Opioids for breathlessness in heart failure

Breathlessness is a common and problematic symptom in heart failure. Opioids have traditionally been considered as analgesics, but a potential role for their use in breathlessness is beginning to emerge. This thesis commences with a review of the existing literature in support of a possible role for opioids in the management of breathless in heart failure. A systematic review of existing human symptom control studies in this thesis suggests that opioid administration may have a small but significant benefit in chronic heart failure. However, only six studies were included in the review and most were either small or of poor methodological quality. This presents a relative gap in the knowledge on this topic. A randomised controlled trial was therefore performed to assess the effect of opioids on breathlessness in chronic heart failure. This crossover trial involved the comparison of two oral opioids with placebo. Thirty-five participants completed the trial, making it the largest trial of its type in this area. Opioid administration was shown to be safe in this patient cohort. No statistically significant differences were demonstrated for breathlessness severity between treatments. Participants were subsequently invited to participate in a three month open label extension. Thirty three participants in total were followed up with thirteen remaining on active therapy. This is the first trial of its type in breathlessness in heart failure and represents the longest participant follow-up in this area. Whilst not as robust as the initial trial, this extension period revealed that opioid continuers rated a statistically significant improvement in breathlessness severity from baseline compared to non-continuers. Finally, a semi-structured interview study in ten participants with heart failure revealed for the first time that opioids are acceptable in this population and they describe troublesome symptoms that might respond to opioid treatment

Isolation of Serpulina pilosicoli from environmental and other sources on a piggery

The intestinal spirochaete Serpulina pilosicoli causes intestinal spirochaetosis (IS), a diarrhoeal disease of pigs and other species. This condition is widespread, though often undiagnosed, and causes losses to the pig industry through reduced growth rates and poor feed conversion (3). Very little is known about the epidemiology. Porcine intestinal spirochaetosis (PIS) is a diarrhoeal disease of weaners and growers, associated with a mild colitis. Control of the aetiological agent, Serpulina pilosicoli, has relied mainly on the use of antimicrobial agents. In contrast, besides the use of antimicrobials and appropriate management practices, it is our experience that the closely related Serpulina hyodysenteriae (the agent of swine dysentery) can also be partially controlled by bacterin vaccines (1), whilst experimentally-infected pigs totally resist challenge if fed• a diet based on cooked white rice and animal protein (4, 5). This diet results in reduced microbial fermentation in the large intestine, and it appears that these conditions inhibit colonisation by the spirochaete. The purpose of the present study was to assess whether the use of a bacterin vaccine or a rice-based diet could similarly inhibit colonisation by S. pilosicoli

Clinically important differences in the intensity of chronic refractory breathlessness

Context: Clinically important differences in chronic refractory breathlessness are ill defined but important in clinical practice and trial design. Objectives: To estimate the clinical relevance of differences in breathlessness intensity using distribution and patient anchor methods. Methods: This was a retrospective data analysis from 213 datasets from four clinical trials for refractory breathlessness. Linear regression was used to explore the relationship between study effect size and change in breathlessness score (0-100 mm visual analogue scale) and to estimate the change in score equivalent to small, moderate, and large effect sizes. Pooled individual blinded patient preference data from three randomized controlled trials were analyzed. The difference between the mean change in Day 4 minus baseline scores between preferred and non-preferred arms was calculated. Results: There was a strong relationship between change in score and effect size (P = 0.001; R 2 = 0.98). Values for small, moderate, and large effects were -5.5, -11.3, and -18.2 mm. The participant preference change in score was -9 mm (95% CI, -15.8, -2.1) (P = 0.008). Conclusion: This larger dataset supports a clinically important difference of 10 mm. Studies should be powered to detect this difference

Transcutaneous electrical nerve stimulation for cancer pain in adults.

Background Cancer-related pain is complex and multi-dimensional but the mainstay of cancer pain management has predominately used a biomedical approach. There is a need for non-pharmacological and innovative approaches. Transcutaneous Electric Nerve Stimulation (TENS) may have a role for a significant number of patients but the effectiveness of TENS is currently unknown. Objectives The aim of this systematic review was to determine the effectiveness of TENS for cancer-related pain in adults. Search strategy We searched The Cochrane Library, MEDLINE, EMBASE, CINAHL, PsychINFO, AMED and PEDRO databases (11/04/08). Selection criteria Only randomised controlled trials (RCTS) investigating the use of TENS for the management of cancer-related pain in adults were included. Data collection and analysis The search strategy identified 37 possible published studies which were divided between two pairs of review authors that decided on study selection. A study eligibility form was used to screen each abstract and where study eligibility could not be determined from the abstract, the full paper was obtained and assessed by one pair of review authors. A standardised data extraction sheet was used to collect information on the studies and the quality of the studies was assessed independently by two review authors using the validated five-point Oxford Quality Scale. Final scores were discussed and agreed between all four review authors. The small sample sizes and differences in patient study populations of the two included studies prevented meta-analysis. Main results Only two RCTs met the eligibility criteria (64 participants). These studies were heterogenous with respect to study population, sample size, study design, methodological quality, mode of TENS, treatment duration, method of administration and outcome measures used. In one RCT, there were no significant differences between TENS and placebo in women with chronic pain secondary to breast cancer treatment. In the other RCT, there were no significant differences between acupuncture-type TENS and sham in palliative care patients; this study was underpowered. Authors' conclusions The results of this systematic review are inconclusive due to a lack of suitable RCTs. Large multi-centre RCTs are required to assess the value of TENS in the management of cancer-related pain in adults

Digitisation Workflow and Guidelines: Digitisation Processes

This document outlines the workflow and best practice required to implement the digitisation of physical objects as part of the CHARTER project. It details the CHARTER scanning requirements and parameters for the creation of preservation master files and compressed images for viewing.JIS

Evaluation of vaccination and diet for the control of Serpulina pilosicoli infection (porcine intestinal spirochaetosis)

Porcine intestinal spirochaetosis (PIS) is a diarrhoeal disease of weaners and growers, associated with a mild colitis. Control of the aetiological agent, Serpulina pilosicoli, has relied mainly on the use of antimicrobial agents. In contrast, besides the use of antimicrobials and appropriate management practices, it is our experience that the closely related Serpulina hyodysenteriae (the agent of swine dysentery) can also be partially controlled by bacterin vaccines (1), whilst experimentally-infected pigs totally resist challenge if fed a diet based on cooked white rice and animal protein (4, 5). This diet results in reduced microbial fermentation in the large intestine, and it appears that these conditions inhibit colonisation by the spirochaete. The purpose of the present study was to assess whether the use of a bacterin vaccine or a rice-based diet could similarly inhibit colonisation by S. pilosicoli

Potential for Zoonotic Transmission of Brachyspira pilosicoli

Anaerobic intestinal spirochetes of the genus Brachyspira colonize the large intestine (1). Most Brachyspira species have a restricted host range, whereas Brachyspira (formerly Serpulina) pilosicoli colonizes a variety of animal and bird species and humans. B. pilosicoli is an important colonic pathogen of pigs and chickens (2). It occurs at high prevalence rates in humans in developing countries and in male homosexuals and HIV-positive persons in industrialized countries (3). Its potential as a human pathogen was emphasized after its identification in the bloodstream of a series of debilitated persons (4)

Establishing global error bounds for model reduction in combustion

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2013.Cataloged from PDF version of thesis.Includes bibliographical references (pages 223-239).In addition to theory and experiment, simulation of reacting flows has become important in policymaking, industry, and combustion science. However, simulations of reacting flows can be extremely computationally demanding due to the wide range of length scales involved in turbulence, the wide range of time scales involved in chemical reactions, and the large number of species in detailed chemical reaction mechanisms in combustion. To compensate for limited available computational resources, reduced chemistry is used. However, the accuracy of these reduced chemistry models is usually unknown, which is of great concern in applications; if the accuracy of a simplified model is unknown, it is risky to rely on the results of that model for critical decision-making. To address this issue, this thesis derives bounds on the global error in reduced chemistry models. First, it is shown that many model reduction methods in combustion are based on projection; all of these methods can be described using the same equation. After that, methods from the numerical solution of ODEs are used to derive separate a priori bounds on the global error in the solutions of reduced chemistry models for both projection-based reduced chemistry models and non-projection-based reduced chemistry models. The distinguishing feature between the two sets of bounds is that bounds on projection-based reduced chemistry models are stronger than those on non-projection-based reduced chemistry models. In both cases, the bounds are tight, but tend to drastically overestimate the error in the reduced chemistry. The a priori bounds on the global error in the solutions of reduced chemistry models demonstrate that if the error in the time derivatives of the state variables in the reduced model is controlled, then the error in the reduced model solution is also controlled; this thesis proves that result for the first time. Source code is included for all results presented. After presenting these results, the development of more accurate global error information is discussed. Using the error bounds above, in concert with more accurate global error information, it should be possible to assess better the accuracy and reliability of reduced chemistry models in applications.by Geoffrey Malcolm Oxberry.Ph.D

Blinded patient preference for morphine compared to placebo in the setting of chronic refractory breathlessness – an exploratory study

Context Patients’ preference for morphine therapy has received little attention in the setting of chronic refractory breathlessness. However, this is one important factor in considering longer term therapy. Objectives The aim of this secondary analysis is to explore blinded patient preference of morphine compared to placebo for this indication and to define any predictors of preference. Methods Data were pooled from three randomized, double-blind, crossover, placebo-controlled studies of morphine (four days each) in chronic refractory breathlessness. Blinded patient preferences were chosen at the end of each study. A multivariable regression model was used to establish patient predictors of preference. Results Sixty-five participants provided sufficient data (60 males; median age 74 years; heart failure 55%, chronic obstructive pulmonary disease 45%; median Eastern Cooperative Oncology Group performance status 2). Forty-three percent of participants preferred morphine (32% placebo and 25% no preference). Morphine preference and younger age were strongly associated: odds ratio = 0.85, 95% confidence interval 0.78, 0.93;