Screening and Audit as Service-Level Strategies to Support Implementation of Australian Guidelines for Cancer Pain Management in Adults: A Feasibility Study

© 2019 Background: Pain in people with cancer is common but often under-recognized and under-treated. Guidelines can improve the quality of pain care, but need targeted strategies to support implementation. Aim: To test the feasibility of two service-level strategies for supporting guideline implementation: a screening system and medical record audit. Design: Multimethods. Setting: One oncology outpatient service, and one palliative care outpatient and inpatient service. Participants: Patients with advanced cancer. Methods: Patients were screened in the waiting room with a modified version of the Edmonton Symptom Assessment System-revised either electronically or in paper-based format. Feasibility indicated the percentage of patients successfully screened from the total number attending the services. An audit assessed adherence to key indicators of pain assessment and management. Feasibility thresholds were set at 75% incidence for screening and a median of 30 minutes per patient for audit. Results: Of 452 patient visits, 95% (n = 429)were successfully screened, 34% (n = 155)electronically and 61% (n = 274)paper-based. Electronic pain screening was technically challenging and time-intensive for nurses. Thirty-one patients consented to have their records audited. The median audit time was 37.5 minutes (range 10-120 minutes). Variability arose from the number and type of record (outpatient or inpatient). Adherence to indicators varied from 63% (pain assessment at first presentation)to 94% (regular pain assessment and medication prescribed at regular intervals). Conclusions: This study confirmed the need to implement evidence-based guidelines for cancer pain and generated useful insights into the feasibility of pain screening and audit

Australian survey of current practice and guideline use in adult cancer pain assessment and management: Perspectives of oncologists

Aims: Cancer pain continues to be undertreated in up to half of cases, despite the availability of evidence-based guidelines. This study aimed to: (i) identify barriers and facilitators to adult cancer pain assessment and management, as perceived by Australian health professionals; (ii) establish the perceived need for new Australian guidelines and implementation strategy; (iii) identify which guidelines are used; (iv) identify barriers and facilitators to guideline use. This article focuses on the perceptions of responding oncologists. Methods: A cross-sectional survey was administered online. Invitations were circulated via peak bodies and clinical leaders. Comments were coded independently by two researchers. Results: In all 76 oncologists self-reported high concordance with evidence-based recommendations, except validated pain scales. Perceived barriers to pain management included insufficient non-pharmacological interventions, access to /coordination between services, and time. Only 22 percent of respondents reported using pain guidelines. Perceived barriers to guideline use included lack of access, awareness and any single standard. Respondents were generally supportive of new Australian guidelines and especially an implementation strategy. Conclusion: Barriers to evidence-based practice and guideline use identified by our survey might be addressed via a clinical pathway that gives step-by-step guidance on evidence-based practice along with a framework for evaluation. Particular attention should be paid to promoting use of validated scales, patient education and non-pharmacological interventions, training of an appropriately skilled workforce and improving care coordination. Challenges are discussed. © 2012 Wiley Publishing Asia Pty Ltd

Permeabilised skeletal muscle reveals mitochondrial deficiency in malignant hyperthermia-susceptible individuals

Background: Individuals genetically susceptible to malignant hyperthermia (MH) exhibit hypermetabolic reactions when exposed to volatile anaesthetics. Mitochondrial dysfunction has previously been associated with the MH-susceptible (MHS) phenotype in animal models, but evidence of this in human MH is limited. Methods: We used high resolution respirometry to compare oxygen consumption rates (oxygen flux) between permeabilised human MHS and MH-negative (MHN) skeletal muscle fibres with or without prior exposure to halothane. A substrate-uncoupler-inhibitor titration protocol was used to measure the following components of the electron transport chain under conditions of oxidative phosphorylation (OXPHOS) or after uncoupling the electron transport system (ETS): complex I (CI), complex II (CII), CI+CII and, as a measure of mitochondrial mass, complex IV (CIV). Results: Baseline comparisons without halothane exposure showed significantly increased mitochondrial mass (CIV, P=0.021) but lower flux control ratios in CI+CII(OXPHOS) and CII(ETS) of MHS mitochondria compared with MHN (P=0.033 and 0.005, respectively) showing that human MHS mitochondria have a functional deficiency. Exposure to halothane triggered a hypermetabolic response in MHS mitochondria, significantly increasing mass-specific oxygen flux in CI(OXPHOS), CI+CII(OXPHOS), CI+CII(ETS), and CII(ETS) (P=0.001–0.012), while the rates in MHN samples were unaltered by halothane exposure. Conclusions: We present evidence of mitochondrial dysfunction in human MHS skeletal muscle both at baseline and after halothane exposure

Novel role of extracellular matrix protein 1 (ECM1) in cardiac aging and myocardial infarction

© 2019 Hardy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Introduction The prevalence of heart failure increases in the aging population and following myocardial infarction (MI), yet the extracellular matrix (ECM) remodeling underpinning the development of aging- and MI-associated cardiac fibrosis remains poorly understood. A link between inflammation and fibrosis in the heart has long been appreciated, but has mechanistically remained undefined. We investigated the expression of a novel protein, extracellular matrix protein 1 (ECM1) in the aging and infarcted heart. Methods Young adult (3-month old) and aging (18-month old) C57BL/6 mice were assessed. Young mice were subjected to left anterior descending artery-ligation to induce MI, or transverse aortic constriction (TAC) surgery to induce pressure-overload cardiomyopathy. Left ventricle (LV) tissue was collected early and late post-MI/TAC. Bone marrow cells (BMCs) were isolated from young healthy mice, and subject to flow cytometry. Human cardiac fibroblast (CFb), myocyte, and coronary artery endothelial & smooth muscle cell lines were cultured; human CFbs were treated with recombinant ECM1. Primary mouse CFbs were cultured and treated with recombinant angiotensin-II or TGF-β1. Immunoblotting, qPCR and mRNA fluorescent in-situ hybridization (mRNA-FISH) were conducted on LV tissue and cells. Results ECM1 expression was upregulated in the aging LV, and in the infarct zone of the LV early post-MI. No significant differences in ECM1 expression were found late post-MI or at any time-point post-TAC. ECM1 was not expressed in any resident cardiac cells, but ECM1 was highly expressed in BMCs, with high ECM1 expression in granulocytes. Flow cytometry of bone marrow revealed ECM1 expression in large granular leucocytes. mRNA-FISH revealed that ECM1 was indeed expressed by inflammatory cells in the infarct zone at day-3 post-MI. ECM1 stimulation of CFbs induced ERK1/2 and AKT activation and collagen-I expression, suggesting a pro-fibrotic role. Conclusions ECM1 expression is increased in ageing and infarcted hearts but is not expressed by resident cardiac cells. Instead it is expressed by bone marrow-derived granulocytes. ECM1 is sufficient to induce cardiac fibroblast stimulation in vitro. Our findings suggest ECM1 is released from infiltrating inflammatory cells, which leads to cardiac fibroblast stimulation and fibrosis in aging and MI. ECM1 may be a novel intermediary between inflammation and fibrosis

Strain-dependent host transcriptional responses to toxoplasma infection are largely conserved in mammalian and avian hosts

Toxoplasma gondii has a remarkable ability to infect an enormous variety of mammalian and avian species. Given this, it is surprising that three strains (Types I/II/III) account for the majority of isolates from Europe/North America. The selective pressures that have driven the emergence of these particular strains, however, remain enigmatic. We hypothesized that strain selection might be partially driven by adaptation of strains for mammalian versus avian hosts. To test this, we examine in vitro, strain-dependent host responses in fibroblasts of a representative avian host, the chicken (Gallus gallus). Using gene expression profiling of infected chicken embryonic fibroblasts and pathway analysis to assess host response, we show here that chicken cells respond with distinct transcriptional profiles upon infection with Type II versus III strains that are reminiscent of profiles observed in mammalian cells. To identify the parasite drivers of these differences, chicken fibroblasts were infected with individual F1 progeny of a Type II x III cross and host gene expression was assessed for each by microarray. QTL mapping of transcriptional differences suggested, and deletion strains confirmed, that, as in mammalian cells, the polymorphic rhoptry kinase ROP16 is the major driver of strain-specific responses. We originally hypothesized that comparing avian versus mammalian host response might reveal an inversion in parasite strain-dependent phenotypes; specifically, for polymorphic effectors like ROP16, we hypothesized that the allele with most activity in mammalian cells might be less active in avian cells. Instead, we found that activity of ROP16 alleles appears to be conserved across host species; moreover, additional parasite loci that were previously mapped for strain-specific effects on mammalian response showed similar strain-specific effects in chicken cells. These results indicate that if different hosts select for different parasite genotypes, the selection operates downstream of the signaling occurring during the beginning of the host's immune response. © 2011 Ong et al

Selection at a single locus leads to widespread expansion of toxoplasma gondii lineages that are virulent in mice

The determinants of virulence are rarely defined for eukaryotic parasites such as T. gondii, a widespread parasite of mammals that also infects humans, sometimes with serious consequences. Recent laboratory studies have established that variation in a single secreted protein, a serine/threonine kinase known as ROPO18, controls whether or not mice survive infection. Here, we establish the extent and nature of variation in ROP18among a collection of parasite strains from geographically diverse regions. Compared to other genes, ROP18 showed extremely high levels of diversification and changes in expression level, which correlated with severity of infection in mice. Comparison with an out-group demonstrated that changes in the upstream region that regulates expression of ROP18 led to an historical increase in the expression and exposed the protein to diversifying selective pressure. Surprisingly, only three atypically distinct protein variants exist despite marked genetic divergence elsewhere in the genome. These three forms of ROP18 are likely adaptations for different niches in nature, and they confer markedly different virulence to mice. The widespread distribution of a single mouse-virulent allele among geographically and genetically disparate parasites may have consequences for transmission and disease in other hosts, including humans

Structural equation and log-linear modeling: a comparison of methods in the analysis of a study on caregivers' health

BACKGROUND: In this paper we compare the results in an analysis of determinants of caregivers' health derived from two approaches, a structural equation model and a log-linear model, using the same data set. METHODS: The data were collected from a cross-sectional population-based sample of 468 families in Ontario, Canada who had a child with cerebral palsy (CP). The self-completed questionnaires and the home-based interviews used in this study included scales reflecting socio-economic status, child and caregiver characteristics, and the physical and psychological well-being of the caregivers. Both analytic models were used to evaluate the relationships between child behaviour, caregiving demands, coping factors, and the well-being of primary caregivers of children with CP. RESULTS: The results were compared, together with an assessment of the positive and negative aspects of each approach, including their practical and conceptual implications. CONCLUSION: No important differences were found in the substantive conclusions of the two analyses. The broad confirmation of the Structural Equation Modeling (SEM) results by the Log-linear Modeling (LLM) provided some reassurance that the SEM had been adequately specified, and that it broadly fitted the data

Discovery of the peculiar supernova 1998bw in the error box of GRB980425

The discovery of X-ray, optical and radio afterglows of gamma-ray bursts (GRBs) and the measurements of the distances to some of them have established that these events come from Gpc distances and are the most powerful photon emitters known in the Universe, with peak luminosities up to 10^52 erg/s. We here report the discovery of an optical transient, in the BeppoSAX Wide Field Camera error box of GRB980425, which occurred within about a day of the gamma-ray burst. Its optical light curve, spectrum and location in a spiral arm of the galaxy ESO 184-G82, at a redshift z = 0.0085, show that the transient is a very luminous type Ic supernova, SN1998bw. The peculiar nature of SN1998bw is emphasized by its extraordinary radio properties which require that the radio emitter expand at relativistical speed. Since SN1998bw is very different from all previously observed afterglows of GRBs, our discovery raises the possibility that very different mechanisms may give rise to GRBs, which differ little in their gamma-ray properties.Comment: Under press embargo at Nature (submitted June 10, 1998

Gastroesophageal reflux disease in 2006: The imperfect diagnosis

There continues to be significant controversy related to diagnostic testing for gastroesophageal reflux disease (GERD). Clearly, barium contrast fluoroscopy is superior to any other test in defining the anatomy of the upper gastrointestinal (UGI) tract. Although fluoroscopy can demonstrate gastroesophageal reflux (GER), this observation does not equate to GERD. Fluoroscopy time should not be prolonged to attempt to demonstrate GER during barium contrast radiography. There are no data to justify prolonging fluoroscopy time to perform provocative maneuvers to demonstrate reflux during barium contrast UGI series. Symptoms of GERD may be associated with physiologic esophageal acid exposure measured by intraesophageal pH monitoring, and a significant percentage of patients with abnormal esophageal acid exposure have no or minimal clinical symptoms of reflux. Abnormal acid exposure defined by pH monitoring over a 24-h period does not equate to GERD. In clinical practice presumptive diagnosis of GERD is reasonably assumed by substantial reduction or elimination of suspected reflux symptoms during therapeutic trial of acid reduction therapy

Demographic and biologic influences on survival in whites and blacks: 40 years of follow-up in the Charleston heart study

BACKGROUND: In the United States, life expectancy is significantly lower among blacks than whites. We examined whether socioeconomic status (SES) and cardiovascular disease (CVD) risk factors may help explain this disparity. METHODS: Forty years (1961 through 2000) of all-cause mortality data were obtained on a population-based cohort of 2,283 subjects in the Charleston Heart Study (CHS). We examined the influence of SES and CVD risk factors on all-cause mortality. RESULTS: Complete data were available on 98% of the original sample (647 white men, 728 white women, 423 black men, and 443 black women). After adjusting for SES and CVD risk factors, the hazard ratios (HRs) for white ethnicity were 1.14 (0.98 to 1.32) among men and 0.90 (0.75 to 1.08) among women, indicating that the mortality risk was 14% greater for white men and 10% lower for white women compared to their black counterparts. However the differences were not statistically significant. CONCLUSION: While there are marked contrasts in mortality among blacks and whites in the CHS, the differences can be largely explained by SES and CVD risk factors. Continued focus on improving and controlling cardiovascular disease risk factors may reduce ethnic disparities in survival