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PloS One 2013We performed a systematic review and meta-analysis to address the (added) value of intraoperative 5-aminolevulinic acid (5-ALA)-guided resection of high-grade malignant... (Meta-Analysis)
Meta-Analysis Review
Intraoperative fluorescence-guided resection of high-grade malignant gliomas using 5-aminolevulinic acid-induced porphyrins: a systematic review and meta-analysis of prospective studies.
BACKGROUND
We performed a systematic review and meta-analysis to address the (added) value of intraoperative 5-aminolevulinic acid (5-ALA)-guided resection of high-grade malignant gliomas compared with conventional neuronavigation-guided resection, with respect to diagnostic accuracy, extent of tumor resection, safety, and survival.
METHODS AND FINDINGS
An electronic database search of Medline, Embase, and the Cochrane Library was undertaken. The review process followed the guidelines of the Cochrane Collaboration. 10 studies matched all selection criteria, and were thus used for qualitative synthesis. 5-ALA-guided resection demonstrated an overall sensitivity of 0.87 (95% confidence interval [CI], 0.81-0.92), specificity of 0.89 (95% CI, 0.79-0.94), positive likelihood ratio (LR) of 7.62 (95% CI, 3.87-15.01), negative LR of 0.14 (95% CI, 0.09-0.23), and diagnostic odds ratio (OR) of 53.06 (95% CI, 18.70-150.51). Summary receiver operating characteristic curves (SROC) showed an area under curve (AUC) of 94%. Contrast-enhancing tumor was completely resected in patients assigned 5-ALA as compared with patients assigned white light. Patients in the 5-ALA group had higher 6-month progression free survival and overall survival than those in the white light group.
CONCLUSION
Based on available literature, there is level 2 evidence that 5-ALA-guided surgery is more effective than conventional neuronavigation-guided surgery in increasing diagnostic accuracy and extent of tumor resection, enhancing quality of life, or prolonging survival in patients with high-grade malignant gliomas.
Topics: Aminolevulinic Acid; Brain Neoplasms; Clinical Trials as Topic; Fluorescence; Glioma; Humans; Intraoperative Care; Neuronavigation; Porphyrins; Prospective Studies; ROC Curve; Sensitivity and Specificity; Survival Analysis
PubMed: 23723993
DOI: 10.1371/journal.pone.0063682 -
The International Journal of... Jul 2013The aim of the study was to evaluate the evidence that serotonin1A (5-HT1A) receptor partial agonists of the azapirone class, which are not antipsychotic, have benefits... (Meta-Analysis)
Meta-Analysis Review
The aim of the study was to evaluate the evidence that serotonin1A (5-HT1A) receptor partial agonists of the azapirone class, which are not antipsychotic, have benefits for adjunctive treatment of overall psychopathology, positive and negative symptoms for patients with schizophrenia. We carried out a systematic review of the literature available through PubMed, Cochrane Library, PsycINFO and Google Scholar during September 2012, followed by a meta-analysis of randomized placebo-controlled trials. Risk ratio (RR), 95% confidence intervals (CI) and standardized mean difference (s.m.d.) were calculated. Four studies, involving 163 patients with schizophrenia, met inclusion criteria: buspirone: three trials and 137 patients; tandospirone: one trial and 26 patients. As adjunctive therapy, 5-HT1A partial agonists were significantly superior to placebo for overall improvement in psychopathology (s.m.d. = -0.46, CI = -0.79 to -0.13, p = 0.006, N = 4, n = 149) and marginally more effective to improve positive symptoms (s.m.d. = -0.31, CI = -0.64 to 0.01, p = 0.06, N = 4, n = 149). However, 5-HT1A partial agonists were not more efficacious than placebo as adjunctive therapy for improving negative symptoms (s.m.d. = -0.09, CI = -0.60 to 0.42, p = 0.72, N = 4, n = 149). In addition, there was no significant difference in discontinuation rates between 5-HT1A partial agonists and placebo (all cause: RR = 0.98, CI = 0.49-1.98, p = 0.96, N = 4, n = 153, side-effects: RR = 1.96, CI = 0.54-7.19, p = 0.31, N = 4, n = 153). 5-HT1A partial agonists as adjunctive therapy improved overall psychopathology with a trend to improve positive symptoms in patients with schizophrenia. Because the number of studies was small, additional controlled clinical trials with larger numbers of patients are indicated.
Topics: Adult; Antipsychotic Agents; Buspirone; Confidence Intervals; Drug Synergism; Female; Humans; Male; Middle Aged; Online Systems; Porphyrins; Randomized Controlled Trials as Topic; Schizophrenia; Serotonin Receptor Agonists
PubMed: 23551924
DOI: 10.1017/S1461145713000151 -
PloS One 2012Emerging evidence from biological and epidemiological studies has suggested that body iron stores and heme-iron intake may be related to the risk of type 2 diabetes... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
Emerging evidence from biological and epidemiological studies has suggested that body iron stores and heme-iron intake may be related to the risk of type 2 diabetes (T2D). We aimed to examine the association of body iron stores and heme-iron intake with T2D risk by conducting a systematic review and meta-analysis of previously published studies.
RESEARCH DESIGN AND METHODS
Systematic review and subsequent meta-analysis were conducted by searching MEDLINE database up to June 22, 2012 to identify studies that analyzed the association of body iron stores or dietary heme-iron intake with T2D risk. The meta-analysis was performed using the effect estimates and 95% confidence intervals (CIs) to calculate the pooled risk estimates, while the heterogeneity among studies was examined using the I(2) and Q statistic.
RESULTS
The meta-analysis included 16 high-quality studies: 12 studies analyzed ferritin levels (4,366 T2D patients and 41,091 controls) and 4 measured heme-iron intake (9,246 T2D patients and 179,689 controls). The combined relative risk (RR) comparing the highest and lowest category of ferritin levels was 1.66 (95% CI: 1.15-2.39) for prospective studies, 2.29 (95% CI: 1.48-3.54) for cross-sectional studies with heterogeneity (Q = 14.84, p = 0.01, I(2) = 66.3%; Q = 44.16, p<0.001, I(2) = 88.7%). The combined RR comparing the highest and lowest category of heme-iron intake was 1.31 (95% CI: 1.21-1.43) with heterogeneity (Q = 1.39, p = 0.71, I(2) = 0%). No publication bias was found. Additional 15 studies that were of good quality, had significant results, and analyzed the association between body iron stores and T2D risk were qualitatively included in the systematic review.
CONCLUSIONS
The meta-analysis and systematic review suggest that increased ferritin levels and heme-iron intake are both associated with higher risk of T2D.
Topics: Animals; Biological Transport; Diabetes Mellitus, Type 2; Heme; Humans; Iron; Risk
PubMed: 22848554
DOI: 10.1371/journal.pone.0041641 -
Journal of Neuro-oncology Jan 2010What evidence is available regarding the emerging and investigational therapies for the treatment of metastatic brain tumors?
QUESTION
What evidence is available regarding the emerging and investigational therapies for the treatment of metastatic brain tumors?
TARGET POPULATION
These recommendations apply to adults with brain metastases.
RECOMMENDATIONS
New radiation sensitizers Level 2 A subgroup analysis of a large prospective randomized controlled trial (RCT) suggested a prolongation of time to neurological progression with the early use of motexafin-gadolinium (MGd). Nonetheless this was not borne out in the overall study population and therefore an unequivocal recommendation to use the currently available radiation sensitizers, motexafin-gadolinium and efaproxiral (RSR 13) cannot be provided. Interstitial modalities There is no evidence to support the routine use of new or existing interstitial radiation, interstitial chemotherapy and or other interstitial modalities outside of approved clinical trials. New chemotherapeutic agents Level 2 Treatment of melanoma brain metastases with whole brain radiation therapy and temozolomide is reasonable based on one class II study. Level 3 Depending on individual circumstances there may be patients who benefit from the use of temozolomide or fotemustine in the therapy of their brain metastases. Molecular targeted agents Level 3 The use of epidermal growth factor receptor inhibitors may be of use in the management of brain metastases from non-small cell lung carcinoma.
Topics: Humans; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Combined Modality Therapy; Cranial Irradiation; Disease Progression; Evidence-Based Medicine; Metalloporphyrins; Radiation-Sensitizing Agents; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 19957013
DOI: 10.1007/s11060-009-0058-3 -
Acta Ophthalmologica Mar 2009Photodynamic therapy (PDT) with verteporfin has been used less comprehensively in the treatment of exudative age-related macular degeneration (AMD), and specifically of... (Review)
Review
Photodynamic therapy with verteporfin in age-related macular degeneration: a systematic review of efficacy, safety, treatment modifications and pharmacoeconomic properties.
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 > or = 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.
Topics: Choroidal Neovascularization; Cost-Benefit Analysis; Drug Costs; Humans; Macular Degeneration; Photochemotherapy; Photosensitizing Agents; Porphyrins; Treatment Outcome; Verteporfin
PubMed: 18577193
DOI: 10.1111/j.1755-3768.2008.01218.x -
The Cochrane Database of Systematic... Apr 2008Age-related macular degeneration (AMD) is a common cause of severe vision loss in people 55 years and older. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Age-related macular degeneration (AMD) is a common cause of severe vision loss in people 55 years and older.
OBJECTIVES
The objective of this review was to investigate the effects of anti-VEGF (vascular endothelial growth factor) modalities for treating neovascular AMD.
SEARCH STRATEGY
We searched CENTRAL, MEDLINE, EMBASE and LILACS. We handsearched ARVO abstracts for 2006, 2007 for ongoing trials.
SELECTION CRITERIA
We included randomized controlled trials (RCTs).
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data. We contacted trial authors for additional data. We summarized outcomes as relative risks (RR), number needed to treat (NNT) and weighted mean differences.
MAIN RESULTS
We included five RCTs of good methodological quality. All five trials were conducted by pharmaceutical companies. An intention-to-treat analysis using the last observation carried forward method was done in most trials. Two trials compared pegaptanib versus sham. One trial compared ranibizumab versus sham, another compared ranibizumab/sham verteporfin PDT versus verteporfin PDT/sham ranibizumab, and the final trial compared ranibizumab plus verteporfin PDT versus verteporfin PDT alone. Fewer patients treated with pegaptanib lost 15 or more letters of visual acuity at one year follow-up compared to sham (pooled relative risk (RR) 0.71; 95% confidence interval (CI) 0.61 to 0.84). The NNT was 6.67 (95% CI 4.35 to 14.28) for 0.3 mg pegaptanib, 6.25 (95% CI 4.17 to 12.5) for 1 mg pegaptanib and 14.28 (95% CI 6.67 to 100) for 3 mg pegaptanib. In a trial of ranibizumab versus sham, RR for loss of 15 or more letters visual acuity at one year was 0.14 (95% CI 0.1 to 0.22) in favour of ranibizumab. The NNT was 3.13 (95% CI 2.56 to 3.84) for 0.3 mg ranibizumab and 3.13 (95% CI 2.56 to 3.84) for 0.5 mg ranibizumab. In a trial of ranibizumab versus verteporfin PDT, RR for loss of 15 or more letters at one year was 0.13 (95% CI 0.07 to 0.23) favouring ranibizumab. The NNT was 3.33 (95% CI 2.56 to 4.76) for 0.3 mg ranibizumab and 3.12 (95% CI 2.43 to 4.17) for 0.5 mg ranibizumab. In another trial of combined ranibizumab plus verteporfin PDT versus verteporfin PDT, RR for loss of 15 or more letters at one year favoured combined therapy (RR 0.3 (95% CI 0.15 to 0.60). The NNT was 4.35 (95% CI 2.78 to 11.11). Pooled RR for gain of 15 or more letters visual acuity at one year was 5.81 (95% CI 3.29 to 10.26) for ranibizumab versus sham, 6.79 (95% CI 3.41 to 13.54) for ranibizumab/sham verteporfin PDT versus verteporfin PDT/sham ranibizumab, and 4.44 (95% CI 1.40 to 14.08) for ranibizumab plus verteporfin PDT versus verteporfin PDT. Frequency of endophthalmitis in included studies was between 0.7% to 4.7% with ranibizumab and 1.3% with pegaptanib. Improvement in vision-specific quality of life was reported for both treatments.
AUTHORS' CONCLUSIONS
Pegaptanib and ranibizumab reduce the risk of visual acuity loss in patients with neovascular AMD. Ranibizumab causes gains in visual acuity in many eyes. Quality of life and cost will be important for treatment decisions. Other agents blocking VEGF are being tested in ongoing trials.
Topics: Aged; Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Aptamers, Nucleotide; Choroidal Neovascularization; Humans; Macular Degeneration; Middle Aged; Porphyrins; Randomized Controlled Trials as Topic; Ranibizumab; Vascular Endothelial Growth Factor A; Verteporfin
PubMed: 18425911
DOI: 10.1002/14651858.CD005139.pub2 -
The British Journal of Ophthalmology Feb 2004In 2001 the National Institute for Clinical Excellence (NICE) was asked to issue guidance for England and Wales on the use of photodynamic therapy (PDT). This process... (Review)
Review
BACKGROUND
In 2001 the National Institute for Clinical Excellence (NICE) was asked to issue guidance for England and Wales on the use of photodynamic therapy (PDT). This process has been protracted, partly because of a dispute over the magnitude of beneficial effect. This article examines the origins of the debate about the true treatment effect size for PDT with verteporfin.
METHODS
A systematic review of the clinical effectiveness of PDT compared with current practice was undertaken. Searches in Medline, Embase, the Cochrane Library, and the Internet, updated to January 2003, revealed two fully published and four ongoing randomised controlled trials.
RESULTS
The results of the two published trials (TAP and VIP) consistently showed that overall, PDT with verteporfin is more effective than placebo in slowing the rate of vision loss. In the TAP trial, 12 or more subgroup analyses were undertaken on the primary outcome measure and in VIP, 10 subgroup analyses but only on a subset of the trial participants. Subgroup analysis results were found to be inconsistent between the two trials, with VIP suggesting that verteporfin was equally effective in occult as in mixed lesions and TAP suggesting that verteporfin was more effective in the predominantly classic subgroup.
DISCUSSION
For several reasons it was considered that the most likely estimate of the predominantly classic subgroup effect size was the whole trial result. This has implications for the relationship between cost and benefit, the subject of intense debate. Results of the ongoing trials should help to clarify this subgroup effect size issue.
Topics: Aged; Female; Humans; Macular Degeneration; Male; Photochemotherapy; Photosensitizing Agents; Porphyrins; Randomized Controlled Trials as Topic; Treatment Outcome; Verteporfin; Visual Acuity
PubMed: 14736777
DOI: 10.1136/bjo.2003.019471 -
The Cochrane Database of Systematic... 2003In neovascular age-related macular degeneration, new vessels grow under the retina, distorting vision and leading to scarring. This is further exacerbated if the blood... (Review)
Review
BACKGROUND
In neovascular age-related macular degeneration, new vessels grow under the retina, distorting vision and leading to scarring. This is further exacerbated if the blood vessels leak. Photodynamic therapy, originally used in cancer treatment, has been investigated as a way to treat the neovascular membranes without affecting the retina.
OBJECTIVES
The aim of this review is to examine the effects of photodynamic therapy in the treatment of neovascular age-related macular degeneration.
SEARCH STRATEGY
We searched for trials in the Cochrane Central Register of Controlled Trials - CENTRAL (which includes the Cochrane Eyes and Vision Group trials register) on the Cochrane Library (Issue 4 2002), MEDLINE (1966 to November 2002) and EMBASE (1980 to November 2002). We used the Science Citation Index to search for reports that cited relevant study reports. We contacted experts in the field and we searched the reference lists of relevant studies for further trial reports.
SELECTION CRITERIA
We included randomised trials of photodynamic therapy in people with choroidal neovascularisation due to age-related macular degeneration.
DATA COLLECTION AND ANALYSIS
Two reviewers extracted the data independently. Relative risks were combined using a fixed effect model after testing for heterogeneity using a chi-square test.
MAIN RESULTS
Two published trials were identified that randomised 948 participants to verteporfin therapy compared to 5% dextrose in water. Both trials were performed by the same investigators using largely the same clinical centres and funded by manufacturers of verteporfin. Outcome data were available at 12 and 24 months after the first treatment. Participants received on average five treatments over two years. The relative risk of losing three or more lines of visual acuity at 24 months comparing the intervention with the control group was 0.77 (95% confidence interval 0.69 to 0.87). The relative risk of losing six or more lines of visual acuity at 24 months comparing the intervention with the control group was 0.62 (95% confidence interval 0.50 to 0.76). The results at 12 months were similar to those at 24 months.
REVIEWER'S CONCLUSIONS
Photodynamic therapy in people with choroidal neovascularisation due to age-related macular degeneration is effective in preventing visual loss. Outcomes and potential adverse effects of this treatment should be monitored closely. Further independent trials of Verteporfin are required to establish that the effects seen in this study are consistent and to determine important questions not yet addressed, particularly relating to quality of life and cost.
Topics: Glucose; Humans; Macular Degeneration; Photochemotherapy; Photosensitizing Agents; Porphyrins; Randomized Controlled Trials as Topic; Retinal Neovascularization; Verteporfin
PubMed: 12804420
DOI: 10.1002/14651858.CD002030