Therapy Study (therapy + study)

Distribution by Scientific Domains

Selected Abstracts

Photodynamic therapy with verteporfin in age-related macular degeneration: a systematic review of efficacy, safety, treatment modifications and pharmacoeconomic properties

Alan F. Cruess
Abstract. Photodynamic therapy (PDT) with verteporfin has been used less comprehensively in the treatment of exudative age-related macular degeneration (AMD), and specifically of choroidal neovascularization (CNV), since the advent of antiangiogenic therapies. Recently, there has been a renewed interest in PDT as an adjunct to these and other agents in the treatment of neovascular AMD. In light of this new development and the European Medicines Evaluation Agency's (EMEA) recent labelling decision to rescind approval for the use of PDT in occult CNV lesions, the present systematic review was undertaken to revisit the evidence supporting its clinical application. Photodynamic therapy provided the first pharmacological treatment for patients suffering from subfoveal CNV, the major cause of severe vision loss in AMD. Key clinical trials evaluating efficacy and safety have examined patients with all lesion subtypes, with the primary labelled indication (i.e. lesions containing a classic component of , 50% ) deriving from the results of the Treatment of Age-related Macular Degeneration with Photodynamic Therapy (TAP) Study. The subsequent TAP Study Group post hoc categorization of lesions as predominantly classic is open to question, however, as it appears that the overall efficacy in this group only may have reflected the especially strong response in 100% classic lesions. Based on a subgroup analysis of the Verteporfin in Photodynamic Therapy Study, the indication for PDT subsequently was expanded in some jurisdictions, including that of the EMEA, to include occult lesions with no classic component. However, the subsequent Visudyne in Occult Study found no benefit in 100% occult lesions, resulting in the EMEA rescinding its approval for this indication. [source]

Effectiveness of interventions that assist caregivers to support people with dementia living in the community: a systematic review

Deborah Parker BA, MSocSci
Executive summary Objectives, The objective of this review was to assess the effectiveness of interventions that assist caregivers to provide support for people living with dementia in the community. Inclusion criteria, Types of participants, Adult caregivers who provide support for people with dementia living in the community (non-institutional care). Types of interventions, Interventions designed to support caregivers in their role such as skills training, education to assist in caring for a person living with dementia and support groups/programs. Interventions of formal approaches to care designed to support caregivers in their role, care planning, case management and specially designated members of the healthcare team , for example dementia nurse specialist or volunteers trained in caring for someone with dementia. Types of studies, This review considered any meta-analyses, systematic reviews, randomised control trials, quasi-experimental studies, cohort studies, case control studies and observational studies without control groups that addressed the effectiveness of interventions that assist caregivers to provide support for people living with dementia in the community. Search strategy, The search sought to identify published studies from 2000 to 2005 through the use of electronic databases. Only studies in English were considered for inclusion. The initial search was conducted of the databases, CINAHL, MEDLINE and PsychINFO using search strategies adapted from the Cochrane Dementia and Cognitive Improvement Group. A second more extensive search was then conducted using the appropriate Medical Subject Headings (MeSH) and keywords for other available databases. Finally, hand searching of reference lists of articles retrieved and of core dementia, geriatric and psycho geriatric journals was undertaken. Assessment of quality, Methodological quality of each of the articles was assessed by two independent reviewers using appraisal checklist developed by the Joanna Briggs Institute and based on the work of the Cochrane Collaboration and Centre for Reviews and Dissemination. Data collection and analysis, Standardised mean differences or weighted mean differences and their 95% confidence intervals were calculated for each included study reported in the meta-analysis. Results from comparable groups of studies were pooled in statistical meta-analysis using Review Manager Software from the Cochrane Collaboration. Heterogeneity between combined studies was tested using standard chi-square test. Where statistical pooling was not appropriate or possible, the findings are summarised in narrative form. Results, A comprehensive search of relevant databases, hand searching and cross referencing found 685 articles that were assessed for relevance to the review. Eighty-five papers appeared to meet the inclusion criteria based on title and abstract, and the full paper was retrieved. Of the 85 full papers reviewed, 40 were accepted for inclusion, three were systematic reviews, three were meta-analysis, and the remaining 34 were randomised controlled trials. For the randomised controlled trials that were able to be included in a meta-analysis, standardised mean differences or weighted mean differences and their 95% confidence intervals were calculated for each. Results from comparable groups of studies were pooled in statistical meta-analysis using Review Manager Software and heterogeneity between combined studies was assessed by using the chi-square test. Where statistical pooling was not appropriate or possible, the findings are summarised in narrative form. The results are discussed in two main sections. Firstly it was possible to assess the effectiveness of different types of caregiver interventions on the outcome categories of depression, health, subjective well-being, self-efficacy and burden. Secondly, results are reported by main outcome category. For each of these sections, meta-analysis was conducted where it was possible; otherwise, a narrative summary describes the findings. Effectiveness of intervention type, Four categories of intervention were included in the review , psycho-educational, support, multi-component and other. Psycho-educational Thirteen studies used psycho-educational interventions, and all but one showed positive results across a range of outcomes. Eight studies were entered in a meta-analysis. No significant impact of psycho-educational interventions was found for the outcome categories of subjective well-being, self-efficacy or health. However, small but significant results were found for the categories of depression and burden. Support Seven studies discussed support only interventions and two of these showed significant results. These two studies were suitable for meta-analysis and demonstrated a small but significant improvement on caregiver burden. Multi-component Twelve of the studies report multi-component interventions and 10 of these report significant outcomes across a broad range of outcome measures including self-efficacy, depression, subjective well-being and burden. Unfortunately because of the heterogeneity of study designs and outcome measures, no meta-analysis was possible. Other interventions Other interventions included the use of exercise or nutrition which resulted in improvements in psychological distress and health benefits. Case management and a computer aided support intervention provided mixed results. One cognitive behavioural therapy study reported a reduction in anxiety and positive impacts on patient behaviour. Effectiveness of interventions using specific outcome categories, In addition to analysis by type of intervention it was possible to analyse results based on some outcome categories that were used across the studies. In particular the impact of interventions on caregiver depression was available for meta-analysis from eight studies. This indicated that multi-component and psycho-educational interventions showed a small but significant positive effect on caregiver depression. Five studies using the outcome category of caregiver burden were entered into a meta-analysis and findings indicated that there were no significant effects of any of interventions. No meta-analysis was possible for the outcome categories of health, self-efficacy or subjective well-being. Implications for practice, From this review there is evidence to support the use of well-designed psycho-educational or multi-component interventions for caregivers of people with dementia who live in the community. Factors that appear to positively contribute to effective interventions are those which: ,,Provide opportunities within the intervention for the person with dementia as well as the caregiver to be involved ,,Encourage active participation in educational interventions for caregivers ,,Offer individualised programs rather than group sessions ,,Provide information on an ongoing basis, with specific information about services and coaching regarding their new role ,,Target the care recipient particularly by reduction in behaviours Factors which do not appear to have benefit in interventions are those which: ,,Simply refer caregivers to support groups ,,Only provide self help materials ,,Only offer peer support [source]

Regulatory issues in cellular therapies

Adrian P. Gee, Article first published online: 23 APR 200
Cellular and gene therapies offer considerable promise as new treatment modalities. The Food and Drug Administration has been developing strategies to regulate these rapidly evolving fields in a manner that sustains progress and also ensures minimization of potential risks. The death of a patient on a gene therapy study highlighted a number of potential problems that have galvanized the agency to examine their strategy and to review current regulations for gene therapy. Meanwhile, a unified regulatory approach is emerging for cell-based therapies. This stratifies the level of regulation based upon the potential risk to the donor of the cells and the recipient. In this article the history and status of regulation of cellular therapy is briefly reviewed. J. Cell. Biochem. Suppl. 38: 104,112, 2002. 2002 Wiley-Liss, Inc. [source]

UICC-2002 TNM classification is not suitable for differentiated thyroid cancer in children and adolescents

Prasad T. Oommen MD
Abstract Background Recently the UICC-TNM classification for differentiated thyroid cancer (DTC) was changed neglecting the special circumstances for children affected by the disease. While the 1997 TNM classification grouped tumours ,1 cm as T1, the 2002 system changed this to a margin of ,2 cm. The consequences of this change were evaluated by analysing patients enrolled in the multicentre interdisciplinary therapy study of the German Society of Paediatric Oncology and Haematology (GPOH) on malignant endocrine tumours in children and adolescents, GPOH-MET 97. Procedure Between 1998 and 2005, 82 patients with histologically proven DTC entered the study. Patients classified according to UICC-TNM classification 1997 were reclassified according to the new classification (2002/2003) and vice versa by cross checking with original pathologist's reports. Results Twenty males and 62 females at a mean age of 12.5 years were evaluated. We observed a definite shift from patients formerly classified as T2 (1,4 cm) to category T1 (,2 cm) according to the 2002 TNM classification. Among these patients a threefold increase of lymph node involvement and/or distant metastases could be demonstrated. Conclusions The 2002 UICC-classification may have a disadvantage for children with tumours measuring between 1 and 2 cm, as those are now classified as T1. A high rate of lymph node involvement in this group reflects the risk of under-diagnosis and -treatment of this group. The current TNM classification for DTC in children should be changed taking the physiological and anatomical differences between children and adults into consideration. Pediatr Blood Cancer 2008;50:1159,1162. 2007 Wiley-Liss, Inc. [source]

Combination Nonviral Interleukin-2 Gene Immunotherapy For Head and Neck Cancer: From Bench Top to Bedside

Bert W. O'Malley Jr MD
Abstract Objective/Hypothesis: Intralesional delivery of cytokine genes has emerged as a promising therapeutic strategy for the treatment of cancer. In addition to the therapeutic effect of the delivered cytokine gene, the components of the gene delivery system also have been shown to induce beneficial immune responses. On the basis of these principles, we hypothesized that a molecular therapy could be developed that would provide synergistic antitumor activity by way of intralesional expression of interleukin (IL)-2 from a recombinant plasmid combined with induction of endogenous interferon (IFN)-, and IL-12 cytokines by immunostimulatory DNA. Our objective in these studies was to create and optimize a novel formulation of cationic lipid and DNA that generates local production of IL-2 protein within a targeted tumor environment with concomitant induction of the antitumor cytokines IFN-, and IL-12. Study Design: Prospective laboratory drug development plan that would produce human clinical trials. Materials and Methods: Engineered bacterial plasmids containing a cytomegalovirus promoter (CMV)-IL-2 expression cassette were specifically formulated with cationic lipids and optimized for antitumor effect in a floor of mouth murine tumor model. The treated tumors were assayed for local expression of IL-2 and concurrent expression of secondary cytokines IFN-, and IL-12. Established tumors in C3H/HeJ mice were treated with various IL-2 gene formulations, and clinical and immunologic responses were evaluated. Immunologic studies were performed and included cytolytic T-cell assays and cytokine expression profiles. For human clinical trials, a phase I 10 patient formulated IL-2 gene therapy study was completed. Subsequently, two large scale, phase II multi-institutional and multi-international studies were initiated comparing non-viral IL-2 gene therapy to palliative methotrexate chemotherapy or in combination with cisplatin. Results: In the preclinical stage, maximum tumor inhibition in animal models was obtained using IL-2 plasmid formulated with 1,2-dioleyloxypropyl-3-trimethyl ammonium chloride (DOTMA):cholesterol (1:1 mol:mol) at a plasmid:lipid charge ratio of 1:0.5 (,/+). Cationic lipid formulated IL-2 plasmid significantly inhibited tumor growth compared with formulated control plasmid (P < .01) or vehicle (lactose; P < .01). Consistent with previously reported studies of the immunostimulatory activity of DNA of bacterial origin, treatment of tumors with control plasmid in cationic lipid formulation induced production of endogenous IFN-, and IL-12 but not IL-2. Treatment of tumors with formulated IL-2 plasmid produced IL-2 protein levels that were 5-fold over background and increased IFN-, by 32-fold (P < .001) and IL-12 by 5.5-fold (P < .001) compared with control plasmid formulations. The phase I human trial demonstrated dose escalation safety, which was its primary objective, and there was one anecdotal reduction in tumor size. The phase II studies have been initiated and focus on either comparing the novel nonviral IL-2 gene immunotherapy formulation alone to methotrexate or comparing IL-2 gene therapy in combination with cisplatin in recurrent or unresectable patients with head and neck squamous cell carcinoma. Conclusions: The preclinical data provided proof of principle for matching a delivered IL-2 transgene with an immunostimulatory nonviral formulation to enhance intralesional production of therapeutic cytokines for the maximization of antitumor response. Human clinical trials have demonstrated this novel therapy to be safe in the human clinical setting. Phase II trials have been initiated to assess efficacy and feasibility as a single or combination therapy for head and neck cancer. [source]