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The role of avoiding known triggers, embracing protectors, and adhering to healthy lifestyle recommendations in migraine prophylaxis: Insights from a prospective cohort of 1125 people with episodic migraine.

Until recently, guidelines for migraine prevention recommended avoiding known migraine headache triggers. Adhering to healthy lifestyle behaviors is also recommended. In a recent cohort study many triggers were found to decrease the probability of migraine attacks in some individuals. The extent to which people with migraine adhere to healthy lifestyle recommendations is unknown. We set out to determine if known migraine trigger factors and daily adherence to healthy lifestyle recommendations are associated with decreased probability of migraine attacks in some individuals.

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Opioid Disposal Practices of Patients with Life-Limiting Cancers in an Outpatient Palliative Care Clinic: A Cross-Sectional Study.

Patients with life-limiting cancers are commonly prescribed opioids to manage pain, dyspnea, and cough. Proper prescription opioid disposal is essential to prevent poisonings and deaths. We examined opioid disposal practices of patients referred to a Canadian outpatient palliative care clinic (OPCC). The primary objective was to determine the prevalence of OPCC patients who did not routinely dispose their opioids. The secondary objectives were to examine their methods of opioid disposal and to identify patient characteristics associated with routine disposal of opioids. This cross-sectional study involved a retrospective chart review of new, adult patients who were seen in a Canadian OPCC (September 2018-August 2019) and completed a survey about opioid-related constructs: source of prescriptions, use, storage, disposal, and knowledge about associated harms. Among the 122 study participants, half (58/111, 52.3%) reported that they did not routinely dispose their opioids. The most common method of disposal was by giving them to pharmacists (69/88, 78.4%). Cannabis use (odds ratio [OR]: 3.7, 95% confidence interval [CI]: 1.1-11.8) and neuropathic medication use (OR: 3.0, 95% CI: 1.2-7.2) were positively associated with routine disposal of opioids. Conversely, reports of an increased amount of opioid use in the past six months were negatively associated with routine disposal of opioids (OR: 0.38, 95% CI: 0.16-0.88). The high prevalence of people with life-limiting illnesses who do not routinely dispose their opioids requires increased attention. Interventions, such as education, are needed to reduce medication waste and opioid-related harms.

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The prevalence and clinical features of fibromyalgia in Chinese hospital patients with primary headache: The survey of fibromyalgia comorbid with headache.

The aims were to explore the prevalence and clinical features of fibromyalgia in Chinese hospital patients with primary headache.

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Recreational cannabis and opioid distribution.

Twenty-one U.S. states have passed recreational cannabis laws as of November 2022. Cannabis may be a substitute for prescription opioids in the treatment of chronic pain. Previous studies have assessed recreational cannabis laws' effects on opioid prescriptions financed by specific private or public payers or dispensed to a unique endpoint. Our study adds to the literature in three important ways: by (1) examining these laws' impacts on prescription opioid dispensing across all payers and endpoints, (2) adjusting for important opioid-related policies such as opioid prescribing limits, and (3) modeling opioids separately by type. We implement two-way fixed-effects regressions and leverage variation from eleven U.S. states that adopted a recreational cannabis law (RCL) between 2010 and 2019. We find that RCLs lead to a reduction in codeine dispensed at retail pharmacies. Among prescription opioids, codeine is particularly likely to be used non-medically. Thus, the finding that RCLs appear to reduce codeine dispensing is potentially promising from a public health perspective.

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Neuropathic pain, cognitive fusion, and alexithymia in patients with multiple sclerosis: Cross-sectional evidence for an explanatory model of anxiety symptoms.

Multiple sclerosis (MS) presents a high prevalence, a marked increase worldwide, and a relevant impact on patients, public health, and society. Anxiety often cooccurs with MS and can contribute to the worsening of MS symptoms. However, knowledge about predictors of anxiety in Patients with MS (PwMS) is scarce.

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Gastroenterologist Primer: Endometriosis for Gastroenterologists.

A comprehensive understanding of endometriosis and its common gastrointestinal presentations are critical for gastroenterologists to ensure appropriate and timely screening and diagnosis. Endometriosis is a common inflammatory disease that frequently presents with gastrointestinal symptoms overlapping with irritable bowel syndrome (IBS) and other gastrointestinal disorders. Many endometriosis patients first present to a gastroenterologist or generalist, which may prolong the time to diagnosis and appropriate care.

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Design of Analgesic Trivalent Peptides with Low Withdrawal Symptoms: Probing the Antinociceptive Profile of Novel Linear and Cyclic Peptides as Opioid Pan Ligands.

The discovery of efficacious and safe analgesics with reduced side effects is the foremost challenge in the pain field. In this work, we report the and evaluation of linear and cyclic analogues of biphalin with the aim to complete the series of structural modifications previously applied in the development of opioid peptides incorporating a xylene bridge. Replacement of Tyr by Dmt (2,5-dimethyltyrosine) in the linear biphalin analogue and cyclic analogue resulted in two new compounds (namely, and ) endowed with improved KOR/MOR/DOR binding affinity. Both compounds showed a strong antinociceptive profile in models of nociception, allodynia, and hyperalgesia via the tail flick, hot plate, and formalin tests after intracerebroventricular and subcutaneous administration. One of these ligands, , was also tested in tolerance and dependence studies, exhibiting very little withdrawal symptoms.

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Estimands for atopic dermatitis clinical trials: expert opinion on the importance of intercurrent events.

Despite the emergence of novel targeted treatments for atopic dermatitis (AD), there is a lack of guidelines on standardizing analysis of clinical trial data. To define and estimate meaningful treatment comparisons, several factors, including intercurrent events, must be taken into account. Intercurrent events are defined as events occurring after treatment initiation that affect either the interpretation or existence of the measurements associated with clinical questions of interest. Due to the relapsing, unpredictable nature of AD, intercurrent events frequently occur in AD trials, such as use of rescue therapy for intense itch and sleep deprivation. Despite the impact of intercurrent events in AD, they are often handled in an inconsistent manner across trials, which limits results interpretation. The estimand framework is increasingly used to estimate treatment effects while accounting for intercurrent events. This review explores how guidance from the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) on the use of estimands can be applied to support AD clinical trial design and analysis. We propose that estimands are used in AD trials and defined early during trial design. The use of estimands can provide clinicians with interventional trial results that are more reflective of clinical practice, help facilitate comparisons across clinical trials, and are more informative to enable improved treatment selection for patients.

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IL-31 and IL-31 receptor alpha in pemphigus: Contributors to more than just itch?

Pemphigus is an autoimmune blistering disorder with four major subtypes: pemphigus vulgaris (PV), pemphigus vegetans (PVe), pemphigus foliaceus (PF), and pemphigus herpetiformis (PH). Among them, PF and PH present itching as a clinical feature; however, the mechanisms behind the pruritus are still unclear. In this report, we sought to investigate the expression of a type 2 inflammation-related pruritogenic cytokine IL-31 and its receptor subunit IL-31RA through immunofluorescence staining analysis. The number of eosinophils, basophils, and mast cells, and the expression levels of thymic stromal lymphopoietin (TSLP) and periostin were also investigated. Evaluation showed an increase in the number of dermal IL-31 cells and IL-31RA cells in PH and PVe. Epidermal expression of IL-31RA increased in PV, PF, and PVe, but not in PH, compared to healthy individuals. The number of dermal eosinophils and basophils was also increased in PVe and PH. The number of dermal mast cells and expression levels of TSLP and periostin did not change among pemphigus subtypes and healthy controls. Collectively, enhanced IL-31/IL-31RA signaling and the increased numbers of dermal eosinophils and basophils may participate in itching in PH. On the other hand, IL-31/IL-31RA signaling seemed unable to provoke itching in PVe, a non-pruritic subtype of pemphigus, although it might contribute to epidermal thickening and dermal fibrosis.

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Pramipexole inhibits formalin-induce acute and long-lasting mechanical hypersensitivity via NF-kB pathway in rats.

Pain is one of the most frequent causes for patients to seek medical care. It interferes with daily functioning and affects the quality of life of the patient. There is a clear need to investigate nonopioid or non-nonsteroidal anti-inflammatory drug alternatives for the treatment of pain. In this study, we determined the effect of acute pre- and posttreatment with pramipexole (PPX), a dopamine D2/D3 selective agonist, on formalin 1%-induced acute and long-lasting nociceptive behavior sensitivity in rats. Moreover, we sought to investigate whether the antiallodynic and antihyperalgesic effect induced by PPX was mediated through the nuclear factor-κB (NF-kB) signaling pathway. Moreover, acute systemic pretreatment with PPX (1 and 3 mg/kg, ip) suppressed the formalin-induced nociceptive behavior during both phases of the formalin test and the development of formalin-induced secondary mechanical allodynia and hyperalgesia in both paws. Acute systemic posttreatment with PPX (3 mg/kg, ip) reverted the formalin-induced long-lasting secondary mechanical allodynia and hyperalgesia. Furthermore, PPX inhibits the protein expression of NF-κB-p65 and the levels of tumor necrosis factor-α and interleukin-1β in the spinal cord of animals with secondary mechanical allodynia and hyperalgesia induced by formalin. These data suggest that PPX has a potential role in producing anti-inflammatory activity. Moreover, the antiallodynic and antihyperalgesic effects induced by PPX can be mediated through the NF-kB signaling pathway.

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