Neoadjuvant hormone therapy for radical prostate radiotherapy:bicalutamide monotherapy vs. luteinizing hormone-releasing hormone agonist monotherapy: a single-institution matched-pair analysis

The purpose of this study was to compare the prostate-specific antigen (PSA) response to either neoadjuvant bicalutamide (BC) monotherapy or neoadjuvant luteinizing hormone-releasing hormone agonist (LHRHa) monotherapy and the subsequent effect on biochemical failure-free survival (BFFS) in men receiving radical radiotherapy (RT) for localized prostate cancer.

A qualitative study exploring the perceived impact of supervision training on cognitive therapy supervisor practice

Although cognitive therapy (CT) has a large empirical base, research is lacking for CT supervision and supervision training, which presents an obstacle for evidence-based practice. A pilot CT supervision training programme, based on Milne’s (2007a, 2009) evidence-based supervision and Roth and Pilling (2008) supervision competences was developed by the Northern Ireland Centre for Trauma and Transformation (NICTT), an organisation specialising in CT therapy provision and training. This study qualitatively explores CT supervisors’ perceptions of the impact the training had on their practice. Semi-structured interviews were conducted with seven participants, transcribed verbatim and analysed using Burnard’s (1991) thematic content analysis.

Findings illustrated that experienced CT supervisors perceived benefit from training and that the majority of supervisors had implemented contracts, used specific supervision models and paid more attention to supervisee learning as a result of the training. Obstacles to ensuring good supervision included the lack of reliable user-friendly evaluation tools and supervisor consultancy structures.

Recommendations are also made for future research to establish the long-term effects of supervision training and its effect on patient outcomes. Implications for future training based on adult learning principles are discussed.

Non-adherence to therapy in children with cystic fibrosis

Hawthorne N., Hawwa A.F., Shields M.D., Reid A.J., McElnay J.C. (2011) Non-adherence to therapy in children with cystic fibrosis. Pediatric Pulmonology, 46: 408.

Inflammatory bowel disease, gut bacteria and probiotic therapy

Crohn's disease (CD) and ulcerative colitis (UC) are the two major forms of inflammatory bowel disease (IBD) and both diseases lead to high morbidity and health care costs. Complex interactions between the immune system, enteric commensal bacteria and host genotype are thought to underlie the development of IBD although the precise aetiology of this group of diseases is still unknown. The understanding of the composition and complexity of the normal gut microbiota has been greatly aided by the use of molecular methods and is likely to be further increased with the advent of metagenomics and metatranscriptomics approaches, which will allow an increasingly more holistic assessment of the microbiome with respect to both diversity and function of the commensal gut microbiota. Studies thus far have shown that the intestinal microbiota drives the development of the gut immune system and can induce immune homeostasis as well as contribute to the development of IBD. Probiotics which deliver some of the beneficial immunomodulatory effects of the commensal gut microbiota and induce immune homeostasis have been proposed as a suitable treatment for mild to moderate IBD. This review provides an overview over the current understanding of the commensal gut microbiota, its interactions with the mucosal immune system and its capacity to induce both gut homeostasis as well as dysregulation of the immune system. Bacterial-host events, including interactions with pattern recognition receptors (PRRs) expressed on epithelial cells and dendritic cells (DCs) and the resultant impact on immune responses at mucosal surfaces will be discussed. (C) 2009 Elsevier GmbH. All rights reserved.

Survival without disability to age 5 years after neonatal caffeine therapy for apnea of prematurity

Very preterm infants are prone to apnea and have an increased risk of death or disability. Caffeine therapy for apnea of prematurity reduces the rates of cerebral palsy and cognitive delay at 18 months of age.

A Randomized Controlled Trial of Trauma-Focused Cognitive Behavioral Therapy for Sexually Exploited, War-Affected Congolese Girls

To assess the efficacy of trauma-focused cognitive behavioral therapy (TF-CBT) delivered by nonclinical facilitators in reducing posttraumatic stress, depression, and anxiety and conduct problems and increasing prosocial behavior in a group of war-affected, sexually exploited girls in a single-blind, parallel-design, randomized,+ controlled trial.

Group Trauma-Focused Cognitive-Behavioural Therapy with Former Child Soldiers and other War-affected Boys in the DR Congo: A Randomised Controlled Trial.

Background: The Democratic Republic of Congo (DRC) has been home to the world’s deadliest con?ict since World War II and is reported to have the largest number of child soldiers in the world. Despite evidence of the debilitating impact of war, no group-based mental health or psychosocial intervention has been evaluated in a randomised controlled trial for psychologically distressed former child soldiers.

Method: A randomised controlled trial involving 50 boys, aged 13–17, including former child soldiers (n = 39) and other war-affected boys (n = 11). They were randomly assigned to an intervention group, or wait-list control group. The intervention group received a 15-session, group-based, culturally adapted Trauma-Focused Cognitive–Behavioural Therapy (TF-CBT) intervention. Assessment interviews were completed at baseline, postintervention and 3-month follow-up (intervention group).

Results: Analysis of Covariance (ANCOVA) demonstrated that, in comparison to the wait-list control group, the TF-CBT intervention group had highly signi?cant reductions in posttraumatic stress symptoms, overall psychosocial distress, depression or anxiety-like symptoms, conduct problems and a signi?cant increase in prosocial behaviour (p < .001 for all). Effect sizes were higher when former child soldier scores were separated for sub-analysis. Three-month follow-up of the intervention group found that treatment gains were maintained.

Conclusions: A culturally modi?ed, group-based TF-CBT intervention was effective in reducing posttraumatic stress and psychosocial distress in former child soldiers and other war-affected boys.

Retinal pigment epithelial atrophy in patients with exudative age-related macular degeneration undergoing anti-vascular endothelial growth factor therapy

PURPOSE:: To evaluate the occurrence of retinal pigment epithelial atrophy in patients with age-related macular degeneration undergoing anti-vascular endothelial growth factor therapy. METHODS:: The study is a retrospective review. Eligible were patients with age-related macular degeneration and choroidal neovascular membranes treated with anti-vascular endothelial growth factor between October 2007 and February 2011; they were followed for >3 months, with fundus photographs and fluorescein angiography at baseline and with autofluorescence and near-infrared autofluorescence images at baseline and follow-up. Demographics, visual acuity, the type of choroidal neovascular membranes, the number of treatments performed, and the length of follow-up were recorded. Autofluorescence and near-infrared autofluorescence images were evaluated for the presence or absence of areas of reduced signal. A multilevel logistic regression model was used to investigate the factors that may be associated with progression of atrophy at follow-up, which was the primary outcome of this study. RESULTS:: Sixty-three patients (72 eyes) were followed for a median of 16 months (range, 3-36 months). Atrophy at baseline was observed in 47% (34/72) of eyes; progression of atrophy occurred in 62% (45/72) of eyes at the last visit. The number of anti-vascular endothelial growth factor injections received was statistically significantly associated with the progression of atrophy at follow-up (odds ratio, 1.35; 95% confidence interval, 1.05-1.73; P = 0.02). CONCLUSION:: Atrophy was frequently observed in patients with age-related macular degeneration and choroidal neovascular membranes undergoing anti-vascular endothelial growth factor therapy.

Demarcation laser therapy in the management of macular-sparing persistent subretinal fluid after scleral buckling procedures

Background: Persistent or recurrent macular-sparing subretinal fluid (SRF) can sometimes occur following scleral buckling procedures. Observation and reoperation have been used in the management of such cases. Demarcation laser therapy (DLT) has been used to treat macular-sparing retinal detachments in the context of cytomegalovirus retinitis and as primary treatment for selected rhegmatogenous retinal detachments. There are, however, scarce data in the literature regarding its use following primary scleral buckling procedures. The current study explores the use of DLT under the latter circumstances. Methods: The medical records of all consecutive patients with persistent SRF sparing the macula following primary rhegmatogenous retinal detachment repair using a scleral buckling procedure were retrospectively reviewed. Only those patients in whom the breaks were localised to the area of indentation and, thus, seemed to be well supported by the buckle were included. Demographics, clinical characteristics of the retinal detachment prior to scleral buckling, extension of the residual SRF observed postoperatively, details of the laser procedure, anatomical and functional outcomes and complications were evaluated. Results: Seven patients, all females, with a mean age of 47.9 years (range: 20-81) were included in the study. The retinal detachments were superior (n=3), inferior (n=3) and subtotal, affecting both superior and inferior retina (n=1). Scleral buckling procedures were used to treat the retinal detachments in all cases. Following demarcation laser therapy, the area of SRF remained stable in two patients, and flattened in four. In one patient, extension of SRF occurred requiring further surgery. Conclusions: Demarcation laser therapy appears to be a reasonable option in the management of patients with persistent or recurrent SRF sparing the macula following scleral buckling surgery. © Springer-Verlag 2006.

Photodynamic therapy for inflammatory choroidal neovascularisation unresponsive to immunosuppression

Aim: To report on visual and angiographic outcomes of a consecutive series of patients with inflammatory choroidal neovascular membranes (CNV) unresponsive to systemic immunosuppression treated with photodynamic therapy (PDT). Methods: The medical records of six consecutive patients with inflammatory CNVs that failed to respond to systemic immunosuppression and that later underwent PDT were retrospectively reviewed. Patient demographics, visual acuity, and fluorescein angiographic findings were evaluated. Results: There were five females and one male with a mean age of 40.8 years (range 35-58 years). Four patients had clinical features consistent with punctate inner choroidopathy and two with presumed ocular histoplasmosis. In all cases clinical signs of CNV activity, including subretinal fluid, subretinal blood, hard exudates, and/or recent decrease in visual acuity were present prior to PDT. All patients had been treated with high dose systemic immunosuppressants, which failed to induce regression of the CNV and/or to improve vision. The CNVs were subfoveal in five patients and juxtafoveal in one; all were classified as predominantly classic. Following PDT an improvement in vision occurred in all cases (median improvement of 18 letters, range 3-42 letters). At last follow up, signs of decreased activity in the CNV were detected in all cases. Patients were followed for a median of 10 months (range 9-20 months). Conclusion: PDT appears to be a useful option in the management of patients with inflammatory CNVs unresponsive to immunosuppressive therapies.

Targeting EGFR Induced Oxidative Stress by PARP1 Inhibition in Glioblastoma Therapy

Despite the critical role of Epidermal Growth Factor Receptor (EGFR) in glioblastoma pathogenesis [1,2], EGFR targeted therapies have achieved limited clinical efficacy [3]. Here we propose an alternate therapeutic strategy based on the conceptual framework of non-oncogene addiction [4,5]. A directed RNAi screen revealed that glioblastoma cells overexpressing EGFRvIII [6], an oncogenic variant of EGFR, become hyper-dependent on a variety of DNA repair genes. Among these, there was an enrichment of Base Excision Repair (BER) genes required for the repair of Reactive Oxygen Species (ROS)-induced DNA damage, including poly-ADP ribose polymerase 1 (PARP1). Subsequent studies revealed that EGFRvIII overexpression in glioblastoma cells caused increased levels of ROS, DNA strand break accumulation, and genome instability. In a panel of primary glioblastoma lines, sensitivity to PARP1 inhibition correlated with the levels of EGFR activation and oxidative stress. Gene expression analysis indicated that reduced expression of BER genes in glioblastomas with high EGFR expression correlated with improved patient survival. These observations suggest that oxidative stress secondary to EGFR hyperactivation necessitates increased cellular reliance on PARP1 mediated BER, and offer critical insights into clinical trial design.