Though chronic pain is widespread, affecting about one-fifth of the world's population, its impacts are disproportionately felt across the population according to socioeconomic determinants such as ...education and income. These factors also influence patients' access to treatment, including pharmacological pain management.
A scoping review was undertaken to better understand the association of socioeconomic factors with physicians' pain management prescribing patterns for adults living with chronic pain.
An electronic literature search was conducted using the EMBASE, CINAHL, SCOPUS, and Ovid MEDLINE databases and 31 retrieved articles deemed relevant for analyses were critically appraised.
The available evidence indicates that patients' lower socioeconomic status is associated with a greater likelihood of being prescribed opioids to manage their chronic pain and a decreased likelihood of receiving prescription medications to manage migraines, rheumatoid arthritis, and osteoarthritis.
These results suggest that individuals with lower socioeconomic status do not receive equal prescription medicine opportunities to manage their chronic pain conditions. This is influenced by a variety of intersecting variables, including access to care, the potential unaffordability of certain therapies, patients' health literacy, and prescribing biases. Future research is needed to identify interventions to improve equity of access to therapies for patients with chronic pain living in lower socioeconomic situations as well as to explain the mechanism through which socioeconomic status affects chronic pain treatment choices by health care providers.
SES: socioeconomic status; RA: rheumatoid arthritis; IV: intravenous; SC: subcutaneous; bDMARDs: biological disease-modifying antirheumatic drugs; DMARDS; disease-modifying antirheumatic drugs; TNFi: tumour necrosis factor inhibitors; NSAIDs: non-steroidal anti-inflammatory drugs
In consensually non-monogamous relationships there is an open agreement that one, both, or all individuals involved in a romantic relationship may also have other sexual and/or romantic partners. ...Research concerning consensual non-monogamy has grown recently but has just begun to determine how relationships amongst partners in consensually non-monogamous arrangements may vary. The current research examines this issue within one type of consensual non-monogamy, specifically polyamory, using a convenience sample of 1,308 self-identified polyamorous individuals who provided responses to various indices of relationship evaluation (e.g. acceptance, secrecy, investment size, satisfaction level, commitment level, relationship communication, and sexual frequency). Measures were compared between perceptions of two concurrent partners within each polyamorous relationship (i.e., primary and secondary partners). Participants reported less stigma as well as more investment, satisfaction, commitment and greater communication about the relationship with primary compared to secondary relationships, but a greater proportion of time on sexual activity with secondary compared to primary relationships. We discuss how these results inform our understanding of the unique costs and rewards of primary-secondary relationships in polyamory and suggest future directions based on these findings.
There is an enormous and ever-growing body of environmental impact assessment (EIA) research, much of which is grounded in practice or seeks to advance it. In this paper we show how the impact of EIA ...research on policy and practice might be conceptualised and how to set about evidencing it. A framework is developed through literature review to account for impact in four areas pertaining to instrumental impact, conceptual impact, capacity building and knowledge brokerage and co-production. Methods for implementing the framework include citations within policy documents along with content analysis to determine influence and interviews or surveys with policy makers and practitioners; all subsequently presented as narratives. We provide examples and further discussion of each, drawn from recent analysis of the EIA research of one of the authors. Whilst proving impact of EIA research on policy and practice is challenging, we found the framework to be a useful way for structuring and guiding such an investigation. This approach to understanding the uptake and influence of EIA research on impact assessment practitioners and other stakeholders (i.e., government regulators/policy-makers, consultants, proponents or NGOs) could be applied by many professionals in the field to showcase positive impact on policy and practice locally, nationally and internationally. It may also usefully serve academic EIA researchers applying for new positions or for promotion within universities.
•The impact of EIA research on policy and practice is investigated.•Interviews and content analysis are important methods for determining impact.•Citations of research in policy show direct impact.•Direct impact also arises from policy development, capacity building and co-produced research.•Indirect influence arises from conceptual impact and knowledge brokerage activities.
Tonometry has been identified as a common method for measuring the intraocular pressure in patients. The direct contact between the tonometer and the eye may contribute to the risk of cross ...infection, especially of viral particles, from one patient to another. A systematic review was undertaken to address the likelihood of human immunodeficiency virus (HIV), hepatitis B virus, hepatitis C virus, and prion diseases transmission through the use of tonometers. Additionally, a comparison of the current tonometer disinfection methods is provided to assist with identifying which technique effectively reduces the risk of disease transmission. An electronic literature search was conducted using the following databases: Web of Science, EMBASE, CINAHL, SCOPUS, Biosis Previews, Cochrane Library, PubMed, and Google Scholar. Dissertation indexes were also searched, and these included: Dissertations and Abstracts, and Dissertations and Abstracts - UK/Ireland. Additionally, the Clinicaltrials.gov trial registry was searched to identify any other relevant literature. Two independent reviewers critically appraised the articles retrieved through the literature search. In total, 11 unique studies were deemed relevant for this systematic review. The available evidence demonstrated that the use of tonometers contributes to the transmission of these infectious diseases
. The results also demonstrated variability in determining the most effective tonometer sterilization technique against these infectious diseases
. There was limited evidence available regarding the transmission of HIV, hepatitis B, hepatitis C, and prion diseases through the use of tonometers. Additionally, due to the variability regarding the most effective sterilization techniques, it is difficult to identify which sterilization technique is most effective or adequately effective against these infectious diseases. Future research studies regarding infectious disease transmission through tonometry and sterilization techniques should be completed to more adequately inform infectious disease control guidelines.
Traumatic brain injury (TBI) initiates a deleterious inflammatory response that exacerbates pathology and worsens outcome. This inflammatory response is partially mediated by a reduction in cAMP and ...a concomitant upregulation of cAMP-hydrolyzing phosphodiesterases (PDEs) acutely after TBI. The PDE4B subfamily, specifically PDE4B2, has been found to regulate cAMP in inflammatory cells, such as neutrophils, macrophages and microglia. To determine if PDE4B regulates inflammation and subsequent pathology after TBI, adult male Sprague Dawley rats received sham surgery or moderate parasagittal fluid-percussion brain injury (2 ± 0.2 atm) and were then treated with a PDE4B - selective inhibitor, A33, or vehicle for up to 3 days post-surgery. Treatment with A33 reduced markers of microglial activation and neutrophil infiltration at 3 and 24 hrs after TBI, respectively. A33 treatment also reduced cortical contusion volume at 3 days post-injury. To determine whether this treatment paradigm attenuated TBI-induced behavioral deficits, animals were evaluated over a period of 6 weeks after surgery for forelimb placement asymmetry, contextual fear conditioning, water maze performance and spatial working memory. A33 treatment significantly improved contextual fear conditioning and water maze retention at 24 hrs post-training. However, this treatment did not rescue sensorimotor or working memory deficits. At 2 months after surgery, atrophy and neuronal loss were measured. A33 treatment significantly reduced neuronal loss in the pericontusional cortex and hippocampal CA3 region. This treatment paradigm also reduced cortical, but not hippocampal, atrophy. Overall, these results suggest that acute PDE4B inhibition may be a viable treatment to reduce inflammation, pathology and memory deficits after TBI.
Learning and memory impairments are common in traumatic brain injury (TBI) survivors. However, there are no effective treatments to improve TBI-induced learning and memory impairments. TBI results in ...decreased cAMP signaling and reduced cAMP-response-element binding protein (CREB) activation, a critical pathway involved in learning and memory. TBI also acutely upregulates phosphodiesterase 4B2 (PDE4B2), which terminates cAMP signaling by hydrolyzing cAMP. We hypothesized that a subtype-selective PDE4B inhibitor could reverse the learning deficits induced by TBI. To test this hypothesis, adult male Sprague-Dawley rats received sham surgery or moderate parasagittal fluid-percussion brain injury. At 3 months postsurgery, animals were administered a selective PDE4B inhibitor or vehicle before cue and contextual fear conditioning, water maze training and a spatial working memory task. Treatment with the PDE4B inhibitor significantly reversed the TBI-induced deficits in cue and contextual fear conditioning and water maze retention. To further understand the underlying mechanisms of these memory impairments, we examined hippocampal long-term potentiation (LTP). TBI resulted in a significant reduction in basal synaptic transmission and impaired expression of LTP. Treatment with the PDE4B inhibitor significantly reduced the deficits in basal synaptic transmission and rescued LTP expression. The PDE4B inhibitor reduced tumor necrosis factor-α levels and increased phosphorylated CREB levels after TBI, suggesting that this drug inhibited molecular pathways in the brain known to be regulated by PDE4B. These results suggest that a subtype-selective PDE4B inhibitor is a potential therapeutic to reverse chronic learning and memory dysfunction and deficits in hippocampal synaptic plasticity following TBI.
Currently, there are an estimated 3.2-5.3 million individuals living with disabilities from traumatic brain injury (TBI) in the United States, and 8 of 10 of these individuals report cognitive disabilities (Thurman et al., 1999; Lew et al., 2006; Zaloshnja et al., 2008). One of the molecular mechanisms associated with chronic cognitive disabilities is impaired cAMP signaling in the hippocampus. In this study, we report that a selective phosphodiesterase 4B (PDE4B) inhibitor reduces chronic cognitive deficits after TBI and rescues deficits in hippocampal long-term potentiation. These results suggest that PDE4B inhibition has the potential to improve learning and memory ability and overall functioning for people living with TBI.
Abstract
Background
ONC201 is a small molecule that can cause nonapoptotic cell death through loss of mitochondrial function. Results from the phase I/II trials of ONC201 in patients with refractory ...solid tumors demonstrated tumor responses and prolonged stable disease in some patients.
Methods
This single-arm, open-label, phase II clinical trial evaluated the efficacy of ONC201 at the recommended phase II dose (RP2D) in patients with recurrent or refractory metastatic breast or endometrial cancer. Fresh tissue biopsies and blood were collected at baseline and at cycle 2 day 2 for correlative studies.
Results
Twenty-two patients were enrolled; 10 patients with endometrial cancer, 7 patients with hormone receptor–positive breast cancer, and 5 patients with triple-negative breast cancer. The overall response rate was 0%, and the clinical benefit rate, defined by complete response (CR) + partial response (PR) + stable disease (SD), was 27% (n = 3/11). All patients experienced an adverse event (AE), which was primarily low grade. Grade 3 AEs occurred in 4 patients; no grade 4 AEs occurred. Tumor biopsies did not show that ONC201 consistently induced mitochondrial damage or alterations in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or the TRAIL death receptors. ONC201 treatment caused alterations in peripheral immune cell subsets.
Conclusion
ONC201 monotherapy did not induce objective responses in recurrent or refractory metastatic breast or endometrial cancer at the RP2D dose of 625 mg weekly but had an acceptable safety profile (ClinicalTrials.gov Identifier: NCT03394027).
This phase II clinical trial evaluated ONC201 monotherapy, using the previously established recommended phase II dose, in patients with recurrent or refractory metastatic breast or endometrial cancer.
Developing therapeutics for traumatic brain injury remains a challenge for all stages of recovery. The pathological features of traumatic brain injury are diverse, and it remains an obstacle to be ...able to target the wide range of pathologies that vary between traumatic brain injured patients and that evolve during recovery. One promising therapeutic avenue is to target the second messengers cAMP and cGMP with phosphodiesterase inhibitors due to their broad effects within the nervous system. Phosphodiesterase inhibitors have the capability to target different injury mechanisms throughout the time course of recovery after brain injury. Inflammation and neuronal death are early targets of phosphodiesterase inhibitors, and synaptic dysfunction and circuitry remodeling are late potential targets of phosphodiesterase inhibitors. This review will discuss how signaling through cyclic nucleotides contributes to the pathology of traumatic brain injury in the acute and chronic stages of recovery. We will review our current knowledge of the successes and challenges of using phosphodiesterase inhibitors for the treatment of traumatic brain injury and conclude with important considerations in developing phosphodiesterase inhibitors as therapeutics for brain trauma.
The neurocognitive impairments associated with mild traumatic brain injury (TBI) often resolve within 1-2 weeks; however, a subset of people exhibit persistent cognitive dysfunction for weeks to ...months after injury. The factors that contribute to these persistent deficits are unknown. One potential risk factor for worsened outcome after TBI is a history of stress experienced by a person early in life. Early life stress (ELS) includes maltreatment such as neglect, and interferes with the normal construction of cortical and hippocampal circuits. We hypothesized that a history of ELS contributes to persistent learning and memory dysfunction following a TBI. To explore this interaction, we modeled ELS by separating Sprague Dawley pups from their nursing mothers from post-natal days 2-14 for 3 h daily. At 2 months of age, male rats received sham surgery or mild to moderate parasagittal fluid-percussion brain injury. We found that the combination of ELS with TBI in adulthood impaired hippocampal-dependent learning, as assessed with contextual fear conditioning, the water maze task, and spatial working memory. Cortical atrophy was significantly exacerbated in TBI animals exposed to ELS compared with normal-reared TBI animals. Changes in corticosterone in response to restraint stress were prolonged in TBI animals that received ELS compared with TBI animals that were normally reared or sham animals that received ELS. Our findings indicate that ELS is a risk factor for worsened outcome after TBI, and results in persistent learning and memory deficits, worsened cortical pathology, and an exacerbation of the hormonal stress response.
Objective: Web-based brief alcohol interventions have the potential to reach a large number of individuals at low cost; however, few controlled evaluations have been conducted to date. The present ...study was designed to evaluate the efficacy of gender-specific versus gender-nonspecific personalized normative feedback (PNF) with single versus biannual administration in a 2-year randomized controlled trial targeting a large sample of heavy-drinking college students. Method: Participants included 818 freshmen (57.6% women; 42% non-Caucasian) who reported 1 or more heavy-drinking episodes in the previous month at baseline. Participants were randomly assigned in a 2 (gender-specific vs. gender-nonspecific PNF) × 2 (single vs. biannual administration of PNF) + 1 (attention control) design. Assessments occurred every 6 months for a 2-year period. Results: Results from hierarchical generalized linear models provided modest effects on weekly drinking and alcohol-related problems but not on heavy episodic drinking. Relative to control, gender-specific biannual PNF was associated with reductions over time in weekly drinking (d = −0.16, 95% CI −0.02, −0.31), and this effect was partially mediated by changes in perceived norms. For women, but not men, gender-specific biannual PNF was associated with reductions over time in alcohol-related problems relative to control (d = −0.29, 95% CI −0.15, −0.58). Few other effects were evident. Conclusions: The present research provides modest support for the use of biannually administered web-based gender-specific PNF as an alternative to more costly indicated prevention strategies.
PDF
