Improvement In Patient Global Impression Of Change Research Articles

Cryoneurolysis versus radiofrequency ablation outcome on pain experience in chronic low back pain (COPE): a single-blinded randomised controlled trial

ObjectiveA comparison of cryoneurolysis or radio frequency (RF) with placebo in patients with facetogenic chronic low back pain (LBP) for patient global impression of change (PGIC), pain intensity, function and...

Comparison of therapeutic effects of N-Acetylcysteine with pregabalin in improving the clinical symptoms of painful diabetic neuropathy: a randomized, double-blind clinical trial

ObjectivesPainful diabetic neuropathy (PDN) is highly prevalent and annoyingly in patients with diabetes. The aim of this study was to investigate the effects of oral N-acetylcysteine (NAC) compared to pregabalin in PDN.MethodsOne hundred two eligible patients with type 2 diabetes and PDN were randomly recievied pregabalin (150 mg/day) or N-Acetylcysteine (NAC) (600 mg/ twice a day) for 8 weeks. Mean pain score, Sleep interference score (SIS), Patient Global Impression of Change (PGIC), Clinical Global Impression of Change (CGIC), and also, serum levels of total antioxidant capacity (TAC), total thiol groups (TTG), catalase activity (CAT), nitric oxide (NO), and malondialdehyde (MDA) were assessed at baseline and at the end of the study.ResultsNAC was well tolerated in all patients. The decrease in mean pain scores and increase in SIS was similar between two groups. More improvement in PGIC and CGIC from the baseline was reported in NAC group. NAC, significantly, decreased serum levels of MDA, and NO, but increased TAC, TTG, and CAT. Pregabalin, significantly, decreased serum levels of MDA, and NO and increased TAC.DiscussionNAC is efficacious in alleviate symptoms of PDN which is probably related to its antioxidant effects.Trial registrationThe research protocol received approval from the Ethics Committee of Hamadan University of Medical Sciences (IR.UMSHA.REC.1397.137). The trial registry URL and number in Iranian Registry of Clinical Trials (IRCT): https://www.irct.ir/trial/33313, IRCT20180814040795N2 (Registration date: 2019-01-21, Retrospectively registered)

Efficacy and Safety of TNX-102 SL (Sublingual Cyclobenzaprine) for the Treatment of Fibromyalgia: Results From the Randomized, Placebo-Controlled RELIEF Trial.

To evaluate the efficacy and safety of TNX-102 SL, a once-nightly sublingual formulation of cyclobenzaprine, in reducing pain in patients with fibromyalgia. RELIEF was a double-blind, randomized, placebo-controlled trial. Overall, 503 patients received TNX-102 SL 2.8 mg for 2 weeks, followed by 5.6 mg for 12 weeks (248 patients), or matching placebo (255 patients). The primary endpoint was change from baseline at week 14 in weekly average of daily pain scores. Secondary endpoints included Patient Global Impression of Change (PGIC) scores, Fibromyalgia Impact Questionnaire Revised (FIQR) scores, Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance and Fatigue scores, and daily sleep quality. Safety was assessed by adverse events (AEs). Reduction in daily pain from baseline at week 14 was significantly greater with TNX-102 SL (LS mean change [95% CI], -1.9 [-2.1 to -1.7]) vs placebo (-1.5 [-1.7 to -1.3]; P=0.01). TNX-102 SL was not associated with significant improvement in PGIC at week 14 but was associated with improvements in FIQR scores, PROMIS scores, and daily sleep quality. Overall, 59.7% of patients receiving TNX-102 SL and 46.3% receiving placebo reported treatment-emergent AEs; the most common were oral hypoesthesia (17.3% with TNX-102 SL vs 0.4% with placebo), oral paresthesia (5.6% vs 0.4%, respectively), and product taste abnormal (4.4% vs 0.4%, respectively). In this phase 3, randomized, controlled trial of patients with fibromyalgia, treatment with TNX-102 SL was associated with significant reductions in daily pain and was safe and well tolerated.

Effects of a mindfulness-based and acceptance-based group programme followed by physical activity for patients with fibromyalgia: a randomised controlled trial

IntroductionNon-pharmacological approaches are recommended as first-line treatment for patients with fibromyalgia. This randomised controlled trial investigated the effects of a multicomponent rehabilitation programme for patients with recently diagnosed fibromyalgia in...

695 Cannabinoids and Sleep Health in Patients with Chronic Neuropathic Pain: A Systematic Review and Meta-Analysis

Abstract Introduction Neuropathic pain (NP) syndromes are debilitating conditions which can impact sleep health and overall quality of life significantly. Pharmacological treatment with cannabinoids has not been evaluated for its impact on sleep health. The objectives of this systematic review and meta-analysis were to determine the effect of cannabinoids on sleep quality, pain control, and patient impression of treatment efficacy. Methods We reviewed randomized controlled trials comparing synthetic and natural cannabinoids (CB) to placebo in patients with central and peripheral neuropathic pain syndromes. A systematic search of the standard literature databases was conducted, including randomized controlled trials evaluating the pharmacological treatment of NP syndromes using cannabinoids. Data on NRS pain scales, sleep quality, daytime somnolence, nausea, dizziness, and patient global impression of change (PGIC) scores were recorded. Meta-analysis using the random effects model was conducted where appropriate. Results Of the 3536 studies screened, a total of 8 randomized controlled trials including 1051 patients (placebo: 478 patients; CB: 573 patients) with neuropathic pain were included. Cannabinoids included in the studies were Sativex (GW-1000–02), Nabilone, and medical cannabis preparations with THC dose ranging from 1mg to 130mg per day. Pain scores were significantly reduced in the CB group (standardized difference in means (SDM) = -0.236, 95% CI=-0.375 to -0.100, p-value = 0.001) compared to placebo (Figure 1). Significant improvement in sleep quality (Figure 2) was also observed in the CB group (SMD 0.389, 95% CI, 0.233 to 0.546, p<0.013). Additionally, patients in the CB group were more likely to report improvement in PGIC scores (OR=2.3, 95% CI 1.37 to 3.9, p=0.002) compared to patients treated with placebo (Figure 3). Notably, CB-treated patients were more likely to experience daytime somnolence (OR=2.2, 95% CI 1.3 to 3.9, p=0.004), nausea (OR=1.7, 95% CI 1.1 to 2.5, p=0.02), and dizziness (OR=3.8, 95% CI 2.6 to 5.7, p<0.001). Conclusion Cannabinoids are useful agents for NP as evidenced by significant improvement in pain, sleep quality, and PGIC. With the advent of new agents and more refined cannabis derivatives, further research is needed to comprehensively explore treatment effectiveness. Future work should incorporate clinically validated measures of sleep health to better evaluate this outcome. Support (if any):

Psychometric assessment of the PROMIS Fatigue Short Form 6a in women with moderate-to-severe endometriosis-associated pain

BackgroundEndometriosis is a common problem in women of reproductive age and has impacts on health-related quality of life and productivity. Fatigue is an important part of the burden of endometriosis, it is not often included as an endpoint in clinical trials.ObjectivesThe study assessed the psychometric properties of the PROMIS Fatigue Short Form 6a in women with moderate-to-severe endometriosis-associated pain.MethodsIn a phase III double-blind, placebo-controlled clinical trial (NCT01620528), women aged 18–49 years with moderate-to-severe endometriosis-related pain were randomized to elagolix 150 mg once daily, elagolix 200 mg twice daily, or placebo for 6 months. PROMIS Fatigue and dysmenorrhea and non-menstrual pelvic pain (NMPP) scores were assessed at baseline and months 1, 3, and 6, and Patient Global Impression of Change (PGIC) was assessed at months 1, 3, and 6. Reliability (internal consistency and test-retest reliability), construct validity (convergent and known groups validity), and responsiveness were evaluated.ResultsThe analysis included 871 women, mean age 31.5 years. Internal consistency supported a single concept (Cronbach’s alpha 0.93). For the 238 patients with no change in PGIC at month 1, the intraclass correlation coefficient for the PROMIS Fatigue T-score was 0.7 and paired t-test statistically significant (2.84, p = 0.0049). Correlations with other measures were expected to be fairly low as concepts were not redundant. The PROMIS Fatigue discriminated among known groups with mean scores of 55.3, 62.3, and 65.8 at month 3 (PGIC improvement, no change, worsening, respectively). Statically significant discrimination, and change score responsiveness, were seen using clinically relevant anchors (dysmenorrhea and NMPP) at months 3 and 6 between responders and non-responders. Anchor-based (PGIC) responsiveness showed significant improvement from baseline to months 3 and 6 (p < 0.0001).ConclusionsPROMIS Fatigue has good reliability, validity, and responsiveness in women with moderate-to-severe endometriosis-associated pain.

A 12-month, dose-level blinded safety and efficacy study of levodopa inhalation powder (CVT-301, Inbrija) in patients with Parkinson's disease

IntroductionCVT-301 (Inbrija®) is a levodopa inhalation powder for on-demand treatment of OFF episodes in Parkinson's disease patients treated with carbidopa/levodopa. Safety and efficacy results of a 12-month, dose-level blinded extension study of a phase 3 trial (SPAN℠-PD) of CVT-301 are presented. MethodsPatients were receiving oral carbidopa/levodopa and adjunctive CVT-301 treatment, blinded to dose (60 mg or 84 mg, N = 325). Study visits occurred every 3 months. Pulmonary function was assessed by spirometry. Other safety assessments included dyskinesia and adverse events (AEs). Secondary objectives of the study included maintenance of improvement assessments for occurrence of an ON state during the 60-min post-dose period, change in total daily OFF time, and Patient Global Impression of Change (PGIC). ResultsMost frequent AEs (≥5%) were cough (15.4%), fall (13.1%), upper respiratory tract infection (7.1%), and dyskinesia (5.1%). Severe AEs (>1 event) were cough (1.9%) and dyskinesia (0.6%). Twelve-month mean changes from baseline for FEV1, FVC, and DLCO were −0.092 L, −0.097 L, and −0.922 mL/min/mmHg, respectively. At 12 months, 73.0% of patients on 84 mg achieved an ON state within 60 min. Total daily OFF time was reduced by 0.55 h (month 1) and 0.88 h (month 12) for the 84 mg dose. Percentage of patients self-reported as improved by PGIC was 65.5–91.9% over 12 months. ConclusionCVT-301 was generally well-tolerated. Twelve-month decline in pulmonary function was consistent with a prior PD control group. Exploratory efficacy results showed CVT-301 maintained improvement at achieving ON states in patients experiencing OFF episodes, decreasing daily OFF time, and maintaining improvement in PGIC.

A Randomized Comparative Trial of Targeted Steroid Injection via Epidural Catheter vs Standard Transforaminal Epidural Injection for the Treatment of Unilateral Cervical Radicular Pain: Six-Month Results.

Compare the effectiveness of catheter-directed cervical interlaminar epidural steroid injection (C-CIESI) with triamcinolone to cervical transforaminal steroid injection (CTFESI) with dexamethasone for the treatment of refractory unilateral radicular pain. Prospective, randomized, comparative trial. Primary outcome: proportion of participants with ≥50% numeric rating scale pain score reduction from baseline "dominant pain" (the greater of arm vs neck) at one month postinjection. Secondary outcomes: ≥30% Neck Disability Index (NDI-5) reduction and Patient Global Impression of Change (PGIC) response indicating "much improved" or "very much improved." One hundred twenty participants (55.6% females, 52.3 ± 12.5 years of age, BMI 28.2 ± 6.5 kg/m2), were enrolled. The proportions of participants who experienced ≥50% pain reduction at one, three, and six months were 68.5% (95% CI = 54.9-79.5%), 59.3% (95% CI = 45.7-71.6%), and 60.8% (95% CI = 46.7-73.2%), respectively, in the C-CIESI group compared with 49.1% (95% CI = 36.4-62.0%), 46.4% (95% CI = 33.8-59.6%), and 51.9% (95% CI = 38.4-65.2%), respectively, in the CTFESI group. The between-group difference at one month was significant (P = 0.038). The proportions of participants who experienced a ≥30% NDI-5 score improvement were 64.0% (95% CI = 49.8-76.1%) and 54.9% (95% CI = 41.1-68.0%) in the C-CIESI and CTFESI groups (P = 0.352). Participants reported similar PGIC improvement in both groups: At six months, 53.2% (95% CI 38.9-67.1%) and 54.5% (95% CI = 39.7-68.7%) of the C-CIESI and CTFESI groups reported being "much improved" or "very much improved," respectively (P = 0.897). Both C-CIESI with triamcinolone and CTFESI with dexamethasone are effective in reducing pain and disability associated with refractory unilateral cervical radiculopathy in a substantial proportion of participants for at least six months.

Inhaled levodopa in Parkinson's disease patients with OFF periods: A randomized 12-month pulmonary safety study

IntroductionCVT-301 is an orally inhaled levodopa therapy approved for the intermittent treatment of OFF episodes in Parkinson's disease patients who are taking a standard oral levodopa regimen. This open-label, randomized, controlled study over 12 months characterizes the safety, including pulmonary safety, of CVT-301 84 mg (nominal respirable levodopa fine-particle dose, 50 mg). MethodsPatients experiencing motor fluctuations were randomized 2:1 to CVT-301 or an observational cohort (OC) receiving oral standard of care. Pulmonary safety was assessed using spirometry and carbon monoxide diffusion capacity (DLCO). Exploratory efficacy endpoints, assessed only for CVT-301, included change in Unified Parkinson's Disease Rating Scale Part III (UPDRS-III), patients achieving ON within 60 min and remaining ON at 60 min, Patient Global Impression of Change (PGIC) scale, and total daily OFF time. ResultsOf 408 patients randomized, 310 completed the study (204 in CVT-301 and 106 in OC). Mean 12-month changes from baseline for CVT-301 were −0.105 L (FEV1) and −0.378 mL/min/mm Hg (DLCO), and for OC were −0.117 L and −0.722 mL/min/mm Hg, respectively. Between-group comparisons were not statistically significant. For FEV1/FVC the 12-month change was −0.3 and −1.6, respectively, which was a significant between-group difference. However, between-group differences were not significant at 3 and 9 months and all changes from baseline were small (<2.0%). UPDRS-III scores improved from predose to 60 min postdose at all assessments; 80%–85% of patients switched ON within 60 min and remained ON; and >75% reported improvement in PGIC. OFF time decreased by 1.32–1.42 h/day. ConclusionCVT-301 84 mg induced no clinically significant differences in pulmonary function compared with the OC. Improvements in motor scores, OFF time, and patient-reported outcomes support clinical efficacy for up to 12 months.

MANIFEST, a Phase 2 Study of CPI-0610, a Bromodomain and Extraterminal Domain Inhibitor (BETi), As Monotherapy or “Add-on” to Ruxolitinib, in Patients with Refractory or Intolerant Advanced Myelofibrosis

MANIFEST, a Phase 2 Study of CPI-0610, a Bromodomain and Extraterminal Domain Inhibitor (BETi), As Monotherapy or “Add-on” to Ruxolitinib, in Patients with Refractory or Intolerant Advanced Myelofibrosis

Ameliorative Effects Of N-Acetylcysteine As Adjunct Therapy On Symptoms Of Painful Diabetic Neuropathy.

PurposePainful diabetic neuropathy (PDN) is a variant of diabetic peripheral neuropathy which is highly prevalent and distressing in diabetic patients. Despite its high burden, the optimal treatment of PDN has remained a clinical challenge. To explain the emergence and maintenance of PDN, increasing attention has been focused on dimensions of inflammation and oxidative toxic stress (OTS). Accordingly, the aim of this study was to investigate the effects of oral N-acetylcysteine (NAC), an agent with known anti-oxidant and anti-inflammatory effects, as an adjunct therapy in patients suffering from PDN.Patients and methods113 eligible patients with type 2 diabetes suffering from PDN were randomly assigned to either the pregabalin + placebo or pregabalin + NAC group for 8 weeks (pregabalin at a dose of 150 mg per day, NAC and matched placebo at doses of 600 mg twice a day). Mean pain score was evaluated at baseline, week 1, 2, 4, 6, and 8 of the study based on the mean 24 hr average pain score, using an 11-point numeric rating scale (NRS). As secondary efficacy measures, mean sleep interference score (SIS) resulting from PDN, responder rates, Patient Global Impression of Change (PGIC), Clinical Global Impression of Change (CGIC), and safety were also assessed. Additionally, serum levels of total antioxidant capacity (TAC), total thiol groups (TTG), catalase activity (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), nitric oxide (NO), and malondialdehyde (MDA) were assessed at baseline and at the end of the study.ResultsNinety patients completed the eight-week course of the study. The decrease in mean pain scores and mean sleep interference score in pregabalin + NAC group was greater in comparison with pregabalin + placebo group (p value<0.001 in both conditions). Moreover, more responders (defined as ≥50% reduction in mean pain score from baseline to end-point) were observed in the pregabalin + NAC group, in comparison with pregabalin + placebo group (72.1% vs 46.8%). More improvement in PGIC and CGIC from baseline to the end of the study was reported in pregabalin + NAC group. Oral NAC had minimal adverse effects and was well tolerated in almost all patients. Furthermore, in respect to OTS biomarkers, adjuvant NAC significantly decreased serum level of MDA and significantly increased serum levels of SOD, GPx, TAC, and TTG.ConclusionThe pattern of results suggests that compared to placebo and over a time period of 8 weeks, adjuvant NAC is more efficacious in improving neuropathic pain associated with diabetic neuropathy than placebo. Ameliorative effects of NAC on OTS biomarkers demonstrated that NAC may alleviate painful symptoms of diabetic neuropathy, at least in part by its antioxidant effects.

Probable factors affecting clinical outcomes of internal jugular vein stenosis.

Internal jugular vein stenosis (IJVS) has recently aroused increasing interests, whereas, the factors affecting its clinical outcomes are not clear. This study aims to explore the probable factors affected clinical prognosis by evaluating the IJVS with different etiologies and strategies. Patients with IJVS confirmed by contrast-enhanced magnetic resonance venography (CE-MRV) were enrolled from October 2017 through October 2018. One-year clinical outcomes of the IJVS cases enrolled in this study were assessed by outpatient and telephone follow-up using the Patient Global Impression of Change (PGIC) scores. According to the etiologies, patients were divided into thrombotic IJVS and non-thrombotic IJVS groups. And further, non-thrombotic IJVS group was divided into external compression and non-external compression subgroups. Outcomes of IJVS with different etiologies and strategies were compared and the probable prognostic factors were analyzed. A total of 118 eligible patients enrolled in this study, including 76 females and 42 males, mean aged 55.07±14.61 years. The average follow-up duration after discharge was 13.22±3.80 months. According to the PGIC scores, we categorized patients as good outcome and poor outcome groups. For thrombotic IJVS, patients underwent standard anticoagulant obtained remarkable PGIC improvement (100.0% vs. 33.3%, P=0.038). For non-thrombotic IJVS, stenting showed benefit in non-external compression subgroup (26.9% vs. 3.3%, P=0.019) but not in external compression subgroup. In addition, we found that in this Chinese IJVS cohort, poor outcomes involved old age (P=0.004), type 2 diabetes mellitus (P=0.036), previous hepatitis B virus (HBV) infection (P=0.027), and head noises (P=0.002). Multivariate logistic regression analysis indicated that continuous head noises [P=0.045, odds ratio (OR): 2.412, 95% confidence interval (CI): 1.019-5.711], as a unique symptom of IJVS may be significantly related to poor outcomes. In this Chinese cohort, elderly degenerative bone compression, type 2 diabetes mellitus, and previous HBV infection are the top-three probable etiologies of non-thrombotic IJVS and may involve poor outcome. Long-term head noises may predict IJVS and with poor outcome. Thrombosis-induced IJVS may get benefit from standard anticoagulation. Non-external compression IJVS can be corrected by stenting.

The efficacy of pregabalin for acute pain control in herpetic neuralgia patients: A meta-analysis.

Objective:This meta-analysis aimed to illustrate the efficacy and safety of preganalin for pain management in patients with postherpetic neuralgia (PHN).Methods:In July 2017, a systematic computer-based search was conducted in PubMed, EMBASE, Web of Science, Cochrane Database of Systematic Reviews, and Google database. Data on patients with PHN that compared pregabalin versus placebo were retrieved. The endpoints were the visual analog scale (VAS) at 8 weeks, the percentage of 30% and 50% pain responders; sleep interference score and improvement in patient global impression of change (PGIC). After testing for publication bias and heterogeneity between studies, data were aggregated for random-effects models when necessary.Results:Seven clinical studies with 2192 patients (pregabalin group = 1381, control group = 811) were finally included in the meta-analysis. Pregabalin was associated with reduced pain scores at 8 weeks, corresponding to a reduction of 11.23 points (95% CI, −14.33, −8.13, P = .000) on a 100-point VAS. Pregabalin was also associated with a more percentage of 30% and 50% pain responders than controls (P < .05). Meanwhile, pregabalin can decrease sleep interference score and improvement in PGIC than control groups (P < .05).Conclusions:Pregabalin was efficacious in the reduction of postoperative pain and improvement the sleep quality in patients with PHN.

Long-term Maintenance of Response Across Multiple Fibromyalgia Symptom Domains in a Randomized Withdrawal Study of Pregabalin

To determine the incidence and duration of response of clinically meaningful improvements with pregabalin across several key symptoms of fibromyalgia (FM). This was a post hoc analysis of data from a multicenter, double-blind, placebo-controlled, randomized, withdrawal study, originally designed to evaluate the efficacy of pregabalin monotherapy for durability of effect on FM pain based on pain and Patient Global Impression of Change (PGIC) criteria. Responder criteria for Fibromyalgia Impact Questionnaire total score (≥16-point change), Medical Outcomes Study Sleep Scale Sleep Disturbance subscale (≥15.8-point change), and the 36-item Short-Form Health Survey Vitality scale (≥10-point change) were used to evaluate the incidence and duration of improvements in function, sleep, and fatigue for pregabalin versus placebo among pain and PGIC responders. A composite responder index consisting of pain, PGIC, function, and sleep endpoints was used to explore multidimensional response. Approximately 80% of patients meeting pain and PGIC improvement criteria at randomization had clinically meaningful improvement in fatigue, sleep, or function. Higher proportions of patients in the pregabalin group maintained a clinically meaningful response, and pregabalin-treated patients had a significantly longer time to loss of therapeutic response compared with the placebo group. Composite responder Kaplan-Meier analysis, performed with patients demonstrating clinically meaningful improvements in pain, PGIC, function, and sleep at randomization showed a significantly longer median time to loss of therapeutic response for pregabalin-treated patients. The results from this post hoc analysis indicate that pregabalin provides long-term effects across multiple domains of FM (ClinicalTrials.gov registry ID: NCT00151489).

Correlations between Fibromyalgia Symptom and Function Domains and Patient Global Impression of Change: A Pooled Analysis of Three Randomized, Placebo-Controlled Trials of Pregabalin

The objective of the study was to conduct an analysis of pooled data from pregabalin fibromyalgia clinical trials to determine which fibromyalgia symptom and function domains drive patient perception of improvement. Data from three double-blind, placebo-controlled trials of pregabalin in fibromyalgia patients were pooled for this analysis. Changes in independent variables, including the Medical Outcomes Study 36-item Short-Form Health Survey, Medical Outcomes Study-Sleep Scale, sleep quality score from the daily sleep diary, pain score from the daily pain diary, Fibromyalgia Impact Questionnaire, and Multidimensional Assessment of Fatigue were analyzed as predictors of outcome on the dependent variable, Patient Global Impression of Change (PGIC). Correlation analysis assessed relationships between the independent variables and PGIC. Cluster analysis identified dependencies among variables, and a shrinkage and selection method and stepwise logistic regression determined rank order of variables. Improvement in PGIC at endpoint showed highest correlation with pain improvement, fatigue, sleep, and work and physical function (0.4 < r < 0.6). Cluster analysis identified three main clusters of symptoms at endpoint: mood (anxiety and depression), pain and sleep, and function and fatigue. Pain was ranked as the most important outcome explaining variability in PGIC, followed by fatigue and sleep. Pain, fatigue, and sleep associate most strongly with improvement in PGIC. Physical- and work-related function also correlated with patients' overall assessment of improvement. These domains and their respective outcome measures can be used to improve assessment of patients' response to treatment.