Psychosocial, educational and communicative interventions for patients with cachexia and their family carers

Purpose of review: Cancer cachexia has a substantial impact on both patients and their family carers. It has been acknowledged as one of the two most frequent and devastating problems of advanced cancer. The impact of cachexia spans biopsychosocial realms. Symptom management in cachexia is fraught with difficulties and globally, there remains no agreed standard care or treatment for this client group. There is a need to address the psychosocial impact of cachexia for both patients and their family carers.

Recent findings: Patients living at home and their family carers are often left to manage the distressing psychosocial impacts of cancer cachexia themselves. Successful symptom management requires healthcare professionals to address the holistic impact of cancer cachexia. High quality and rigorous research details the existential impact of cachexia on patients and their family carers. This information needs to inform psychosocial, educational and communicative supportive healthcare interventions to help both patients and their family carers better cope with the effects of cachexia.

Summary: Supportive interventions need to inform both patients and their family carers of the expected impacts of cachexia, and address how to cope with them to retain a functional, supported family unit who are informed about and equipped to care for a loved one with cachexia.

‘I don’t think I’d be frightened if the statins went’: a phenomenological qualitative study exploring medicines use in palliative care patients, carers and healthcare professionals

Background

An exploration into the palliative and end-of-life experiences of carers of people with Parkinson's disease

Although most people with Parkinson's disease are cared for in the community, little is known about family members' lived experiences of palliative or end-of-life care. The aim of this study was to explore former carers' lived experiences of palliative and end-of-life care. In total, 15 former family caregivers of patients who had died with Parkinson's disease were interviewed using a semi-structured topic list. Findings indicated that some palliative and end-of-life care needs had not been fully addressed. Lack of communication, knowledge and coordination of services resulted in many people caring for someone with Parkinson's disease not accessing specialist palliative care services. Participants also reflected upon the physical and psychological impact of caring in the advanced stage of Parkinson's. A multi-disciplinary team-based approach was advocated by participants. These findings provide important insights into the experience of caregiving to patients with Parkinson's disease in the home at the end-of-life stage. According to palliative care standards, patients and their carers are the unit of care; in reality, however, this standard is not being met.

PAlliative Care in chronic Kidney diSease: the PACKS study—quality of life, decision making, costs and impact on carers in people managed without dialysis

BACKGROUND: The number of patients with advanced chronic kidney disease opting for conservative management rather than dialysis is unknown but likely to be growing as increasingly frail patients with advanced renal disease present to renal services. Conservative kidney management includes ongoing medical input and support from a multidisciplinary team. There is limited evidence concerning patient and carer experience of this choice. This study will explore quality of life, symptoms, cognition, frailty, performance decision making, costs and impact on carers in people with advanced chronic kidney disease managed without dialysis and is funded by the National Institute of Health Research in the UK.

METHODS: In this prospective, multicentre, longitudinal study, patients will be recruited in the UK, by renal research nurses, once they have made the decision not to embark on dialysis. Carers will be asked to 'opt-in' with consent from patients. The approach includes longitudinal quantitative surveys of quality of life, symptoms, decision making and costs for patients and quality of life and costs for carers, with questionnaires administered quarterly over 12 months. Additionally, the decision making process will be explored via qualitative interviews with renal physicians/clinical nurse specialists.

DISCUSSION: The study is designed to capture patient and carer profiles when conservative kidney management is implemented, and understand trajectories of care-receiving and care-giving with the aim of optimising palliative care for this population. It will explore the interactions that lead to clinical care decisions and the impact of these decisions on informal carers with the intention of improving clinical outcomes for patients and the experiences of care givers.

Homocysteine and B-group vitamins in renal transplant patients

Increased plasma homocysteine is an independent risk factor for cardiovascular disease. We have investigated homocysteine and B-group vitamin levels in renal transplant patients. Fasting blood was collected from 55 renal transplant recipients with good renal function and 32 age/sex matched control subjects. Total homocysteine was increased in transplant recipients in comparison to controls (10.9+/-1.5 vs. 6.7+/-1.3 micromol/l, P < 0.001). There was no difference in homocysteine between patients receiving cyclosporin (n = 39, homocysteine 11.0+/-1.5 micromol/l) and patients receiving prednisolone + azathioprine (n = 16, 10.8+/-1.6 micromol/l, mean+/-S.D.), although there was a significant correlation between homocysteine and serum cyclosporin concentration in the sub-group of patients receiving that immunosuppressive regimen (r = 0.42, P < 0.05). Levels of B-group vitamins were similar in patients and controls. Plasma homocysteine is increased in renal transplant recipients even in the presence of minor degrees of renal impairment and normal levels of B-group vitamins.

Oesophageal cancer: caregiver mental health and strain

Objective: To investigate strain and mental health among family caregivers of oesophageal cancer patients and possible factors associated with caregiver mental health and strain.

Methods: Patients with oesophageal adenocarcinoma in Ireland were recruited into the FINBAR study (the main aim of which was to investigate factors influencing the Barrett's adenocarcinoma relationship). Carers completed the 13-item Caregiver Strain Index and the General Health Questionnaire-30 (GHQ) in the context of a brief interview with trained research staff that was undertaken separately from the interview with each cancer patient.

Results: Two hundred and twenty-seven patients participated in the FINBAR study. A total of 39 patients did not have a family carer or the carer could not be identified. Fifty percent (94/188) of carers completed the questionnaires. Mean (SD) scores for strain (6.65, SD=3.63) and mental health status (10.21, SD=7.30) were high and 71% of carers scored >5 on the GHQ indicating psychological distress. There was a statistically significant positive relationship between level of strain experienced by caregivers and the severity of their mental health status and whether or not carers scored >5 on the GHQ. Relatives were 1.70 (95% CI 1.34-2.15) times more likely to be defined as high scorers with each unit increase in the CSI score.

Conclusions: A significant proportion of caregivers experienced high levels of strain and psychological distress. There is a need to provide appropriate support and services targeted specifically at reducing the considerable strain of caring for patients with oesophageal cancer, particularly for carers of patients from lower socioeconomic groups.

Identifying strategies to maximise recruitment and retention of practices and patients in a multicentre randomised controlled trial of an intervention to optimise secondary prevention for coronary heart disease in primary care.

Background Recruitment and retention of patients and healthcare providers in randomised controlled trials (RCTs) is important in order to determine the effectiveness of interventions. However, failure to achieve recruitment targets is common and reasons why a particular recruitment strategy works for one study and not another remain unclear. We sought to describe a strategy used in a multicentre RCT in primary care, to report researchers’ and participants’ experiences of its implementation and to inform future strategies to maximise recruitment and retention. Methods In total 48 general practices and 903 patients were recruited from three different areas of Ireland to a RCT of an intervention designed to optimise secondary prevention of coronary heart disease. The recruitment process involved telephoning practices, posting information, visiting practices, identifying potential participants, posting invitations and obtaining consent. Retention involved patients attending reviews and responding to questionnaires and practices facilitating data collection. Results We achieved high retention rates for practices (100%) and for patients (85%) over an 18-month intervention period. Pilot work, knowledge of the setting, awareness of change in staff and organisation amongst participant sites, rapid responses to queries and acknowledgement of practitioners’ contributions were identified as being important. Minor variations in protocol and research support helped to meet varied, complex and changing individual needs of practitioners and patients and encouraged retention in the trial. A collaborative relationship between researcher and practice staff which required time to develop was perceived as vital for both recruitment and retention. Conclusions Recruiting and retaining the numbers of practices and patients estimated as required to provide findings with adequate power contributes to increased confidence in the validity and generalisability of RCT results. A continuous dynamic process of monitoring progress within trials and tailoring strategies to particular circumstances, whilst not compromising trial protocols, should allow maximal recruitment and retention.

Tooth loss and implant outcomes in patients refractory to treatment in a periodontal practice

Aim: The aim of this study was to investigate the factors associated with continued significant tooth loss due to periodontal reasons during maintenance following periodontal therapy in a specialist periodontal practice in Norway.
Material and Methods: A case-control design was used. Refractory cases were patients who lost multiple teeth during a maintenance period of 13.4 (range 8-19) years following definitive periodontal treatment in a specialist practice. Controls were age- and gender-matched maintenance patients from the same practice. Characteristics and treatment outcomes were assessed, and all teeth classified as being lost due to periodontal disease during follow-up were identified. The use of implants in refractory cases and any complications relating to such a treatment were recorded.
Results: Only 27 (2.2%) patients who received periodontal treatment between 1986 and 1998 in a specialist practice met the criteria for inclusion in the refractory to treatment group. Each refractory subject lost 10.4 (range 4-16) teeth, which represented 50% of the teeth present at baseline. The rate of tooth loss in the refractory group was 0.78 teeth per year, which was 35 times greater than that in the control group. Multivariate analysis indicated that being in the refractory group was predicted by heavy smoking (p=0.026), being stressed (p=0.016) or having a family history of periodontitis (p=0.002). Implants were placed in 14 of the refractory patients and nine (64%) of these lost at least one implant. In total, 17 (25%) of the implants placed in the refractory group were lost during the study period.
Conclusions: A small number of periodontal maintenance patients are refractive to treatment and go on to experience significant tooth loss. These subjects also have a high level of implant complications and failure. Heavy smoking, stress and a family history of periodontal disease were identified as factors associated with a refractory outcome.

Enteral feeding methods for nutritional management in patients with head and neck cancers being treated with radiotherapy and/or chemotherapy

Background: This is an update of a Cochrane review first published in The Cochrane Library in Issue 3, 2010.
For many patients with head and neck cancer, oral nutrition will not provide adequate nourishment during treatment with radiotherapy or chemoradiotherapy due to the acute toxicity of treatment, obstruction caused by the tumour, or both. The optimal method of enteral feeding for this patient group has yet to be established.

Objectives: To compare the effectiveness of different enteral feeding methods used in the nutritional management of patients with head and neck cancer receiving radiotherapy or chemoradiotherapy using the clinical outcomes, nutritional status, quality of life and rates of complications.

Search methods: Our extensive search included the Cochrane ENT Group Trials Register, CENTRAL, PubMed, EMBASE, CINAHL, AMED and ISI Web of Science. The date of the most recent search was 13 February 2012.

Selection criteria:Randomised controlled trials comparing one method of enteral feeding with another, e.g. nasogastric (NG) or percutaneous endoscopic gastrostomy (PEG) feeding, for adult patients with a diagnosis of head and neck cancer receiving radiotherapy and/or chemoradiotherapy.

Data collection and analysis:Two authors independently assessed trial quality and extracted data using standardised forms. We contacted study authors for additional information.

Main results: One randomised controlled trial met the criteria for inclusion in this review. No further studies were identified when we updated the searches in 2012.
Patients diagnosed with head and neck cancer, being treated with chemoradiotherapy, were randomised to PEG or NG feeding. In total only 33 patients were eligible for analysis as the trial was terminated early due to poor accrual. A high degree of bias was identified in the study.
Weight loss was greater for the NG group at six weeks post-treatment than for the PEG group (P = 0.001). At six months post-treatment, however, there was no significant difference in weight loss between the two groups. Anthropometric measurements recorded six weeks post-treatment demonstrated lower triceps skin fold thickness for the NG group compared to the PEG group (P = 0.03). No statistically significant difference was found between the two different enteral feeding techniques in relation to complication rates or patient satisfaction. The duration of PEG feeding was significantly longer than for the NG group (P = 0.0006). In addition, the study calculated the cost of PEG feeding to be 10 times greater than that of NG, though this was not found to be significant. There was no difference in the treatment received by the two groups. However, four PEG fed patients and two NG fed patients required unscheduled treatment breaks of a median of two and six days respectively.
We identified no studies of enteral feeding involving any form of radiologically inserted gastrostomy (RIG) feeding or comparing prophylactic PEG versus PEG for inclusion in the review.

Authors' conclusions: There is not sufficient evidence to determine the optimal method of enteral feeding for patients with head and neck cancer receiving radiotherapy and/or chemoradiotherapy. Further trials of the two methods of enteral feeding, incorporating larger sample sizes, are required.

C5a-mediated neutrophil phagocytic dysfunction is RhoA-dependent and predicts nosocomial infection in critically ill patients.

Critically ill patients are at heightened risk for nosocomial infections. The anaphylatoxin C5a impairs phagocytosis by neutrophils. However, the mechanisms by which this occurs and the relevance for acquisition of nosocomial infection remain undetermined. We aimed to characterize mechanisms by which C5a inhibits phagocytosis in vitro and in critically ill patients, and to define the relationship between C5a-mediated dysfunction and acquisition of nosocomial infection. In healthy human neutrophils, C5a significantly inhibited RhoA activation, preventing actin polymerization and phagocytosis. RhoA inhibition was mediated by PI3Kd. The effects on RhoA, actin, and phagocytosis were fully reversed by GM-CSF. Parallel observations were made in neutrophils from critically ill patients, that is, impaired phagocytosis was associated with inhibition of RhoA and actin polymerization, and reversed by GM-CSF. Among a cohort of 60 critically ill patients, C5a-mediated neutrophil dysfunction (as determined by reduced CD88 expression) was a strong predictor for subsequent acquisition of nosocomial infection (relative risk, 5.8; 95% confidence interval, 1.5-22; P = .0007), and remained independent of time effects as assessed by survival analysis (hazard ratio, 5.0; 95% confidence interval, 1.3-8.3; P = .01). In conclusion, this study provides new insight into the mechanisms underlying immunocompromise in critical illness and suggests novel avenues for therapy and prevention of nosocomial infection.

Phase I study of GSK461364, a specific and competitive Polo-like Kinase 1 (PLK1) inhibitor in patients with advanced solid malignancies.

Purpose: GSK461364 is an ATP-competitive inhibitor of polo-like kinase 1 (Plk1). A phase I study of two schedules of intravenous GSK461364 was conducted. Experimental Design: GSK461364 was administered in escalating doses to patients with solid malignancies by two schedules, either on days 1, 8, and 15 of 28-day cycles (schedule A) or on days 1, 2, 8, 9, 15, and 16 of 28-day cycles (schedule B). Assessments included pharmacokinetic and pharmacodynamic profiles, as well as marker expression studies in pretreatment tumor biopsies. Results: Forty patients received GSK461364: 23 patients in schedule A and 17 in schedule B. Dose-limiting toxicities (DLT) in schedule A at 300 mg (2 of 7 patients) and 225 mg (1 of 8 patients) cohorts included grade 4 neutropenia and/or grade 3–4 thrombocytopenia. In schedule B, DLTs of grade 4 pulmonary emboli and grade 4 neutropenia occurred at 7 or more days at 100 mg dose level. Venous thrombotic emboli (VTE) and myelosuppression were the most common grade 3–4, drug-related events. Pharmacokinetic data indicated that AUC (area under the curve) and C max (maximum concentration) were proportional across doses, with a half-life of 9 to 13 hours. Pharmacodynamic studies in circulating tumor cells revealed an increase in phosphorylated histone H3 (pHH3) following drug administration. A best response of prolonged stable disease of more than 16 weeks occurred in 6 (15%) patients, including 4 esophageal cancer patients. Those with prolonged stable disease had greater expression of Ki-67, pHH3, and Plk1 in archived tumor biopsies. Conclusions: The final recommended phase II dose for GSK461364 was 225 mg administered intravenously in schedule A. Because of the high incidence (20%) of VTE, for further clinical evaluation, GSK461364 should involve coadministration of prophylactic anticoagulation.

Influence of drugs, demographics and medical history on hospital readmission of elderly patients - A predictive model

Objective: To investigate factors that influence hospital readmissions of elderly patients and to construct a robust hospital readmissions predictive model.

Utility, Caller, and Patient Profile of a Novel Chemotherapy Telephone Helpline Service Within a Regional Cancer Centre in Northern Ireland

Background: The telephone is an accepted and useful means of communication for the management of patient care. The Chemotherapy Telephone Helpline (CTH) service, located in a large inner-city Trust within the United Kingdom, is a unique nurse-led service within Northern Ireland.

Objective: The objective of the study was to investigate the utility, caller, and patient profile of a novel CTH.

Methods: This was a retrospective study of telephone contacts during 2007 to the CTH. Calls were categorized by caller and patient characteristics, reason for call, and subsequent action.

Results: A total of 7498 calls were made to the CTH during 2007. Of these, 25.6% occurred outside 8AM-4PM. Callers included patients (45.8%), lay carers (31%), and health care professionals (20.5%); 35.2% of calls concerned patients with polysymptomatic problems; 36.8% of calls led directly to patients being medically assessed.

Conclusions: The utility of the CTH service confirms the need of this nurse-led service. This service facilitates access to specialist advice and support for patients, their families, and allied health care professionals.

Implications for Practice: The international significance of these findings for practice includes its demonstration of the multifaceted symptom experience of patients receiving chemotherapy and highlights the importance of rapid access to specialist cancer services for patients and their lay and professional carers. In addition, it demonstrates the capacity of helplines to identify gaps in professional skills and training.

Secondary prevention in the clinical management of patients with cardiovascular diseases. Core components, standards and outcome measures for referral and delivery.

Despite major improvements in diagnostics and interventional therapies, cardiovascular diseases remain a major health care and socio-economic burden both in western and developing countries, in which this burden is increasing in close correlation to economic growth. Health authorities and the general population have started to recognize that the fight against these diseases can only be won if their burden is faced by increasing our investment on interventions in lifestyle changes and prevention. There is an overwhelming evidence of the efficacy of secondary prevention initiatives including cardiac rehabilitation in terms of reduction in morbidity and mortality. However, secondary prevention is still too poorly implemented in clinical practice, often only on selected populations and over a limited period of time. The development of systematic and full comprehensive preventive programmes is warranted, integrated in the organization of national health systems. Furthermore, systematic monitoring of the process of delivery and outcomes is a necessity. Cardiology and secondary prevention, including cardiac rehabilitation, have evolved almost independently of each other and although each makes a unique contribution it is now time to join forces under the banner of preventive cardiology and create a comprehensive model that optimizes long term outcomes for patients and reduces the future burden on health care services. These are the aims that the Cardiac Rehabilitation Section of the European Association for Cardiovascular Prevention & Rehabilitation has foreseen to promote secondary preventive cardiology in clinical practice.

Use of adhesion counts to help predict symptomatic infection and the ability of fluoroquinolones to penetrate bacterial biofilms on the bladder cells of spinal cord injured patients

There were three objectives to the present study: (1) compare the bladder infection rate and extent of biofilm formation for seven untreated spinal cord injured (SCI) patients and seven given prophylactic co-trimoxazole, (2) identify a level of bacterial adhesion to bladder cells which could be used to help predict symptomatic infection, and (3) determine from in vivo and in vitro studies whether fluoroquinolones were effective at penetrating bacterial biofilms. The results showed that the infection rate had not changed with the introduction of prophylaxis. However, the uropathogenic population had altered subsequent to the introduction of prophylaxis with E. coli being replaced by E. faecalis as the most common cause of infection. In 63% of the specimens from asymptomatic patients, the bacterial counts per cell were <20, while 81% of specimens from patients with at least one sign and one symptom of urinary tract infection (UTI) had > 20 adherent bacteria per bladder cell. Therefore, it is proposed that counts of > 20 bacteria adherent to sediment transitional epithelial bladder cells may be predictive of symptomatic UTI. Clinical data showed that fluoroquinolone therapy reduced the adhesion counts to <20 per cell in 63% of cases, while trimethoprim-sulfamethoxazole only did so in 44%. Further in vitro testing showed that ciprofloxacin (0.1, 0.5 and 1.0 micrograms/ml) partially or completely eradicated adherent biofilms from 92% of spinal cord injured patients' bladder cells, while ofloxacin did so in 71% cases and norfloxacin in 56%. These findings have important implications for the detection and treatment of bacteriuria in spinal cord injured patients.