Frequency of cannabis and illicit opioid use among people who use drugs and report chronic pain: A longitudinal analysis.

BACKGROUND:Ecological research suggests that increased access to cannabis may facilitate reductions in opioid use and harms, and medical cannabis patients describe the substitution of opioids with cannabis for pain management. However, there is a lack of research using individual-level data to explore this question. We aimed to investigate the longitudinal association between frequency of cannabis use and illicit opioid use among people who use drugs (PWUD) experiencing chronic pain. METHODS AND FINDINGS:This study included data from people in 2 prospective cohorts of PWUD in Vancouver, Canada, who reported major or persistent pain from June 1, 2014, to December 1, 2017 (n = 1,152). We used descriptive statistics to examine reasons for cannabis use and a multivariable generalized linear mixed-effects model to estimate the relationship between daily (once or more per day) cannabis use and daily illicit opioid use. There were 424 (36.8%) women in the study, and the median age at baseline was 49.3 years (IQR 42.3-54.9). In total, 455 (40%) reported daily illicit opioid use, and 410 (36%) reported daily cannabis use during at least one 6-month follow-up period. The most commonly reported therapeutic reasons for cannabis use were pain (36%), sleep (35%), stress (31%), and nausea (30%). After adjusting for demographic characteristics, substance use, and health-related factors, daily cannabis use was associated with significantly lower odds of daily illicit opioid use (adjusted odds ratio 0.50, 95% CI 0.34-0.74, p < 0.001). Limitations of the study included self-reported measures of substance use and chronic pain, and a lack of data for cannabis preparations, dosages, and modes of administration. CONCLUSIONS:We observed an independent negative association between frequent cannabis use and frequent illicit opioid use among PWUD with chronic pain. These findings provide longitudinal observational evidence that cannabis may serve as an adjunct to or substitute for illicit opioid use among PWUD with chronic pain

An audit of the quality of inpatient care for adults with learning disability in the UK

OBJECTIVES: To audit patient hospital records to evaluate the performance of acute general and mental health services in delivering inpatient care to people with learning disability and explore the influence of organisational factors on the quality of care they deliver. SETTING: Nine acute general hospital Trusts and six mental health services. PARTICIPANTS: Adults with learning disability who received inpatient hospital care between May 2013 and April 2014. PRIMARY AND SECONDARY OUTCOME MEASURES: Data on seven key indicators of high-quality care were collected from 176 patients. These covered physical health/monitoring, communication and meeting needs, capacity and decision-making, discharge planning and carer involvement. The impact of services having an electronic system for flagging patients with learning disability and employing a learning disability liaison nurse was assessed. RESULTS: Indicators of physical healthcare (body mass index, swallowing assessment, epilepsy risk assessment) were poorly recorded in acute general and mental health inpatient settings. Overall, only 34 (19.3%) patients received any assessment of swallowing and 12 of the 57 with epilepsy (21.1%) had an epilepsy risk assessment. For most quality indicators, there was a non-statistically significant trend for improved performance in services with a learning disability liaison nurse. The presence of an electronic flagging system showed less evidence of benefit. CONCLUSIONS: Inpatient care for people with learning disability needs to be improved. The work gives tentative support to the role of a learning disability liaison nurse in acute general and mental health services, but further work is needed to confirm these benefits and to trial other interventions that might improve the quality and safety of care for this high-need group

The geochemistry and petrogenesis of the Paleoproterozoic du Chef dyke swarm, Québec, Canada

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.The du Chef dyke swarm in southern Québec, Canada is composed of numerous northeast trending, greenschist-amphibolite facies, gabbronoritic dykes that crop out either side of the Grenville Front. The age of the du Chef swarm (2408 ± 3 Ga) has led previous authors to suggest a genetic link between the du Chef dykes and coeval swarms (including the Ringvassøy, Scourie, Widgemooltha and Sebanga) preserved on other Archean cratons. These now disparate dyke swarms are proposed to have formed in response to mantle plume-induced continental breakup during the early Proterozoic. This work represents the first geochemical study of the du Chef dykes and shows that the swarm evolved through fractional crystallisation of a tholeiitic parent magma that remained largely uncontaminated during its residence in, and ascent through, the crust. We also show that the primary magma for the du Chef swarm was derived through partial melting of an enriched region of the mantle, with a similar trace element composition to the modern-day HIMU reservoir and that the magma produced was significantly hotter than the ambient mantle at the time. We contend that the du Chef dykes are the product of early Proterozoic mantle plume magmatism and may help pinpoint an ancient hotspot centre that initiated continental break up along the margin of the Superior Craton at ∼2.4 Ga. Other dyke swarms proposed to be genetically linked with the du Chef dykes record a distinctly different petrogenetic history to that of the du Chef dykes, as evidenced by their more volcanic arc-like geochemical signature. These contrasting geochemical signatures in supposedly cogenetic continental tholeiitic rocks may be evidence of early Proterozoic mantle heterogeneity sampled by the rising du Chef mantle plume.This study forms part of a Ph.D. dissertation undertaken by T.J.R.C. at the University of Cardiff, United Kingdom. A. Okrugin's assistance in the field is acknowledged. J. Strongman, J. Fletcher and J. Pett are thanked for their permission of use of the petrographic equipment at Petrolab Ltd. L. Badham, A. Oldroyd, L. Woolley and P. Fisher are thanked for their help in preparation and analysis of samples. This is publication number 38 of the Large Igneous Provinces, Supercontinent Reconstruction, Resource Exploration Project (www.supercontinent.org)

Rofecoxib and cardiovascular adverse events in adjuvant treatment of colorectal cancer

Background Selective cyclooxygenase inhibitors may retard the progression of cancer, but they have enhanced thrombotic potential. We report on cardiovascular adverse events in patients receiving rofecoxib to reduce rates of recurrence of colorectal cancer. Methods All serious adverse events that were cardiovascular thrombotic events were reviewed in 2434 patients with stage II or III colorectal cancer participating in a randomized, placebo-controlled trial of rofecoxib, 25 mg daily, started after potentially curative tumor resection and chemotherapy or radiotherapy as indicated. The trial was terminated prematurely owing to worldwide withdrawal of rofecoxib. To examine possible persistent risks, we examined cardiovascular thrombotic events reported up to 24 months after the trial was closed. Results The median duration of active treatment was 7.4 months. The 1167 patients receiving rofecoxib and the 1160 patients receiving placebo were well matched, with a median follow-up period of 33.0 months (interquartile range, 27.6 to 40.1) and 33.4 months (27.7 to 40.4), respectively. Of the 23 confirmed cardiovascular thrombotic events, 16 occurred in the rofecoxib group during or within 14 days after the treatment period, with an estimated relative risk of 2.66 (from the Cox proportional-hazards model; 95% confidence interval [CI], 1.03 to 6.86; P = 0.04). Analysis of the Antiplatelet Trialists’ Collaboration end point (the combined incidence of death from cardiovascular, hemorrhagic, and unknown causes; of nonfatal myocardial infarction; and of nonfatal ischemic and hemorrhagic stroke) gave an unadjusted relative risk of 1.60 (95% CI, 0.57 to 4.51; P = 0.37). Fourteen more cardiovascular thrombotic events, six in the rofecoxib group, were reported within the 2 years after trial closure, with an overall unadjusted relative risk of 1.50 (95% CI, 0.76 to 2.94; P = 0.24). Four patients in the rofecoxib group and two in the placebo group died from thrombotic causes during or within 14 days after the treatment period, and during the follow-up period, one patient in the rofecoxib group and five patients in the placebo group died from cardiovascular causes. Conclusions Rofecoxib therapy was associated with an increased frequency of adverse cardiovascular events among patients with a median study treatment of 7.4 months’ duration. (Current Controlled Trials number, ISRCTN98278138.

Visfatin reduces gap junction mediated cell-to-cell communication in proximal tubule-derived epithelial cells

Aim: Associated with obesity, visfatin may have a role in the pathogenesis of diabetic nephropathy in type II diabetes. This study identifies a link between the visfatin, TGF-β1 and reduced cell-to-cell coupling in proximal tubule derived epithelial cells. Methods: Western blot analysis confirmed changes in expression of connexins Cx26, Cx40 and Cx43 in HK2-cells +/- visfatin &/or TGF-β1. Visfatin evoked increases in TGF-β1 secretion were determined by ELISA, and functional intercellular communication assessed via Lucifer yellow dye transfer and paired-whole cell patch clamp electrophysiology. Results: Visfatin (10, 100 and 200ng/mL) decreased expression of Cx26 to 58±11%, 40± 3% and 21±2% and Cx43 to 73±5%, 44± 4% and 29±6% as compared to control at 48hrs (n=3; P<0.01). The effects were not dependent on changes in membrane integrity, cytotoxicity or cell viability as assessed by MTT, crystal-violet and lactate-dehydrogenase assays. Expression of Cx40 was unaffected by the adipocytokine. Visfatin (200ng/ml) increased TGF-β1 secretion by 154% of control (n=3; p<0.01). Visfatin-evoked changes in Cx26 and Cx43 expression were mimicked by exogenous application of TGF-β1 (2-10ng/ml, p<0.001 n=3). Visfatin reduced dye transfer between coupled-cells and decreased functional conductance by 63% as compared to control (n=6; p<0.01). Conclusions: Visfatin reduced connexin expression in HK2-cells, an effect mirrored by a loss in functional conductance between coupled cells. Visfatin increased TGF-β secretion and the pattern of change for connexin expression was mimicked by exogenous application of the pro-fibrotic cytokine. These data suggest that visfatin reduces connexin-mediated intercellular communication in proximal tubule-derived epithelial cells via a TGF-β dependent pathway. This work is supported by a grant from Diabetes UK (BDA: 11/0004215)

Nucleosomes in pancreatic cancer patients during radiochemotherapy

Nucleosomes appear spontaneously in elevated concentrations in the serum of patients with malignant diseases as well as during chemo- and radiotherapy. We analyzed whether their kinetics show typical characteristics during radiochemotherapy and enable an early estimation of therapy efficacy. We used the Cell Death Detection Elisaplus ( Roche Diagnostics) and investigated the course of nucleosomes in the serum of 32 patients with a local stage of pancreatic cancer who were treated with radiochemotherapy for several weeks. Ten of them received postsurgical therapy, 21 received primary therapy and 1 received therapy for local relapse. Blood was taken before the beginning of therapy, daily during the first week, once weekly during the following weeks and at the end of radiochemotherapy. The response to therapy was defined according to the kinetics of CA 19-9: a decrease of CA 19-9 650% after radiochemotherapy was considered as `remission'; an increase of >= 100% ( which was confirmed by two following values) was defined as `progression'. Patients with `stable disease' ranged intermediately. Most of the examined patients showed a decrease of the concentration of nucleosomes within 6 h after the first dose of radiation. Afterwards, nucleosome levels increased rapidly, reaching their maximum during the following days. Patients receiving postsurgery, primary or relapse therapies did not show significant differences in nucleosome values during the time of treatment. Single nucleosome values, measured at 6, 24 and 48 h after the application of therapy, could not discriminate significantly between patients with no progression and those with progression of disease. However, the area under the curve of the first 3 days, which integrated all variables of the initial therapeutic phase, showed a significant correlation with the progression-free interval ( p = 0.008). Our results indicate that the area under the curve of nucleosomes during the initial phase of radiochemotherapy could be valuable for the early prediction of the progression-free interval. Copyright (C) 2005 S. Karger AG, Basel

An audit of the quality of inpatient care for adults with learning disability in the UK

OBJECTIVES: To audit patient hospital records to evaluate the performance of acute general and mental health services in delivering inpatient care to people with learning disability and explore the influence of organisational factors on the quality of care they deliver. SETTING: Nine acute general hospital Trusts and six mental health services. PARTICIPANTS: Adults with learning disability who received inpatient hospital care between May 2013 and April 2014. PRIMARY AND SECONDARY OUTCOME MEASURES: Data on seven key indicators of high-quality care were collected from 176 patients. These covered physical health/monitoring, communication and meeting needs, capacity and decision-making, discharge planning and carer involvement. The impact of services having an electronic system for flagging patients with learning disability and employing a learning disability liaison nurse was assessed. RESULTS: Indicators of physical healthcare (body mass index, swallowing assessment, epilepsy risk assessment) were poorly recorded in acute general and mental health inpatient settings. Overall, only 34 (19.3%) patients received any assessment of swallowing and 12 of the 57 with epilepsy (21.1%) had an epilepsy risk assessment. For most quality indicators, there was a non-statistically significant trend for improved performance in services with a learning disability liaison nurse. The presence of an electronic flagging system showed less evidence of benefit. CONCLUSIONS: Inpatient care for people with learning disability needs to be improved. The work gives tentative support to the role of a learning disability liaison nurse in acute general and mental health services, but further work is needed to confirm these benefits and to trial other interventions that might improve the quality and safety of care for this high-need group

Increasing the frequency of hand washing by healthcare workers does not lead to commensurate reductions in staphylococcal infection in a hospital ward

Hand hygiene is generally considered to be the most important measure that can be applied to prevent the spread of healthcare-associated infection (HAI). Continuous emphasis on this intervention has lead to the widespread opinion that HAI rates can be greatly reduced by increased hand hygiene compliance alone. However, this assumes that the effectiveness of hand hygiene is not constrained by other factors and that improved compliance in excess of a given level, in itself, will result in a commensurate reduction in the incidence of HAI. However, several researchers have found the law of diminishing returns to apply to hand hygiene, with the greatest benefits occurring in the first 20% or so of compliance, and others have demonstrated that poor cohorting of nursing staff profoundly influences the effectiveness of hand hygiene measures. Collectively, these findings raise intriguing questions about the extent to which increasing compliance alone can further reduce rates of HAI. In order to investigate these issues further, we constructed a deterministic Ross-Macdonald model and applied it to a hypothetical general medical ward. In this model the transmission of staphylococcal infection was assumed to occur after contact with the transiently colonized hands of HCWs, who, in turn, acquire contamination only by touching colonized patients. The aim of the study was to evaluate the impact of imperfect hand cleansing on the transmission of staphylococcal infection and to identify, whether there is a limit, above which further hand hygiene compliance is unlikely to be of benefit. The model demonstrated that if transmission is solely via the hands of HCWs, it should, under most circumstances, be possible to prevent outbreaks of staphylococcal infection from occurring at a hand cleansing frequencies <50%, even with imperfect hand hygiene. The analysis also indicated that the relationship between hand cleansing efficacy and frequency is not linear - as efficacy decreases, so the hand cleansing frequency required to ensure R0<1 increases disproportionately. Although our study confirmed hand hygiene to be an effective control measure, it demonstrated that the law of diminishing returns applies, with the greatest benefit derived from the first 20% or so of compliance. Indeed, our analysis suggests that there is little benefit to be accrued from very high levels of hand cleansing and that in most situations compliance >40% should be enough to prevent outbreaks of staphylococcal infection occurring, if transmission is solely via the hands of HCWs. Furthermore we identified a non-linear relationship between hand cleansing efficacy and frequency, suggesting that it is important to maximise the efficacy of the hand cleansing process