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Drug delivery systems for ovarian cancer treatment: a systematic review and meta-analysis of animal studies.

ABSTRACT: Current ovarian cancer treatment involves chemotherapy that has serious limitations, such as rapid clearance, unfavorable biodistribution and severe side effects. To overcome these limitations, drug delivery systems (DDS) have been developed to encapsulate chemotherapeutics for delivery to tumor cells. However, no systematic assessment of the efficacy of chemotherapy by DDS compared to free chemotherapy (not in a DDS) has been performed for animal studies. Here, we assess the efficacy of chemotherapy in DDS on survival and tumor growth inhibition in animal studies. We searched PubMed and EMBASE (via OvidSP) to systematically identify studies evaluating chemotherapeutics encapsulated in DDS for ovarian cancer treatment in animal studies. Studies were assessed for quality and risk of bias. Study characteristics were collected and outcome data (survival/hazard ratio or tumor growth inhibition) were extracted and used for meta-analyses. Meta-analysis was performed to identify and explore which characteristics of DDS influenced treatment efficacy. A total of 44 studies were included after thorough literature screening (2,735 studies found after initial search). The risk of bias was difficult to assess, mainly because of incomplete reporting. A total of 17 studies (377 animals) and 16 studies (259 animals) could be included in the meta-analysis for survival and tumor growth inhibition, respectively. In the majority of the included studies chemotherapeutics entrapped in a DDS significantly improved efficacy over free chemotherapeutics regarding both survival and tumor growth inhibition. Subgroup analyses, however, revealed that cisplatin entrapped in a DDS did not result in additional tumor growth inhibition compared to free cisplatin, although it did result in improved survival. Micelles did not show a significant tumor growth inhibition compared to free chemotherapeutics, which indicates that micelles may not be a suitable DDS for ovarian cancer treatment. Other subgroup analyses, such as targeted versus non-targeted DDS or IV versus IP administration route, did not identify specific characteristics of DDS that affected treatment efficacy. This systematic review shows the potential, but also the limitations of chemotherapy by drug delivery systems for ovarian cancer treatment. For future animal research, we emphasize that data need to be reported with ample attention to detailed reporting.

SUBMITTER: Raave R

PROVIDER: S-EPMC4690347 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Project description:BackgroundThere are concerns that the use of electronic nicotine delivery systems (ENDS) and electronic non-nicotine delivery systems (ENNDS) in children and adolescents could potentially be harmful to health. Understanding the extent of use of these devices is crucial to informing public health policy. We aimed to synthesise the prevalence of ENDS or ENNDS use in children and adolescents younger than 20 years.MethodsIn this systematic review and meta-analysis, we undertook an electronic search in five databases (MEDLINE, Web of Science, Cumulative Index to Nursing and Allied Health Literature, Embase, and Wiley Cochrane Library) from Jan 1, 2016, to Aug 31, 2020, and a grey literature search. Included studies reported on the prevalence of ENDS or ENNDS use in nationally representative samples in populations younger than 20 years and collected data between the years 2016 and 2020. Studies were excluded if they were done in those aged 20 years or older, used data from specialist panels that did not apply appropriate weighting, or did not use methods that ensured recruitment of a nationally representative sample. We included the most recent data for each country. We combined multiple national estimates for a country if they were done in the same year. We undertook risk of bias assessment for all surveys included in the review using the Joanna Briggs Institute Critical Appraisal Checklist (by two reviewers in the author list). A random effects meta-analysis was used to pool overall prevalence estimates for ever, current, occasional, and daily use. This study was prospectively registered with PROSPERO, CRD42020199485.FindingsThe most recent prevalence data from 26 national surveys representing 69 countries and territories, with a median sample size of 3925 (IQR 1=2266, IQR 3=10 593) children and adolescents was included. In children and adolescents aged between 8 years and younger than 20 years, the pooled prevalence for ever (defined as any lifetime use) ENDS or ENNDS use was 17·2% (95% CI 15-20, I2=99·9%), whereas for current use (defined as use in past 30 days) the pooled prevalence estimate was 7·8% (6-9, I2=99·8%). The pooled estimate for occasional use was 0·8% (0·5-1·2, I2=99·4%) for daily use and 7·5% (6·1-9·1, I2=99·4%) for occasional use. Prevalence of ENDS or ENNDS use was highest in high-income geographical regions. In terms of study quality, all surveys scored had a low risk of bias for the sampling frame used, due to the nationally representative nature of the studies. The most poorly conducted methodological feature of the included studies was subjects and setting described in detail. Few surveys reported on the use of flavours or types of ENDS or ENNDS.InterpretationThere is significant variability in the prevalence of ENDS and ENNDS use in children and adolescents globally by country income status. These findings are possibly due to differences in regulatory context, market availability, and differences in surveillance systems.FundingWorld Health Organization and the Bill & Melinda Gates Foundation.

Project description:IntroductionCanine osteoarthritis (OA) is a degenerative disease with chronic inflammation of internal and external joint structures in dogs. Cannabis spp. contains cannabidiol (CBD), a substance known for various potential indications, such as pain relief and anti-inflammatory in various types of animals, including dogs with OA. As CBD is increasingly in the spotlight for medical use, we aimed to perform a systematic review and meta-analysis to evaluate the efficacy and safety of CBD in treating canine OA.MethodsWe searched PubMed, Embase, Scopus, and CAB Direct for animal intervention studies investigating the effects of CBD for canine OA from database inception until February 28, 2023. Study characteristics and findings were summarized. A risk of bias in the included studies was assessed. Meta-analyses were performed using a random-effects model to estimate the effects of CBD on pain scores (0-10), expressed as mean difference (MD) and 95% confidence interval (95% CI). Certainty of evidence was assessed using GRADE.ResultsFive articles were included, which investigated the effects of CBD in 117 dogs with OA. All studies were rated as having a high risk of bias. CBD products varied substantially, i.e., oral full-spectrum CBD oil in four studies, and isolated CBD oil and liposomal CBD oil in another study. Treatment duration varied from 4-12 weeks. Meta-analyses of three studies found that, in dogs with OA, treatment with oral full-spectrum CBD oil may reduce pain severity scores (MD; -0.60, 95% CI; -1.51 to 0.31, I2 = 45.64%, p = 0.19) and pain interference scores (MD; -1.52, 95% CI; -3.84 to 0.80, I2 = 89.59%, p = 0.20) but the certainty of evidence was very low. CBD is generally considered safe and well-tolerated in the short-run, with few mild adverse events observed, such as vomiting and asymptomatic increase in alkaline phosphatase level.ConclusionCBD is considered safe for treating canine OA. CBD may reduce pain scores, but the evidence is very uncertain to conclude its clinical efficacy. High-quality clinical trials are needed to further evaluate the roles of CBD in canine OA.

Project description:Both preclinical and clinical studies indicate that raised intra-abdominal pressure (IAP) associated with pneumoperitoneum during laparoscopic surgical procedures can cause renal damage, the severity of which may be influenced by variables such as pressure level and duration. Several of these variables have been investigated in animal studies, but synthesis of all preclinical data has not been performed. This systematic review summarizes all available pre-clinical evidence on this topic, including an assessment of its quality and risk of bias. We performed meta-analysis to assess which aspects of the pneumoperitoneum determine the severity of its adverse effects. A systematic search in two databases identified 55 studies on the effect of pneumoperitoneum on renal function which met our inclusion criteria. There was high heterogeneity between the studies regarding study design, species, sex, pressure and duration of pneumoperitoneum, and type of gas used. Measures to reduce bias were poorly reported, leading to an unclear risk of bias in the majority of studies. Details on randomisation, blinding and a sample size calculation were not reported in ≥80% of the studies. Meta-analysis showed an overall increase in serum creatinine during pneumoperitoneum, and a decrease in urine output and renal blood flow. Subgroup analysis indicated that for serum creatinine, this effect differed between species. Subgroup analysis of pressure level indicated that urine output decreased as IAP level increased. No differences between types of gas were observed. Data were insufficient to reliably assess whether sex or IAP duration modulate the effect of pneumoperitoneum. Four studies assessing long-term effects indicated that serum creatinine normalized ≥24 hours after desufflation of pneumoperitoneum at 15mmHg. We conclude that harmful effects on renal function and perfusion during pneumoperitoneum appear to be robust, but evidence on long-term effects is very limited. The reliability and clinical relevance of these findings for healthy patients and patients at high risk of renal impairment remain uncertain. We emphasize the need for rigorous reporting of preclinical research methodology, which is of vital importance for clinical translation of preclinical data.

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Drug delivery systems for ovarian cancer treatment: a systematic review and meta-analysis of animal studies.

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