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Individuals with chronic low back pain (cLBP) may benefit from multimodal functional restoration programs (FRPs).
Learn More >Constipation is the most common adverse event (AE) of opioid therapy. This multicenter, phase 2 study evaluated the efficacy and safety of linaclotide in treating opioid-induced constipation (OIC) in patients with chronic noncancer pain syndromes (NCT02270983). Adults with OIC (<3 spontaneous bowel movements [SBMs]/week) related to chronic noncancer pain were randomized 1:1:1 to receive linaclotide 145 µg, linaclotide 290 µg, or placebo once daily for 8 weeks. The primary endpoint was change from baseline in 8-week SBM frequency rate (SBMs/week). Secondary efficacy endpoints included 6/8-week SBM 3 + 1 responders, time to first SBM, and changes from baseline in 8-week stool consistency, abdominal bloating, and straining. Additional endpoints included treatment satisfaction and adequate relief responders. In total, 254 patients were randomized: 87, 88, and 79 received linaclotide 145 µg, linaclotide 290 µg, and placebo, respectively. The mean changes from baseline in SBMs/week during the treatment period were 2.9 and 3.5 in the linaclotide 145 and 290 µg groups (P < 0.01 for both doses), respectively, vs 1.6 in the placebo group. Diarrhea, the most common AE, was generally mild, resulting in 1.1%, 5.7%, and 1.3% of patients discontinuing in the linaclotide 145 μg, linaclotide 290 μg, and placebo groups, respectively. No serious AEs related to diarrhea were reported in any treatment group. Compared with placebo, linaclotide-treated patients had significant improvements in stool consistency, straining, abdominal bloating, and treatment satisfaction scores (P < 0.05). Linaclotide significantly improved OIC symptoms and was well tolerated in patients with chronic noncancer pain.
Learn More >This study sought to characterize central sensitization further among women with chronic pelvic pain by identifying temporal summation using a cotton swab (Q-tip) test that can be used at the bedside.
Learn More >Chronic lower back pain (CLBP) is a major health care burden and often results in workplace absenteeism. It is a priority for appropriate management of CLBP to get individuals back to work as early as possible. Interventions informed by the flags approach, which integrates cognitive and behavioral approaches via identification of biopsychosocial barriers to recovery, have resulted in reduced pain-related work absences and increased return to work for individuals with CLBP. However, research indicates that physicians' adherence to biopsychosocial guidelines is low.
Learn More >Ubrogepant (MK-1602) is a novel, oral, calcitonin gene-related peptide receptor antagonist in clinical development with positive Phase III outcomes for acute treatment of migraine. This paper describes the population exposure-response (E-R) modeling and simulations which were used to inform the Phase III dose-selection rationale, based on approximately 800 participants pooled across two Phase IIb randomized dose-finding clinical trials. The E-R model describes the placebo and ubrogepant treatment effects based on migraine pain endpoints (2-hour pain relief and 2-hour pain freedom) at various dose levels. Sensitivity analyses were conducted to evaluate various assumptions of placebo response in light of the high placebo response observed in one Phase II trial. A population PK model describing the effect of formulations was included in the E-R simulation framework to assess potential dose implications of a formulation switch from Phase II to Phase III. Model-based simulations predict that a dose of 25 mg or higher is likely to achieve significantly better efficacy than placebo with desirable efficacy levels. The understanding of E-R helped support the dose selection for the Phase III clinical trials.
Learn More >Although white matter lesions are frequently detected in migraine patients, underlying mechanisms remain unclear. Low carotid artery endothelial shear stress has been associated with white matter lesions. We aimed to investigate the association between carotid artery endothelial shear stress and white matter lesions in migraine. In 40 elderly migraine patients ( = 29 females, 75 years [SD 3]) and 219 controls ( = 80 females, 74 years [SD 3]) from the PROSPER-MRI study, carotid artery endothelial shear stress was estimated on 1.5 T gradient-echo phase contrast MRI. White matter lesion volumes were calculated from structural MRI scans. Analyses were adjusted for age, sex, cardiovascular risk factors and cardiovascular disease. Migraine patients had lower mean endothelial shear stress compared to controls (0.90 [SD 0.15] vs. 0.98 [SD 0.16] Pa; = 0.03). The association between mean endothelial shear stress and white matter lesion volume was greater for the migraine group than control group ( for interaction = 0.05). Within the migraine group, white matter lesion volume increased with decreasing endothelial shear stress (β-0.421; = 0.01). In conclusion, migraine patients had lower endothelial shear stress which was associated with higher white matter lesion volume.
Learn More >A proper antalgic treatment is based on the use of titrated drugs to provide adequate relief and a good tolerability profile. Therapies have a variable effectiveness among subjects depending on medical and genetic conditions. CYP2D6 variations determine a different clinical response to most analgesic drugs commonly used in daily clinical practice by influencing the drugs' pharmacokinetics. This study was a monocentric clinical trial exploring the CYP2D6 variants in 100 patients with a diagnosis of chronic pain.
Learn More >Painful distal symmetrical polyneuropathy is common in HIV and is associated with reduced quality of life. Research has not explored the experience of neuropathic pain in people with HIV from a person-centred perspective. Therefore, a qualitative interview study was conducted to more deeply understand the experience and impact of neuropathic pain in this population. Semi-structured interviews were conducted with 26 people with HIV and peripheral neuropathic pain symptoms. Interviews explored the impact of pain and participants' pain management strategies. Interviews were transcribed verbatim and analysed using thematic analysis. Four themes and 11 subthemes were identified. Theme one reflects the complex characterisation of neuropathic pain, including the perceived unusual nature of this pain and diagnostic uncertainty. Theme two centred on the interconnected impacts of pain on mood and functioning and includes how pain disrupts relationships and threatens social inclusion. Theme three reflects the struggle for pain relief, including participants' attempts to 'exhaust all options' and limited success in finding lasting relief. The final theme describes how pain management is complicated by living with HIV; this theme includes the influence of HIV stigma on pain communication and pain as an unwanted reminder of HIV. These data support the relevance of investigating and targeting psychosocial factors to manage neuropathic pain in HIV.
Learn More >Conventional MRI of patients with trigeminal neuralgia (TN) does not typically reveal associated brain lesions. Here, we identify a unique group of TN patients that present with a single brainstem lesion, who do not fulfill diagnostic criteria for multiple sclerosis (MS). We aim to define this new clinical syndrome, which we term TN associated with solitary pontine lesion (SPL-TN), using a clinical and neuroimaging approach. We identified 24 cases of SPL-TN, 18 of which had clinical follow-up for assessment of treatment response. Lesion mapping was performed to determine the exact location of the lesions and site of maximum overlap across patients. Diffusion tensor imaging was used to assess the white matter microstructural properties of the lesions. Diffusivity metrics were extracted from the (1) SPL-TN lesions, (2) contralateral, unaffected side, (3) MS brainstem plaques from 17 patients with TN secondary to MS, (4) and healthy controls. We found that 17/18 patients were non-responders to surgical treatment. The lesions were uniformly located along the affected trigeminal pontine pathway, where the site of maximum overlap across patients was in the area of the trigeminal nucleus. The lesions demonstrated abnormal white matter microstructure, characterized by lower fractional anisotropy, and higher mean, radial, and axial diffusivities compared to the unaffected side. The brainstem trigeminal fiber microstructure within a lesion highlighted the difference between SPL-TN lesions and MS plaques. In conclusion, SPL-TN patients have identical clinical features to TN, but have a single pontine lesion not in keeping with MS, and are refractory to surgical management.
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