Would people with Parkinson's disease benefit from palliative care?

Parkinson's disease (PD) is a chronic, progressive, degenerative disorder of the nervous system, causing substantial morbidity and has the capacity to shorten life. People with PD and their families can find the disease devastating. Nevertheless, this population of patients is not usually considered a group to be supported by palliative care specialists. But the nature of the illness and the challenges of managing its many physical and psychological effects raises questions about the potential benefits of a palliative care approach. The purpose of this project was to describe the experience of PD and consider the relevance of palliative care for this population. Semi-structured interviews were conducted with eight people with PD, 21 family caregivers and six health professionals. Five themes were developed from the data analysis: (1) emotional impact of diagnosis; (2) staying connected; (3) enduring financial hardship; (4) managing physical challenges; and (5) finding help for advanced stages. These data revealed that people with PD and family caregivers are confronted with similar issues to people with typical palliative care diagnoses, such as advanced cancer, and that a palliative approach may be helpful in the care of people with PD and their families.

Lymphocytic follicles and aggregates are a determinant of mucosal damage and duration of diarrhea

Nonspecific changes (nonspecific chronic inflammation) in patients with chronic diarrhea represent the commonest diagnosis in colorectal biopsy interpretation, but these changes are of little clinical significance.

Dual-colour HER2/chromosome 17 chromogenic in situ hybridisation enables accurate assessment of HER2 genomic status in ovarian tumours

Ovarian cancer is a leading cause of gynaecological cancer-related morbidity and mortality. There has been increasing interest in the potential utility of anti-human epidermal growth factor receptor 2 (anti-HER2) agents in the treatment of this disease, with the attendant need to identify suitable predictive biomarkers of response to treatment.

Lipoxidation products as biomarkers of oxidative damage to proteins during lipid peroxidation reactions

Oxidative stress is implicated in the pathogenesis of numerous disease processes including diabetes mellitus, atherosclerosis, ischaemia reperfusion injury and rheumatoid arthritis. Chemical modification of amino acids in protein during lipid peroxidation results in the formation of lipoxidation products which may serve as indicators of oxidative stress in vivo. The focus of the studies described here was initially to identify chemical modifications of protein derived exclusively from lipids in order to assess the role of lipid peroxidative damage in the pathogenesis of disease. Malondialdehye (MDA) and 4-hydroxynonenal (HNE) are well characterized oxidation products of polyunsaturated fatty acids on low-density lipoprotein (LDL) and adducts of these compounds have been detected by immunological means in atherosclerotic plaque. Thus, we first developed gas chromatography-mass spectrometry assays for the Schiff base adduct of MDA to lysine, the lysine-MDA-lysine diimine cross-link and the Michael addition product of HNE to lysine. Using these assays, we showed that the concentrations of all three compounds increased significantly in LDL during metal-catalysed oxidation in vitro. The concentration of the advanced glycation end-product N epsilon-(carboxymethyl)lysine (CML) also increased during LDL oxidation, while that of its putative carbohydrate precursor the Amadori compound N epsilon-(1-deoxyfructose-1-yl)lysine did not change, demonstrating that CML is a marker of both glycoxidation and lipoxidation reactions. These results suggest that MDA and HNE adducts to lysine residues should serve as biomarkers of lipid modification resulting from lipid peroxidation reactions, while CML may serve as a biomarker of general oxidative stress resulting from both carbohydrate and lipid oxidation reactions.

Th1 not Th17 cells drive spontaneous MS-like disease despite a functional regulatory T cell response

Multiple sclerosis is considered a disease of complex autoimmune etiology, yet there remains a lack of consensus as to specific immune effector mechanisms. Recent analyses of experimental autoimmune encephalomyelitis, the common mouse model of multiple sclerosis, have investigated the relative contribution of Th1 and Th17 CD4 T cell subsets to initial autoimmune central nervous system (CNS) damage. However, inherent in these studies are biases influenced by the adjuvant and toxin needed to break self-tolerance. We investigated spontaneous CNS disease in a clinically relevant, humanized, T cell receptor transgenic mouse model. Mice develop spontaneous, ascending paralysis, allowing unbiased characterization of T cell immunity in an HLA-DR15-restricted T cell repertoire. Analysis of naturally progressing disease shows that IFN?(+) cells dominate disease initiation with IL-17(+) cells apparent in affected tissue only once disease is established. Tregs accumulate in the CNS but are ultimately ineffective at halting disease progression. However, ablation of Tregs causes profound acceleration of disease, with uncontrolled infiltration of lymphocytes into the CNS. This synchronous, severe disease allows characterization of the responses that are deregulated in exacerbated disease: the correlation is with increased CNS CD4 and CD8 IFN? responses. Recovery of the ablated Treg population halts ongoing disease progression and Tregs extracted from the central nervous system at peak disease are functionally competent to regulate myelin specific T cell responses. Thus, in a clinically relevant mouse model of MS, initial disease is IFN? driven and the enhanced central nervous system responses unleashed through Treg ablation comprise IFN? cytokine production by CD4 and CD8 cells, but not IL-17 responses.

Survival in dialysis patients is different between patients with diabetes as primary renal disease and patients with diabetes as a co-morbid condition.

AIMS/HYPOTHESIS:

A previous study in Dutch dialysis patients showed no survival difference between patients with diabetes as primary renal disease and those with diabetes as a co-morbid condition. As this was not in line with our hypothesis, we aimed to verify these results in a larger international cohort of dialysis patients.

METHODS:

For the present prospective study, we used data from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry. Incident dialysis patients with data on co-morbidities (n?=?15,419) were monitored until kidney transplantation, death or end of the study period (5 years). Cox regression was performed to compare survival for patients with diabetes as primary renal disease, patients with diabetes as a co-morbid condition and non-diabetic patients.

RESULTS:

Of the study population, 3,624 patients (24%) had diabetes as primary renal disease and 1,193 (11%) had diabetes as a co-morbid condition whereas the majority had no diabetes (n?=?10,602). During follow-up, 7,584 (49%) patients died. In both groups of diabetic patients mortality was higher compared with the non-diabetic patients. Mortality was higher in patients with diabetes as primary renal disease than in patients with diabetes as a co-morbid condition, adjusted for age, sex, country and malignancy (HR 1.20, 95% CI 1.10, 1.30). An analysis stratified by dialysis modality yielded similar results.

CONCLUSIONS/INTERPRETATION:

Overall mortality was significantly higher in patients with diabetes as primary renal disease compared with those with diabetes as a co-morbid condition. This suggests that survival in diabetic dialysis patients is affected by the extent to which diabetes has induced organ damage.

Management of Hyperphosphataemia in Chronic Kidney Disease:Summary of National Institute for Health and Clinical Excellence (NICE) Guideline

Bone disease and ectopic calcification are the two main consequences of hyperphosphataemia of chronic kidney disease (CKD). Observational studies have demonstrated that hyperphosphataemia in CKD is associated with increased mortality. Furthermore, the use of phosphate binders in dialysis patients is associated with significantly lower mortality. The UK Renal Registry data show significant underachievement of phosphate targets in dialysis patients. It is believed to be due to wide variation in how management interventions are used. The National Institute for Health and Clinical Excellence (NICE) has developed a guideline on the management of hyperphosphataemia in CKD. This is based on the evidence currently available using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. This review outlines the recommendations including research recommendations and discusses methodology, rationale and challenges faced in developing this guideline and the health economic model used to assess the cost-effectiveness of different phosphate binders. © 2013 S. Karger AG, Basel.

Physical activity assessment in practice: a mixed methods study of GPPAQ use in primary care

Background: Insufficient physical activity (PA) levels which increase the risk of chronic disease are reported by almost two-thirds of the population. More evidence is needed about how PA promotion can be effectively implemented in general practice (GP), particularly in socio-economically disadvantaged communities. One tool recommended for the assessment of PA in GP and supported by NICE (National Institute for Health and Care Excellence) is The General Practice Physical Activity Questionnaire (GPPAQ) but details of how it may be used and of its acceptability to practitioners and patients are limited. This study aims to examine aspects of GPPAQ administration in non-urgent patient contacts using different primary care electronic recording systems and to explore the views of health professionals regarding its use.

Methods: Four general practices, selected because of their location within socio-economically disadvantaged areas, were invited to administer GPPAQs to patients, aged 35-75 years, attending non-urgent consultations, over two-week periods. They used different methods of administration and different electronic medical record systems (EMIS, Premiere, Vision). Participants’ (general practitioners (GPs), nurses and receptionists) views regarding GPPAQ use were explored via questionnaires and focus groups.

Results: Of 2,154 eligible consultations, 192 (8.9%) completed GPPAQs; of these 83 (43%) were categorised as inactive. All practices were located within areas ranked as being in the tertile of greatest socio-economic deprivation in Northern Ireland. GPs/nurses in two practices invited completion of the GPPAQ, receptionists did so in two. One practice used an electronic template; three used paper copies of the questionnaires. End-of-study questionnaires, completed by 11 GPs, 3 nurses and 2 receptionists and two focus groups, with GPs (n = 8) and nurses (n = 4) indicated that practitioners considered the GPPAQ easy to use but not in every consultation. Its use extended consultation time, particularly for patients with complex problems who could potentially benefit from PA promotion.

Conclusions: GPs and nurses reported that the GPPAQ itself was an easy tool with which to assess PA levels in general practice and feasible to use in a range of electronic record systems but integration within routine practice is constrained by time and complex consultations. Further exploration of ways to facilitate PA promotion into practice is needed.

Shame, intimacy and self-definition: An assessment of the emotional foundation and intimate relationship consequences of an introjective personality orientation.

The current study sought to elaborate and test a theoretical proposition that introjective personality functioning, which has been implicated in various psychological difficulties (e.g., self-critical depression, obsessive-compulsive disorder), has an emotional foundation in the self-conscious emotion of shame and is supported by dissociation. Moreover, introjective functioning was predicted to be associated with reduced interpersonal intimacy. To test the model, a Web-based survey design using path analysis was used. Three hundred and fifteen university students were assessed with measures of self-conscious emotions (i.e., shame, guilt, and embarrassment), introjective (self-definition) and anaclitic (relational) personality style, pathological dissociation, and interpersonal intimacy. Introjective personality was found to be associated with increased shame and reduced interpersonal intimacy. However, the path between pathological dissociation and introjective functioning was not significant. The results are discussed with reference to the moderating influence of introjective functioning between shame and reduced interpersonal intimacy.

The use of an instrumented vehicle in a wavelet based damage detection approach for bridge structures

Periodic monitoring of structures such as bridges is necessary as their condition can deteriorate due to environmental conditions and ageing, causing the bridge to become unsafe. This monitoring - so called Structural Health Monitoring (SHM) - can give an early warning if a bridge becomes unsafe. This paper investigates an alternative wavelet-based approach for the monitoring of bridge structures which consists of the use of a vehicle fitted with accelerometers on its axles. A simplified vehicle-bridge interaction model is used in theoretical simulations to examine the effectiveness of the approach in detecting damage in the bridge. The accelerations of the vehicle are processed using a continuous wavelet transform, allowing a time-frequency analysis to be performed. This enables the identification of both the existence and location of damage from the vehicle response. Based on this analysis, a damage index is established. A parametric study is carried out to investigate the effect of parameters such as the bridge span length, vehicle speed, vehicle mass, damage level, signal noise level and road surface roughness on the accuracy of results. In addition, a laboratory experiment is carried out to validate the results of the theoretical analysis and assess the ability of the approach to detect changes in the bridge response.

Could occupational physical activity mitigate the link between moderate kidney dysfunction and coronary heart disease?

Background

Chronic kidney disease is now regarded as a risk factor for cardiovascular disease. The impact of occupational or non-occupational physical activity (PA) on moderate decreases of renal function is uncertain.

We aimed to identify the potential association of PA (occupational and leisure-time) on early decline of estimated glomerular filtration rate (eGFR) and to determine the potential mediating effect of PA on the relationship between eGFR and heart disease.

From the PRIME study analyses were conducted in 1058 employed men. Energy expended during leisure, work and commuting was calculated. Linear regression analyses were used to determine the link between types of PA and moderate decrements of eGFR determined with the KDIGO guideline at the baseline assessment. Cox proportional hazards analyses were used to explore the potential effect of PA on the relationship between eGFR and heart disease, ascertained during follow-up over 10 years.

For these employed men, and after adjustment for known confounders of GFR change, more time spent sitting at work was associated with increased risk of moderate decline in kidney function, while carrying objects or being active at work was associated with decreased risk. In contrast, no significant link with leisure PA was apparent. No potential mediating effect of occupational PA was found for the relationship between eGFR and coronary heart disease.

Occupational PA (potential modifiable factors) could provide a dual role on early impairment of renal function, without influence on the relationship between early decrease of e-GFR and CHD risk.

Investigation of physiological properties of nerves and muscles using electromyography.

The measurement and representation of the electrical activity of muscles [electromyography (EMG)] have a long history from the Victorian Era until today. Currently, EMG has uses both as a research tool, in noninvasively recording muscle activation, and clinically in the diagnosis and assessment of nerve and muscle disease and injury as well as in assessing the recovery of neuromuscular function after nerve damage. In the present report, we describe the use of a basic EMG setup in our teaching laboratories to demonstrate some of these current applications. Our practical also illustrates some fundamental physiological and structural properties of nerves and muscles. Learning activities include 1) displaying the recruitment of muscle fibers with increasing force development; 2) the measurement of conduction velocity of motor nerves; 3) the assessment of reflex delay and demonstration of Jendrassik's maneuver; and 4) a Hoffman reflex experiment that illustrates the composition of mixed nerves and the differential excitability thresholds of fibers within the same nerve, thus aiding an understanding of the reflex nature of muscle control. We can set up the classes at various levels of inquiry depending on the needs/professional requirements of the class. The results can then provide an ideal platform for a discovery learning session/tutorial on how the central nervous system controls muscles, giving insights on how supraspinal control interacts with reflexes to give smooth, precise muscular activation.

An Appraisal of End-of-Life Care in Persons with Chronic Kidney Disease Dying in Hospital Wards

AIM: To review end-of-life care provided by renal healthcare professionals to hospital in-patients with chronic kidney disease, and their carers, over a 12-month period in Northern Ireland.

METHODS: Retrospective review of 100 patients.

RESULTS: Mean age at death was 72 years (19-95) and 56% were male. Eighty three percent of patients had a 'Not For Attempted Resuscitation' order during their last admission and this was implemented in 42%. Less than 20% of all patients died in a hospital ward. No patients had an advanced care plan, although 42% had commenced the Liverpool Care Pathway for the Dying Patient. Patients suffered excessive end-of-life symptoms. In addition, there was limited documentation of carer involvement and carer needs were not formally assessed.

CONCLUSION: End-of-life care for patients with advanced chronic renal disease can be enhanced. There is significant variation in the recording of discussions regarding impending death and little preparation. There is poor recording of the patients' wishes regarding death. Those with declining functional status, including those frequently admitted to hospital require holistic assessment regarding end-of-life needs. More effective communication between the patient, family and multi-professional team is required for patients who are dying and those caring for them.

Minimal intervention dentistry and older patients Part 1: Risk assessment and caries prevention

Ten million people in the UK today are aged over 65. The latest projections estimate that there will be 5 1/2 million more people aged 65 and older in the next 20 years. This projected pattern of population ageing will have profound consequences for dentistry. Minimal intervention dentistry (MID) is a modern evidence-based approach to caries management in dentate patients that uses the 'medical model' whereby disease is controlled by the 'oral physician'. This approach offers considerable benefits over conventional dentistry for older patients. It encourages patients to be responsible for their oral health through the provision of both knowledge and motivation. MID encompasses risk assessment for dental disease, early detection and control of disease processes, and minimally invasive treatment. 

Clinical Relevance: Risk assessment tools can aid the general dental practitioner and the patient to develop a suitable caries prevention programme for that individual and reduce the need for future operative intervention.

The application of metabolomic biomarker screening tools for improved Bovine Respiratory Disease diagnosis and management

Bovine Respiratory Disease (BRD) is considered to be one of the most significant causes of economic loss in cattle worldwide. The disease has multifactorial aetiology, where viral induced respiratory damage can predispose animals to developing secondary bacterial infections. Accurate identification of viral infected animals prior to the onset of bacterial infection is necessary to reduce the overuse of antimicrobial treatments and minimize further economic losses from reduced production capacity and death. This research focuses on Bovine Parainfluenza Virus Type 3 (BPIV-3), one of the viruses involved in generating BRD. Vaccination measures for BPIV-3 can induce a level of immunity preventing disease progression, however, not all animals respond equally and immunization can complicate disease diagnosis. Alternative diagnostic approaches are required to identify animals which fail to respond to vaccination during infection outbreaks and are therefore likely to be more susceptible to secondary bacterial infections. Mass spectrometry based metabolomics was employed to identify plasma markers capable of differentiating between vaccinated and non-vaccinated calves after challenge with BPIV-3. Differentiation of vaccinated and non-vaccinated study groups (n=6) was possible as early as day 2 post-BPIV-3 challenge up until day 20 using a panel of potential metabolite markers. This study illustrates the potential for metabolomics to provide more detailed information on animal vaccination status that could be used to develop tools for improved herd health management, reduce economic loss through rapid identification and isolation of animals without immune protection (improving herd level immunity) and help reduce the usage of antimicrobial therapeutic treatments in animals.