Intervention With an Erythropoietin-Derived Peptide Protects Against Neuroglial and Vascular Degeneration During Diabetic Retinopathy.

OBJECTIVE:
Erythropoietin (EPO) may be protective for early stage diabetic retinopathy, although there are concerns that it could exacerbate retinal angiogenesis and thrombosis. A peptide based on the EPO helix-B domain (helix B-surface peptide [pHBSP]) is nonerythrogenic but retains tissue-protective properties, and this study evaluates its therapeutic potential in diabetic retinopathy.
RESEARCH DESIGN AND METHODS:
After 6 months of streptozotocin-induced diabetes, rats (n = 12) and age-matched nondiabetic controls (n = 12) were evenly split into pHBSP and scrambled peptide groups and injected daily (10 µg/kg per day) for 1 month. The retina was investigated for glial dysfunction, microglial activation, and neuronal DNA damage. The vasculature was dual stained with isolectin and collagen IV. Retinal cytokine expression was quantified using real-time RT-PCR. In parallel, oxygen-induced retinopathy (OIR) was used to evaluate the effects of pHBSP on retinal ischemia and neovascularization (1-30 µg/kg pHBSP or control peptide).
RESULTS:
pHBSP or scrambled peptide treatment did not alter hematocrit. In the diabetic retina, Müller glial expression of glial fibrillary acidic protein was increased when compared with nondiabetic controls, but pHBSP significantly reduced this stress-related response (P < 0.001). CD11b+ microglia and proinflammatory cytokines were elevated in diabetic retina responses, and some of these responses were attenuated by pHBSP (P < 0.01-0.001). pHBSP significantly reduced diabetes-linked DNA damage as determined by 8-hydroxydeoxyguanosine and transferase-mediated dUTP nick-end labeling positivity and also prevented acellular capillary formation (P < 0.05). In OIR, pHBSP had no effect on preretinal neovascularization at any dose.
CONCLUSIONS:
Treatment with an EPO-derived peptide after diabetes is fully established can significantly protect against neuroglial and vascular degenerative pathology without altering hematocrit or exacerbating neovascularization. These findings have therapeutic implications for disorders such as diabetic retinopathy.

Are causal and intervention judgments inextricably linked? A developmental study.

The application of the formal framework of causal Bayesian Networks to children's causal learning provides the motivation to examine the link between judgments about the causal structure of a system, and the ability to make inferences about interventions on components of the system. Three experiments examined whether children are able to make correct inferences about interventions on different causal structures. The first two experiments examined whether children's causal structure and intervention judgments were consistent with one another. In Experiment 1, children aged between 4 and 8years made causal structure judgments on a three-component causal system followed by counterfactual intervention judgments. In Experiment 2, children's causal structure judgments were followed by intervention judgments phrased as future hypotheticals. In Experiment 3, we explicitly told children what the correct causal structure was and asked them to make intervention judgments. The results of the three experiments suggest that the representations that support causal structure judgments do not easily support simple judgments about interventions in children. We discuss our findings in light of strong interventionist claims that the two types of judgments should be closely linked. © 2011 Cognitive Science Society, Inc.


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Reaxys Database Information|

Reflexology for symptom relief in patients with cancer

Complementary therapies are increasingly being used in hospices and hospitals alongside orthodox treatments in an attempt to improve patients' emotional, spiritual, psychological, and physical well-being. An average of 31% of UK patients with cancer use some form of complementary therapy. Many UK cancer centers, out-patient units, and hospices are providing complementary services. There is strong anecdotal evidence that complementary therapies assist in the palliation of physical and psychological symptoms. This systematic review examines the research evidence base for the effectiveness of reflexology in cancer care. The study reports the results of a systematic review following the Cochrane principles of systematic reviewing. No meta-analysis was possible. Studies were retrieved from a comprehensive search of electronic databases from their start dates. An initial search was carried out in 2003 and updated in 2005 to 2006. Eligible studies were randomized controlled trials, controlled before and after studies, and interrupted time-series studies. Participants were adults with a diagnosis of cancer, receiving care in any healthcare setting. Interventions were limited to reflexology carried out by a qualified therapist as distinguished from another healthcare professional carrying out a reflexology intervention. Outcome measures were patient-reported levels of physical and psychological indices of symptom distress and quality of life (measured using validated assessment tools). Copyright © 2008 Lippincott Williams & Wilkins

Using bar-code technology to capture clinical intervention data in a hospital with a stand-alone pharmacy computer system

The use of barcode technology to capture data on pharmacists' clinical interventions is described.

Treatment Foster Care for improving outcomes in children and young people (Review)

Background: Treatment foster care (TFC) is a foster family-based intervention that aims to provide young people (and, where appropriate, their families) with a tailored programme designed to effect positive changes in their lives. TFC was designed specifically to cater for the needs of children whose difficulties or circumstances place them at risk of multiple placements and/or more restrictive placements such as hospital or secure residential or youth justice settings.

Objectives: To assess the impact of TFC on psychosocial and behavioural outcomes, delinquency, placement stability, and discharge status for children and adolescents who require out-of-home placement.

Search methods: We searched the Cochrane Controlled Trials Register (CENTRAL) 2006 (Issue 4), MEDLINE (1966 to January 2007), CINAHL (1982 to December 2006), PsycINFO (1872 to January 2007), ASSIA (1987 to January 2007), LILACS (1982 to January 2007), ERIC (1966 to January 2007), Sociological Abstracts (1963 to January 2007), and the National Research Register 2006 (Issue 4).

Selection criteria: Included studies were randomised controlled trials investigating the effectiveness of TFC with children and young people up to the age of 18 who, for reasons of severe medical, social, psychological and behavioural problems, were placed in out of home care in restrictive settings (e.g. secure residential care, psychiatric hospital) or at risk of placement in such settings.

Data collection and analysis: Titles and abstracts identified in the search were independently assessed for eligibility by the two authors (GM and WT) who also extracted and entered into REVMAN. Date were synthesised on the few occasions where this was possible. Results are presented in tabular, graphical (forest plots) and textual form.

Main results: Five studies including 390 participants were included in this review. Data suggest that treatment foster care may be a useful intervention for children and young people with complex emotional, psychological and behavioural need, who are at risk of placements in nonfamily settings that restrict their liberty and opportunities for social inclusion.

Authors’ conclusions: Although the inclusion criteria for this systematic review set a study design threshold higher than that of previous reviews, the results mirror those of earlier reviews but also highlights the tendency of the perceived effectiveness of popular interventions to outstrip their evidence base. Whilst the results of individual studies generally indicate that TFC is a promising intervention for children and youth experiencing mental health problems, behavioural problems or problems of delinquency, the evidence base is less robust than that usually reported.The Cochrane Database of Systematic Reviews is a peer reviewed, international journal, published electronically each month. The 2010 Inpact Factor for the Cochrane Database of Systematic Reviews was 6.185.The CDSR is now ranked in the top 10 of the 151 in the Medicine, General & Internal category.

Cognitive-behavioural interventions for children who have been sexually abused

Background: Despite differences in how it is defined, there is a general consensus amongst clinicians and researchers that the sexual abuse of children and adolescents (’child sexual abuse’) is a substantial social problem worldwide. The effects of sexual abuse manifest in a wide range of symptoms, including fear, anxiety, post-traumatic stress disorder and various externalising and internalising behaviour problems, such as inappropriate sexual behaviours. Child sexual abuse is associated with increased risk of psychological problems in adulthood. Cognitive-behavioural approaches are used to help children and their non-offending or ’safe’ parent tomanage the sequelae of childhood sexual abuse. This review updates the first Cochrane review of cognitive-behavioural approaches interventions for children who have been sexually abused, which was first published in 2006.

Objectives: To assess the efficacy of cognitive-behavioural approaches (CBT) in addressing the immediate and longer-term sequelae of sexual abuse on children and young people up to 18 years of age.

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2011 Issue 4); MEDLINE (1950 to November Week
3 2011); EMBASE (1980 to Week 47 2011); CINAHL (1937 to 2 December 2011); PsycINFO (1887 to November Week 5 2011); LILACS (1982 to 2 December 2011) and OpenGrey, previously OpenSIGLE (1980 to 2 December 2011). For this update we also searched ClinicalTrials.gov and the International Clinical Trials Registry Platform (ICTRP).

Selection criteria: We included randomised or quasi-randomised controlled trials of CBT used with children and adolescents up to age 18 years who had experienced being sexually abused, compared with treatment as usual, with or without placebo control.

Data collection and analysis: At least two review authors independently assessed the eligibility of titles and abstracts identified in the search. Two review authors independently extracted data from included studies and entered these into Review Manager 5 software. We synthesised and presented data in both written and graphical form (forest plots).

Main results: We included 10 trials, involving 847 participants. All studies examined CBT programmes provided to children or children and a nonoffending parent. Control groups included wait list controls (n = 1) or treatment as usual (n = 9). Treatment as usual was, for the most part, supportive, unstructured psychotherapy. Generally the reporting of studies was poor. Only four studies were judged ’low risk of bias’ with regards to sequence generation and only one study was judged ’low risk of bias’ in relation to allocation concealment. All studies were judged ’high risk of bias’ in relation to the blinding of outcome assessors or personnel; most studies did not report on these, or other issues of bias. Most studies reported results for study completers rather than for those recruited.

Depression, post-traumatic stress disorder (PTSD), anxiety and child behaviour problems were the primary outcomes. Data suggest that CBT may have a positive impact on the sequelae of child sexual abuse, but most results were not statistically significant. Strongest evidence for positive effects of CBT appears to be in reducing PTSD and anxiety symptoms, but even in these areas effects tend to be 'moderate’ at best. Meta-analysis of data from five studies suggested an average decrease of 1.9 points on the Child Depression Inventory immediately after intervention (95% confidence interval (CI) decrease of 4.0 to increase of 0.4; I2 = 53%; P value for heterogeneity = 0.08), representing a small to moderate effect size. Data from six studies yielded an average decrease of 0.44 standard deviations on a variety of child post-traumatic stress disorder scales (95% CI 0.16 to 0.73; I2 = 46%; P value for heterogeneity = 0.10). Combined data from five studies yielded an average decrease of 0.23 standard deviations on various child anxiety scales (95% CI 0.3 to 0.4; I2=0%; P value for heterogeneity = 0.84). No study reported adverse effects.

Authors’ conclusions: The conclusions of this updated review remain the same as those when it was first published. The review confirms the potential of CBT to address the adverse consequences of child sexual abuse, but highlights the limitations of the evidence base and the need for more carefully conducted and better reported trials.

Behavioural and cognitive behavioural training interventions for assisting foster carers in the management of difficult behaviour.

Background The provision of training for foster carers is now seen as an important factor contributing to the successful outcome of foster care placements. Since the late 1960s, foster carer training programs have proliferated, and few of the many published and unpublished training curricula have been systematically evaluated. The advent of cognitive-behavioural therapy (CBT) and the research evidence demonstrating its effectiveness as a psychotherapeutic treatment of choice for a range of emotional and behavioural problems, has prompted the development of CBT-based training programmes. CBT approaches to foster care training derive from a ’skill-based’ training format that also seeks to identify and correct problematic thinking patterns that are associated with dysfunctional behaviour by changing and/or challenging maladaptive thoughts and beliefs. Objectives To assess the effectiveness of cognitive-behavioural training interventions in improving a) looked-after children’s behavioural/relationship problems, b) foster carers’ psychological well-being and functioning, c) foster family functioning, d) foster agency outcomes. Search methods We searched databases including: CENTRAL (Cochrane Library Issue 3, 2006), MEDLINE (January 1966 to September 2006), EMBASE (January 1980 to September 2006), CINAHL (January 1982 to September 2006), PsycINFO (January 1872 to September 2006), ASSIA (January 1987 to September 2006), LILACS (up to September 2006), ERIC (January 1965 to September 2006), Sociological Abstracts (January 1963 to September 2006), and the National Research Register 2006 (Issue 3).We contacted experts in the field concerning current research. Selection criteria Random or quasi randomised studies comparing behavioural or cognitive-behavioural-base Data collection and analysis Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. Main results Six trials involving 463 foster carers were included. Behavioural and cognitive-behavioural training interventions evaluated to date appear to have very little effect on outcomes relating to looked-after children, assessed in relation to psychological functioning, extent of behavioural problems and interpersonal functioning. Results relating to foster carer(s) outcomes also show no evidence of effectiveness in measures of behavioural management skills, attitudes and psychological functioning. Analysis pertaining to fostering agency outcomes did not show any significant results. However, caution is needed in interpreting these findings as their confidence intervals are wide. Authors’ conclusions There is currently little evidence about the efficacy of behavioural or cognitive-behavioural training intervention for foster carers. The need for further research in this area is highlighted.

Patient selection for oncology phase I trials: a multi-institutional study of prognostic factors.

PURPOSE The appropriate selection of patients for early clinical trials presents a major challenge. Previous analyses focusing on this problem were limited by small size and by interpractice heterogeneity. This study aims to define prognostic factors to guide risk-benefit assessments by using a large patient database from multiple phase I trials. PATIENTS AND METHODS Data were collected from 2,182 eligible patients treated in phase I trials between 2005 and 2007 in 14 European institutions. We derived and validated independent prognostic factors for 90-day mortality by using multivariate logistic regression analysis. Results The 90-day mortality was 16.5% with a drug-related death rate of 0.4%. Trial discontinuation within 3 weeks occurred in 14% of patients primarily because of disease progression. Eight different prognostic variables for 90-day mortality were validated: performance status (PS), albumin, lactate dehydrogenase, alkaline phosphatase, number of metastatic sites, clinical tumor growth rate, lymphocytes, and WBC. Two different models of prognostic scores for 90-day mortality were generated by using these factors, including or excluding PS; both achieved specificities of more than 85% and sensitivities of approximately 50% when using a score cutoff of 5 or higher. These models were not superior to the previously published Royal Marsden Hospital score in their ability to predict 90-day mortality. CONCLUSION Patient selection using any of these prognostic scores will reduce non-drug-related 90-day mortality among patients enrolled in phase I trials by 50%. However, this can be achieved only by an overall reduction in recruitment to phase I studies of 20%, more than half of whom would in fact have survived beyond 90 days.