Cannabidiol (CBD) for the treatment of subcutaneous treprostinil (Remodulin®) site pain: a case report

BackgroundPulmonary arterial hypertension occurs as a result of vascular remodeling and dysregulation of endothelial cells that narrows small pulmonary arteries and raises precapillary pressures. Pulmonary arterial hypertension is a rare and progressive disease characterized by dyspnea, chest pain, and syncope. Parenteral treprostinil is indicated for the treatment of pulmonary arterial hypertension to diminish symptoms associated with exercise. Up to 92% of patients treated with treprostinil via subcutaneous delivery experienced infusion site pain and approximately 23% discontinued treatment due to site pain. Cannabidiol salve may have analgesic and anti-inflammatory properties and could be an additional option for patients with infusion site pain.Case reportTwo patients with pulmonary arterial hypertension were treated with cannabidiol salve. Both patients reported a reduction in infusion site pain without the need for narcotics.ConclusionThese two cases suggest that cannabidiol salve may help to minimize redness and alleviate pain at the infusion site. Additional studies are required to test the effectiveness of cannabidiol in a larger group of patients with infusion site pain

Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma

Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight into the biological basis of MM.</p

Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma

Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight

Anti-hapten antibodies in response to skin sensitization.

Whereas T lymphocyte (T cell) activation is the key event in the acquisition of skin sensitization and subsequent elicitation of allergic contact dermatitis, the humoral component of immune responses to organic contact allergens has received little consideration. There is evidence that, in experimental animals, topical exposure to potent contact allergens is associated with B cell activation and proliferation, and hapten-specific antibody production. However, there is very limited evidence available for anti-hapten antibody responses being induced following topical exposure of humans to contact allergens. Nevertheless, it is important to appreciate that there are almost no negative studies in which evidence for antibody production as the result of skin sensitization has been sought and not found. That is, there is absence of evidence rather than evidence of absence. Furthermore, exposure to chemical respiratory allergens, in which the skin has been implicated as a potential route of sensitization, results in anti-hapten antibody responses. It is proposed that skin sensitization to contact allergens will normally be accompanied by antibody production. The phenomenon is worthy of investigation, as anti-hapten antibodies could potentially influence and/or regulate the induction of skin sensitization. Moreover, such antibodies may provide an informative correlate of the extent to which sensitization has been acquired

A community-based service enhancement model of training and employing Ear Health Facilitators to address the crisis in ear and hearing health of Aboriginal children in the Northern Territory, the Hearing for Learning Initiative (the HfLI): study protocol for a stepped-wedge cluster randomised trial

Abstract Background Almost all Aboriginal children in remote communities have persistent bilateral otitis media affecting hearing and learning throughout early childhood and school years, with consequences for social and educational outcomes, and later employment opportunities. Current primary health care and specialist services do not have the resources to meet the complex needs of these children. Method/design This stepped-wedge cluster randomised trial will allocate 18 communities to one of five 6-monthly intervention start dates. Stratification will be by region and population size. The intervention (Hearing for Learning Initiative, HfLI) consists of six 20-h weeks of training (delivered over 3 months) that includes Certificate II in Aboriginal Primary Health Care (3 modules) and competencies in ear and hearing data collection (otoscopy, tympanometry and hearScreen), plus 3 weeks of assisted integration into the health service, then part-time employment as Ear Health Facilitators to the end of the trial. Unblinding will occur 6 months prior to each allocated start date, to allow Community Reference Groups to be involved in co-design of the HfLI implementation in their community. Relevant health service data will be extracted 6-monthly from all 18 communities. The primary outcome is the difference in proportion of children (0 to 16 years of age) who have at least one ear assessment (diagnosis) documented in their medical record within each 6-month period, compared to control periods (no HfLI). Secondary outcomes include data on sustainability, adherence to evidence-based clinical guidelines for otitis media, including follow-up and specialist referrals, and school attendance. Structured interviews with staff working in health and education services, Ear Health Trainees, Ear Health Facilitators and families will assess process outcomes and the HfLI broader impact. Discussion The impact of training and employment of Ear Health Facilitators on service enhancement will inform the health, education and employment sectors about effectiveness of skills and job creation that empowers community members to contribute to addressing issues of local importance, in this instance ear and hearing health of children. Trial registration ClinicalTrials.gov NCT03916029 . Registered on 16 April 2019

Anti-hapten antibodies in response to skin sensitization.

Whereas T lymphocyte (T cell) activation is the key event in the acquisition of skin sensitization and subsequent elicitation of allergic contact dermatitis, the humoral component of immune responses to organic contact allergens has received little consideration. There is evidence that, in experimental animals, topical exposure to potent contact allergens is associated with B cell activation and proliferation, and hapten-specific antibody production. However, there is very limited evidence available for anti-hapten antibody responses being induced following topical exposure of humans to contact allergens. Nevertheless, it is important to appreciate that there are almost no negative studies in which evidence for antibody production as the result of skin sensitization has been sought and not found. That is, there is absence of evidence rather than evidence of absence. Furthermore, exposure to chemical respiratory allergens, in which the skin has been implicated as a potential route of sensitization, results in anti-hapten antibody responses. It is proposed that skin sensitization to contact allergens will normally be accompanied by antibody production. The phenomenon is worthy of investigation, as anti-hapten antibodies could potentially influence and/or regulate the induction of skin sensitization. Moreover, such antibodies may provide an informative correlate of the extent to which sensitization has been acquired

EFFECTS OF EXERCISE ON THE PLASMA LIPID PROFILE IN HISPANIOLAN AMAZON PARROTS (AMAZONA VENTRALIS) WITH NATURALLY OCCURRING HYPERCHOLESTEROLEMIA

Hypercholesterolemia is common in psittacines, and Amazon parrots ( Amazona spp.) are particularly susceptible. Associations have been demonstrated between naturally occurring and experimentally induced hypercholesterolemia and atherosclerosis in psittacines. Daily exercise improves lipid metabolism in humans and other mammals, as well as pigeons and chickens, under varying experimental conditions. Hispaniolan Amazon parrots ( Amazona ventralis ) with naturally occurring hypercholesterolemia (343-576 mg/dl) were divided into two groups. An exercised group (n = 8) was housed as a flock and exercised daily with 30 min of aviary flight and 30 min walking on a rotating perch. A sedentary control group (n = 4) was housed in individual cages with no exercise regime. A plasma lipid panel, including total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, and triglycerides, was validated for this species. Body weight, chest girth, and the lipid panel were measured at 0, 61, and 105 days. Hematology and plasma biochemistry were measured at 0 and 105 days. Weight and girth were significantly lower in exercised than sedentary parrots at 61 and 105 days. HDL-C concentrations were significantly higher in exercised parrots at 61 days but returned to near baseline by 105 days. There were no significant changes in hematology, biochemistry, or other lipid panel parameters. Results were similar to studies in humans and animal models, in which increased HDL-C was the most consistent effect of exercise on circulating lipid and lipoprotein parameters. The return toward baseline HDL-C may have resulted from decreased participation in aviary flight. Additional investigation will be required to determine the amount of exercise and change in circulating lipid-related parameters necessary to improve long-term wellness in psittacine species predisposed to hypercholesterolemia

Opioid substitution therapy as a strategy to reduce deaths in prison : retrospective cohort study

Objectives: To describe deaths in prison among opioid-dependent people, and examine associations between receipt of opioid substitution therapy (OST) and risk of death in prison. Design: Retrospective cohort study. Setting: Adult prisons in New South Wales (NSW), Australia. Participants: 16 715 opioid-dependent people who were received to prison between 2000 and 2012. Interventions: Opioid substitution therapy. Primary outcome measures: Natural and unnatural (suicide, drug-induced, violent and other injury) deaths in prison. Results: Cohort members were in prison for 30 998 person-years (PY), during which time there were 51 deaths. The all-cause crude mortality rate (CMR) in prison was 1.6/1000 PY (95% CI 1.2 to 2.2/1000 PY), and the unnatural death CMR was 1.1/1000 PY (95% CI 0.8 to 1.6/1000 PY). Compared to time out of OST, the hazard of all-cause death was 74% lower while in OST (adjusted HR (AHR): 0.26; 95% CI 0.13 to 0.50), and the hazard of unnatural death was 87% lower while in OST (AHR: 0.13; 95% CI 0.05 to 0.35). The all-cause and unnatural death CMRs during the first 4 weeks of incarceration were 6.6/1000 PY (95% CI 3.8 to 10.6/1000 PY) and 5.5/1000 PY (95% CI 2.9 to 9.4/1000 PY), respectively. Compared to periods not in OST, the hazard of all-cause death during the first 4 weeks of incarceration was 94% lower while in OST (AHR: 0.06; 95% CI 0.01 to 0.48), and the hazard of unnatural death was 93% lower while in OST (AHR: 0.07; 95% CI 0.01 to 0.53). Conclusions: Mortality of opioid-dependent prisoners was significantly lower while in receipt of OST

T lymphocyte phenotype of contact-allergic patients: experience with nickel and p-phenylenediamine

Background: There is considerable interest in understanding the immunological variables that have the greatest influence on the effectiveness of sensitization by contact allergens, particularly in the context of developing new paradigms for risk assessment of novel compounds. Objectives: To examine the relationship between patch test score for three different contact allergens and the characteristics of T cell responses. Methods: A total of 192 patients with confirmed nickel, p‐phenylenediamine (PPD) or methylisothiazolinone (MI) allergy were recruited from the Contact Dermatitis Investigation Unit at Salford Royal Hospital. Severity of allergy was scored by the use of patch testing, peripheral blood lymphocytes were characterized for T cell phenotype by flow cytometry, and proliferative activity was characterized by radiolabelled thymidine incorporation. Comparisons were drawn with buffy coat samples from healthy volunteers. Results: Patch test positivity for nickel, PPD and MI was associated with changes in the phenotype of peripheral blood T cells: increases in naïve cells, decreases in regulatory T cell frequency and the CD4+/CD8hi ratio, and increased expression of the skin‐homing marker cutaneous lymphocyte antigen (CLA), particularly for those patients with a +++ patch test score. Conclusions: This increased understanding of the characteristics of the T cell responses to contact allergens may provide parameters with which to better measure health risks associated with skin sensitization

Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma

Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight into the biological basis of MM