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Targeted Oncology Jun 2013In patients with advanced non-small cell lung cancer (NSCLC), the benefit-to-risk ratio of doublet-targeted agents versus single agent is not clear. A systematic review... (Meta-Analysis)
Meta-Analysis Review
Comparison of the efficacy and safety of single-agent erlotinib and doublet molecular targeted agents based on erlotinib in advanced non-small cell lung cancer (NSCLC): a systematic review and meta-analysis.
In patients with advanced non-small cell lung cancer (NSCLC), the benefit-to-risk ratio of doublet-targeted agents versus single agent is not clear. A systematic review and quantitative meta-analysis were, therefore, undertaken to evaluate the available evidence from randomized trials. This study aims to evaluate the efficacy and safety of erlotinib versus doublets (erlotinib plus another targeted agent) in advanced NSCLC and, if adequate data are available, to investigate whether or not predefined patient groups benefit more or less from doublet-targeted therapy based on erlotinib. Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched. Randomized controlled clinical trials were conducted in which any erlotinib was compared with doublets based on erlotinib in patients with NSCLC who had failed to respond to any previous chemotherapy regimen. Two review authors independently selected studies for inclusion in the review and extracted data. A systematic review and meta-analysis based on aggregate data extracted from trial publications were carried out to assess the effectiveness of doublets (erlotinib plus another targeted drug) in NSCLC treatment. The efficacy outcomes were objective response rate (ORR), complete response plus partial response; disease control rate (DCR), complete response plus partial response and stable disease; and 1-year overall survival (OS). The adverse effects (AEs) were also considered. This involved identifying eligible randomized controlled trials (RCTs) and extracting aggregate data from the reports of these RCTs. Hazard ratios were calculated from published summary statistics and then combined to give pooled estimates of treatment efficacy. This meta-analysis comprised five studies including 2,100 patients (mean age 63; 1,224 men and 876 women; 118 stage IIIB and 1,180 stage IV; 441 squamous cell cancers, 1,287 adenocarcinomas, and 372 other pathological types). Doublets regimen significantly improved ORR [hazard ratio (HR) 1.49, 1.13-1.98, p < 0.05] and DCR (HR 1.25, 1.12-1.39, p < 0.05) compared with single erlotinib, but 1-year OS was not significantly improved for doublets [HR 1.06; 95 % confidence interval (CI), 0.95-1.18]. All-grade rash, anemia, diarrhea, anorexia, and fatigue were not significantly different between doublet and erlotinib groups (HR 1.25, 0.99-1.58; 0.98, 0.78-1.24; 1.43, 0.97-2.11; 1.18, 0.84-1.65; and 1.23, 0.86-1.77, respectively). The total grade of ≥3 AEs was also not significantly different (HR 1.40, 95 % CI 0.97-2.01). Compared with single-agent erlotinib, doublets (erlotinib plus another targeted agent) significantly improve ORR and DCR, but not OS, and induce no significance of more frequent and serious AEs. The benefit-to-risk ratio of doublets in advanced NSCLC may be more favorable than that of single-agent. The results of this systematic review suggest that patients with advanced NSCLC might benefit from doublet-targeted therapy based on erlotinib compared to erlotinib alone. However, an individual patient data systematic review and meta-analysis are needed to give us a more reliable assessment of the size of benefits and to explore whether doublet therapy may be more or less effective for particular types of patients.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Erlotinib Hydrochloride; Humans; Lung Neoplasms; Protein Kinase Inhibitors; Quinazolines; Randomized Controlled Trials as Topic
PubMed: 23516098
DOI: 10.1007/s11523-013-0272-y -
Journal of Dentistry Nov 2023There is limited scientific evidence regarding the medication-related osteonecrosis of the jaw (MRONJ) induced by regenerative therapy (RT) associated with dental... (Review)
Review
OBJECTIVES
There is limited scientific evidence regarding the medication-related osteonecrosis of the jaw (MRONJ) induced by regenerative therapy (RT) associated with dental implant treatment. Thus, the current scoping review systematically maps the MRONJ research induced by RTs in implant dentistry and recognizes the existing gaps in knowledge.
DATA
Original studies and reviews investigating the impact of RT on the development of MRONJ were included.
SOURCES
Two reviewers independently searched the MEDLINE-PubMed and Scopus databases according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) extension for Scoping Review and included articles published in English up to March 31, 2023.
STUDY SELECTION
Eighteen articles that fulfilled the inclusion and exclusion criteria were included in this study. Ten mapping parameters for investigating the association of RTs with MRONJ development were examined and evaluated within the selected articles.
RESULTS
There was severely limited information regarding the procedures of RTs including; the grafting materials, surgical protocols, and success and failure rates. The RT associated with MRONJ cases was sinus floor augmentation in patients taking bisphosphonate and denosumab. Moreover, there were limited data on the implant treatment associated with RTs such as time of insertion, implant length and diameter, and loading protocol.
CONCLUSION
The current scoping review revealed that some specific RTs associated with other factors hold a potential risk of MRONJ occurrence. However, the scientific evidence is limited with many gaps. Further investigations are needed to establish an evidence-based clinical guideline for treating high-risk patients.
CLINICAL SIGNIFICANCE
Clinicians should cautiously assess the risk of MRONJ development during implant treatment planning for patients undertaking antiresorptive medications. The adverse outcome of RT procedures should not be underestimated and a complete explanation of the possible risks should be given to the patients.
Topics: Humans; Bisphosphonate-Associated Osteonecrosis of the Jaw; Bone Density Conservation Agents; Diphosphonates; Sinus Floor Augmentation
PubMed: 37708930
DOI: 10.1016/j.jdent.2023.104682 -
Cancers Jun 2023An optimized lymph node yield leads to better survival in colon cancer, but extended lymphadenectomy is not associated with survival benefits. Lymphatic mapping shows... (Review)
Review
An optimized lymph node yield leads to better survival in colon cancer, but extended lymphadenectomy is not associated with survival benefits. Lymphatic mapping shows several colon cancers feature aberrant drainage pathways inducing local recurrence when not resected. Currently, different protocols exist for lymphatic mapping procedures. This meta-analysis assessed which protocol has the best capacity to detect tumor-draining and possibly metastatic lymph nodes. A systematic review was conducted according to PRISMA guidelines, including prospective trials with in vivo tracer application. The risk of bias was evaluated using the QUADAS-2 tool. Traced lymph nodes, total resected lymph nodes, and aberrant drainage detection rate were analyzed. Fifty-eight studies met the inclusion criteria, of which 42 searched for aberrant drainage. While a preoperative tracer injection significantly increased the traced lymph node rates compared to intraoperative tracing (30.1% (15.4, 47.3) vs. 14.1% (11.9, 16.5), = 0.03), no effect was shown for the tracer used ( = 0.740) or the application sites comparing submucosal and subserosal injection (22.9% (14.1, 33.1) vs. 14.3% (12.1, 16.8), = 0.07). Preoperative tracer injection resulted in a significantly higher rate of detected aberrant lymph nodes compared to intraoperative injection (26.3% [95% CI 11.5, 44.0] vs. 2.5% [95% CI 0.8, 4.7], < 0.001). Analyzing 112 individual patient datasets from eight studies revealed a significant impact on aberrant drainage detection for injection timing, favoring preoperative over intraoperative injection (OR 0.050 [95% CI 0.010-0.176], < 0.001) while indocyanine green presented itself as the superior tracer (OR 0.127 [95% CI 0.018-0.528], = 0.012). Optimized lymphatic mapping techniques result in significantly higher detection of aberrant lymphatic drainage patterns and thus enable a personalized approach to reducing local recurrence.
PubMed: 37370806
DOI: 10.3390/cancers15123196 -
The Cochrane Database of Systematic... Jun 2013People with intermittent claudication (IC) suffer from pain in the muscles of the leg occurring during exercise which is relieved by a short period of rest. Symptomatic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
People with intermittent claudication (IC) suffer from pain in the muscles of the leg occurring during exercise which is relieved by a short period of rest. Symptomatic relief can be achieved by (supervised) exercise therapy and pharmacological treatments. Ginkgo biloba is a vasoactive agent and is used to treat IC.
OBJECTIVES
To assess the effect of Ginkgo biloba on walking distance in people with intermittent claudication.
SEARCH METHODS
For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (March 2013) and CENTRAL (2013, Issue 2).
SELECTION CRITERIA
Randomised controlled trials of Ginkgo biloba extract, irrespective of dosage, versus placebo in people with IC.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trials for selection, assessed study quality and extracted data. We extracted number of patients, mean walking distances or times and standard deviations. To standardise walking distance or time, caloric expenditures were used to express the difference between the different treadmill protocols, which were calculated from the speed and incline of the treadmill.
MAIN RESULTS
Fourteen trials with a total of 739 participants were included. Eleven trials involving 477 participants compared Ginkgo biloba with placebo and assessed the absolute claudication distance (ACD). Following treatment with Ginkgo biloba at the end of the study the ACD increased with an overall effect size of 3.57 kilocalories (confidence interval (CI) -0.10 to 7.23, P = 0.06), compared with placebo. This translates to an increase of just 64.5 ( CI -1.8 to 130.7) metres on a flat treadmill with an average speed of 3.2 km/h. Publication bias leading to missing data or "negative" trials is likely to have inflated the effect size.
AUTHORS' CONCLUSIONS
Overall, there is no evidence that Ginkgo biloba has a clinically significant benefit for patients with peripheral arterial disease.
Topics: Ginkgo biloba; Humans; Intermittent Claudication; Phytotherapy; Randomized Controlled Trials as Topic; Treatment Outcome; Vasodilator Agents
PubMed: 23744597
DOI: 10.1002/14651858.CD006888.pub3 -
Frontiers in Reproductive Health 2022The aim of this study was to evaluate six vaginal douching agents (Iodine, Saline, Iodine followed by saline, chlorhexidine acetate followed by saline, Ozone, Potassium... (Review)
Review
OBJECTIVE
The aim of this study was to evaluate six vaginal douching agents (Iodine, Saline, Iodine followed by saline, chlorhexidine acetate followed by saline, Ozone, Potassium permanganate) on oocytes pick-up related pelvic infection (OPU-PI) and IVF outcome in patients underwent assisted reproduction technology (ART).
DESIGN
Through searching PubMed, Embase, Cochrane Library, Web of Science, Ovid, CINAHL CNKI, only human clinical trials were collected to study the effects of the six vaginal douching agents on OPU-PI and IVF outcomes. The included studies were evaluated for methodological quality by the Cochrane bias risk assessment tool, and the data analysis software was used to analyze the data accordingly.
RESULTS
The clinical trials were collected between the earliest available date and June 2022. Eight studies were included, the total sample size used in the study was 12,567. The results of the network meta-analysis showed that Ozone can significantly decrease OPU-PI; Iodine followed by saline can be a antiseptic protocol ranked first without affecting the quality of oocytes and Chlorhexidine acetate followed by saline can improve patients' clinical pregnancy rate.
CONCLUSION
Based on Ranking Plot of the Network, this review reports the best evidence available regarding different vaginal douching agents used before OPU.
PubMed: 36406889
DOI: 10.3389/frph.2022.1032062 -
Nanosilver fluoride as a caries arresting agent in children: A systematic review and meta- analysis.Journal of the Indian Society of... 2022Dental caries is one of the most common concerns in oral health of children. Arresting these lesions is a treatment which is gaining momentum as against conventional...
BACKGROUND
Dental caries is one of the most common concerns in oral health of children. Arresting these lesions is a treatment which is gaining momentum as against conventional restorative approaches.
AIM
The aim is to evaluate the efficacy of nanosilver fluoride (NSF) as a caries arresting agent in primary teeth or first permanent molars in children.
DESIGN
The protocol for the systematic review has been registered with PROSPERO database (CRD42020162386). Several databases, such as PubMed®/MEDLINE, Web of Science™, Scopus®, Google Scholar, LILACS, Cochrane Library, ProQuest, and BBO, were searched for randomized controlled trials (RCTs) which evaluated the arrestment of caries, in primary teeth and first permanent molars in children, with a minimum follow-up of 6 months. The Risk of Bias tool by Cochrane reviews system software, Revman 5.4.1, was used for quality assessment of the included RCTs. The quality evaluation was done using the GRADE approach. Heterogeneity was assessed using Cochrane's Q and I statistics.
RESULTS
Five studies were included for qualitative and quantitative analysis. The Risk Ratio for NSF versus active control group was assessed to be 1.09 (0.93-1.28) with 95% Confidence Interval and for placebo control was 0.49 (0.35-0.67).
CONCLUSION
NSF shows promise as a caries arrestment agent when applied in primary teeth.
PROSPERO REGISTRATION
This review was registered with the PROSPERO database (CRD42020162386).
Topics: Child; Humans; Fluorides; Dental Caries; Dental Caries Susceptibility; Molar; Oral Health
PubMed: 36260462
DOI: 10.4103/jisppd.jisppd_224_22 -
Expert Review of Anticancer Therapy Oct 2017Multimodality treatment of patients with locally advanced rectal cancer (LARC) has significantly improved local disease control, however the unaltered overall survival... (Comparative Study)
Comparative Study Meta-Analysis Review
INTRODUCTION
Multimodality treatment of patients with locally advanced rectal cancer (LARC) has significantly improved local disease control, however the unaltered overall survival (OS) implicates an inability to further control micrometastases, providing rationale for intensified systemic treatment. A systematic review was conducted to evaluate the efficacy and toxicity of adding oxaliplatin to a fluoropyrimidine (intervention) compared with fluoropyrimidine alone (control) in the treatment of LARC.
METHODS
We searched CENTRAL, Medline Ovid, PubMed and EMBASE databases. Randomised trials comparing the intervention and control delivered either pre- or post-operatively were included.
RESULTS
Seven trials involving 4444 patients were identified; five studies evaluated the intervention vs control preoperatively; one study peri-operatively; and one, post-operatively. There was no significant difference in OS with oxaliplatin addition, HR 0.89, 95% CI, 0.75 to 1.06. There was however an improvement in disease free survival, 3-year local and distant recurrence rates (RR) favouring oxaliplatin. Preoperative oxaliplatin improved pathological complete response (pCR), but with a greater toxicity and reduced compliance with radiation.
CONCLUSION
There is no OS benefit with oxaliplatin, despite improved pCR, local and distant RR. Before drawing definitive conclusions, longer follow-up in included trials and availability of published data from other eligible studies, including the induction setting, are needed.
Topics: Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Disease-Free Survival; Fluorouracil; Humans; Neoplasm Recurrence, Local; Organoplatinum Compounds; Oxaliplatin; Pyrimidines; Randomized Controlled Trials as Topic; Rectal Neoplasms; Survival Rate
PubMed: 28819989
DOI: 10.1080/14737140.2017.1369881 -
Clinical Orthopaedics and Related... Sep 2021Lung cancer is one of the most commonly diagnosed cancers and is the leading cause of cancer-related deaths. Metastatic bone disease occurs in 20% to 40% of patients... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Lung cancer is one of the most commonly diagnosed cancers and is the leading cause of cancer-related deaths. Metastatic bone disease occurs in 20% to 40% of patients with lung cancer, and these patients often present with pain or skeletal-related events (SREs) that are associated with decreased survival. Bone-modifying agents such as denosumab or bisphosphonates are routinely used; however, to our knowledge, there has been no quantitative synthesis of randomized controlled trial data to determine the most effective pharmacologic treatment of metastatic bone disease because of lung cancer.
QUESTIONS/PURPOSES
We aimed to perform a network meta-analysis of randomized trials to identify the bone-modifying agent that is associated with the (1) highest overall survival, (2) longest time to SRE, (3) lowest SRE incidence, and (4) greatest likelihood of pain resolution.
METHODS
We conducted our study according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol and pre-registered the analysis on PROSPERO (ID: CRD42019124364). We performed a librarian-assisted search of MEDLINE, PubMed, EMBASE, Cochrane Library, and Chinese databases including China National Knowledge Infrastructure and Wanfang Data. We included randomized controlled trials reporting outcomes specifically for patients with lung cancer treated with a bisphosphonate or denosumab. SREs included pathologic fractures, spinal cord compression, hypercalcemia of malignancy, or pain resulting in surgical intervention or radiation therapy. We excluded trials exclusively reporting surrogate outcomes such as changes in bone turnover markers. Screening, data extraction, risk of bias evaluation, and Grading of Recommendations Assessment, Development, and Evaluation evaluations were performed in duplicate. We included 131 randomized controlled trials that evaluated 11,105 patients with skeletal metastases from lung cancer. The network meta-analysis was performed using a frequentist model and the R statistical software. Results are reported as relative risks or mean differences, and the I2 value is reported for heterogeneity. The P-score, a measure of ranking certainty that accounts for standard error, is reported for each outcome. Heterogeneity in the network was considered moderate for overall survival and time to SRE, mild for the incidence of SRE, and low for pain resolution.
RESULTS
For overall survival, denosumab was ranked above zoledronic acid and estimated to confer a mean of 3.3 months (95% CI 0.3-6.3) of increased overall survival compared with untreated patients (P-score = 89%). For the time to SRE, denosumab was ranked first with a mean of 9.1 additional SRE-free months (95% CI 6.7-11.5) compared with untreated patients (P-score = 99%), while zoledronic acid conferred an additional 4.8 SRE-free months (95% CI 3.6-6.1). Reduction in the incidence of SREs was not different between patients treated with denosumab (relative risk 0.54; 95% CI 0.33-0.87) and those treated with zoledronic acid (relative risk 0.56; 95% CI 0.46-0.67). Patients treated with the combination of ibandronate and systemic therapy were more likely to experience successful pain resolution than untreated patients (relative risk 2.4; 95% CI 1.8-3.2).
CONCLUSION
In this comprehensive synthesis of all available randomized controlled trial evidence guiding the pharmacologic treatment of bone metastases from lung cancer, denosumab was ranked above zoledronic acid for overall survival and time to SRE and was not different for reducing the incidence of SRE. Both were superior to no treatment for each of these outcomes. Given this, we encourage physicians to consider the use of denosumab or zoledronic acid in treating this patient population. The combination of ibandronate and systemic therapy was the most effective at reducing pain because of metastases. No cost-effectiveness analysis has yet been performed for denosumab and zoledronic acid on patients with metastatic lung cancer, and this represents an avenue for future research.
LEVEL OF EVIDENCE
Level I, therapeutic study.
Topics: Bone Density Conservation Agents; Bone Neoplasms; Denosumab; Diphosphonates; Drug Therapy, Combination; Humans; Ibandronic Acid; Lung Neoplasms; Randomized Controlled Trials as Topic; Zoledronic Acid
PubMed: 33835092
DOI: 10.1097/CORR.0000000000001749 -
Natural Hazards (Dordrecht, Netherlands) 2023This systematic review provides a comprehensive overview of tsunami evacuation models. The review covers scientific studies from the last decade (2012-2021) and is... (Review)
Review
UNLABELLED
This systematic review provides a comprehensive overview of tsunami evacuation models. The review covers scientific studies from the last decade (2012-2021) and is explicitly focused on models using an agent-based approach. The PRISMA methodology was used to analyze 171 selected papers, resulting in over 53 studies included in the detailed full-text analysis. This review is divided into two main parts: (1) a descriptive analysis of the presented models (focused on the modeling tools, validation, and software platform used, etc.), and (2) model analysis (e.g., model purpose, types of agents, input and output data, and modeled area). Special attention was given to the features of these models specifically associated with an agent-based approach. The results lead to the conclusion that the research domain of agent-based tsunami evacuation models is quite narrow and specialized, with a high degree of variability in the model attributes and properties. At the same time, the application of agent-specific methodologies, protocols, organizational paradigms, or standards is sparse.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s11069-022-05643-x.
PubMed: 36212893
DOI: 10.1007/s11069-022-05643-x -
Acta Ophthalmologica May 2017Keratoconus can behave more aggressively in pediatric than in adult patients. We systematically reviewed the literature to determine the effectiveness of corneal... (Meta-Analysis)
Meta-Analysis Review
Keratoconus can behave more aggressively in pediatric than in adult patients. We systematically reviewed the literature to determine the effectiveness of corneal collagen cross-linking (CXL) in children. For this study, MEDLINE and Cochrane databases were searched for all studies examining the effects of standard, trans-epithelial or accelerated CXL protocols in patients age 18 years or younger. Primary outcomes were; uncorrected visual acuity (UCVA) and maximum keratometry (Kmax) and secondary outcomes were; best-corrected visual acuity (BCVA), mean refractive spherical equivalent (MRSE), central corneal thickness (CCT) and endothelial cell density (ECD). Standardized mean differences (SMD) and 95% confidence intervals were calculated, comparing baseline values with those at 6, 12 and 24 months. A total of 13 papers, published between May 2011 and December 2014 examining 490 eyes of 401 patients with a mean age of 15.25 (±1.5) years, were included in the qualitative analysis in this review. Nine papers were included in the meta-analysis, showing significant improvement in UCVA and BCVA and stable Kmax at 12 months, and stable UCVA, improved BCVA and improved Kmax at 24 months in the standard protocol group UCVA, BCVA and KMax were stable at 12 months in the trans-epithelial group. Mean refractive spherical equivalent (MRSE), CCT and ECD remained stable in both groups. In conclusion it was found that standard CXL may be effective in halting progression of keratoconus in pediatric patients at 1 year. However, larger, more long-term studies are required to ascertain its effectiveness.
Topics: Collagen; Cornea; Corneal Topography; Cross-Linking Reagents; Humans; Keratoconus; Photochemotherapy; Photosensitizing Agents; Ultraviolet Rays
PubMed: 27678078
DOI: 10.1111/aos.13224