An exploration of the experience of cancer cachexia: What patients and their families want from health care professionals

The aim of this paper is to investigate the perceptions of patients and family members with regard to care received for cancer cachexia. A qualitative study recruited 27 participants, of which 15 were patients with advanced cancer who had primary cachexia and 12 were family members. Participants were recruited from a regional cancer centre in the UK. All participants took part in a domiciliary interview, which was transcribed verbatim for analysis. A major finding from analysis was ‘lack of response from health care professionals’ in relation to cancer cachexia management. This finding illuminated that patients and their family members wanted three things from healthcare professionals. They wanted their profound weight loss acknowledged, they wanted information about it and why it was happening and they wanted interventions to deal with it. This paper provides powerful messages for healthcare professionals and highlights the needs of patients and their family regarding cancer cachexia management. Patients and their families want this problem addressed by healthcare professionals. This client group requires supportive healthcare interventions, so that they can understand the nature and impact of this syndrome.

The Effects of Anti-Hypertensive Drugs Evaluated Using Markov Modelling for Northern Ireland Chronic Kidney Disease Patients

The aim of this paper is to use Markov modelling to
investigate survival for particular types of kidney patients
in relation to their exposure to anti-hypertensive treatment
drugs. In order to monitor kidney function an intuitive three
point assessment is proposed through the collection of blood
samples in relation to Chronic Kidney Disease for Northern
Ireland patients. A five state Markov Model was devised
using specific transition probabilities for males and
females over all age groups. These transition probabilities
were then adjusted appropriately using relative risk scores
for the event death for different subgroups of patients. The
model was built using TreeAge software package in order to
explore the effects of anti-hypertensive drugs on patients.

Comparison of techniques to examine the diversity of fungi in adult patients with cystic fibrosis

This study compares conventional and molecular techniques for the detection of fungi in 77 adult cystic fibrosis (CF) patients. Three different methods were investigated, i.e., (1) conventional microbiological culture (including yeasts and filamentous fungi), (2) mycological culture with CF-derived fungal specific culture media, and (3) Non-culture and direct DNA extraction from patient sputa. Fungi isolated from environmental air samples of the CF unit were compared to fungi in sputa from CF patients. Fungi (n = 107) were detected in 14/77(18%) of patients by method 1, in 60/77 (78%) of patients by method 2 and with method 3, in 77/77(100%) of the patients. The majority of yeasts isolated were Candida albicans and C. dubliniensis. Exophiala (Wangiella) dermatitidis, Scedosporiumapiospermum, Penicillium spp., Aspergillus fumigatus, and Aspergillus versicolor were also identified by sequence analysis of the rDNA short internal transcribed spacer (ITS2) region. Conventional laboratory analysis failed to detect fungi in 63 patients mainly due to overgrowth by Gram-negative organisms. Mycological culture with antibiotics dramatically increased the number of fungi that could be detected. Molecular techniques detected fungi such as Saccharomyces cerevisiae, Malassezia spp., Fuscoporia ferrea, Fusarium culmorum, Acremonium strictum, Thanatephorus cucumeris and Cladosporium spp. which were not found with other methods. This study demonstrates that several potentially important fungi may not be detected if mycological culture methods alone are used. A polyphasic approach employing both enhanced mycological culture with molecular detection will help determine the presence of fungi in the sputa of patients with CF and their healthcare environment.

European development of clofarabine as treatment for older patients with acute myeloid leukemia considered unsuitable for intensive chemotherapy.

PURPOSE:
Treatment options for older patients with acute myeloid leukemia (AML) who are not considered suitable for intensive chemotherapy are limited. We assessed the second-generation purine nucleoside analog, clofarabine, in two similar phase II studies in this group of patients.
PATIENTS AND METHODS:
Two consecutive studies, UWCM-001 and BIOV-121, recruited untreated older patients with AML to receive up to four or six 5-day courses of clofarabine. Patients in UWCM-001 were either older than 70 years or 60 to 69 years of age with poor performance status (WHO > 2) or with cardiac comorbidity. Patients in BIOV-121 were >or= 65 years of age and deemed unsuitable for intensive chemotherapy.
RESULTS:
A total of 106 patients were treated in the two monotherapy studies. Median age was 71 years (range, 60 to 84 years), 30% had adverse-risk cytogenetics, and 36% had a WHO performance score >or= 2. Forty-eight percent had a complete response (32% complete remission, 16% complete remission with incomplete peripheral blood count recovery), and 18% died within 30 days. Interestingly, response and overall survival were not inferior in the adverse cytogenetic risk group. The safety profile of clofarabine in these elderly patients with AML who were unsuitable for intensive chemotherapy was manageable and typical of a cytotoxic agent in patients with acute leukemia. Patients had similar prognostic characteristics to matched patients treated with low-dose cytarabine in the United Kingdom AML14 trial, but had significantly superior response and overall survival.
CONCLUSION:
Clofarabine is active and generally well tolerated in this patient group. It is worthy of further evaluation in comparative trials and might be of particular use in patients with adverse cytogenetics.

An evaluation of a domiciliary blood transfusion serivce for palliative care patients in Northern Ireland

Marie Curie Cancer Care (MCCC) is a national charitable organisation which provides specialist palliative care services to patients with cancer and other life limiting illnesses. Marie Curie Nursing Service (MCNS) provides nursing services to patients in their own homes. The administration of blood transfusions to palliative care patients is required to improve symptom management and quality of life; however this procedure often results in unnecessary hospital admissions. Recognising that the majority of patients wish to be cared for and die in their own home, and with National Guidance recommending that specialist palliative care services should be provided to patients in their preferred place of care, a recent service initiative by MCNS was domiciliary blood transfusions. Whilst this is not a new service within domiciliary care, this pilot project aimed to capture patient views to evaluate this service initiative. Telephone interviews were conducted, using a questionnaire, with 11 patients who had received the service. Findings indicated positive evaluation of the service. Domiciliary blood transfusions helped to avoid unnecessary hospital admissions, the quality of life of patients and their families was improved in the palliative phase of illness and they received the service in their preferred place of care.

Blood pressure lowering in patients without prior cerebrovascular disease for prevention of cognitive impairment and dementia

Background: This is an update of a previous review (McGuinness 2006). Hypertension and cognitive impairment are prevalent in older people. Hypertension is a direct risk factor for vascular dementia (VaD) and recent studies have suggested hypertension impacts upon prevalence of Alzheimer's disease (AD). Therefore does treatment of hypertension prevent cognitive decline?
Objectives: To assess the effects of blood pressure lowering treatments for the prevention of dementia and cognitive decline in patients with hypertension but no history of cerebrovascular disease.
Search strategy: The Specialized Register of the Cochrane Dementia and Cognitive Improvement Group, The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS as well as many trials databases and grey literature sources were searched on 13 February 2008 using the terms: hypertens$ OR anti-hypertens$. Selection criteria: Randomized, double-blind, placebo controlled trials in which pharmacological or non-pharmacological interventions to lower blood pressure were given for at least six months.
Data collection and analysis: Two independent reviewers assessed trial quality and extracted data. The following outcomes were assessed: incidence of dementia, cognitive change from baseline, blood pressure level, incidence and severity of side effects and quality of life.
Main results: Four trials including 15,936 hypertensive subjects were identified. Average age was 75.4 years. Mean blood pressure at entry across the studies was 171/86 mmHg. The combined result of the four trials reporting incidence of dementia indicated no significant difference between treatment and placebo (236/7767 versus 259/7660, Odds Ratio (OR) = 0.89, 95% CI 0.74, 1.07) and there was considerable heterogeneity between the trials. The combined results from the three trials reporting change in Mini Mental State Examination (MMSE) did not indicate a benefit from treatment (Weighted Mean Difference (WMD) = 0.42, 95%CI 0.30, 0.53). Both systolic and diastolic blood pressure levels were reduced significantly in the three trials assessing this outcome (WMD = -10.22, 95% CI -10.78, -9.66 for systolic blood pressure, WMD = -4.28, 95% CI -4.58, -3.98 for diastolic blood pressure). Three trials reported adverse effects requiring discontinuation of treatment and the combined results indicated no significant difference (OR = 1.01, 95% CI 0.92, 1.11). When analysed separately, however, more patients on placebo in Syst Eur 1997 were likely to discontinue treatment due to side effects; the converse was true in SHEP 1991. Quality of life data could not be analysed in the four studies. Analysis of the included studies in this review was problematic as many of the control subjects received antihypertensive treatment because their blood pressures exceeded pre-set values. In most cases the study became a comparison between the study drug against a usual antihypertensive regimen.
Authors' conclusions: There is no convincing evidence fromthe trials identified that blood pressure lowering in late-life prevents the development of dementia or cognitive impairment in hypertensive patients with no apparent prior cerebrovascular disease. There were significant problems identified with analysing the data, however, due to the number of patients lost to follow-up and the number of placebo patients who received active treatment. This introduced bias. More robust results may be obtained by conducting a meta-analysis using individual patient data.

Risk of Malignant Progression in Barrett’s Esophagus Patients: Results from a Large Population-Based Study

Background: Barrett's esophagus (BE) is a premalignant lesion that predisposes to esophageal adenocarcinoma. However, the reported incidence of esophageal adenocarcinoma in patients with BE varies widely. We examined the risk of malignant progression in patients with BE using data from the Northern Ireland Barrett's esophagus Register (NIBR), one of the largest population-based registries of BE worldwide, which includes every adult diagnosed with BE in Northern Ireland between 1993 and 2005.

Subjects and Methods: We followed 8522 patients with BE, defined as columnar lined epithelium of the esophagus with or without specialized intestinal metaplasia (SIM), until the end of 2008. Patients with incident adenocarcinomas of the esophagus or gastric cardia or with high-grade dysplasia of the esophagus were identified by matching the NIBR with the Northern Ireland Cancer Registry, and deaths were identified by matching with records from the Registrar General's Office. Incidence of cancer outcomes or high-grade dysplasia was calculated as events per 100 person-years (% per year) of follow-up, and Cox proportional hazard models were used to determine incidence by age, sex, length of BE segment, presence of SIM, macroscopic BE, or low-grade dysplasia. All P values were from two-sided tests.

Results: After a mean of 7.0 years of follow-up, 79 patients were diagnosed with esophageal cancer, 16 with cancer of the gastric cardia, and 36 with high-grade dysplasia. In the entire cohort, incidence of esophageal or gastric cardia cancer or high-grade dysplasia combined was 0.22% per year (95% confidence interval [CI] = 0.19% to 0.26%). SIM was found in 46.0% of patients. In patients with SIM, the combined incidence was 0.38% per year (95% CI = 0.31 to 0.46%). The risk of cancer was statistically significantly elevated in patients with vs without SIM at index biopsy (0.38% per year vs 0.07% per year; hazard ratio [HR] = 3.54, 95% CI = 2.09 to 6.00, P <. 001), in men compared with women (0.28% per year vs 0.13% per year; HR = 2.11, 95% CI = 1.41 to 3.16, P <. 001), and in patients with low-grade dysplasia compared with no dysplasia (1.40% per year vs 0.17% per year; HR = 5.67, 95% CI = 3.77 to 8.53, P <. 001).

Conclusion: We found the risk of malignant progression among patients with BE to be lower than previously reported, suggesting that currently recommended surveillance strategies may not be cost-effective. © The Author 2011. Published by Oxford University Press. All rights reserved.

Potentially Inappropriate Medications Defined by STOPP Criteria and the Risk of Adverse Drug Events in Older Hospitalized Patients

Background: Previous studies have not demonstrated a consistent association between potentially inappropriate medicines (PIMs) in older patients as defined by Beers criteria and avoidable adverse drug events (ADEs). This study aimed to assess whether PIMs defined by new STOPP (Screening Tool of Older Persons’ potentially inappropriate Prescriptions) criteria are significantly associated with ADEs in older people with acute illness.

Methods: We prospectively studied 600 consecutive patients 65 years or older who were admitted with acute illness to a university teaching hospital over a 4-month interval. Potentially inappropriate medicines were defined by both Beers and STOPP criteria. Adverse drug events were defined by World Health Organization–Uppsala Monitoring Centre criteria and verified by a local expert consensus panel, which also assessed whether ADEs were causal or contributory to current hospitalization. Hallas criteria defined ADE avoidability.Wecompared the proportions of patients taking Beers criteria PIMs
and STOPP criteria PIMs with avoidable ADEs that were causal or contributory to admission.

Results: A total of 329 ADEs were detected in 158 of 600 patients (26.3%); 219 of 329 ADEs (66.6%) were considered causal or contributory to admission. Of the 219 ADEs, 151(68.9%)considered causal or contributory to admission were avoidable or potentially avoidable. After adjusting for age, sex, comorbidity, dementia, baseline activities of daily living function, and number of medications, the likelihood of a serious avoidable ADE increased significantly when STOPP PIMs were prescribed (odds ratio, 1.847; 95% confidence interval [CI], 1.506-2.264; P.001); prescription of Beers criteria PIMs did not significantly increase ADE risk (odds ratio, 1.276; 95% CI, 0.945-1.722; P=.11).

Conclusion: STOPP criteria PIMs,unlike Beers criteria PIMs, are significantly associated with avoidable ADEs in older people that cause or contribute to urgent hospitalization.

Decreased respiratory system compliance on the sixth day of mechanical ventilation is a predictor of death in patients with established acute lung injury

Background: Multiple studies have identified single variables or composite scores that help risk stratify patients at the time of acute lung injury (ALI) diagnosis. However, few studies have addressed the important question of how changes in pulmonary physiologic variables might predict mortality in patients during the subacute or chronic phases of ALI. We studied pulmonary physiologic variables, including respiratory system compliance, P/F ratio and oxygenation index, in a cohort of patients with ALI who survived more than 6 days of mechanical ventilation to see if changes in these variables were predictive of death and whether they are informative about the pathophysiology of subacute ALI.

EFFECT OF EXERCISE ON THE NASAL TRANSMUCOSAL POTENTIAL DIFFERENCE IN PATIENTS WITH CYSTIC-FIBROSIS AND NORMAL SUBJECTS

Background - Normal subjects have a negative nasal transmucosal potential difference (TPD) at rest which becomes more negative with exercise. Patients with cystic fibrosis have a more negative resting nasal TPD than controls. The present study was designed to determine the effects of exercise on the TPD of patients with cystic fibrosis.

The addition of arsenic trioxide to low-dose Ara-C in older patients with AML does not improve outcome

Most patients with acute myeloid leukaemia (AML) are older, with many unsuitable for conventional chemotherapy. Low-dose Ara-C (LDAC) is superior to best supportive care but is still inadequate. The combination of arsenic trioxide (ATO) and LDAC showed promise in an unrandomised study. We report a randomised trial of LDAC versus LDAC + ATO. Patients with AML according to WHO criteria or myelodysplastic syndrome with > 10% blasts, considered as unfit for conventional chemotherapy, were randomised between subcutaneous Ara-C (20mg b.d. for 10 days) and the same LDAC schedule with ATO (0.25 mg/kg) on days 1-5, 9 and 11, for at least four courses every 4 to 6 weeks. Overall 166 patients were entered; the trial was terminated on the advice of the DMC, as the projected benefit was not observed. Overall 14% of patients achieved complete remission (CR) and 7% CRi. Median survival was 5.5 months and 19 months for responders (CR: not reached; CRi: 14 months; non-responders: 4 months). There were no differences in response or survival between the arms. Grade 3/4 cardiac and liver toxicity, and supportive care requirements were greater in the ATO arm. This randomised comparison demonstrates that adding ATO to LDAC provides no benefit for older patients with AML. Leukemia (2011) 25, 1122-1127; doi:10.1038/leu.2011.59; published online 8 April 2011

Circulating and synovial antibody profiling of juvenile arthritis patients by nucleic acid programmable protein arrays.

Introduction Juvenile idiopathic arthritis (JIA) is a heterogeneous disease characterized by chronic joint inflammation of unknown cause in children. JIA is an autoimmune disease and small numbers of auto-antibodies have been reported in JIA patients. The identification of antibody markers could improve the existing clinical management of patients. Methods A pilot study was performed on the application of a high-throughput platform, nucleic acid programmable protein arrays (NAPPA), to assess the levels of antibodies present in the systemic circulation and synovial joint of a small cohort of juvenile arthritis patients. Plasma and synovial fluid from ten JIA patients was screened for antibodies against 768 proteins on NAPPA. Results Quantitative reproducibility of NAPPA was demonstrated with >0.95 intra- and inter- array correlations. A strong correlation was also observed for the levels of antibodies between plasma and synovial fluid across the study cohort (r=0.96). Differences in the levels of 18 antibodies were revealed between sample types across all patients. Patients were segregated into two clinical subtypes with distinct antibody signatures by unsupervised hierarchical cluster analysis. Conclusions NAPPA provides a high-throughput quantitatively reproducible platform to screen for disease specific autoantibodies at the proteome level on a microscope slide. The strong correlation between the circulating antibody levels and those of the inflamed joint represents a novel finding and provides confidence to use plasma for discovery of autoantibodies in JIA, thus circumventing the challenges associated with joint aspiration. We expect that autoantibody profiling of JIA patients on NAPPA could yield antibody markers that can act as criteria to stratify patients, predict outcomes and understand disease etiology at the molecular level.

New prognostic markers, determined using gene expression analyses, reveal two distinct subtypes of chronic myelomonocytic leukaemia patients

Chronic myelomonocytic leukaemia (CMML) is a heterogeneous haematopoietic disorder characterized by myeloproliferative or myelodysplastic features. At present, the pathogenesis of this malignancy is not completely understood. In this study, we sought to analyse gene expression profiles of CMML in order to characterize new molecular outcome predictors. A learning set of 32 untreated CMML patients at diagnosis was available for TaqMan low-density array gene expression analysis. From 93 selected genes related to cancer and cell cycle, we built a five-gene prognostic index after multiplicity correction. Using this index, we characterized two categories of patients with distinct overall survival (94% vs. 19% for good and poor overall survival, respectively; P = 0.007) and we successfully validated its strength on an independent cohort of 21 CMML patients with Affymetrix gene expression data. We found no specific patterns of association with traditional prognostic stratification parameters in the learning cohort. However, the poor survival group strongly correlated with high-risk treated patients and transformation to acute myeloid leukaemia. We report here a new multigene prognostic index for CMML, independent of the gene expression measurement method, which could be used as a powerful tool to predict clinical outcome and help physicians to evaluate criteria for treatments.

Safety and efficacy of a CXCR2 antagonist in patients with severe asthma and sputum neutrophils:a randomized, placebo-controlled clinical trial

Increased numbers of neutrophils are reported in the airways of patients with severe asthma. It is not clear if they contribute to the lack of control and severity. There are currently no strategies to investigate this by decreasing neutrophil numbers in the airways.

Experiences of carers supporting dying renal patients managed without dialysis

Aim: To explore the impact of being a family carer to patients with stage 5 chronic kidney disease managed without dialysis.
Background: Increasing numbers of patients with renal disease worldwide are making the decision not to embark on dialysis. This group has significant physical and psychological symptom burdens similar to or greater than those in advanced cancer patients. Little is known about the impact on family carers.
Design: Exploratory, qualitative design.
Methods: The study was undertaken with 19 carers caring for patients managed in a Renal Supportive Care Service in the UK between 2006–2008. Sixty-one semi-structured interviews and detailed field notes inform the analysis.
Findings: ‘Caring from diagnosis to death’ was the overarching theme illustrated by three sub-themes: (i) Caregiver's plight – making sense of the disease and potential deterioration; (ii) Having to care indefinitely; and (iii) Avoiding talk of death. ‘Caring from diagnosis to death’ coincides with an original concept analysis of renal supportive care, which is considered an adjunct to the management of patients with renal disease at all stages of their illness.
Conclusion: There is a clear need for further research internationally and theory-based nursing interventions to support carers of patients managed without dialysis. The development of a holistic, integrated care pathway based on carer perspectives, which includes identification of information needs related to original diagnosis, associated comorbidities, treatment options, prognosis, and assistance in developing strategies to manage communication with patients as the end of life approaches, is required.