Global Impression Of Change Scores Research Articles

Safety and effectiveness of integrative Korean medicine for the management of patients sustaining injuries in traffic accidents during pregnancy: A retrospective chart review and questionnaire survey.

The number of traffic accidents (TAs) is rising each year, and the severity of injuries can vary. Many people experience limitations in activities of daily living following TAs, affecting their quality of life. In pregnant women, even simple injuries caused by a TA could lead to unfavorable obstetric outcomes. Thus, we conducted a retrospective chart review and follow-up questionnaire survey to assess the safety and effectiveness of integrative Korean medicine (KM) treatment for pregnant women injured in TAs. To assess integrative KM effectiveness, the numeric rating scale (NRS) for TA-related symptoms, neck disability index (NDI) score, Oswestry disability index (ODI) score, shoulder pain and disability index score, Western Ontario and McMaster Universities Arthritis Index score, EuroQol 5-dimension 5-level (EQ-5D-5L) score, and patient global impression of change score were investigated for pregnant women injured in TAs. Additionally, for safety evaluation, obstetric and neonatal outcomes, as well as symptoms related to pregnancy, were assessed. At the end of treatment and follow-up, there were significant reductions in NDI and ODI scores, as well as NRS for neck pain, lower back pain, and headache, compared to scores at baseline. EQ-5D-5L scores significantly increased. A follow-up of 50 patients showed no major differences in obstetric and neonatal outcomes compared to the typical outcomes that occur in pregnant women and neonates. Major improvements were observed in the symptoms of patients who underwent integrative KM treatment after being injured in TAs. The symptoms occurred at a rate similar to those in typical pregnant women, while causality with integrative KM treatment was assessed to be unlikely or unclear. Therefore, integrative KM treatment may be considered an alternative treatment option for pregnant women who currently have limited treatment options.

Rose geranium in sesame oil nasal spray to improve nasal vestibulitis symptoms: a randomized controlled trial.

The purpose of this phase III randomized double-blinded controlled trial was to investigate the efficacy of a rose geranium in sesame oil (RG) nasal spray compared with an isotonic saline (IS) nasal spray for alleviating nasal vestibulitis symptoms among patients undergoing chemotherapy. Patients undergoing active chemotherapy who reported associated nasal symptoms were randomized 1:1 to receive RG or IS, administered twice daily for 2 weeks. Consenting participants completed nasal symptom questionnaires at baseline and then weekly while on treatment. The proportion of patients experiencing improvements in their nasal symptoms 2weeks after initiating the nasal spray, using a six-point global impression of change score, was estimated within and between each randomized arm, and compared between arms, using Fisher's exact test. The estimated odds ratio was determined (95% confidence interval). One hundred and six patients consented to this study; 43 participants in the RG arm and 41 in the IS arm were evaluable for the primary endpoint. Participants had a mean age of 57.8years (SD 13.9). Demographic characteristics and baseline nasal symptoms were similar between arms. Of the evaluable participants who received RG, 67.4% reported improved nasal symptoms, compared with 36.6% of the participants who received IS (P = 0.009). Adverse events were sparse and did not differ between arms. Rose geranium in sesame oil significantly improves nasal vestibulitis symptoms among patients undergoing chemotherapy. NCT04620369.

Prospective Six-Month Analysis of Multiarea Burst Spinal Cord Stimulation: Correlating Intraoperative Neuromonitoring With Postoperative Programming and Clinical Outcomes

IntroductionDeRidder burst spinal cord stimulation (SCS) has shown superior relief from overall pain to traditional tonic neurostimulation therapies and a reduction in back and leg pain. However, nearly 80% of patients have two or more noncontiguous pain areas. This affects the ability to effectively program stimulation and deliver long-term efficacy of the therapy. Multiple DeRidder burst region programming is an option to treat multisite pain by interleaving stimulation at multiple areas along the spinal cord. Previous intraoperative neuromonitoring studies have shown that DeRidder burst stimulation provides broader myotomal coverage at a lower recruitment threshold. The goal of this study is to correlate intraoperative electromyogram (EMG) threshold and postsynaptic excitability with postoperative paresthesia thresholds and optimal burst stimulation programming. Materials and MethodsNeuromonitoring was performed during permanent implant of SCS leads in ten patients diagnosed with chronic intractable back and/or leg pain. Each patient underwent the surgical placement of a Penta Paddle electrode through laminectomy at the T8–T11 spinal levels. Subdermal electrode needles were placed into lower extremity muscle groups, in addition to the rectus abdominis muscles, for EMG recording. Evoked responses were compared across multiple trials of burst stimulation in which the number of independent burst areas was varied. After intraoperative data collection, all patients were programmed with single- and multiarea DeRidder burst. Intermittent dosing was delivered at 30:90, 120:360, 120:720, and 120:1440 (seconds ON/OFF) intervals. Numerical rating scale (NRS) and Patient Global Impression of Change scores were evaluated at one, two, three, four, and six months after permanent implant. ResultsThe thresholds for EMG recruitment after DeRidder burst differed across all patients owing to anatomical and physiological variations. After a 30-second dose of stimulation, the average decrease in thresholds was 1.25 mA for two-area and 0.9 mA for four-area DeRidder burst. Furthermore, a 30-second dose of multisite DeRidder burst produced a 0.25 mA reduction in the postoperative paresthesia thresholds. Across all patients, the baseline NRS score was 6.5 ± 0.5, and the NRS score after single or multiarea DeRidder burst therapy was 2.87 ± 1.50. Eight of ten patients reported a ≥50% decrease in their pain scores through the six-month follow-up visit. Pain outcomes using intermittent multiarea stimulation with longer OFF times (120:360, 120:720, 120:1440) were comparable to those using single-area DeRidder burst at 30:90 up to six months after implant with patient preference being two-area DeRidder burst. ConclusionsThis study aims to evaluate the use of intraoperative neuromonitoring to optimize stimulation programming for multisite pain and correlate it with postoperative programming and efficacy. These results suggest that multisite programming can be used to further customize DeRidder burst stimulation to each individual patient and improve outcomes and quality of life for patients receiving SCS therapy for multisite pain.

The effect of MemoVigor 2 on recent-onset idiopathic tinnitus: a randomized double-blind placebo-controlled clinical trial.

Background: Tinnitus is a common symptom associated with the conscious perception of sound in the absence of a corresponding external or internal sound source, which can severely impact quality of life. Because of the current limited understanding of the precise pathophysiological mechanism of idiopathic tinnitus, no curable treatment has been attained yet. A food supplement trading as MemoVigor 2, which contains a combination of therapeutic ingredients with mainly antioxidant activity, has been used in the treatment of tinnitus. The objective of our study was to evaluate the effectiveness of MemoVigor 2 in the treatment of recent-onset idiopathic tinnitus. Methods: In a prospective single-centre randomized, double-blind, placebo-controlled clinical trial we studied 204 patients with idiopathic tinnitus divided into two groups: 104 patients who received MemoVigor 2 and 100 patients treated with placebo. To evaluate changes in tinnitus we used (1) audiometry/tympanometry; (2) specific measures of tinnitus perception, including tinnitus pitch, loudness at tinnitus pitch, loudness at 1kHz, minimum masking level, and residual inhibition; (3) questionnaires of tinnitus handicap inventory, mini tinnitus questionnaire and patients' global impression of change. All patients underwent this test battery at the beginning of the study and in a repeat post-3-month session. Results: All tinnitus measures, including pitch, loudness, minimum masking level and residual inhibition improved significantly in the intervention group. Most of these measures improved in the placebo group too, but in a lesser degree. All questionnaire scores diminished significantly in both groups, but the degree of decrease was greater in the intervention group. The participants' tinnitus outcome reported after treatment using the patients' global impression of change score differed significantly between the two groups, with greater improvement observed in the intervention group. Conclusion: We found that the use of MemoVigor 2 improved recent-onset tinnitus, as proved by a set of tests performed for its evaluation, including audiometric measures, specific measures of tinnitus perception and tinnitus questionnaires. Tinnitus in the placebo group improved too, but to a lesser degree. Clinical Trial Registration: isrctn.com, Identifier ISRCTN16025480.

Masupirdine (SUVN‐502) for the Potential Treatment of Agitation in Patients with Dementia of the Alzheimer’s Type: Preliminary Efficacy and Phase‐3 Study Design

AbstractBackgroundAlzheimer’s disease (AD) is a progressive neurodegenerative disorder with manifestations in cognitive, functional and neuropsychiatric symptoms (NPS). Agitation is one of the most prevalent and challenging NPS to manage. Antipsychotics are widely used for the pharmacological management of agitation. However, they offer modest efficacy, and the side effects are substantial.Serotonin‐6 receptor (5‐HT6) blockade may have therapeutic utility in the management of disorders associated with mood and behavior. Masupirdine is a potent and selective 5‐HT6 receptor antagonist.MethodMasupirdine has been evaluated in a phase‐2, 26‐week proof‐of‐concept clinical study (NCT02580305). Subgroup analyses of study results based on the neuropsychiatric inventory scale was carried out. Masupirdine was also evaluated in animal models to assess its effect on behavior and brain neurotransmitters modulations.A double‐blind, randomized, placebo‐controlled, parallel group, adequately powered global phase‐3 study is in progress to evaluate the efficacy, safety, tolerability, and pharmacokinetics of masupirdine for the treatment of agitation in participants with dementia of the Alzheimer’s type (NCT05397639). A total of 375 patients are planned to be enrolled in the study who will be randomly assigned to receive either 50 mg masupirdine or 100 mg masupirdine or placebo. Patients will be treated for 12 weeks. The primary efficacy endpoint of this study is the Cohen‐Mansfield Agitation Inventory items score aligning to the international psychogeriatric association agitation criteria domains (physical aggression, excessive motor activity, and verbal aggression) and the key secondary endpoint is improvement in modified Alzheimer’s Disease Cooperative Study‐Clinical Global Impression of Change score as related to agitation.ResultThe observations from the post hoc analysis of phase‐2 clinical study in AD patients and animal models support the potential beneficial effects of masupirdine on agitation.The phase‐3 study has been initiated in USA and Europe, and the subject enrolment is expected to be completed by Q3 2024.ConclusionThe need for new treatments for the management of agitation is significant and unmet. The Phase‐3 study results will inform the utility of masupirdine for the potential treatment of agitation in patients with dementia of Alzheimer’s type. Phase‐3 study data readout is anticipated in Q1/Q2 2025.

Nitrous oxide for the treatment of complex regional pain syndrome: a randomized blinded trial

IntroductionComplex Regional Pain Syndrome (CRPS) is a debilitating neuropathic condition often refractory to conventional treatments. N-methyl-D-aspartate (NMDA) receptor antagonists have a well-established role in the development and modulation of chronic...

Standardized Stretching Postural postures to treat low-back pain in pregnancy: the GEMALODO randomized clinical trial

Two-thirds of pregnant women suffer from low-back pain during pregnancy, which leads to negative effects on quality of everyday life. According to the literature, an 8- to 12-week program of adapted physical activity during pregnancy has proven its efficacy in treatment of low-back pain and functional disability. Stretching Postural is a nondynamic technique using muscular contractions and stretches that act mainly on the back and that can be practiced alone. This study aimed to assess the effect of an 8-week program of standardized Stretching Postural postures in low-risk pregnant women suffering from low-back pain. This was an open-label, randomized, controlled trial in 1 French university hospital. Women with a singleton low-risk pregnancy between 15 and 32 weeks of gestation and with back, lumbar, or sacroiliac pain were randomly assigned (1:1) to either undergo an 8-week program of standardized Stretching Postural with basic advice (intervention group) or to receive basic advice only (control group). Both groups received ergonomic advice and encouragement to practice physical activity. The primary endpoint was the pain assessment at 8 weeks (defined by the mean pain level estimated by women in the previous week, scored on a numeric scale from 0 to 10). Secondary endpoints were pain after 4 weeks of follow-up, quality of life (12-item Short Form Survey), satisfaction (Patient Global Impression of Change), and delivery outcomes. The main analysis was intention-to-treat. From January 2019 to August 2020, 60 women were randomized: 30 were assigned to the intervention group and 30 to the control group. The mean level of pain at 8 weeks was significantly lower in the intervention group than in the control group (1.6±1.4 vs 4.1±2.2; P<.01). The mean 12-item Short Form Survey scores were significantly higher in the posture group than in the control group (Physical Component Score, 45.7±7.8 vs 37.4±8.5; P<.01; Mental Component Score, 54.3±5.8 vs 50.4±7.1; P=.04), and the Patient Global Impression of Change score was also significantly higher (6.1±1.5 vs 3.9±2.3; P<.01). No adverse effects were found. Stretching Postural appears to be a safe and efficient nondrug therapy to treat low-back pain during low-risk pregnancy.

#5571 THERAPY WITH BUROSUMAB IN ADULT PATIENTS WITH X-LINKED HYPOPHOSPHATEMIA: A YEAR OF FOLLOW-UP

Abstract Background and Aims X-linked hypophosphatemic rickets (XLH) is a genetic disorder secondary to the mutation of the PHEX gene that results in increased circulating levels of FGF23. Increased FGF23 causes hypophosphatemia secondary to renal phosphate loss. Clinically, the disease is characterized by reduced growth, bone alterations, weakness, chronic pain and reduced mobility. From a biochemical point of view, patients have hypophosphatemia, increased values of alkaline phosphatase, increased fraction excretion of phosphate (FEP). Recently, therapy with Burosumab, a monoclonal antibody against FGF23, has been introduced. Burosumab by reducing the receptor availability of circulating FGF23 reduces its activity. This leads to a normalization of serum phosphate and in paediatric patients an improvement of the clinical phenotype. In adult patients, the effectiveness of therapy in improving the clinical outcome and quality of life is being investigated. The purpose of the study was to evaluate the efficacy in improving the biochemical, bone and clinical picture of adult patients with XLH in therapy with Burosumab for one year. Method We enrolled patients with XLH naive for Burosumab therapy. In all we evaluated the biochemical aspects (phospahatemia, alkaline phosphatase, FEP), bone Radiographic Global Impression of Change score and clinical improvements (six-minute walk test, UP and go timed test, WOMAC Index) pre therapy and after a year of therapy. Burosumab was administered monthly at a dose of 1 mg/Kg. Results We enrolled 5 patients (45 ± 10 year old, weight 60 ± 10 Kg, Burosumab dose 60 ±10 mg) with genetic diagnosis of XLH. The comparison between pre therapy and post-one-year therapy showed in all patients: increase in average phosphatemia (pre 1.9± 0.5 mg/dl vs post 3.4 ±0.6 mg/dl p = 0.003), reduction in FEP (pre 50 ±15% vs 20 ±10% p = 0.004), reduction of UP and go timed test (pre 20± 5 sec vs post 11 ±5 sec p = 0.005) increase of the distance in the six minutes’ walk test (pre 150 ± 30 meters vs post 250 ± 50 meters p = 0.01), improvement of the WOMAC test (pre 15± 3 vs post 5± 2; p = 0.008) and reduction of the Radiographic Global Impression of Change score (pre -2 ±0.5 and post 2± 0.4; p = 0.001). The serum value of alkaline phosphate was high and it did not change with the Burosumab therapy (pre 200±50 UI/L vs post 220±60 UI/L; p: n.s. n.v. 33–98 UI/L). No patients had significant complications during the first year of treatment. Conclusion The therapy with Burosumab was well tolerated by patients. It resulted in a marked improvement in the biochemical picture associated with a better quality of life identified by increased strength (improved walk test and UP and go timed test) reduction of pain (best WOMAC test) and bone damage score. In conclusion, Burosumab may be a good and safe therapy option for adults’ patients with XLH.

Psychometric Validation and Meaningful Change Thresholds of the New Nasal Polyposis Symptom Diary.

The Nasal Polyposis Symptom Diary (NPSD) is a novel and short patient-reported outcome (PRO) tool specifically developed to assess important and relevant symptoms reported by patients with chronic rhinosinusitis with nasal polyposis (CRSwNP). We evaluated the psychometric properties of 4 predefined NPSD-derived scores intended to support symptom-improvement assessments of investigational therapies for inclusion in product labeling. Five hundred eighteen patients with severe CRSwNP from a Phase III clinical trial (NCT03401229) completed the NPSD, comprising 11 items: 8 symptom-specific, 2 symptom-impact, and 1 optional medication-compliance. The psychometric characteristics of 3 single-item symptom scores (Nasal Blockage Score [NBS], Nasal Congestion Score [NCS], and Difficulty with Sense of Smell Score [DSS]) and a Total Symptom Score (TSS, summary of the 8 symptom-specific items) were evaluated for reliability, validity, and ability to detect change. Within-patient meaningful change thresholds (MCTs) were established using anchor- and distribution-based methods. Comparative PROs included the 22-item Sino-Nasal Outcome Test (SNOT-22) and Patient Global Impression of Severity (PGI-S). The TSS exhibited strong internal consistency (Cronbach α = .88) and test-retest reliability (intraclass correlation coefficient >.80). Correlation between the TSS and SNOT-22 total score indicated good convergent validity (r = .70). All 4 NPSD scores demonstrated known-groups validity (significant differences among subgroups of patients with predetermined disease severity levels based on PGI-S categories) and were sensitive to detect change in patients' clinical status (significant differences among subgroups of patients with reported changes between 2 time-points in PGI-S and Patient Global Impression of Change scores). MCTs for improvement were established at 1.0 point for NBS, NCS, and DSS, and 4.0 points for TSS. These findings support the reliability, validity, and suitability of the 4 NPSD-derived scores for evaluating treatment effect on CRSwNP symptoms and their use in clinical trials with predetermined MCTs for improvement.

Rose geranium in sesame oil nasal spray to improve symptoms of nasal vestibulitis: A phase III double blinded randomized controlled trial.

12114 Background: A retrospective study suggested a potential benefit from rose geranium in sesame oil nasal spray for alleviating nasal vestibulitis symptoms in patients (pts) undergoing chemotherapy. Methods: Pts undergoing active chemotherapy who reported moderate or worse nasal symptoms were randomized 1:1 to receive a rose geranium in sesame oil nasal spray (RG) or an isotonic saline nasal spray (IS), administered twice daily for two weeks. Consenting pts completed nasal symptom questionnaires at baseline and then weekly while on treatment. The number and percentage of pts experiencing improvements in their nasal symptoms 2 weeks after initiating the nasal spray, defined as symptoms moderately (2) or very much (3) better on a 7-point global impression of change score (ranging from scores of -3: very much worse, to 3: very much better), was estimated within and then between each randomized arm, using Fisher’s exact test (5% significance level). The estimated odds ratio was determined (95% confidence interval). After 2 weeks, pts initially randomized to IS were allowed to cross-over to RG and completed weekly surveys. Results: 106 pts consented to this study; 43 pts in the RG arm and 41 in the IS arm were evaluable for the primary endpoint. Pts had a mean age of 57.8 (SD 13.9). Demographic characteristics and baseline nasal symptoms were similar between arms. The most prominent baseline nasal symptoms were dryness (36%) and bleeding (35%). Of the 43 evaluable pts who received RG, 67.4% reported improved nasal symptoms, compared with 36.6% of the 41 pts who received IS (p=0.009; Table). On the global impression of change score, pts who received RG had a mean score of 1.93 (SD 1.16), compared to a mean score of 0.98 (SD 1.41) among pts who received IS. Adjusting for potential confounding factors, pts who received RG had a 4.56 odds of responding to the nasal spray, compared with those who received IS (p=0.005). There were no significant differences between pt responses based upon type of nasal symptoms, age, allergies, or gender. Adverse events were sparse and did not differ between arms. 34 pts crossed over to RG after week 2. Among the 29 pts who completed final surveys, 37% reported a response on IS, 79% reported a response on RG. Conclusions: Rose geranium in sesame oil nasal spray significantly improves nasal vestibulitis symptoms among patients undergoing chemotherapy. Clinical trial information: NCT04620369 . [Table: see text]

Resolution of Pain after Percutaneous Image-Guided Cryoablation of Extraperitoneal Endometriosis

PurposeTo retrospectively evaluate the relief of pain after percutaneous image-guided cryoablation of symptomatic extraperitoneal endometriosis (EE). Material and MethodsFrom 2017 to 2022, cryoablation of EE was performed at a single institution on a total of 47 lesions in 42 consecutive patients (median age, 37 years; interquartile range [IQR], 33–39.5 years). Patient and procedural characteristics were reviewed retrospectively. Tolerance and outcomes in terms of pain and patient satisfaction were evaluated. ResultsThe median follow-up duration was 13.5 months (IQR, 1.1–37.7 months) after cryoablation. The median pain-free survival rate was 93.8% (95% confidence interval [CI], 77.3–98.4) at 6 months and 82.7% (95% CI, 58.8–93.5) after 12 months. Pain decreased from a median of 8/10 (IQR, 7–9) on the visual analog scale to 0/10 (IQR, 0–1) at the last follow-up (P < .0001). The median Patient Global Impression of Change score recorded at the last follow-up was 1/7 (IQR, 1–2). The efficacy rate of cryoablation to avoid secondary surgery was 92.8% (39/42) per patient and 93.6% (44/47) per nodule treated. Four patients (9.5%, 4/42) experienced an adverse event in the days following the procedure, and 1 patient (2%) experienced a severe adverse event. ConclusionsPercutaneous cryoablation is safe and effective in significantly reducing pain and obtaining local control of EE.

Treatment of postsurgical trigeminal neuralgia with Fu's subcutaneous needling therapy resulted in prompt complete relief: Two case reports.

Trigeminal neuralgia is a recurrent unilateral transient electroshock-like pain. Fu's subcutaneous needling (FSN), used to treat the musculoskeletal problems, has not been reported in this field. The pain extent of case 1 had no reduction after the previous microvascular decompression, the pain of case 2 relapsed 4 years after the microvascular decompression. Postsurgical trigeminal neuralgia. FSN therapy was applied on the muscles around the neck and face area, which the myofascial trigger points were palpated in these muscles. The FSN needle was inserted into the subcutaneous layer and the needle tip was pointed toward the myofascial trigger point. The following outcome measurements were observed before and after treatment, including numerical rating scale, Barrow Neurology Institute Pain Scale scores, Constant Face Pain Questionnaire scores, Brief Pain Inventory-Facial scores, Patient Global Impression of Change scores, and medication dosage. The follow-up surveys were made after 2 and 4 months respectively. The pain of Case 1 was significantly reduced after 7 times FSN treatments and the pain of Case 2 was even disappeared after 6 times FSN treatments. This case report suggested that FSN can relieve postsurgical trigeminal neuralgia safely and effectively. Clinical randomized controlled studies are needed to be further conducted.

The Negative Prognostic Role of Inflammatory Biomarkers in Patients With Chronic Cerebrospinal Venous Insufficiency.

The pathologic consequences of inflammatory responses in chronic cerebrospinal venous insufficiency (CCSVI) remains poorly understood. Hence, this study was aimed to evaluate the peripheral inflammatory biomarkers in patients with intracranial and extracranial CCSVI pathology. In addition, the relationship between inflammatory cytokine profile and CCSVI prognosis was also evaluated. Patients diagnosed with CCSVI between July 2017 and July 2019 were included and subsequently divided into 3 groups based on the location of stenosis. The inflammatory biomarker assay included neutrophil-to-lymphocyte ratios (NLRs), platelet-to-lymphocyte ratios (PLRs), red blood cell distribution widths (RDW), C-reactive protein (CRP) levels, interleukin-6 (IL-6) levels, and neuron-specific enolase levels. Clinical outcomes were assessed using the modified Rankin Scale and Patient Global Impression of Change score. Univariate and multivariate regression analyses were performed to identify significant prognostic factors for poorer outcomes. Finally, we established a nomogram based on the multivariate regression analysis. We enrolled 248 patients in total, including 102 males and 146 females, with an average age of 57.85±12.28 years. Compared with patients with internal jugular vein stenosis, cerebral venous sinus stenosis (CVSS) patients were mostly younger and had been suffering from headaches and severe papilledema. Higher levels of NLR, RDW, and CRP were also observed in the CVSS group. Multivariate analysis indicated that NLR, PLR, and IL-6 were the independent prognostic factors for poor CCSVI outcomes. The clinical presentations and increases in NLR, PLR, IL-6, and CRP levels could be distinctly marked in patients with CVSS-related CCSVI than that in internal jugular vein stenosis-related CCSVI, indicating poor prognostic outcomes in these patients. A proinflammatory state might be associated with CCSVI pathology.

Arbaclofen extended-release tablets for spasticity in multiple sclerosis: randomized, controlled clinical trial.

Baclofen, a racemic GABA-B (GABAB) 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 GABAB receptor compared with the S-enantiomer and ∼5-fold greater potency compared with racemic baclofen. Arbaclofen extended-release tablets have a dosing interval of 12 hours and have shown a favourable safety and efficacy profile in early-phase clinical development. The current Phase 3 study was designed to evaluate the efficacy and safety of arbaclofen extended-release tablets in patients with multiple sclerosis-related spasticity. In this multicentre, double-blind, placebo-controlled study, adults with multiple sclerosis-related spasticity were randomized to arbaclofen extended-release 40 mg/day, arbaclofen extended-release 80 mg/day or placebo for 12 weeks. The co-primary end-points were the change from baseline to Week 12 in the Total Numeric-transformed Modified Ashworth Scale in the Most Affected Limb score and the Clinical Global Impression of Change score. A hierarchical testing procedure was used to evaluate the co-primary end-points; analyses for the 80 mg/day group were considered inferential only if the arbaclofen extended-release 40 mg/day and placebo groups demonstrated a statistically significant difference (P ≤ 0.05) for both end-points. Five hundred thirty-six patients were included in the study. At Week 12, the least squares mean change from baseline in Total Numeric-transformed Modified Ashworth Scale in the Most Affected Limb score was -1.67 (95% confidence interval: -1.97 to -1.36) and -1.28 (95% confidence interval: -1.57 to -0.99) in the arbaclofen extended-release 40 mg/day and placebo groups, respectively (least squares mean difference: -0.39; P < 0.048). Improvements were seen in the mean Clinical Global Impression of Change scores for both the arbaclofen extended-release 40 mg/day and placebo groups; however, no statistically significant difference was observed between them (least squares mean difference: -0.10; P = 0.43). Most adverse events were of mild-moderate severity. Arbaclofen extended-release 40 mg/day for 12 weeks significantly reduced multiple sclerosis-related spasticity compared with placebo and was safe and well tolerated over the 12-week treatment period. Although arbaclofen extended-release 40 mg/day improved Clinical Global Impression of Change scores, a significant difference from placebo was not observed.

Responsiveness of the German version of the Neck Disability Index in chronic neck pain patients: a prospective cohort study with a seven-week follow-up

BackgroundThe need for an efficient and feasible strategy to deal with neck pain has a high priority for many countries. Validated assessment tools like the Neck Disability Index (NDI) to evaluate the functional status of a neck pain patient are urgently needed to treat and to follow-up patients purposefully. A German version (NDI-G) was shown to be valid and reliable, but has so far not been tested for responsiveness. The aim of this study was to evaluate the NDI-G`s responsiveness.MethodsThis was a prospective cohort study with a seven-week follow-up. Fifty chronic neck pain patients filled out NDI-G twice. Additionally, the Patients’ Global Impression of Change score (PGIC) was assessed at follow-up. Wilcoxon and Spearman tests were used to assess direction and strength of the association between the change in NDI-G and PGIC. The receiver operating characteristics method and the area under the curve (AUC) were calculated to assess sensitivity and specificity of the NDI-G change over time.ResultsThe Wilcoxon test showed statistically significant differences for NDI-G at baseline and follow-up in the total sample, the “clinically improved” and “clinically not improved” subgroups as indicated in the PGIC. Spearman test resulted in a moderate correlation between the NDI-G and the PGIC (rS = -0.53, p = 0.01) at follow-up. AUC showed an acceptable discrimination [AUC = 0.78 (95% confidence interval 0.64 – 0.91)] of the NDI-G, with a cutoff score of 1.5, between clinically improved and clinically not improved patients, based on the PGIC.ConclusionsThe NDI-G is responsive to change in chronic neck pain. Together with the results of a previous study on its validity and reliability, the NDI-G can be recommended for research and clinical settings in patients with neck pain in German speaking countries.Trial registrationNCT02676141. February 8, 2016.

Pentoxifylline significantly reduces radicular pain secondary to lumbar disc hernia: A prospective, randomized crossover, single-blind controlled pilot study

Background and objectivesOptimal medical treatment for low back pain, sometimes associated to radicular pain, has yet to be established. Herniated nucleus pulposus has been found to release TNFα, a pro-inflammatory cytokine involved in radiculopathy. Interestingly, Pentoxifylline (PTX), a phosphodiesterase inhibitor, blocks the activity of TNFα. The aim of this study is to assess the effectiveness of PTX when added to the treatment protocol of radiculopathy in lumbar disc herniation. MethodsFifty-eight patients with radicular pain secondary to a lumbar disc hernia were included in this prospective, randomized crossover, single-blind controlled study. PTX was added randomly to the same treatment protocol (ibuprofen + paracetamol + pregabalin) either during the first or the second 15 days of treatment. Patients’ pain was assessed at day 15 via the Numeric Rating Scale (NRS) and the Patient’s Global Impression of Change score (PGIC). D15 NRS value was considered as the primary outcome measure. ResultsMean D15 NRS score was 3.2 ± 0.84 during the 15-days treatment with PTX, and 5,1 ± 0.97 during the 15-days treatment without PTX (p < 0.0001). During the 15 days treatment period with/without PTX, PGIC score was (7) in 19/3 patients, (6) in 30/10 patients, (5) in 7/27 patients and (4) in 2/18 patients respectively, difference being highly significant (p < 0.0000). ConclusionAdjunction of PTX to the standard medical treatment of radicular pain associated with lumbar disc hernia seems to significantly decrease patients’ pain intensity in addition to improving their global satisfaction with treatment.

A comparative study on efficacy and safety of tablet duloxetine 60 mg and tablet gabapentin 300 mg among patients with diabetic polyneuropathy – A randomized double-blind study

Background: Diabetic peripheral neuropathy is defined as the presence of symptoms and signs of peripheral nerve damage among patients with diabetes, after ruling out other potential causes. Diabetic neuropathies are one among the most common long-term complications of diabetes. About 60% of diabetic patients are affected by neuropathy. Aim and Objectives: This study aims to study the efficacy and safety of tablet duloxetine 60 mg and tablet gabapentin 300 mg among patients with diabetic polyneuropathy. Materials and Methods: This study was randomized, comparative, double-blind parallel group study which was conducted for a period of 6 months. Sixty patients with diabetic polyneuropathic pain were randomly allocated into two groups. One group received duloxetine 60 mg and other group received gabapentin 300 mg. Efficacy was assessed using visual analog scale (VAS), short form of McGill pain questionnaire, and patients global impression of change score. Safety was assessed using adverse drug reaction profile. Results: In the duloxetine group, the mean VAS score at the baseline was 54.97 ± 6.75, and at 3 months, it was 20.07 ± 5.32 which was statistically significant. In the gabapentin group, the mean score at baseline was 53.57 ± 7.85, and at 3 months, it was 26.57 ± 4.39 which was also statistically significant. The difference between the baseline and 3rd month mean McGill score in both groups was statistically significant. Conclusions: We found that both duloxetine 60 mg once daily and gabapentin 300 mg once daily are effective in the treatment of diabetic polyneuropathic pain. However, duloxetine 60 mg once daily is more efficacious than gabapentin 300 mg once daily in the treatment of diabetic neuropathic pain. Both the drugs are well tolerated but gabapentin is better tolerated than duloxetine.

Efficacy of Dapoxetine in the Treatment of Patients With Lifelong Premature Ejaculation as an Alternative to Sertraline Therapy.

IntroductionBefore dapoxetine was approved for the treatment of lifelong premature ejaculation (LPE) in China, daily dosing with off-label sertraline was common.AimTo investigate the efficacy of dapoxetine in the treatment of patients with LPE as an alternative to sertraline therapy.MethodsThis prospective study included LPE patients who previously attempted treatment with sertraline and who agree to receive dapoxetine therapy in our hospital from January 2020 to March 2021. Patients who received any PE therapy in the two months prior to the dapoxetine therapy were excluded. All patients received dapoxetine 30 mg (taken 1–3 hours before sexual intercourse) for 12 weeks, and they were not taking sertraline during the trial.Main Outcome MeasureData on their intravaginal ejaculatory latency time and premature ejaculation profile were recorded before and after the dapoxetine treatment. Clinical Global Impression of Change scores and data on Treatment-Emergent adverse events were collected after treatment.ResultsA total of 144 patients with LPE completed this study; including 64 patients who reported that previous sertraline treatment was satisfactory (group A) and 80 patients for whom previous sertraline therapy was unsatisfactory in treating PE (group B). Both groups experienced significantly increased intravaginal ejaculatory latency time. Dapoxetine therapy was reported satisfactory by 67.5% of patients with LPE in whom sertraline therapy unsatisfactory according to their Clinical Global Impression of Change score, which was not different from those who reported this result in group A (62.5%). Similar outcomes were also reported for premature ejaculation profile and treatment-emergent adverse events.Conclusion: Although both dapoxetine and sertraline are selective serotonin re-uptake inhibitors, dapoxetine therapy is satisfactory in 67.5% of patients with LPE in whom sertraline treatment unsatisfactory, and the effect of dapoxetine was independent of the effect of sertraline.Liu G, Yin Y, Zhang L. et al., Efficacy of Dapoxetine in the Treatment of Patients With Lifelong Premature Ejaculation as an Alternative to Sertraline Therapy. Sex Med 2021;10:100473.

Association between 5-HTTLPR and STin2 VNTR polymorphisms in the serotonin transporter gene and clinical response of a selective serotonin reuptake inhibitor (dapoxetine) in lifelong premature ejaculation

Association between 5-HTTLPR and STin2 VNTR polymorphisms in the serotonin transporter gene and clinical response of a selective serotonin reuptake inhibitor (dapoxetine) in lifelong premature ejaculation

Stress and Pain Before, During and After the First Wave of the COVID-19 Pandemic: An Exploratory Longitudinal Mixed Methods Study.

Aims: This study explores the association between subjective feeling of stress and pain experience in the context of the COVID-19 pandemic with a focus on characteristics known to trigger a physiological stress response [sense of low control, threat to ego, unpredictability and novelty (STUN)].Methods: This exploratory longitudinal convergent mixed methods design consisted of online questionnaires over three time points (before, during and after the 1st wave of the COVID-19 pandemic) (N = 49) and qualitative interviews (N = 27) during the 1st wave of the pandemic on distinct samples of individuals living with chronic pain (CP). Both types of data sources were mixed upon integration using joint display.Results: Mean pain intensity scores remained stable across time points, while pain unpleasantness and pain interference scores significantly improved. Global impression of change scores measured during the first wave of the pandemic do not entirely concord with pain scores evolution. Two thirds of participants reported a global deterioration of their pain condition at the beginning of the pandemic. Stress and pain catastrophizing before the pandemic were associated with pain scores throughout the pandemic; while most specific measures of stress due to the novel, uncontrollable, unpredictable and threatening nature of the pandemic were not. Qualitative data demonstrated that the deterioration reported in pain status reflected additional dimensions, including spatial expansion of the painful area, reduced access to treatments and challenges in adapting pain management strategies.Conclusions: Helping individuals to negotiate stressful aspects of the pandemic might help offset the negative impacts of stress on pain status in this context or other important life events.