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Mobile Health Interventions for Modifying Indigenous Maternal and Child-Health Related Behaviors: Systematic Review.
Background: Mobile health (mHealth) interventions promoting healthy lifestyle changes offer an adaptable and inexpensive method for accessing health information but require cultural appropriateness and suitability for acceptance and effectiveness in Indigenous populations. No systematic review on effective mHealth interventions for Indigenous women during pregnancy and the early childhood years has been conducted. Objective: This review evaluated the effectiveness of mHealth interventions promoting healthy behaviors for Indigenous mothers and children from conception to 5 years post partum. It also aimed to explore the observed effectiveness differences based on participant engagement, intervention design, and provision of context. Further, the review explored if the interventions were co-designed. Methods: A systematic search of 5 databases was conducted: SCOPUS, MEDLINE, CINAHL, PsycINFO, and ProQuest (Dissertation or Thesis). Studies were included if they were either a randomized controlled trial, pre-post comparison, or a cohort study using mHealth with Indigenous women for maternal and child health following a preregistered PROSPERO protocol (CRD42023395710). HealthInfoNet was searched for gray literature and the reference lists of included studies were hand searched. The initial title and abstract screen for eligibility were performed by 1 reviewer. A full-text screen of eligible studies and a quality appraisal of included studies was performed by 2 reviewers independently. The appraisal tools used were the Mixed Methods Quality Appraisal Tool and the Centre of Excellence in Aboriginal Chronic Disease Knowledge Translation and Exchange (CREATE). A descriptive synthesis of the extracted data was performed. Results: Of the 663 articles screened, only 3 met the eligibility criteria. Each paper evaluated a different mHealth intervention: Remote Prenatal Education; the SMS Parent Action Intervention (two-way text messaging); and the Screening, Brief Intervention and Referral to Treatment (SBIRT) eCHECKUP To Go (web-based screening and intervention). Statistically significant changes were reported in some outcomes, including an increase in the parental participation rate in face-to-face prenatal education; increased rate of breastfeeding initiation and exclusive breastfeeding (2-12 months); improved overall children's behavior related to sleep, diet, physical activity, screen time, and intake of sugary beverages; improved individual children's behavior related to physical activity and sleep; and decrease in alcohol drinks per week and binge drinking episodes per 2 weeks due to time effect. However, no study provided a sample size calculation for the reported significant outcomes. Also, due to the small number of included studies and each study evaluating a different intervention, it was not possible to combine results to ascertain if the participant engagement, intervention design, or community context had any impact on the effectiveness. Conclusions: Due to the lack of sample size calculation, it was not possible to establish whether differences in the effectiveness were due to the interventions or a type I statistical error. Therefore, caution is required in the interpretation of these findings. Trial registration: PROSPERO CRD42023395710; https://www.crd.york.ac.uk/PROSPERO/view/CRD42023395710.
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Efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy in hematologic malignancies: a living systematic review on comparative studies
Background: Chimeric antigen receptor T-cell (CAR-T) cell therapies have been claimed to be curative in responsive patients. Nonetheless, response rates can vary according to different characteristics, and these therapies are associated with important adverse events such as cytokine release syndrome, neurologic adverse events, and B-cell aplasia. Objectives: This living systematic review aims to provide a timely, rigorous, and continuously updated synthesis of the evidence available on the role of CAR-T therapy for the treatment of patients with hematologic malignancies. Design: A systematic review with meta-analysis of randomized controlled trials (RCTs) and comparative non-randomized studies of interventions (NRSI), evaluating the effect of CAR-T therapy versus other active treatments, hematopoietic stem cell transplantation, standard of care (SoC) or any other intervention, was performed in patients with hematologic malignancies. The primary outcome is overall survival (OS). Certainty of the evidence was determined using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Data sources and Methods: Searches were performed in the Epistemonikos database, which collates information from multiple sources to identify systematic reviews and their included primary studies, including Cochrane Database of Systematic Reviews, MEDLINE, EMBASE, CINAHL, PsycINFO, LILACS, DARE, HTA Database, Campbell database, JBI Database of Systematic Reviews and Implementation Reports, EPPI-Centre Evidence Library. A manual search was also carried out. We included the evidence published up to 1 July 2022. Results: We included the evidence published up to 1 July 2022. We considered 139 RCTs and 1725 NRSI as potentially eligible. Two RCTs (N = 681) comparing CAR-T therapy with SoC in patients with recurrent/relapsed (R/R) B-cell lymphoma were included. RCTs did not show statistical differences in OS, serious adverse events, or total adverse events with grade. 3. Higher complete response with substantial heterogeneity [risk ratio = 1.59; 95% confidence interval (CI) = (1.30-1.93); I2 = 89%; 2 studies; 681 participants; very low certainty evidence] and higher progression-free survival [hazard ratio for progression or death = 0.49; 95% CI = (0.37-0.65); 1 study; 359 participants; moderate certainty evidence] were reported with CAR-T therapies. Nine NRSI (N = 540) in patients with T or B-cell acute lymphoblastic leukemia or R/R B-cell lymphoma were also included, providing secondary data. In general, the GRADE certainty of the evidence for main outcomes was mostly low or very low. Conclusion: So far, assuming important limitations in the level of certainty due to scarce and heterogenous comparative studies, CAR-T therapies have shown some benefit in terms of progression-free survival, but no overall survival, in patients with R/R B-cell lymphoma. Despite one-arm trials have already facilitated approval of CAR-T cell treatments, additional evidence from large comparative studies is still needed to better characterize the benefit-harm ratio of the use of CAR-T in a variety of patient populations with hematological malignancies.
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Nurse-led telehealth interventions for symptom management in patients with cancer receiving systemic or radiation therapy: A systematic review and meta-analysis
PURPOSE: Patients receiving cancer treatments experience many treatment-related symptoms. Telehealth is increasingly being used to support symptom management. The overall aim was to determine the effectiveness of nurse-led telehealth symptom management interventions for patients with cancer receiving systemic or radiation therapy compared to usual care on health service use, quality of life, and symptom severity. METHODS: A systematic review was conducted following the Cochrane Handbook and PRISMA reporting guidelines. Five electronic databases were searched. Two independent reviewers screened articles and extracted data. Meta-analysis was performed if data were clinically and methodologically homogeneous. Subanalysis was conducted on reactive and scheduled telehealth interventions. RESULTS: Of 7749 citations screened, 10 studies were included (8 randomized control trials, 2 quasi-experimental). Five were reactive telehealth interventions with patient-initiated contact and five evaluated scheduled telehealth interventions initiated by nurses. Compared to usual care (typically patient-initiated calls), nurse-led telehealth interventions for symptom management showed no statistically significant difference in hospitalizations, emergency department visits, or unscheduled clinic visits. Two of three studies of reactive telehealth interventions showed improved quality of life. All telehealth interventions showed reduction in the severity of most symptoms. Pain severity was significantly reduced (standard mean difference - 0.54; 95% CI - 0.88, - 0.19). Significant heterogeneity prevented meta-analysis for most outcomes. CONCLUSION: Few studies evaluated nurse-led telehealth interventions for cancer symptom management. Compared to usual care, patients exposed to telehealth interventions had reduced symptom severity and no difference in health services use. Future research should focus on better reporting intervention characteristics and consistently measuring outcomes.
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Implementation barriers to integrating exercise as medicine in oncology: An ecological scoping review
PURPOSE: While calls have been made for exercise to become standard practice in oncology, barriers to implementation in real-world settings are not well described. This systematic scoping review aimed to comprehensively describe barriers impeding integration of exercise into routine oncology care within healthcare systems. METHODS: A systematic literature search was conducted across six electronic databases (since 2010) to identify barriers to implementing exercise into real-world settings. An ecological framework was used to classify barriers according to their respective level within the healthcare system. RESULTS: A total of 1,376 results were retrieved; 50 articles describing implementation barriers in real-world exercise oncology settings were reviewed. Two hundred and forty-three barriers were identified across all levels of the healthcare system. Nearly 40% of barriers existed at the organizational level (n = 93). Lack of structures to support exercise integration and absence of staff/resources to facilitate its delivery were the most common issues reported. Despite the frequency of barriers at the organizational level, organizational stakeholders were largely absent from the research. CONCLUSIONS: Implementing exercise into routine cancer care is hindered by a web of interrelated barriers across all levels of the healthcare system. Organizational barriers are central to most issues. Future work should take an interdisciplinary approach to explore best practices for overcoming implementation barriers, with organizations as a central focus. IMPLICATIONS FOR CANCER SURVIVORS: This blueprint of implementation barriers highlights critical issues that need to be overcome to ensure people with cancer have access to the therapeutic benefits of exercise during treatment and beyond.
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Parenting Interventions for Mothers With Problematic Substance Use: A Systematic Review of Research and Community Practice.
Women with problematic substance use are frequently referred to interventions to promote positive parenting. Parenting interventions that attend to the unique risks faced by this population may enhance engagement and outcomes. While reviews of extant parenting interventions in the research literature have been undertaken, no studies have examined parenting interventions being implemented in community practice and the extent to which these are informed by current research. We systematically compared parenting interventions offered in 12 maternal substance use treatment programs in one Canadian province with those described in the research literature (K = 21). Few parenting interventions were replicated, either within or across the two samples. However, parenting interventions within both samples were largely similar in their objectives. Across both research and community samples, approximately half of the interventions were developed or adapted for a problematic substance use population. Parenting knowledge, psychosocial risk, and maternal emotional regulation were most commonly addressed. Risks pertaining to the impact of drug craving and substance-related changes in neurobiology associted with parenting were less commonly addressed. Findings highlight current strengths and limitations of parenting interventions within research and community settings, with recommendations offered for future research and knowledge translation.
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Maternal asthma and the risk of hypertensive disorders of pregnancy: a systematic review and meta-analysis of cohort studies
Objective: The aim of this study was to demonstrate the association between maternal asthma and the risk of hypertensive disorders of pregnancy.Methods: A systematic search of seven databases was conducted. A meta-analysis was performed to calculate risk ratios and 95% CI using random-effects models.Results: Asthma was associated with an increased risk of pregnancy-induced hypertension (RR 1.45, 95%CI 1.29-1.63), transient hypertension of pregnancy (RR 2.00, 95%CI 1.52-2.63), preeclampsia or eclampsia (RR 1.28, 95%CI 1.25-1.32), preeclampsia (RR 1.43, 95%CI 1.31-1.57) and eclampsia (RR 1.56, 95%CI 1.13-2.15).Conclusion: The meta-analysis illustrated that asthma was significantly increased risk of hypertension during pregnancy.
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A systematic review and network meta-analysis protocol of adjuvant chemotherapy regimens for resected gastric cancer
Background: Gastric cancer is the third leading cause of cancer death in the world. The benefit of adjuvant chemotherapy has been demonstrated by published individual patient data meta-analysis and Cochrane systematic review. However, there is no consensus on which is the optimal adjuvant chemotherapy regimens. Present network meta-analysis aims to compare the differences of effect between all available adjuvant chemotherapy regimens in improving overall survival and disease-free survival, and to rate the certainty of evidence from present network meta-analysis. Methods: We will conduct this systematic review and network meta-analysis using Bayesian method and according to Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) statement. We will search PubMed, EMBASE.com, the Cochrane Central Register of Controlled Trials (CENTRAL), Chinese National Knowledge Infrastructure (CNKI), and Chinese Biological Medical Database (CBM), and ClinicalTrials.gov () to identify randomized controlled trials (RCTs) comparing adjuvant chemotherapy to surgery alone. We will assess the risk of bias of individual RCTs using a modified version of Cochrane tool. We will also use the advance of GRADE to rate the certainty of network meta-analysis. Data analysis will be performed with R-3.4.1 and WinBUGS software. Results: The results of this study will be published in a peer-reviewed journal. Discussion: To the best of our knowledge, this systematic review and network meta-analysis will firstly use both direct and indirect evidence to compare the differences of all available adjuvant chemotherapy regimens for resected gastric cancer patients. This is a protocol of systematic review and meta-analysis, so the ethical approval and patient consent are not required.
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Electronic systems for patients to report and manage side effects of cancer treatment: Systematic review
BACKGROUND: There has been a dramatic increase in the development of electronic systems to support cancer patients to report and manage side effects of treatment from home. Systems vary in the features they offer to patients, which may affect how patients engage with them and how they improve patient-centered outcomes. OBJECTIVE: This review aimed to (1) describe the features and functions of existing electronic symptom reporting systems (eg, symptom monitoring, tailored self-management advice), and (2) explore which features may be associated with patient engagement and patient-centered outcomes. METHODS: The review was registered with the International Prospective Register of Systematic Reviews (PROSPERO) and followed guidelines from the Centre for Reviews and Dissemination (University of York, United Kingdom). Primary searches were undertaken of MEDLINE, Embase, PsycInfo, Web of Science, Cochrane Central Register of Controlled Trials, and the Health Technology Assessment databases. Secondary searches were undertaken by screening reference lists and citations. Two researchers applied broad inclusion criteria to identify and select relevant records. Data were extracted and summarized using Microsoft Excel. In order to meet the aims, the study selection, data extraction, and data synthesis comprised two stages: (1) identifying and characterizing available systems and (2) summarizing data on patient engagement and patient-centered outcomes. RESULTS: We identified 77 publications relating to 41 distinct systems. In Stage 1, all publications were included (N=77). The features identified that supported clinicians and care were facility for health professionals to remotely access and monitor patient-reported data (24/41, 58%) and function to send alerts to health professionals for severe symptoms (17/41, 41%). Features that supported patients were facility for patients to monitor/review their symptom reports over time (eg, graphs) (19/41, 46%), general patient information about cancer treatment and side effects (17/41, 41%), tailored automated patient advice on symptom management (12/41, 29%), feature for patients to communicate with the health care team (6/41, 15%), and a forum for patients to communicate with one another (4/41, 10%). In Stage 2, only publications that included some data on patient engagement or patient-centered outcomes were included (N=29). A lack of consistency between studies in how engagement was defined, measured, or reported, and a wide range of methods chosen to evaluate systems meant that it was not possible to compare across studies or make conclusions on relationships with system features. CONCLUSIONS: Electronic systems have the potential to help patients manage side effects of cancer treatment, with some evidence to suggest a positive effect on patient-centered outcomes. However, comparison across studies is difficult due to the wide range of assessment tools used. There is a need to develop guidelines for assessing and reporting engagement with systems, and a set of core outcomes for evaluation. We hope that this review will contribute to the field by introducing a taxonomy for characterizing system features.
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A meta-analysis of effectiveness of interventions to improve adherence in pregnant women receiving antiretroviral therapy in sub-Saharan Africa
OBJECTIVE: We evaluated the effectiveness of interventions aimed at improving antiretroviral therapy (ART) adherence during pregnancy in sub-Saharan Africa. METHODS: For this meta-analysis, the following databases were searched: MEDLINE Complete, Embase, Global Health, CINAHL Complete, and Google Scholar. Randomized and nonrandomized studies were considered for inclusion if they involved an intervention with the intent of improving medication adherence among pregnant women taking ART in sub-Saharan Africa. Databases were searched from inception to the end of August 2017. The primary outcome assessed was adherence to ART, defined as the proportion of women adherent to treatment in the control and intervention groups. Risk ratios and random effect meta-analysis were undertaken, and heterogeneity was examined with the I(2) statistic. RESULTS: The systematic search of databases yielded a total of 402 articles, of which 19 studies were selected for meta-analysis with a total of 27,974 participants. Nine types of interventions were identified in the 19 studies to improve ART adherence. The test for the subgroup differences showed that there was a statistically significant difference among the 9 subgroups of interventions, chi(2) (8)=102.38; p=0.00001. Collectively, in the meta-analysis, the various intervention types made a significant impact on improving medication adherence. The overall effect estimate with 95% CI was as follows: 1.25 (95% CI=1.03, 1.52, p=0.03). The following risk ratio results for meta-analysis were obtained for the three interventions that showed significant impact on adherence; namely social support and structural support, 1.58 (95% CI=1.36, 1.84, p <0.00001); education, social support and structural support=2.60 (95% CI=1.95, 3.45, p <0.00001); and device reminder=1.13 (95% CI=1.05, 1.20, p=0.0004).The proportion of women who were adherent to ART as a result of the interventions was 59.3% compared with 22.5% in the control groups. CONCLUSION: The use of device reminder, a combination of social support and structural support, and education, social support and structural support has the potential to improve ART adherence during pregnancy. Good quality prospective observational studies and randomized control trials are needed in sub-Saharan Africa to determine the most effective interventions.
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A systematic review of decision aids for patients making a decision about treatment for early breast cancer
Several complex treatment decisions may be offered to women with early stage breast cancer, about a range of treatments from different modalities including surgery, radiotherapy, and endocrine and chemotherapy. Decision aids can facilitate shared decision-making and improve decision-related outcomes. We aimed to systematically identify, describe and appraise the literature on treatment decision aids for women with early breast cancer, synthesise the data and identify breast cancer decisions that lack a decision aid. A prospectively developed search strategy was applied to MEDLINE, the Cochrane databases, EMBASE, PsycINFO, Web of Science and abstract databases from major conferences. Data were extracted into a pre-piloted form. Quality and risk of bias were measured using Qualsyst criteria. Results were synthesised into narrative format. Thirty-three eligible articles were identified, evaluating 23 individual treatment decision aids, comprising 13 randomised controlled trial reports, seven non-randomised comparative studies, eight single-arm pre-post studies and five cross-sectional studies. The decisions addressed by these decision aids were: breast conserving surgery versus mastectomy (+/- reconstruction); use of chemotherapy and/or endocrine therapy; radiotherapy; and fertility preservation. Outcome measures were heterogeneous, precluding meta-analysis. Decisional conflict decreased, and knowledge and satisfaction increased, without any change in anxiety or depression, in most studies. No studies were identified that evaluated decision aids for neoadjuvant systemic therapy, or contralateral prophylactic mastectomy. Decision aids are available and improved decision-related outcomes for many breast cancer treatment decisions including surgery, radiotherapy, and endocrine and chemotherapy. Decision aids for neoadjuvant systemic therapy and contralateral prophylactic mastectomy could not be found, and may be warranted
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Role of antimicrobial photodynamic therapy in the treatment of aggressive periodontitis: a systematic review
BACKGROUND: The aim was to assess the efficacy of antimicrobial photodynamic therapy(aPDT) in the treatment of aggressive periodontitis (AgP). METHODS: The addressed focused question was 'Is aPDT effective in the treatment of AgP?'MEDLINE/PubMed, EMBASE, Scopus, ISI Web of knowledge and Google-Scholar databases were searched from 1977 till May 2015 using combinations of the following key words: antimicrobial; photochemotherapy; photodynamic therapy; photosensitizing agents; AgP; scaling and root-planing (SRP). Reviews, case reports, commentaries, and articles published in languages other than English were excluded. RESULTS: Seven studies were included. In 5 studies aPDT was performed as an adjunct to SRP. Laserwavelengths and duration of irradiation ranged between
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Impact of service provision platforms on maternal and newborn health in conflict areas and their acceptability in Pakistan: A systematic review
Various models and strategies have been implemented over the years in different parts of the world to improve maternal and newborn health (MNH) in conflict affected areas. These strategies are based on specific needs and acceptability of local communities. This paper has undertaken a systematic review of global and local (Pakistan) information from conflict areas on platforms of health service provision in the last 10 years and information on acceptability from local stakeholders on effective models of service delivery; and drafted key recommendations for improving coverage of health services in conflict affected areas. The literature search revealed ten studies that described MNH service delivery platforms. The results from the systematic review showed that with utilisation of community outreach services, the greatest impacts were observed in skilled birth attendance and antenatal consultation rates. Facility level services, on the other hand, showed that labour room services for an internally displaced population (IDP) improved antenatal care coverage, contraceptive prevalence rate and maternal mortality. Consultative meetings and discussions conducted in Quetta and Peshawar (capitals of conflict affected provinces) with relevant stakeholders revealed that no systematic models of MNH service delivery, especially tailored for conflict areas, are available. During conflict, even previously available services and infrastructure suffered due to various barriers specific to times of conflict and unrest. A number of barriers that hinder MNH services were discussed. Suggestions for improving MNH services in conflict areas were also laid down by participants. The review identified some important steps that can be undertaken to mitigate the effects of conflict on MNH services, which include: improve provision and access to infrastructure and equipment; development and training of healthcare providers; and advocacy at different levels for free access to healthcare services and for the introduction of the programme model in existing healthcare system. The obligation is enormous, however, for a sustainable programme, it is important to work closely with both the IDP and host community, and collaborating with the government and non-government organisations
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The effectiveness of therapeutic patient education on adherence to oral anti-cancer medicines in adult cancer patients in ambulatory care settings: A systematic review
BACKGROUND: Adherence to oral cancer medicines is a challenge for adult patients with cancer. Education specifically tailored for an individual patient with cancer may improve adherence. Therapeutic patient education when utilized effectively may maximize health outcomes and positively affect the quality of life of adult patients with cancer. Currently, there are no published systematic reviews specific to the effectiveness of therapeutic patient education on improvement of oral anti-cancer medicines adherence in patients with cancer. OBJECTIVES: To synthesize the best available evidence on the effectiveness of therapeutic patient education on adherence to oral anti-cancer medicines in adult cancer patients 18 years and older in an ambulatory care setting. INCLUSION CRITERIA: Types of participants: This review considered studies involving adults of any ethnicity, race or gender, aged 18 years or older who were diagnosed with any form of cancer, receiving oral anti-cancer medicines in an ambulatory care setting. Types of intervention(s): This review considered studies on the use of therapeutic patient education as the additional intervention to routine patient education for promoting oral anti-cancer medicine adherence in adult patients with cancer in an ambulatory care setting. Routine patient education was considered as a comparator. Types of outcomes: The outcome considered was adherence to prescribed oral anti-cancer medicines. Types of studies: This review considered experimental and observational studies. SEARCH STRATEGY: The literature search included published and unpublished studies in the English Language from 1953 through August 2014. A search of PubMed, CINAHL, Excerpta Medica Database, Academic Search Premier, Cochrane Library, PsycINFO, and Health Source: Nursing/Academic Edition was conducted using identified keywords and indexed terms across all included databases. A search for grey literature and electronic hand searching of relevant journals was also performed. METHODOLOGICAL QUALITY: Two reviewers independently evaluated the included studies for methodological quality utilizing standardized critical appraisal instruments from the Joanna Briggs Institute. DATA COLLECTION: Standardized data extraction tools were used by two reviewers independently as per the Joanna Briggs Institute for data extraction. DATA SYNTHESIS: Due to clinical and methodological heterogeneity between the included studies, statistical meta-analysis was not feasible. The results are presented in a narrative form. RESULTS: Two studies were included in this review, one randomized controlled trial and one cohort study. Both studies had small sample sizes and were moderate and low quality. The clinical significance of therapeutic patient education interventions and the relationship between behavior changes and health outcome changes remain unclear. The randomized clinical trial found a benefit in medication adherence rates in the tailored education intervention group compared to the standard education group at two and four months. Adherence rates measured by self-report (91.3% and 95.1%) and pharmacy refill rates (80% and 73.7%) were superior for the intervention group; however pharmacy refill rates were lower than self-reports of adherence. Tailored educational interventions were only beneficial on pharmacy refill rates (p=.0048) for promoting adherence at the two-month time interval. The cohort study found the intensified pharmaceutical educational intervention group demonstrated enhanced overall medication adherence then the standard education group TRUNCATED AT 500 WORDS
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Vascular endothelial growth factor receptor tyrosine kinase inhibitors versus bevacizumab in metastatic colorectal cancer: A systematic review and meta-analysis
Bevacizumab has demonstrated a survival benefit in patients with metastatic colorectal cancer (mCRC) when combined with chemotherapy. Several randomized clinical trials comparing the efficacy and toxicity of vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) against bevacizumab have been reported. The present meta-analysis was conducted to identify the potentially significant benefit of the combined treatment regimens in patients with mCRC. PubMed, Embase and Cochrane Library databases were searched for the randomized controlled trials published on or before September 2014, which compared the efficacy and toxicity of VEGFR TKIs with bevacizumab in combination with chemotherapy in patients with mCRC. The primary endpoints included progression-free survival (PFS), overall survival (OS) and overall response rate (ORR), and secondary endpoints were the toxicity profiles. Relative risks (RRs) with 95% confidence intervals (CIs) for response rate and adverse events (AEs) were calculated, as well as hazard ratios (HRs) for PFS and OS. The final analysis included 4 studies comprising a total of 1,929 intent-to-treat patients with mCRC, which compared VEGFR TKIs (cediranib and axitinib) plus chemotherapy with bevacizumab plus chemotherapy. Results demonstrated that VEGFR TKIs plus chemotherapy significantly resulted in a modest but significantly shorter PFS [hazard ratio (HR), 1.12; 95% CI, 1.00-1.25; P=0.05] compared with that of bevacizumab plus chemotherapy but not in OS (HR, 1.10; 95% CI, 0.88-1.17; P=0.87) and ORR (RR, 0.95; 95% CI, 0.85-1.05; P=0.30). VEGFR TKIs treatment showed a less favorable AE profile compared with bevacizumab, with higher rates of grade-III/IV diarrhea, fatigue, hypertension, neutropenia and thrombocytopenia, whereas a higher incidence of peripheral neuropathy associated with the bevacizumab group was observed. In conclusion, the addition of VEGFR TKIs to chemotherapy resulted in a modest but significantly shorter PFS but not in OS and ORR compared with bevacizumab. The VEGFR TKIs group showed a less favorable AE profile with higher rates of diarrhea, fatigue, hypertension, neutropenia and thrombocytopenia, whereas a higher incidence of peripheral neuropathy associated with the bevacizumab was observed
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