Rejected

Opioids continue to be widely prescribed for chronic noncancer pain, despite the awareness that opioids provide only short-time pain relief, lead to dose accumulation, have numerous adverse effects, and are difficult to wean. As an alternative, we previously showed advantages of using pharmaceutical-grade cannabis in a population of chronic pain patients with fibromyalgia. It remains unknown whether combining an opioid with pharmaceutical-grade cannabis has advantages, such as fewer side effects from lesser opioid consumption in chronic pain.

Age-related delays in bone repair remains an important clinical issue that can prolong pain and suffering. It is now well established that inflammation increases with aging and that this exacerbated inflammatory response can influence skeletal regeneration. Recently, simple dietary supplementation with beneficial probiotic bacteria has been shown to influence fracture repair in young mice. However, the contribution of the gut microbiota to age-related impairments in fracture healing remains unknown. Here, we sought to determine whether supplementation with a single beneficial probiotic species, Bifidobacterium longum (B. longum), would promote fracture repair in aged (18-month-old) female mice. We found that B. longum supplementation accelerated bony callus formation which improved mechanical properties of the fractured limb. We attribute these pro-regenerative effects of B. longum to preservation of intestinal barrier, dampened systemic inflammation, and maintenance of the microbiota community structure. Moreover, B. longum attenuated many of the fracture-induced systemic pathologies. Our study provides evidence that targeting the gut microbiota using simple dietary approaches can improve fracture healing outcomes and minimize systemic pathologies in the context of aging.

Alzheimer's disease (AD) is a debilitating and highly heritable neurodegenerative disease. Early-onset AD (EOAD) was defined as AD occurring before age 65. Although it has a high genetic risk, EOAD due to PSEN2 variation is very rare. ABCA7 is an important risk gene for AD. Previously reported cases mainly carried variations in a single pathogenic or risk gene. METHODS AND RESULTS: In this study, we report a 35-year-old female carrying variants in both the PSEN2 gene (c.640G > T p.V214L) and ABCA7 gene (c.2848G > A p.V950M). Four previously reported cases carried PSEN2 V214L, and no reported cases carried ABCA7 V950M. She had a history of migraine, patent foramen ovale, spontaneous subarachnoid hemorrhage without aneurysm, and multiple cerebral microhemorrhages. Her MMSE score was 24/30, and her MoCA score was 22/30. The concentration of Aβ42 and the ratio of Aβ42 to Aβ40 in cerebral spinal fluid were obviously decreased. Published variants of PSEN2 and ABCA7 in PubMed were reviewed, and the patients' characteristics were summarized and compared to provide information for the clinical diagnosis of AD.

A "brain-skin" connection has been long been observed between chronic stress and chronic inflammatory skin disease including urticaria, psoriasis, atopic dermatitis, and prurigo nodularis. The relationship appears to be bidirectional. Chronic psychological stress has been shown to sustain hyperactivity of the sympathetic branch of the autonomic nervous system. Chronic stress is proinflammatory and in the context of several dermatologic disorders may be associated with an increase in dermal nerve fiber density, mast cells, nerve growth factor and calcitonin-gene-related peptide (CGRP). Furthermore, CGRP elicits a T2-polarized T-cell response that is a hallmark of chronic pruritic conditions such as atopic dermatitis and prurigo nodularis. This T2 response contributes directly to acute pruritus as well as the sensitization of cutaneous sensory neurons that are critical for chronic pruritus. Prurigo nodularis is a debilitating skin disorder featuring prominent nerve structural, neuropeptide, and T2 cytokine aberrations that is a model deserving of future study.

Neuropathic cancer pain (NCP) is prevalent affecting up to 58% of those with persistent pain following cancer treatment. Neuropathic pain can develop from malignancy, after neural tissue insult during surgery and/or exposure to radiation or neurotoxic agents used as part of cancer treatment regimens. Pain following cancer treatment is commonly under-treated and one barrier identified is poor recognition of pain and inadequate assessment. Recognition of the presence of NCP is important to inform pain management, which is challenging to treat and warrants the use of specific treatments to target neuropathic mechanisms. In this review, approaches for screening and classifying NCP are described. These include screening questionnaires and the application of the updated neuropathic pain grading system in a cancer context. The evidence from neuropathic pain related assessments in cancer populations is provided and highlighted under different neuropathic pain grades. Recommendations for assessment in practice are provided.

To evaluate the burden of disease, investigate the treatment and response to treatment caused by exposure to stinging tree plants presenting to Cairns Hospital over a 3-year period. Our secondary aim was to examine the benefit from treating such exposures with topical dilute hydrochloric acid (HCl).

Not available.

Introduction. Adequate sedation and analgesia is essential in the management of patients requiring mechanical ventilation (MV). The implementation of protocols and their monitoring is recommended; mixed results on adherence and impact have been reported. Objectives. To assess the impact of the implementation of a sedation and analgesia protocol on the use of benzodiazepines, opioids, and evolution in the pediatric intensive care unit (PICU) in patients requiring MV for more than 72 hours. Methods. Before-and-after, uncontrolled study in the PICU of a children’s hospital. The study was developed in 3 stages: pre-intervention for situational diagnosis (from April to September 2019), intervention,and post-intervention for implementation of a sedation and analgesia protocol, education on use, and monitoring of adherence and impact (from October 2019 to October 2021). Results. A total of 99 and 92 patients were included in the study in the pre- and post-intervention stages, respectively. Patients had a more severe condition, were younger, and had a lower weight in the preintervention period. After adjusting for severity and age, the group comparison in the post-intervention stage showed a reduction in days of continuous infusion of opioids (6 ± 5.2 versus 7.6–5.8, p = 0.018) and days of continuous infusion of benzodiazepines (3.3 ± 3.5 versus 7.6 ± 6.8, p = 0.001). No significantdifferences were observed in days of MV and total days of benzodiazepine use. Conclusion. The implementation of a sedation and analgesia protocol resulted in a reduction in the use of continuous infusion of drugs.

BACKGROUND Unwashed or unprocessed poppy seeds may be an underrecognized substance that can lead to dependence, abuse, and an opioid use disorder. Poppy seeds can be purchased in an unwashed or unprocessed form, and these seeds can be contaminated with the opium alkaloids morphine, codeine, and thebaine on their surfaces. Poppy seeds that are commercially available, such as those used for baking and in other food products, are legal to purchase, as they do not contain the opium alkaloids on their seed coats. Purchase and possession of the unwashed or unprocessed seeds are not legal in the United States. These contaminated poppy seeds can then be put through a process in which they are washed, and the supernatant (tea) is collected and consumed to experience its intoxicating effect or for the treatment of pain or opioid withdrawal. CASE REPORT A 65-year-old man with a history of alcohol use disorder, cannabis use, and chronic pain began using this poppy seed tea for treatment of chronic pain after his provider had stopped prescribing opioid pain medications for him. He developed a dependence on the tea. He had reached out for assistance as it was his desire to stop using the poppy seed tea. The diagnosis of an opioid use disorder was made using the DSM-V criteria. He was successfully induced and maintained on a buprenorphine/naloxone product. CONCLUSIONS Poppy seeds in their unwashed and unprocessed form can be misused and could lead to an opioid use disorder. This disorder can be treated with buprenorphine/naloxone products.

To investigate the effects of oral administration of magnesium-L-threonate, a novel magnesium compound, on the analgesic effect of opioids in patients with advanced cancer.