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Physics in Medicine and Biology Apr 2022. A systematic review of dosimetry in Targeted Alpha Therapy (TAT) has been performed, identifying the common issues.. The systematic review was performed in accordance... (Review)
Review
. A systematic review of dosimetry in Targeted Alpha Therapy (TAT) has been performed, identifying the common issues.. The systematic review was performed in accordance with the PRISMA guidelines, and the literature was searched using the Scopus and PubMed databases.. From the systematic review, three key points should be considered when performing dosimetry in TAT. (1) Biodistribution/Biokinetics: the accuracy of the biodistribution data is a limit to accurate dosimetry in TAT. The biodistribution of alpha-emitting radionuclides throughout the body is difficult to image directly, with surrogate radionuclide imaging, blood/faecal sampling, and animal studies able to provide information. (2) Daughter radionuclides: the decay energy of the alpha-emissions is sufficient to break the bond to the targeting vector, resulting in a release of free daughter radionuclides in the body. Accounting for daughter radionuclide migration is essential. (3) Small-scale dosimetry and microdosimetry: due to the short path length and heterogeneous distribution of alpha-emitters at the target site, small-scale/microdosimetry are important to account for the non-uniform dose distribution in a target region, organ or cell and for assessing the biological effect of alpha-particle radiation.. TAT is a form of cancer treatment capable of delivering a highly localised dose to the tumour environment while sparing the surrounding healthy tissue. Dosimetry is an important part of treatment planning and follow up. Being able to accurately predict the radiation dose to the target region and healthy organs could guide the optimal prescribed activity. Detailed dosimetry models accounting for the three points mentioned above will help give confidence in and guide the clinical application of alpha-emitting radionuclides in targeted cancer therapy.
Topics: Alpha Particles; Animals; Monte Carlo Method; Neoplasms; Radioisotopes; Radiometry; Tissue Distribution
PubMed: 35316802
DOI: 10.1088/1361-6560/ac5fe0 -
European Journal of Cancer (Oxford,... Dec 2012Positron emission tomography (PET) imaging using the radiotracer 18F-Fluorothymidine (FLT) has been proposed as an imaging biomarker of tumour proliferation. If FLT-PET... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Positron emission tomography (PET) imaging using the radiotracer 18F-Fluorothymidine (FLT) has been proposed as an imaging biomarker of tumour proliferation. If FLT-PET can be established as such it will provide a non-invasive, quantitative measurement of tumour proliferation across the entire tumour. Results from validation studies have so far been conflicting with some studies confirming a good correlation between FLT uptake and Ki-67 score and others presenting negative results.
METHODS
Firstly we performed a systematic review of published studies between 1998 and 2011 that explored the correlation between FLT uptake and Ki-67 score and examined possible variations in the methods used. Studies were eligible if they: (a) included patients with cancer, (b) investigated the correlation between Ki-67 measured by immunohistochemistry and FLT uptake measured with PET scanning, and (c) were published as a full paper in a peer-reviewed scientific journal. Secondly a meta-analysis of the correlation coefficient values reported from each study was performed. Correlation coefficient (r) values were extracted from each study and 95% confidence intervals (CIs) were calculated after applying Fisher's z transformation. For subgroup analysis, studies were classified by the index used to characterise Ki-67 expression (average or maximum expression), the nature of the sample (whole specimen or biopsy) and the cancer type.
FINDINGS
Twenty-seven studies were identified as eligible for the meta-analysis. In the studies we examined there were variations in aspects of the methods and reporting. The meta-analysis showed that given an appropriate study design the FLT/Ki-67 correlation is significant and independent of cancer type. Specifically subgroup analysis showed that FLT/Ki-67 correlation was high in studies measuring the Ki-67 average expression regardless of use of surgery or biopsy samples (r=0.70, 95% CI=0.43-0.86, p<0.001). Of the studies that measured Ki-67 maximum expression, only those that used the whole surgical specimen provided a significant r value (r=0.72, 95% CI=0.54-0.84, p<0.001). Studies that used biopsy samples for Ki-67 maximum measurements did not produce a significant r value (r=0.04, 95% CI=-0.18-0.26, p=0.71). In terms of the cancer type subgroup analysis there is sufficient data to support a strong FLT/Ki-67 correlation for brain, lung and breast cancer. No publication bias was detected.
INTERPRETATION
This systematic review and meta-analysis highlights the importance of the methods used in validation studies comparing FLT-PET imaging with the biomarker Ki-67. The correlation is significant and independent of cancer type provided a study design that uses Ki-67 average measurements, regardless of nature of sample, or whole surgical samples when measuring Ki-67 maximum expression. Sufficient data to support a strong correlation for brain, lung and breast cancer exist. However, larger, prospective studies with improved study design are warranted to validate these findings for the rest of the cancer types.
Topics: Antigens, Neoplasm; Bias; Biomarkers; Biopsy; Cell Division; Clinical Trials as Topic; Dideoxynucleosides; Female; Fluorine Radioisotopes; Humans; Immunohistochemistry; Ki-67 Antigen; Male; Neoplasms; Positron-Emission Tomography; Radiopharmaceuticals; Research Design; Surveys and Questionnaires; Tissue Distribution
PubMed: 22658807
DOI: 10.1016/j.ejca.2012.05.001 -
The Brazilian Journal of Infectious... 2017The current increment of invasive fungal infections and the availability of new broad-spectrum antifungal agents has increased the use of these agents by non-expert... (Review)
Review
The current increment of invasive fungal infections and the availability of new broad-spectrum antifungal agents has increased the use of these agents by non-expert practitioners, without an impact on mortality. To improve efficacy while minimizing prescription errors and to reduce the high monetary cost to the health systems, the principles of pharmacokinetics (PK) and pharmacodynamics (PD) are necessary. A systematic review of the PD of antifungals agents was performed aiming at the practicing physician without expertise in this field. The initial section of this review focuses on the general concepts of antimicrobial PD. In vitro studies, fungal susceptibility and antifungal serum concentrations are related with different doses and dosing schedules, determining the PD indices and the magnitude required to obtain a specific outcome. Herein the PD of the most used antifungal drug classes in Latin America (polyenes, azoles, and echinocandins) is discussed.
Topics: Antifungal Agents; Area Under Curve; Aspergillosis; Azoles; Candidiasis; Dose-Response Relationship, Drug; Echinocandins; Humans; Latin America; Microbial Sensitivity Tests; Polyenes; Triazoles
PubMed: 27821250
DOI: 10.1016/j.bjid.2016.09.009 -
Journal of Athletic Training 2014To determine the effects of various therapeutic interventions on increasing voluntary quadriceps muscle activation. (Comparative Study)
Comparative Study Review
OBJECTIVE
To determine the effects of various therapeutic interventions on increasing voluntary quadriceps muscle activation.
BACKGROUND
Decreased voluntary quadriceps activation is commonly associated with knee injury. Recently, research has focused on developing specific disinhibitory interventions to improve voluntary quadriceps activation; yet, it remains unknown which interventions are most effective in promoting this improvement.
DATA SOURCES
We searched Web of Science from January 1, 1965 through September 27, 2012, using the key words quadriceps activation and transcutaneous electrical nerve stimulation, transcranial magnetic stimulation, cryotherapy, focal joint cooling, joint mobilization, joint mobilisation, joint manipulation, manual therapy, and neuromuscular electrical stimulation.
STUDY SELECTION
Studies evaluating the effect of disinhibitory interventions on volitional quadriceps activation were used in our review. Standardized effect sizes (Cohen d) and 95% confidence intervals (CIs) were calculated from voluntary quadriceps activation means and standard deviations measured at baseline and at all available postintervention time points from each study.
DATA SYNTHESIS
Ten studies were grouped into 5 categories based on intervention type: manual therapy (4 studies), transcutaneous electrical nerve stimulation (2 studies), cryotherapy (2 studies), neuromuscular electrical stimulation (2 studies), and transcranial magnetic stimulation (1 study). Transcutaneous electrical nerve stimulation demonstrated the strongest immediate effects (d = 1.03; 95% CI = 0.06, 1.92) and long-term effects (d = 1.93; 95% CI = 0.91, 2.83). Cryotherapy (d = 0.76; 95% CI = -0.13, 1.59) and transcranial magnetic stimulation (d = 0.54; 95% CI = -0.33, 1.37) had moderate immediate effects in improving voluntary quadriceps activation, whereas manual therapy (d = 0.38; 95% CI = -0.35, 1.09) elicited only weak immediate effects. Neuromuscular electrical stimulation produced weak negative to strong positive effects (range of d values = -0.50 to 1.87) over a period of 3 weeks to 6 months.
CONCLUSIONS
Transcutaneous electrical nerve stimulation demonstrated the strongest and most consistent effects in increasing voluntary quadriceps activation and may be the best disinhibitory intervention for improving the same.
Topics: Activation, Metabolic; Cryotherapy; Humans; Knee Injuries; Musculoskeletal Manipulations; Quadriceps Muscle; Time; Transcranial Magnetic Stimulation; Transcutaneous Electric Nerve Stimulation
PubMed: 24490843
DOI: 10.4085/1062-6050-49.1.04 -
Journal of Psychiatric Research Nov 2022Research has posited that machine learning could improve suicide risk prediction models, which have traditionally performed poorly. This systematic review and... (Meta-Analysis)
Meta-Analysis Review
Research has posited that machine learning could improve suicide risk prediction models, which have traditionally performed poorly. This systematic review and meta-analysis evaluated the performance of machine learning models in predicting longitudinal outcomes of suicide-related outcomes of ideation, attempt, and death and examines outcome, data, and model types as potential covariates of model performance. Studies were extracted from PubMed, Web of Science, Embase, and PsycINFO. A bivariate mixed effects meta-analysis and meta-regression analyses were performed for studies using machine learning to predict future events of suicidal ideation, attempts, and/or deaths. Risk of bias was assessed for each study using an adaptation of the Prediction model Risk Of Bias Assessment Tool. Narrative review included 56 studies, and analyses examined 54 models from 35 studies. The models achieved a very good pooled AUC of 0.86, sensitivity of 0.66 (95% CI [0.60, 0.72)], and specificity of 0.87 (95% CI [0.84, 0.90]). Pooled AUCs for ideation, attempt, and death were similar at 0.88, 0.87, and 0.84 respectively. Model performance was highly varied; however, meta-regressions did not provide evidence that performance varied by outcome, data, or model types. Findings suggest that machine learning has the potential to improve suicide risk detection, with pooled estimates of machine learning performance comparing favourably to performance of traditional suicide prediction models. However, more studies with lower risk of bias are necessary to improve the application of machine learning in suicidology.
Topics: Area Under Curve; Humans; Machine Learning; Suicidal Ideation; Suicide; Suicide, Attempted
PubMed: 36206602
DOI: 10.1016/j.jpsychires.2022.09.050 -
Progress in Lipid Research Apr 2022Intestinal cholesterol absorption varies widely between individuals, which may translate into differences in responsiveness to cholesterol-lowering drugs or diets.... (Review)
Review
Intestinal cholesterol absorption varies widely between individuals, which may translate into differences in responsiveness to cholesterol-lowering drugs or diets. Therefore, understanding the importance of genetic variation on cholesterol absorption rates and the complex intestinal cholesterol network is important. Based on a systematic review, genetic variants in seven genes (ABCG5, ABCG8, ABO, APOE, MTTP, NPC1L1, and LDLR) were identified that were associated with intestinal cholesterol absorption. No clear associations were found for variants in APOA4, APOB, CETP, CYP7A1, HMGCR, SCARB1, SLCO1B1, and SREBF1. The seven genes were used to construct an intestinal cholesterol absorption network. Finally, a network with fifteen additional genes (APOA1, APOA4, APOB, APOC2, APOC3, CETP, HSPG2, LCAT, LDLRAP1, LIPC, LRP1, OLR1, P4HB, SAR1B, and SDC1) was generated. The constructed network shows that cholesterol absorption is complex. Further studies are needed to validate and improve this network, which may ultimately lead to a better understanding of the wide inter-individual variability in intestinal cholesterol absorption and the development of personalized interventions.
Topics: Cholesterol; Gene Regulatory Networks; Genetic Variation; Humans; Intestinal Absorption
PubMed: 35390434
DOI: 10.1016/j.plipres.2022.101164 -
Journal of the Neurological Sciences Jan 2021In order to better educate patients, predictive models have been implemented to stratify surgical risk, thereby instituting greater uniformity across surgical practices...
In order to better educate patients, predictive models have been implemented to stratify surgical risk, thereby instituting greater uniformity across surgical practices and prioritizing the safety and outcomes of patients. The purpose of this study is to conduct a systematic review summarizing the major predictive models used to evaluate patients as candidates for spinal surgery. A search was conducted for articles related to predictive modeling in spinal surgeries using PubMed, MEDLINE, and Scopus databases. Papers with area under the receiver operating curve (AUROC) scores reported were included in the analysis. Models not relevant to spinal procedures were excluded. Comparison between models was only attainable for those that reported AUROCs for individual procedures. Based on a combination of AUROC scores and demonstrated applicability to spinal procedures, the models by Scheer et al. (0.89), Ratliff et al. (0.70), the Seattle Spine Score (0.712), Risk Assessment Tool (0.67-0.7), and the Spine Sage calculator (0.81-0.85) were determined to be ideal for predictive modeling in spinal surgeries and were subsequently broken down into their individual inputs and outputs to determine what elements a theoretical model should assimilate. Alongside the model by Scheer et al., the Spine Sage calculator, Seattle Spine Score, Risk Assessment Tool, and a model by Ratliff et al. showed the most promise for patients undergoing spinal procedures. Using the first model as a springboard, new spinal predictive models can be optimized through use of larger prospective databases, with longer follow-up times, and greater inclusion of reliable high impact variables.
Topics: Algorithms; Area Under Curve; Humans; Neurosurgical Procedures; Risk Assessment; Spine
PubMed: 33203588
DOI: 10.1016/j.jns.2020.117184 -
Molecular Aspects of Medicine Feb 2023This systematic review summarizes findings from human studies investigating the different routes of absorption, metabolism, distribution and excretion (ADME) of dietary... (Review)
Review
This systematic review summarizes findings from human studies investigating the different routes of absorption, metabolism, distribution and excretion (ADME) of dietary flavan-3-ols and their circulating metabolites in healthy subjects. Literature searches were performed in PubMed, Scopus and the Web of Science. Human intervention studies using single and/or multiple intake of flavan-3-ols from food, extracts, and pure compounds were included. Forty-nine human intervention studies met inclusion criteria. Up to 180 metabolites were quantified from blood and urine samples following intake of flavan-3-ols, mainly as phase 2 conjugates of microbial catabolites (n = 97), with phenyl-γ-valerolactones being the most representative ones (n = 34). Phase 2 conjugates of monomers and phenyl-γ-valerolactones, the main compounds in both plasma and urine, reached two peak plasma concentrations (C) of 260 and 88 nmol/L at 1.8 and 5.3 h (T) after flavan-3-ol intake. They contributed to the bioavailability of flavan-3-ols for over 20%. Mean bioavailability for flavan-3-ols was moderate (31 ± 23%, n bioavailability values = 20), and it seems to be scarcely affected by the amount of ingested compounds. While intra- and inter-source differences in flavan-3-ol bioavailability emerged, mean flavan-3-ol bioavailability was 82% (n = 1) and 63% (n = 2) after (-)-epicatechin and nut (hazelnuts, almonds) intake, respectively, followed by 25% after consumption of tea (n = 7), cocoa (n = 5), apples (n = 3) and grape (n = 2). This highlights the need to better clarify the metabolic yield with which monomer flavan-3-ols and proanthocyanidins are metabolized in humans. This work clarified in a comprehensive way for the first time the ADME of a (poly)phenol family, highlighting the pool of circulating compounds that might be determinants of the putative beneficial effects linked to flavan-3-ol intake. Lastly, methodological inputs for implementing well-designed human and experimental model studies were provided.
Topics: Humans; Biological Availability; Catechin; Proanthocyanidins; Diet
PubMed: 36207170
DOI: 10.1016/j.mam.2022.101146 -
American Journal of Nephrology 2016Concerns exist over the extrapolation of bioavailability studies of generic immunosuppressive drugs in healthy volunteers, regarding their efficacy and safety in kidney... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Concerns exist over the extrapolation of bioavailability studies of generic immunosuppressive drugs in healthy volunteers, regarding their efficacy and safety in kidney transplant recipients. We conducted a meta-analysis of trials examining the bioavailability of generic (test) immunosuppressive drugs relative to their brand (reference) counterparts in healthy volunteers, based on the US Food and Drug Administration requirements for approval of generics, and their efficacy and safety in kidney transplant recipients.
METHODS
Eligible studies were identified in PubMed, Cochrane Central Register of Controlled Trials, Scopus, ClinicalTrials.gov, and conference abstracts.
RESULTS
Twenty crossover trials of healthy volunteers (n = 641) and 6 parallel-arm randomized controlled trials of kidney transplant recipients (n = 594) were identified. The 90% CI of the pooled test-to-reference drug ratio for maximum or peak plasma concentration (Cmax) and area under the plasma concentration time-curve from time 0 to time of last determinable concentration (AUC(0-t)) fell within the required range (0.80-1.25) for cyclosporine (Cmax 0.91; 90% CI 0.86-0.95; and AUC(0-t) 0.97; 90% CI 0.94-1.00), tacrolimus (Cmax 1.17; 90% CI 1.09-1.24; and AUC(0-t) 1.00; 90% CI 0.97-1.03) and mycophenolate mofetil (Cmax 0.98; 90% CI 0.96-1.01; and AUC(0-t) 1.00; 90% CI 0.99-1.01). In subgroup analyses, some generic cyclosporine formulations did not meet criteria for bioequivalence. No significant differences were observed in the time to maximum plasma concentration and terminal plasma half-life between generic and brand drugs. In parallel-arm trials, generic cyclosporine was non-inferior to brand counterpart in terms of acute allograft rejection, infections, and death.
CONCLUSIONS
Not all generic immunosuppressive drugs have similar relative bioavailability to their brand name counterparts. Evidence on their efficacy and safety is inconclusive. Tighter regulatory requirement for approval of generic drugs with narrow therapeutic index is needed.
Topics: Biological Availability; Cyclosporine; Drugs, Generic; Humans; Immunosuppressive Agents; Kidney Transplantation; Mycophenolic Acid; Tacrolimus; Therapeutic Equivalency
PubMed: 27576318
DOI: 10.1159/000449020 -
Gastrointestinal Endoscopy Aug 2022This systematic review and meta-analysis aims to compare the pooled diagnostic accuracy of the currently available esophageal squamous cell carcinoma (ESCC) screening... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
This systematic review and meta-analysis aims to compare the pooled diagnostic accuracy of the currently available esophageal squamous cell carcinoma (ESCC) screening tests.
METHODS
A comprehensive literature search of Embase and Medline (up to October 31, 2020) was performed to identify eligible studies. We pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio for ESCC screening tools using a bivariate random-effects model. The summary receiver operating characteristic curves with area under the curve (AUC) were plotted for each screening test.
RESULTS
We included 161 studies conducted in 81 research articles involving 32,209 subjects. The pooled sensitivity, specificity, and AUC of the major screening tools were respectively as follows: endoscopy (peroral endoscopy): .94 (95% confidence interval [CI], .87-.97), .92 (95% CI, .87-.95), and .97 (95% CI, .96-.99); endoscopy (transnasal endoscopy): .85 (95% CI, .70-.93), .96 (95% CI, .91-.98), and .97 (95% CI, .95-.98); microRNA: .77 (95% CI, .75-.80), .78 (95% CI, .75-.80), and .85 (95% CI, .81-.87); autoantibody: .45 (95% CI, .36-.53), .91 (95% CI, .89-.93), and .84 (95% CI, .81-.87); and cytology: .82 (95% CI, .60-.93), .97 (95% CI, .88-.99), and .97 (95% CI, .95-.98). There was high heterogeneity.
CONCLUSIONS
The diagnostic accuracy seemed to be comparable between cytology and endoscopy, whereas autoantibody and microRNAs bear potential as future noninvasive screening tools for ESCC. To reduce ESCC-related death in high-risk populations, it is important to develop a more accurate and less-invasive screening test.
Topics: Area Under Curve; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Humans; ROC Curve; Sensitivity and Specificity
PubMed: 35413332
DOI: 10.1016/j.gie.2022.04.005