A distinct DNA methylation signature defines pediatric pre-B cell acute lymphoblastic leukemia

Pre-B cell acute lymphoblastic leukemia (ALL) is the most prevalent childhood malignancy and remains one of the highest causes of childhood mortality. Despite this, the mechanisms leading to disease remain poorly understood. We asked if recurrent aberrant DNA methylation plays a role in childhood ALL and have defined a genome-scale DNA methylation profile associated with the ETV6-RUNX1 subtype of pediatric ALL. Archival bone marrow smears from 19 children collected at diagnosis and remission were used to derive a disease specific DNA methylation profile. The gene signature was confirmed in an independent cohort of 86 patients. A further 163 patients were analyzed for DNA methylation of a three gene signature. We found that the DNA methylation signature at diagnosis was unique from remission. Fifteen loci were sufficient to discriminate leukemia from disease-free samples and purified CD34+ cells. DNA methylation of these loci was recurrent irrespective of cytogenetic subtype of pre-B cell ALL. We show that recurrent aberrant genomic methylation is a common feature of pre-B ALL, suggesting a shared pathway for disease development. By revealing new DNA methylation markers associated with disease, this study has identified putative targets for development of novel epigenetic-based therapies.

The acute effects of caffeine in a sugar-sweetened beverage on energy consumption

Background: It has been suggested that those who are habitually high caffeine consumers ingest greater quantities of snack foods both in and outside the laboratory. Sugar-sweetened beverages (SSBs) are a major contributor to caffeine consumption and evidence links SSB consumption with poor dietary intake.

Objective: To determine whether varying the concentration of caffeine in SSBs influences snack food consumption and energy intake.

Methods: Caffeine taste thresholds were assessed using the International Standards Organization method for assessing taste sensitivity. In a crossover study design, participants (n=23, 26±5 years old, 58% female) were provided with a standardized meal on 4 days and simultaneously consumed SSBs with varied levels of caffeine (0, 0.67, 1.16, and 1.65 mM). The intake of food and beverage was recorded following each meal session.

Results: A one way between groups analysis of variance revealed no significant main effect of caffeine concentration on consumption of SSBs [F (3, 92)=0.154, p=0.927] or food [F (3, 92)=0.305, p=0.822]. Pearson correlation analysis identified no significant correlations between the amount of food and SSB consumed (R=−0.031–0.415, p=0.062–0.893), or the amount of food and SSB consumed with body mass index and waist circumference (R=0.000 to −0.380, p=0.073–0.999). An individual's oral sensitivity to caffeine was not associated with SSB consumption (R=0.045 to −0.309, p=0.152–0.839) or the consumption of food (R=−0.052 to −0.327, p=0.128–0.812).

Conclusions: The concentration of caffeine in SSBs did not influence the amount of food or SSB consumed.

Risk factors for incident delirium in acute medical in-patients. A systematic review

Review question/objective
What risk factors are associated with incident delirium in adult patients during an acute medical hospitalisation?
More specifically, the objectives are to:
Identify and synthesise the best available evidence on the factors which are associated with delirium in adult patients admitted to acute medical facilities.

Types of participants
This review will consider studies that include adults (defined as 18 years and above) who were admitted to an acute medical setting (e.g. general medical units, stroke units, short stay units and neuromedical units) who were not delirious on admission (in order to differentiate incident delirium) but who developed incident delirium during hospitalisation

The review will exclude patients who were:
- critically ill and admitted to specialist unit e.g. ICU or CCU
- admitted for any type of surgery
- admitted for alcohol related reasons
- admitted to psychiatric facility
These patients will be excluded in order to determine factors that may be exclusive to the medical in patient setting.

Types of intervention(s)/phenomena of interest
This review will consider studies that evaluate any risk factors that may contribute to the development of delirium during in-patient hospitalisation. The review will look at factors present on admission (predisposing) and also factors that may occur during hospitalisation (precipitating) that contribute to incident delirium.

Types of outcomes
This review will consider studies that include the following outcome measures: the incidence of delirium as related to individual risk factors.

Characteristics and outcomes of patients requiring unplanned transfer from subacute to acute care

The study aims to identify the reasons for, and outcomes from, unplanned transfers from subacute care to acute care. A retrospective patient record review of patients requiring unplanned transfer from subacute to an acute care emergency department (ED) from 1 July 2008 to 30 June 2009 was undertaken. Data collected included patient demographics, clinical characteristics in preceding transfer, and on ED arrival and outcome data. There were 136 patients included in the study with a median age of 81 years. The most common reasons for transfer were respiratory problems and altered conscious state. In the 24 h preceding transfer, 92.6% of patients had ≥ 1 physiological abnormality and 10.3% of patients had no physiological parameters documented. On ED arrival, 75% of patients had physiological abnormalities. Hospital admission occurred in 75% of patients and the inpatient mortality rate was 14.7%. Factors associated with inpatient mortality were tachypnoea and severe hypoxaemia in 24 h preceding transfer and tachypnoea, hypoxaemia, hypoxaemia, severe hypoxaemia and hypothermia on ED arrival. Patients requiring unplanned transfer had higher inpatient mortality than older hospital users. Reasons for unplanned transfer reflect known predictors of in-hospital adverse events so predictive use of physiological data and patient characteristics might optimize patient safety.

Assessing risk post intervention for an acute coronary syndrome: a review of the risk assessment tools and their development

Considerable variability in survival rate after an acute myocardial infarction exists and accurate risk stratification is of significant importance. The American College of Cardiology and the American Heart Association has recommended early risk stratification using several clinical risk scoring instruments to identify high risk patients. The aim of this paper is to identify secondary cardiovascular risk scoring instruments that could be utilized at the time of intervention for acute coronary syndromes and compare their psychometric properties as they were developed. A search using Medline, Cumulative Index to Nursing and Allied Health Literature and the Psychology and Behavioral Sciences Collection data-bases identified studies published between January 1990 and January 2010 used to measure risk after intervention for acute coronary syndrome. Four validated secondary risk prediction scoring instruments were identified for comparison.Secondary risk prediction scoring instruments for the acute coronary syndrome patient population are evidence based, valid and reliable. Use of the instruments by cardiac focused clinicians will aid in the determination of treatment strategies, and estimation of short and long term events and mortality.

Risk factors for incident delirium in acute medical in-patients: a systematic review

Delirium is a serious problem that can occur in many older people admitted to hospital. Delirium has the potential to dramatically complicate the hospitalisation of a patient, and often results in functional decline, an increased likelihood of complications associated with longer hospital stays, increasing the risk of admission to a care facility post discharge, a greater incidence of falls and is associated with high mortality and morbidity rates. Understanding the factors that contribute to delirium can provide insights into the mechanisms that underlie the syndrome.

The 6-PACK programme to decrease falls and fall-related injuries in acute hospitals : protocol for an economic evaluation alongside a cluster randomised controlled trial

Background Falls are a common hospital occurrence complicating the care of patients. From an economic perspective, the impact of in-hospital falls and related injuries is substantial. However, few studies have examined the economic implications of falls prevention interventions in an acute care setting. The 6-PACK programme is a targeted nurse delivered falls prevention programme designed specifically for acute hospital wards. It includes a risk assessment tool and six simple strategies that nurses apply to patients classified as high-risk by the tool.
Objective To examine the incremental cost-effectiveness of the 6-PACK programme for the prevention of falls and fall-related injuries, compared with usual care practice, from an acute hospital perspective.
Methods and design The 6-PACK project is a multicentre cluster randomised controlled trial (RCT) that includes 24 acute medical and surgical wards from six hospitals in Australia to investigate the efficacy of the 6-PACK programme. This economic evaluation will be conducted alongside the 6-PACK cluster RCT. Outcome and hospitalisation cost data will be prospectively collected on approximately 16 000 patients admitted to the participating wards during the 12-month trial period. The results of the economic evaluation will be expressed as ‘cost or saving per fall prevented’ and ‘cost or saving per fall-related injury prevented’ calculated from differences in mean costs and effects in the intervention and control groups, to generate an incremental cost-effectiveness ratio (ICER).
Discussion This economic evaluation will provide an opportunity to explore the cost-effectiveness of a targeted nurse delivered falls prevention programme for reducing in-hospital falls and fall-related injuries. This protocol provides a detailed statement of a planned economic evaluation conducted alongside a cluster RCT to investigate the efficacy of the 6-PACK programme to prevent falls and fall-related injuries.

Treatment response for acute depression is not associated with number of previous episodes: lack of evidence for a clinical staging model for major depressive disorder

Mental illness has been observed to follow a neuroprogressive course, commencing with prodrome, then onset, recurrence and finally chronic illness. In bipolar disorder and schizophrenia responsiveness to treatment mirrors these stages of illness progression, with greater response to treatment in the earlier stages of illness and greater treatment resistance in chronic late stage illness.

Using data from 5627 participants in 15 controlled trials of duloxetine, comparator arm (paroxetine, venlafaxine, escitalopram) or placebo for the treatment of an acute depressive episode, the relationship between treatment response and number of previous depressive episodes was determined. Data was dichotomised for comparisons between participants who had >3 previous episodes (n=1697) or ≤3 previous episodes (n=3930), and additionally for no previous episodes (n=1381) or at least one previous episode (n=4246). Analyses were conducted by study arm for each clinical trial, and results were then pooled.

There was no significant difference between treatment response and number of previous depressive episodes. This unexpected finding suggests that treatments to reduce symptoms of depression during acute illness do not lose efficacy for patients with a longer history of illness.