Reduction in cytokine production in colorectal cancer patients: association with stage and reversal by resection

The aim of this study was to assess monocyte/macrophage function, as defined by lipopolysaccharide (LPS)-induced production of tumour necrosis factor (TNF)-α, interleukin (IL)-10 and interferon (IFN)-γ by stimulated whole blood cultures in patients with colorectal carcinoma before and after surgical resection. Forty colorectal cancer patients prior to surgery and 31 healthy controls were studied. Heparinized venous blood was taken from colorectal cancer patients prior to surgery and from healthy controls. Serial samples were obtained at least 3–6 weeks post-operatively. Blood was stimulated with LPS for 24 h and supernatants were assayed for TNF-α, IFN-γ and IL-10 by enzyme-linked immunosorbent assay. LPS-induced production of TNF-α and of IFN-γ was reduced in patients with colorectal carcinoma compared to controls (TNF-α, 11 269 pg ml−1{12 598}; IFN-γ, 0.00 pg ml−1{226}; median {IQR}) (TNF-α, 20 576 pg ml−1{11 637}, P< 0.0001; IFN-γ, 1048 {2428}, P = 0.0051, Mann–Whitney U -test). Production in patients after surgery had increased (TNF-α: 17 620 pg ml−1{7986}; IFN-γ: 410 pg ml−1{2696}; mean {s.d.}) and were no longer significantly reduced when compared to controls (TNF-α, P = 0.28; IFN-γ, P = 0.76). Production of TNF-α and IFN-γ prior to surgery were reduced to a greater extent in patients with Dukes' stage C tumours compared to those with Dukes' stage A and B stage. There was no difference in IL-10 production between any group. Monocytes/macrophages from patients with colorectal carcinoma are refractory to LPS stimulation as reflected by reduction in TNF-α and IFN-γ production and this is more pronounced in patients with advanced stage tumours. This suppression is not mediated by IL-10 and disappears following surgical resection of the tumour. This provides evidence for tumour induced suppression of immune function in patients with colorectal cancer and identifies a potential therapeutic avenue. © 2000 Cancer Research Campaig

Interprofessional Communication of Clinicians Using a Mobile Phone App: A Randomized Crossover Trial Using Simulated Patients

Background: Most hospitals use paging systems as the principal communication system, despite general dissatisfaction by end users. To this end, we developed an app-based communication system (called Hark) to facilitate and improve the quality of interpersonal communication. Objective: The objectives of our study were (1) to assess the quality of information transfer using pager- and app-based (Hark) communication systems, (2) to determine whether using mobile phone apps for escalation of care results in additional delays in communication, and (3) to determine how end users perceive mobile phone apps as an alternative to pagers. Methods: We recruited junior (postgraduate year 1 and 2) doctors and nurses from a range of specialties and randomly assigned them to 2 groups who used either a pager device or the mobile phone-based Hark app. We asked nurses to hand off simulated patients while doctors were asked to receive handoff information using these devices. The quality of information transfer, time taken to respond to messages, and users’ satisfaction with each device was recorded. Each participant used both devices with a 2-week washout period in between uses. Results: We recruited 22 participants (13 nurses, 9 doctors). The quality of the referrals made by nurses was significantly better when using Hark (Hark median 118, range 100–121 versus pager median 77, range 39–104; P=.001). Doctors responded to messages using Hark more quickly than when responding to pagers, although this difference was not statistically significant (Hark mean 86.6 seconds, SD 96.2 versus pager mean 136.5 seconds, SD 201.0; P=.12). Users rated Hark as significantly better on 11 of the 18 criteria of an information transfer device (P<.05) These included “enhances interprofessional efficiency,” “results in less disturbance,” “performed desired functions reliably,” and “allows me to clearly transfer information.” Conclusions: Hark improved the quality of transfer of information about simulated patients and was rated by users as more effective and efficient, and less distracting than pagers. Using this device did not result in delay in patient care

National observational study to evaluate the "cleanyourhands" campaign (NOSEC): a questionnaire based study of national implementation

INTRODUCTION: The number of national hand-hygiene campaigns has increased recently, following the World Health Organisation's (WHO) "Save Lives: clean your hands" initiative (2009), which offers hospitals a multi-component hand-hygiene intervention. The number of campaigns to be evaluated remains small. Most evaluations focus on consumption of alcohol hand rub (AHR). We are not aware of any evaluation reporting implementation of all campaign components. In a previously published report, we evaluated the effects of the English and Welsh cleanyourhands campaign (2004-8) on procurement of AHR and soap, and on selected healthcare associated infections. We now report on the implementation of each individual campaign component: provision of bedside AHR, ward posters, patient empowerment materials, audit and feedback, and guidance to secure institutional engagement. METHOD: SETTING: all 189 acute National Health Service (NHS) hospitals in England and Wales (December 2005-June 2008). Six postal questionnaires (five voluntary, one mandatory) were distributed to infection control teams six-monthly from 6 to 36 months post roll-out. Selection and attrition bias were measured. RESULTS: Response rates fell from 134 (71 %) at 6 months to 82 (44 %) at 30 months, rising to 167 (90 %) for the final mandatory one (36 months). There was no evidence of attrition or selection bias. Hospitals reported widespread early implementation of bedside AHR and posters and a gradual rise in audit. At 36 months, 90 % of respondents reported the campaign to be a top hospital priority, with implementation of AHR, posters and audit reported by 96 %, 97 % and 91 % respectively. Patient empowerment was less successful. CONCLUSIONS: The study suggests that all campaign components, apart from patient empowerment, were widely implemented and sustained. It supports previous work suggesting that adequate piloting, strong governmental support, refreshment of campaigns, and sufficient time to engage institutions help secure sustained implementation of a campaign's key components. The results should encourage countries wishing to launch coordinated national campaigns for hospitals to participate in the WHO's "Save Lives" initiative, which offers hospitals a similar multi-component intervention

Comparison of the airway microbiota in children with chronic suppurative lung disease

Rationale: The airway microbiota is important in chronic suppurative lung diseases (CSLD), such as primary ciliary dyskinesia (PCD) and cystic fibrosis (CF). This comparison has not previously been described but is important because difference between the two diseases may relate to the differing prognoses and lead to pathological insights and potentially, new treatments. Objectives: To compare the longitudinal development of the airway microbiota in children with PCD to that of CF and relate this to age and clinical status. Methods: Sixty-two age-matched children (age range 0.5–17 years) with PCD or CF (n=31 in each group) were recruited prospectively and followed for 1.1 years. Throat swabs or sputum as well as clinical information were collected at routine clinical appointments. 16S rRNA gene sequencing was performed. Measurements and Main Results: The microbiota was highly individual and more diverse in PCD and differed in community composition when compared with CF. Whilst Streptococcus was the most abundant genus in both conditions, Pseudomonas was more abundant in CF with Haemophilus more abundant in PCD (Padj=0.0005). In PCD only, an inverse relationship was seen in the relative abundance of Streptococcus and Haemophilus with age. Conclusions: Bacterial community composition differs between children with PCD and those with CF. Pseudomonas is more prevalent in CF and Haemophilus in PCD, at least until infection with Pseudomonas supervenes. Interactions between organisms, particularly members of Haemophilus, Streptococcus, and Pseudomonas genera appear important. Study of the interactions between these organisms may lead to new therapies or risk stratification

Use of performance feedback to increase healthcare worker hand-hygiene behaviour

We will present some (formal) arguments that any Feynman diagram can be understood as a particular case of a Horn-type multivariable hypergeometric function. The advantages and disadvantages of this type of approach to the evaluation of Feynman diagrams is discussed

Balancing equity and efficiency in the Dutch basic benefits package using the principle of proportional shortfall

Economic evaluations are increasingly used to inform decisions regarding the allocation of scarce health care resources. To systematically incorporate societal preferences into these evaluations, quality-adjusted life year gains could be weighted according to some equity principle, the most suitable of which is a matter of frequent debate. While many countries still struggle with equity concerns for priority setting in health care, the Netherlands has reached a broad consensus to use the concept of proportional shortfall. Our study evaluates the concept and its support in the Dutch health care context. We discuss arguments in the Netherlands for using proportional shortfall and difficulties in transitioning from principle to practice. In doing so, we address universal issues leading to a systematic consideration of equity concerns for priority setting in health care. The article thus has relevance to all countries struggling with the formalization of equity concerns for priority setting

Mutations in CHMP2B in lower motor neuron predominant amyotrophic lateral sclerosis (ALS)

Background: Amyotrophic lateral sclerosis (ALS), a common late-onset neurodegenerative disease, is associated with fronto-temporal dementia (FTD) in 3-10% of patients. A mutation in CHMP2B was recently identified in a Danish pedigree with autosomal dominant FTD. Subsequently, two unrelated patients with familial ALS, one of whom also showed features of FTD, were shown to carry missense mutations in CHMP2B. The initial aim of this study was to determine whether mutations in CHMP2B contribute more broadly to ALS pathogenesis. Methodology/Principal Findings: Sequencing of CHMP2B in 433 ALS cases from the North of England identified 4 cases carrying 3 missense mutations, including one novel mutation, p. Thr104Asn, none of which were present in 500 neurologically normal controls. Analysis of clinical and neuropathological data of these 4 cases showed a phenotype consistent with the lower motor neuron predominant (progressive muscular atrophy (PMA)) variant of ALS. Only one had a recognised family history of ALS and none had clinically apparent dementia. Microarray analysis of motor neurons from CHMP2B cases, compared to controls, showed a distinct gene expression signature with significant differential expression predicting disassembly of cell structure; increased calcium concentration in the ER lumen; decrease in the availability of ATP; down-regulation of the classical and p38 MAPK signalling pathways, reduction in autophagy initiation and a global repression of translation. Transfection of mutant CHMP2B into HEK-293 and COS-7 cells resulted in the formation of large cytoplasmic vacuoles, aberrant lysosomal localisation demonstrated by CD63 staining and impairment of autophagy indicated by increased levels of LC3-II protein. These changes were absent in control cells transfected with wild-type CHMP2B. Conclusions/Significance: We conclude that in a population drawn from North of England pathogenic CHMP2B mutations are found in approximately 1% of cases of ALS and 10% of those with lower motor neuron predominant ALS. We provide a body of evidence indicating the likely pathogenicity of the reported gene alterations. However, absolute confirmation of pathogenicity requires further evidence, including documentation of familial transmission in ALS pedigrees which might be most fruitfully explored in cases with a LMN predominant phenotype