Rejected

This double-blind placebo-controlled, fixed/flexible-dose phase 2 trial assessed the efficacy, safety, and tolerability of cariprazine vs. placebo for depressive episodes associated with bipolar I or II disorder. Primary endpoint was change in Montgomery-Åsberg Depression Rating Scale (MADRS) total scores (baseline to week 8), and secondary endpoint was mean Clinical Global Impressions-Improvement score (week 8). Patients were randomized (N = 233) 1:1:1 to placebo, 'low-dose' 0.25-0.5 mg/day or 'high-dose' 1.5-3.0 mg/day cariprazine. Adverse events, laboratory results, vital signs, extrapyramidal symptoms, and suicide risk were monitored. Neither cariprazine group significantly separated from placebo in primary (mixed-effect model repeated measures MADRS least-squares mean differences: low-dose = -0.7, P = 0.7408; high-dose = 0.0, P = 0.9961) or secondary efficacy measures. No new safety signals with cariprazine were observed and common treatment-emergent adverse events (≥5% of cariprazine patients and twice the rate of placebo) included insomnia, akathisia, dry mouth, nausea, weight increased, diarrhea, restlessness, vomiting, musculoskeletal stiffness, migraine, and cough. Metabolic and weight changes were generally similar for cariprazine and placebo. Factors that may have affected the outcome of the trial were identified, which helped to inform the design and conduct of subsequent phase 2b/3 clinical trials of cariprazine in bipolar depression.

Neuropathic pain is a complex, chronic pain state that is heterogeneous in nature and caused by the consequence of a lesion or disease affecting the somatosensory system. Current medications give a long-lasting pain relief only in a limited percentage of patients also associated with numerous side effects. Stem cell transplantation is one of the attractive therapeutic platforms for the treatment of a variety of diseases such as neuropathic pain. Here, the authors review the therapeutic effects of stem cell transplantation of different origin and species in different models of neuropathic pain disorders. Stem cell transplantation could alleviate the neuropathic pain; indeed, stem cells are the source of cells, which differentiate into a variety of cell types and lead trophic factors to migrate to the lesion site opposing the effects of damage. In conclusion, this review suggests that stem cell therapy can be a novel approach for the treatment of neuropathic pain.

To investigate the efficacy of continuous wound infusion (CWI) with local anesthetics for reducing postoperative pain compared with placebo in patients undergoing benign gynecologic laparoscopy.

To review the literature about the acute presentation of Chiari 1 malformation in children, with a focus on acute cervical cord syndromes with impairment of the cortico-spinal tract. To analyze the possible precipitating factors and the pathophysiology of the acute onset.

Osteoarthritis (OA) is a chronic, debilitating disease affecting millions of people worldwide. Management of OA involves pharmacological and non-pharmacological approaches. Conventional pharmacological treatments have limited efficacy and are associated with a number of side-effects, restricting the number of patients who can use them. New pharmacological therapies for managing OA are required and a number have been developed targeting different tissues in OA: bone and cartilage, synovium and nerves. However, there has been overall limited success. Disease-modifying osteoarthritis drugs (DMOADs) are a putative class of therapies aimed at improving OA structural pathologies and consequent symptoms. Recent DMOAD studies have demonstrated some promising therapies but also provided new considerations for future trials.

Extracorporeal shockwave therapy (ESWT) is proposed to be effective in reducing pain and improving functional outcome in chronic plantar fasciitis. However, no long-term reports exist on the changes in plantar fascia (PF) elasticity after ESWT. We aimed to evaluate the changes in PF stiffness in patients with plantar fasciitis undergoing ESWT. The visual analogue scale (VAS, 0-100) was used for evaluating heel pain severity. B-mode sonography and strain sonoelastography were used for evaluating the PF thickness and stiffness. The sonoelastogram was analyzed using hue histogram analysis (value: 0-255, from stiffer to softer). All evaluations were recorded before ESWT, and 1 week, 1 month, 3 months, 6 months, and 12 months after ESWT. Repeated measures ANOVA was used to compare pain VAS, PF thickness, and PF hue value at different follow-up time-points. Twenty-two participants (8 men, 14 women) completed all measurements for 12 months. The VAS of heel pain, PF thickness, and PF hue values at pre-ESWT, and 1-week, 1-month, 3-month, 6-month, and 12-month evaluations after ESWT were 62.4 ± 4.2, 49.3 ± 5.8, 38.3 ± 5.7, 27.9 ± 5.3, 18.9 ± 4.7, and 13.2 ± 3.0 (p < 0.01 in all measurements post ESWT versus pre-ESWT); 5.57 ± 0.22 mm, 5.64 ± 0.18 mm, 5.45 ± 0.24 mm, 5.37 ± 0.20 mm, 5.08 ± 0.20 mm, and 4.62 ± 0.15 mm (p < 0.01 at 6-month; otherwise p > 0.05); and 24.5 ± 2.4, 35.2 ± 3.1, 31.0 ± 4.1, 30.5 ± 3.9, 21.4 ± 2.1, and 15.9 ± 1.6 (p < 0.01 at 1-week and 6-month; otherwise p > 0.05), respectively. In conclusion, the heel pain intensity and PF thickness reduced gradually over 12 months after ESWT. The PF stiffness decreased during the first week and increased thereafter; at the 12-month follow-up, stiffness was more than at pre-ESWT.

Scalp nerve block with ropivacaine has been shown to provide perioperative analgesia. However, the best concentration of ropivacaine is still unknown for optimal analgesic effects. We performed a prospective study to evaluate the effects of scalp nerve block with varied concentration of ropivacaine on postoperative pain and intraoperative hemodynamic variables in patients undergoing craniotomy under general anesthesia. Eighty-five patients were randomly assigned to receive scalp block with either 0.2% ropivacaine, 0.33% ropivacaine, 0.5% ropivacaine, or normal saline. Intraoperative hemodynamics and post-operative pain scores at 2, 4, 6, 24 hours postoperatively were recorded. We found that scalp blockage with 0.2% and 0.33% ropivacaine provided adequate postoperative pain relief up to 2 h, while administration of 0.5% ropivacaine had a longer duration of action (up to 4 hour after craniotomy). Scalp nerve block with varied concentration of ropivacaine blunted the increase of mean arterial pressure in response to noxious stimuli during incision, drilling, and sawing skull bone. 0.2% and 0.5% ropivacaine decreased heart rate response to incision and drilling. We concluded that scalp block using 0.5% ropivacaine obtain preferable postoperative analgesia compared to lower concentrations. And scalp block with ropivacaine also reduced hemodynamic fluctuations in craniotomy operations.

The last decade has seen an explosion in the interest in using biologics for regenerative medicine applications, including umbilical cord-derived Wharton's Jelly. There is insufficient literature assessing the amount of growth factors, cytokines, hyaluronic acid, and extracellular vesicles including exosomes in these products. The present study reports the development of a novel Wharton's jelly formulation and evaluates the presence of growth factors, cytokines, hyaluronic acid, and extracellular vesicles including exosomes.

The aim of this study was to investigate the medium- to long-term effects of radiofrequency (RF) ablation of genicular nerves for chronic refractory knee pain due to osteoarthritis (OA).