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Expert Review of Clinical Pharmacology Sep 2017This systematic review of therapeutic drug monitoring (TDM) identifies three long-acting injectable (LAI) risperidone formulations. Areas covered: Limited data is... (Review)
Review
This systematic review of therapeutic drug monitoring (TDM) identifies three long-acting injectable (LAI) risperidone formulations. Areas covered: Limited data is available on two formulations (RBP-7000 and in Situ Microparticle), but 20 TDM articles on the microsphere formulation were found. Risperidone TDM includes the serum concentrations of risperidone and its active metabolite, 9-hydroxyrisperidone, used for calculating: 1) the risperidone/9-hydroxyrisperidone (R/9-OH-R) ratio (a measure of CYP2D6; values >1 are indicative of a CYP2D6 poor metabolizer) and 2) the total risperidone concentration-to-dose (C/D) ratio (a measure of risperidone clearance with a normal value around 7 in oral risperidone). The weighted mean R/9-OH-R ratio was 0.48 (approximately twice that of oral risperidone TDM) in a combined analysis from 329 patients in 6 risperidone LAI studies without major confounders. The total C/D ratios from 297 patients in 6 risperidone LAI studies ranged from 7.4 to 9.7 ng/ml/mg/day with a weighted mean of 8.8 ng/ml/mg/day. Expert commentary: Clinicians using TDM for risperidone LAI microsphere formulation need to: 1) consider steady state to be reached ≥ 6 weeks after the first injection, 2) pay attention to a) co-medications with inducers/inhibitors, b) severe inflammations/infections, and c) hepatic/renal impairment, and 3) use Castberg's recommendation to calculate risperidone dosing.
Topics: Administration, Oral; Animals; Antipsychotic Agents; Delayed-Action Preparations; Drug Monitoring; Humans; Injections; Microspheres; Paliperidone Palmitate; Risperidone
PubMed: 28699847
DOI: 10.1080/17512433.2017.1345623 -
Journal of Radiation Oncology 2017The purpose of this study was to review the role of radioactive microparticles (1-100 μm) for the treatment of solid tumors and provide a comprehensive overview of the... (Review)
Review
PURPOSE
The purpose of this study was to review the role of radioactive microparticles (1-100 μm) for the treatment of solid tumors and provide a comprehensive overview of the feasibility, safety, and efficacy.
METHODS
A systematic search was performed in MEDLINE, EMBASE, and The Cochrane Library (January 2017) by combining synonyms for the determinants "tumor," "injection," and "radionuclide." Data on injection technique, toxicity, tumor response, and survival were collected.
RESULTS
The search yielded 7271 studies, and 37 were included for analysis. Twelve studies were performed in human patients and 25 animal studies. The studies were heterogeneous in patient population, tumors, follow-up time, and treatment characteristics. The direct intratumoral injection of radioactive microparticles resulted in a response rate of 71% in a variety of tumors and uncomplicated procedures with high cumulative doses of >19,000 Gy were reported.
CONCLUSION
The large variety of particles, techniques, and treated tumors in the studies provided an important insight into issues concerning efficacy, safety, particle and isotope choice, and other concepts for future research. Animal studies showed efficacy and a dose response. Most studies in humans concluded that intratumoral treatment with radioactive beta-emitting microparticles is relatively safe and effective. Conflicting evidence about safety and efficacy might be explained by the considerable variation in the treatment characteristics. Larger particles had a better retention which resulted in higher anti-tumor effect. Leakage seems to follow the path of least resistance depending on anatomical structures. Subsequently, a grid-like injection procedure with small volume depots is advised over a single large infusion. Controlled image-guided treatment is necessary because inadequate local delivery and inhomogeneous dose distribution result in reduced treatment efficacy and in potential complications.
PubMed: 29213358
DOI: 10.1007/s13566-017-0315-6 -
Hepatology (Baltimore, Md.) Sep 2017Selective internal radiation therapy (or radioembolization) by intra-arterial injection of radioactive yttrium-90-loaded microspheres is increasingly used for the... (Review)
Review
Selective internal radiation therapy (or radioembolization) by intra-arterial injection of radioactive yttrium-90-loaded microspheres is increasingly used for the treatment of patients with liver metastases or primary liver cancer. The high-dose beta-radiation penetrates an average of only 2.5 mm from the source, thus limiting its effects to the site of delivery. However, the off-target diversion of yttrium-90 microspheres to tissues other than the tumor may lead to complications. The most prominent of these complications include radiation gastritis and gastrointestinal ulcers, cholecystitis, radiation pneumonitis, and radioembolization-induced liver disease, which may occur despite careful pretreatment planning. Thus, selective internal radiation therapy demands an expert multidisciplinary team approach in order to provide comprehensive care for patients. This review provides recommendations to multidisciplinary teams on the optimal medical processes in order to ensure the safe delivery of selective internal radiation therapy. Based on the best available published evidence and expert opinion, we recommend the most appropriate strategies for the prevention, early diagnosis, and management of potential radiation injury to the liver and to other organs. (Hepatology 2017;66:969-982).
Topics: Brachytherapy; Dose-Response Relationship, Radiation; Female; Humans; Liver Neoplasms; Male; Microspheres; Practice Guidelines as Topic; Prognosis; Radiation Injuries; Radiation Pneumonitis; Retrospective Studies; Treatment Outcome; Yttrium Radioisotopes
PubMed: 28407278
DOI: 10.1002/hep.29207 -
Journal of Vascular and Interventional... Dec 2022To assess the safety and effectiveness of transarterial radioembolization (TARE) in the treatment of hepatic metastases from pancreatic ductal adenocarcinoma (PDAC). (Review)
Review
PURPOSE
To assess the safety and effectiveness of transarterial radioembolization (TARE) in the treatment of hepatic metastases from pancreatic ductal adenocarcinoma (PDAC).
MATERIALS AND METHODS
A systematic search of the Embase and MEDLINE databases was conducted using keywords and Medical Subject Headings terms related to TARE and hepatic metastases from PDAC. Observational studies and clinical trials reporting overall survival (OS), hepatic progression-free survival (hPFS), or tumor response after TARE were included.
RESULTS
Eight studies, comprising 145 patients with metastatic PDAC, met the inclusion criteria. No randomized controlled trials were identified, and 4 studies were prospective. Forty-four (30.3%) patients underwent previous pancreatic resection, and 66 (45.5%) had extrahepatic metastases at the time of TARE. Most studies (n = 6) used resin microspheres for TARE. The pooled disease control rate was 69.4% at a median of 3 months. The median OS from the time of TARE ranged from 3.7 to 9 months. The median hPFS ranged from 2.4 to 5.2 months. There were 31 Grade 3-4 biochemical toxicities and 4 treatment-related deaths.
CONCLUSIONS
The role of TARE in patients with hepatic metastases from PDAC remains unclear owing to low patient numbers, limited prospective data, and heterogeneity in the study design. Further prospective studies are required to evaluate the role of TARE in carefully selected patients with liver-only metastatic disease.
Topics: Humans; Yttrium Radioisotopes; Adenocarcinoma; Pancreatic Neoplasms; Treatment Outcome; Liver Neoplasms; Embolization, Therapeutic; Carcinoma, Pancreatic Ductal; Carcinoma, Hepatocellular; Retrospective Studies
PubMed: 36084842
DOI: 10.1016/j.jvir.2022.08.031 -
BMC Oral Health Oct 2023Periodontal pockets are characteristic of periodontitis. Scaling and root planing is the gold standard for periodontitis treatment. Additional local antimicrobials are... (Meta-Analysis)
Meta-Analysis
Periodontal pockets are characteristic of periodontitis. Scaling and root planing is the gold standard for periodontitis treatment. Additional local antimicrobials are recommended in patients with a probing depth of ≥ 5 mm. This study aims to determine the effectiveness of chlorhexidine compared to other local antimicrobials in periodontitis. Searches were conducted using the Preferred Reporting Items for Systematic Reviews and Meta Analysis (PRISMA) guidelines. Meta-analysis was performed on studies that met inclusion criteria after risk of bias assessment. Meta-analysis between chlorhexidine chips and other antimicrobials showed a mean difference in probing depth after one month of 0.58 mm (p < 0.00001) whereas after three months the mean difference in probing depth was 0.50 mm (p = 0.001), index plaque 0.01 (p = 0.94) and gingival index - 0.11 mm (p = 0.02). Between chlorhexidine gel and other antimicrobials showed a mean difference in probing depth of 0.40 mm (p = 0.30), plaque index of 0.20 mm (p = 0.0008) and gingival index of -0.04 mm (p = 0.83) after one month. Chlorhexidine chips were more effective on the gingival index than other antimicrobials after three months. The other antimicrobials were more effective than chlorhexidine chips on probing depth after one and three months, and than chlorhexidine gels on plaque index after one month.
Topics: Humans; Chlorhexidine; Root Planing; Anti-Infective Agents, Local; Dental Scaling; Periodontitis; Gels
PubMed: 37899443
DOI: 10.1186/s12903-023-03241-2 -
European Journal of Radiology Mar 2018To evaluate the value of yttrium-90 (Y) microspheres in the management of unresectable liver metastases secondary to neuroendocrine tumors (NETs). (Review)
Review
OBJECTIVE
To evaluate the value of yttrium-90 (Y) microspheres in the management of unresectable liver metastases secondary to neuroendocrine tumors (NETs).
MATERIALS AND METHODS
PubMed, EMBASE, the Cochrane Database of Systematic Reviews, and the "gray" literature (Google Scholar) were searched for all studies related to Y therapy for unresectable liver metastases of NETs.
RESULTS
A total of 11 studies and 7 abstracts involving 870 patients were included in the final analysis. In 11 of these studies, 19.8% (77/388) of patients had undergone transarterial bland embolization (TABE) or transarterial chemoembolization (TACE) before Y therapy. The median disease control rate among all patients was 86% at 3 months after Y therapy. The median survival was 28 months, with 1-, 2-, and 3-year survival rates of 72.5%, 57%, and 45%, respectively. The median survival values for patients who received resin- and glass-based Y treatment were 27.6 and 31.7 months, respectively. The survival values for patients with carcinoid, pancreatic, and unclassified origin of NETs were 56, 31, and 28 months, respectively; the survival values for patients with grade I, II, and III NETs were 71, 56, and 28 months, respectively. Carcinoid syndrome was reported in 52.4% (55/105) of patients, and 69.1% of those with clinical symptoms demonstrated improvement in symptoms after Y radioembolization. Complications were reported in 9 studies, including radiation gastritis (n = 4), duodenal ulcer (n = 2), death due to liver failure (n = 1), and radiation cholecystitis (n = 1). The most common side effects were abdominal pain (median, 32.6%), nausea/vomiting (median, 32.5%), and fatigue (median, 30.4%).
CONCLUSIONS
Y radioembolization can be used as an alternative therapy for unresectable liver metastases of NETs, with an improved survival rate and tumor response. This treatment is also effective for patients who have undergone unsuccessful TABE/TACE therapy and for the relief of symptoms in patients with carcinoid syndrome.
Topics: Aged; Brachytherapy; Female; Humans; Liver Neoplasms; Male; Middle Aged; Neuroendocrine Tumors; Survival Rate; Treatment Outcome; Young Adult; Yttrium Radioisotopes
PubMed: 29496075
DOI: 10.1016/j.ejrad.2018.01.012 -
Cardiovascular and Interventional... Oct 2014This study was designed to undertake systematic review and meta-analysis of published comparative trials comparing embolic agents used in uterine artery embolisation... (Comparative Study)
Comparative Study Meta-Analysis Review
PURPOSE
This study was designed to undertake systematic review and meta-analysis of published comparative trials comparing embolic agents used in uterine artery embolisation (UAE) for uterine leiomyomata.
METHODS
Systematic literature searches were performed in MEDLINE, Embase, PubMed, and Cochrane Central databases from database inception to July 2012. Randomised and nonrandomised trials comparing two or more embolic agents used in UAE were included. Assessment included five widely used embolic agents: nonspherical polyvinyl alcohol (PVA) (Contour PVA, Boston Scientific or PVA Cook Medical); spherical PVA (Contour SE, Boston Scientific); acrylamido PVA (Beadblock, Biocompatibles, Terumo); tris-acryl gelatin microspheres (TAGM) (Embospheres, Merit Medical Inc); and polyzene-F hydrogel microspheres (Embozenes, CeloNova Biosciences). Outcomes assessed included: quality of life (QOL), assessment, magnetic resonance imaging (MRI), uterine and fibroid volumes and degrees of MRI fibroid enhancement and devascularisation. A total of 262 citations were reviewed with 5 randomised, controlled trials involving 295 women and 5 non-RCTs involving 617 women included.
RESULTS
No evidence of superiority of any embolic agent was demonstrated. Meta-analysis was performed between TAGM (Embospheres) and spherical PVA microspheres. Two RCTs found a trend toward greater uterine and dominant fibroid volume reductions with Embospheres but the combined differences were not statistically significant (p = 0.78 and p = 0.94 respectively). Embospheres demonstrated greater percentage fibroid devascularisation than spherical PVA (p = 0.039).
CONCLUSIONS
This study confirms that the current evidence demonstrates superiority of Embospheres over spherical PVA but no reported differences in outcomes between any of the other agents. Comparison of embolic agents was limited by lack of RCT data and further research is warranted.
Topics: Acrylic Resins; Female; Gelatin; Humans; Leiomyoma; Microspheres; Polyvinyl Alcohol; Treatment Outcome; Uterine Artery Embolization; Uterine Neoplasms
PubMed: 24305981
DOI: 10.1007/s00270-013-0790-0 -
Biomaterials Science Feb 2023Glioblastoma (GBM) is an aggressive malignant cancer associated with bleak prognosis and high mortality. The current standard of care for GBM is maximum surgical... (Meta-Analysis)
Meta-Analysis Review
Glioblastoma (GBM) is an aggressive malignant cancer associated with bleak prognosis and high mortality. The current standard of care for GBM is maximum surgical resection plus radiotherapy and temozolomide (TMZ) chemotherapy. The blood brain barrier (BBB) remains the main obstacle for chemotherapy and severely limits the choice of therapeutic agents. Local treatment allows drugs to circumvent the BBB and reduces systemic side effects. Despite much research effort, to date, no drug delivery system (DDS) designed to be directly injected into brain tumors has been clinically approved, and a systematic overview of the progress in this field, or lack thereof, is missing. In this review, a systematic search of pre-clinical literature was conducted which resulted in 36 original articles on injectable DDS for local treatment of GBM which met the inclusion criteria. A wide range of injectable DDS have been developed and tested pre-clinically which include nanoparticles, liposomes, microspheres, hydrogels and others. -Analyses of the included studies showed that, overall, local administration of injectable DDS was beneficial to increase the animal's survival time. Finally, this review summarized the therapeutic effect after local treatment and discussed the shortcomings of the experimental setting in studies.
Topics: Animals; Glioblastoma; Temozolomide; Drug Delivery Systems; Brain Neoplasms; Liposomes
PubMed: 36655634
DOI: 10.1039/d2bm01534j -
ClinicoEconomics and Outcomes Research... 2021Quality of life is among the most important considerations in the treatment of hepatocellular carcinoma (HCC), arguably second only to overall survival. Measuring and... (Review)
Review
Effects of Trial Population Selection on Quality of Life and Healthcare Decision-Making: A Systematic Review and Example in the Treatment of Hepatocellular Carcinoma with Radioembolization.
BACKGROUND AND AIMS
Quality of life is among the most important considerations in the treatment of hepatocellular carcinoma (HCC), arguably second only to overall survival. Measuring and modeling patient quality of life is also crucial in the evaluation of the cost-effectiveness of health interventions. In the present study, we aimed to identify cost-utility analyses comparing selective internal radiation therapy (SIRT) with systemic therapy in patients with unresectable HCC and to compare the modeled incremental quality of life differences between the two therapies.
METHODS
A systematic literature review was conducted. PubMed, EMBASE, the Cochrane Library, and health technology assessment agency websites were searched to identify cost-utility studies of SIRT versus systemic therapies in the treatment of HCC. Key characteristics of the studies, modeled populations and incremental quality of life outcomes were extracted from the included studies.
RESULTS
The systematic literature review retrieved 1140 studies, of which four were ultimately included. Hand searches then identified two distinct analyses, and an updated version of one of the four studies identified initially. From these seven studies, 18 analyses were included. Analyses using data from the overall trial populations reported incremental quality-of-life estimates spanning -0.09 to +0.28 quality-adjusted life years (QALYs), with that range expanding to -0.09 to +0.60 QALYs when also considering post hoc sub-group analyses.
CONCLUSION
The wide range of incremental QALYs, with substantial differences between overall trial populations and subgroups, illustrates the impact that the choice of target population may have on the relative quality of life outcomes of the compared interventions, which may in turn affect clinical decision-making. The small differences also highlight both the importance of reporting measures of dispersion around the findings, and the limitations of the incremental cost-effectiveness ratio (ICER) for assessing the relative cost-effectiveness of interventions that are predicted to result in similar quality-of-life outcomes.
PubMed: 34588788
DOI: 10.2147/CEOR.S319857 -
Cancers Jan 2020Radioembolization with Y-microspheres has been reported to induce contralateral liver hypertrophy with simultaneous ipsilateral control of tumor growth. The aim of the... (Review)
Review
Radioembolization with Y-microspheres has been reported to induce contralateral liver hypertrophy with simultaneous ipsilateral control of tumor growth. The aim of the present systematic review was to summarize the evidence of contralateral liver hypertrophy and oncological outcome following unilateral treatment with radioembolization. A systematic literature search using the MEDLINE, EMBASE, and Cochrane libraries for studies published between 2008 and 2020 was performed. A total of 16 studies, comprising 602 patients, were included. The median kinetic growth rate per week of the contralateral liver lobe was 0.7% and declined slightly over time. The local tumor control was 84%. Surgical resection after radioembolization was carried out in 109 out of 362 patients (30%). Although the available data suggest that radioembolization prior to major hepatectomy is safe with a promising oncological outcome, the definitive role of radioembolization requires assessment within controlled clinical trials.
PubMed: 32012709
DOI: 10.3390/cancers12020294