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The COVID-19 pandemic had remarkable effects on psychological distress. The main stressors were prolonged quarantine and social isolation, fear of infection and death, stigmatization, infodemic, financial difficulties, and job loss. These negative stressors, which affect mental and physical health, make people more vulnerable to nocebo-related risk behaviors. We aimed to summarize data on nocebo behaviors, such as the negative psychological consequences of the COVID-19 pandemic in terms of how people perceive and interpret medical services and treatments.
Learn More >Administration of a widely used 5-hydroxytryptamine receptor (5HT R) antagonist (ondansetron) potently inhibited the development of experimentally induced opioid dependence and withdrawal responses in mice and humans. However, in several studies examining withdrawal symptoms in subjects with chronic opioid use disorders (OUD), ondansetron exhibited reduced or absent efficacy. Since attenuation of opioid withdrawal symptomatology is mediated within the brain, this study examined single-dose ondansetron pharmacokinetics in the blood and brain of mice. We demonstrate that ondansetron concentrations in brain (C ng/mg) are 1000-fold lower than the blood concentrations (C ng/ml) and decrease rapidly after ondansetron administration; and that a large percentage of brain ondansetron remains in the ventricular fluid. These results indicate that the ondansetron dose, and the time window between ondansetron and opioid administration and when withdrawal is assessed are critical considerations for clinical studies involving subjects with chronic OUD. The pharmacokinetic results and the dosing considerations discussed here can be used to improve the design of subsequent clinical trials, which will test whether a more prolonged period of ondansetron administration can provide a desperately needed therapy that can prevent the development of the Neonatal Opioid Withdrawal Syndrome (NOWS) in babies born to mothers with chronic OUD.
Learn More >The COVID-19 pandemic has disrupted seeking and delivery of healthcare. Different Australian jurisdictions implemented different COVID-19 restrictions. We used Australian national pharmacy dispensing data to conduct interrupted time series analyses to examine the incidence and prevalence of opioid dispensing in different jurisdictions. Following nationwide COVID-19 restrictions, the incidence dropped by -0.40 [-0.50, -0.31], -0.33 [-0.46, -0.21] and -0.21 [-0.37, -0.04] /1000 people/week and prevalence dropped by -0.85 [-1.39, -0.31], -0.54 [-1.01, -0.07] and -0.62 [-0.99, -0.25] /1000 people/week in Victoria, New South Wales and other jurisdictions, respectively. Incidence and prevalence increased by 0.29 [0.13, 0.44] and 0.72 [0.11, 1.33] /1000 people/week, respectively in Victoria post-lockdown; no significant changes were observed in other jurisdictions. No significant changes were observed in the initiation of long-term opioid use in any jurisdictions. More stringent restrictions coincided with more pronounced reductions in overall opioid initiation, but initiation of long-term opioid use did not change.
Learn More >Lower back pain (LBP) and osteoarthritis (OA) are common musculoskeletal disorders and account for around 17.0% of years lived with disability worldwide; however, there is a lack of real-world data on these conditions. Paracetamol brands are frequently prescribed in France for musculoskeletal pain and include Doliprane, Dafalgan, and Ixprim (tramadol-paracetamol).
Learn More >We sought to predict analgesic response to daily oral nonsteroidal anti-inflammatory drugs (NSAIDs) or subcutaneous tanezumab 2.5 mg (every 8 weeks) at week 16 in patients with moderate-to-severe osteoarthritis, based on initial treatment response over 8 weeks.
Learn More >Gabapentin is a recommended first-line agent for treating neuropathic pain; however, its efficacy rate is reportedly low, and the risk of adverse events is high. A plausible explanation for this lies with its wide range of actions, the entirety of which have yet to be fully elucidated.
Learn More >Manifestations of psoriasis in special areas are difficult to treat and are associated with a high disease burden and significant quality of life (QoL) impairment. Topical therapies may be inadequate for these patients, necessitating systemic treatment.
Learn More >Psoriasis is a common, chronic immune-mediated skin disease frequently associated to inflammatory and metabolic comorbidities. About 20-30% of patients are affected by moderate-to-severe psoriasis and require a systemic treatment, which include traditional and biological drugs. The objective of this manuscript is to provide criteria for a personalized biological treatment.
Learn More >Migraine is thought to involve sensitization of the trigeminal nociceptive system. In preclinical pain models, activation of MNK-eIF4E signaling contributes to nociceptor sensitization and the development of persistent pain. Despite these observations, the role of MNK signaling in migraine remains unclear. Here, we investigate whether activation of MNK contributes to hypersensitivity in two rodent models of migraine. Female and male wild-type (WT) and MNK1 knock-out (KO) mice were subjected to repeated restraint stress or a dural injection of interleukin-6 (IL-6) and tested for periorbital hypersensitivity and grimacing. Upon returning to baseline thresholds, stressed mice were administered a low dose of the nitric oxide donor sodium nitroprusside (SNP) and mice previously injected with IL-6 were given a second dural injection of pH 7.0 to test for hyperalgesic priming. MNK1 KO mice were significantly less hypersensitive than WTs following dural IL-6 and did not prime to pH 7.0 or SNP. Furthermore, treatment with the selective MNK inhibitor, eFT508, in WT mice prevented hypersensitivity caused by dural IL-6 or pH 7.0. Together, these results implicate MNK-eIF4E signaling in the development of pain originating from the dura and strongly suggest that targeting MNK inhibition may have significant therapeutic potential as a treatment for migraine.
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