCD) is an inheritable hemoglobinopathy with great impact on patients’ quality of life and healthcare costs. In 2019, crizanlizumab, the first-in-class monoclonal antibody that target the cell adhesion molecule P-selectin, was approved by the FDA to reduce the rate of vaso-occlusive crisis in patients with SCD ≥16 years old, based on the results of the SUSTAIN trial [1]. Aim: To study the real-world effectiveness of crizanlizumab in patients with SCD ≥16 years old treated with crizanlizumab 5.0 mg/kg, with or without hydroxyurea, from 2019 to 2022 in our comprehensive sickle cell center. Methods: This is a retrospective cohort analysis of patients with SCD (all genotyped, ≥16 years old) who received at least 2 consecutive doses of crizanlizumab. Demographics and laboratory findings before and after crizanlizumab were collected and analyzed. Only data available from patients’ electronic medical records (and other secondary data sources) 1 year before (pre-index data) and after (post-index data) the ≥2 consecutive crizanlizumab doses were analyzed. Objective clinical improvement was captured using the Patients’ Global Impression of Change (PGIC) score. Descriptive statistics are presented in percentages, medians, and interquartile ranges. An independent group unpaired Student's t-test was used to determine, where appropriate, the level of significant differences among normal distribution continuous variable with p value <0.05 considered statistically significant. Data was analyzed using GraphPad Prism version 9.0.2. Results:As of July 2022, there were 18 patients eligible for analysis. The median age of patients was 30.5 (range, 19-47) years, 7 (38%) males and 11 (61%) females (Table 1). Eight patients had the HbSS genotype, 7 HbSC, and 3 HbSB null. The median duration of exposure to crizanlizumab was 53.6 weeks, and 16 (89%) patients received crizanlizumab for ≥26 weeks. Crizanlizumab is very well tolerated with no serious adverse events (grade ≥3) related to treatment reported. The most commonly reported adverse events were fatigue (n=3), followed by headache (n=2) and nausea (n=2). There was no significant difference in laboratory parameters (hemoglobin, hematocrit, total bilirubin, creatinine, or protein/creatinine ratio) between pre-index and post-index values (Table 2). Although there was improvement in reticulocytes (6.5% vs. 5.1%) and LDH (336.5 vs. 279 U/L) compared with baseline, this was not statistically significant, likely due to the small sample size (p=0.71 and p=0.98, respectively). There was a remarkable improvement in patients’ subjective response with crizanlizumab infusion. The median PGIC score of our patients was 5, signifying moderately better with noticeable changes, although slight. Twelve (67%) patients provided a score of ≥4, which signifies feeling better with changes. Conclusions: This is one of the first retrospective studies to use PGIC to capture the effectiveness of crizanlizumab in patients with SCD. This study shows that crizanlizumab was associated with an improvement in patient response that was directly and indirectly related to the reduction of vaso-occlusive crisis, consistent with findings from the SUSTAIN trial. Further large-scale studies are needed to corroborate these findings.

Active Study: Impact of Voxelotor on Sleep Quality, Physical Activity, and Patient-Reported Outcomes

Background: Sickle cell disease (SCD) is an inherited disorder in which sickle hemoglobin (HbS) polymerization causes red blood cell sickling, resulting in complications such as chronic hemolytic anemia, vaso-occlusion, end-organ damage, and decreased quality of life. Voxelotor is a first-in-class HbS polymerization inhibitor approved in the US for the treatment of SCD in patients aged ≥4 years. The pivotal phase 3 HOPE and phase 2a HOPE-KIDS 1 trials demonstrated the safety and efficacy of voxelotor in increasing hemoglobin (Hb) and decreasing hemolytic markers. Objective: Here we report Hb response, patient-reported quality-of-life (QOL) outcomes, and safety data from the ongoing ActIVe study (NCT04400487), a phase 4, multicenter, open-label study evaluating the effect of voxelotor on physical activity, sleep quality, and overall well-being in patients with SCD. Methods: Patients aged 12 to 55 years with SCD received voxelotor 1500 mg/day for up to 24 weeks across 10 US sites. QOL assessments were completed during baseline (BL) run-in before the start of voxelotor. Hb levels were measured via laboratory assessments at BL and at weeks 2, 12, and 24. The proportion of patients with any increase in Hb from BL was noted. Patient-reported outcomes were evaluated using the Patient Global Impression of Change (PGI-C) scale, the National Institutes of Health Patient-Reported Outcome Measurement Information System-43 (PROMIS-43) for adults (>17 years), PROMIS-37 for adolescents (≤17 years), and a 10-point numeric rating scale (NRS) for pain intensity. A minimum response deemed meaningful was interpreted at the group level as a ≥5-point change from BL (CFB) in PROMIS domains and a ≥2-point change on the NRS. Clinicians' perceptions of the impacts of voxelotor on patients' overall health status were captured using the Clinical Global Impression of Change (CGI-C). All treatment-emergent adverse events (TEAEs) were recorded from the time of consent/assent to 28 days after the last dose of voxelotor. Results: A total of 25 patients were enrolled, with a median (range) age of 20.0 (12-51) years; 64.0% of patients were female and 92.0% were Black or African American. Two (8.0%) patients permanently discontinued voxelotor due to non-compliance and loss to follow-up. A total of 14 of 18 (78%) patients had an increase in Hb at week 24; the mean (SD) increase was 0.53 (0.839) g/dL. Clinicians reported an improvement in health status among 84.6% (11/13) of patients at week 24: 7.7% (1/13) were "very much improved," 46.2% (6/13) were "much improved," and 30.8% (4/13) were minimally improved; 2 patients had no change. At week 24, 92.9% (13/14) of patients self-reported improved health status: 21.4% (3/14) were "very much improved," 42.9% (6/14) were "much improved," and 28.6% (4/14) were minimally improved; 1 patient reported minimally worse health status. At week 24, 14 patients (9 adults, 5 adolescents) completed PROMIS measures; improvements in the mean CFB were reported across several PROMIS health domains. In adults, a meaningful CFB was found for both fatigue and pain interference. Some domains reached near-meaningful improvements, including anxiety, sleep disturbance, and ability to participate (in social roles/other activities), and others improved more modestly (Table 1). While some domains improved among adolescents, none reached a meaningful level (Table 2). A total of 18 (72.0%) patients had ≥1 non-SCD-related TEAE, and 3 (12.0%) patients had ≥1 grade 3 non-SCD-related TEAE. No non-SCD TEAEs of grade 4 or higher were reported. The most common non-SCD-related TEAEs (>10%) were diarrhea (32.0%), headache (20.0%), nausea (20.0%), and vomiting (12.0%). Conclusions: Over three-quarters of voxelotor-treated patients achieved an increase in Hb at week 24, and most patients and clinicians reported improvement in patients' overall health status. The PROMIS data in voxelotor-treated adults provided insights into improvements in general well-being, such as fatigue, pain interference, and ability to participate; most notable were fatigue and pain interference, both of which reached a CFB threshold considered meaningful. The safety profile reported in ActIVe is consistent with previous studies of voxelotor treatment. Overall, results suggest that voxelotor-treated patients may experience improvements in QOL, including in their physical and emotional well-being. Funding: Global Blood Therapeutics. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal