Possibility Of Dose Reduction Research Articles

Growth Promotion of Raphanus Sativus L. under Doses of Phosphorus with Application of Trichoderma Spp.

This study aimed to evaluate the growth of Raphanus sativus L. under six phosphorus doses in combination with three strains of Trichoderma spp. The design was a randomized block design with seven replications in a factorial scheme, 4 x 5 (treatments and doses). Treatments related to Trichoderma spp. were T1 – control, without application of T. harzianum strain; T2 – T. harzianum ESALQ 1306, T3 – T. harzianum IBLF 006 WP, and T4 – T. asperellum URM 5911, at doses of 0, 40, 80, 120, 160, and 200 kg ha-1 of P2O5, in a greenhouse. The evaluated characteristics were tuberous root diameter (RDI), tuberous root length (RLE), relative chlorophyll index (RCI), leaf dry mass (LDM), tuberous root fresh mass (FTRM), and tuberous root dry mass (TRDM). It was observed that there was a significant difference for the different sources of variation evaluated, indicating an interaction between the different isolates and doses. It is concluded that the application of Trichoderma harzianum - ESALQ 1306 strain is recommended for radish cultivation, with increases of 13% for tuberous root length, 7% for relative chlorophyll index, 23% for leaf dry mass, 35% for tuberous root fresh mass, and 12% for tuberous root dry mass compared to the control, at a dose of 104 kg ha-1 of P2O5, with the possibility of dose reduction and more sustainable management. Additionally, strains T. harzianum IBLF 006 WP (T3) and T. asperellum URM 5911 (T4) are not recommended for radish cultivation.

The Meteoritics Trial: efficacy of methotrexate after remission-induction with tocilizumab and glucocorticoids in giant cell arteritis—study protocol for a randomized, double-blind, placebo-controlled, parallel-group phase II study

BackgroundGlucocorticoids (GC) are the standard treatment for giant cell arteritis (GCA), even though they are associated with adverse side effects and high relapse rates. Tocilizumab (TCZ), an interleukin-6 receptor antagonist, has shown promise in sustaining remission and reducing the cumulative GC dosage, but it increases the risk of infections and is expensive. After discontinuation of TCZ, only about half of patients remain in remission. Additionally, only few studies have been conducted looking at remission maintenance, highlighting the need for alternative strategies to maintain remission in GCA. Methotrexate (MTX) has been shown to significantly decrease the risk of relapse in new-onset GCA and is already a proven safe drug in many rheumatologic diseases.MethodsThis study aims to evaluate the efficacy and safety of MTX in maintaining remission in patients with GCA who have previously been treated with GC and at least 6 months with TCZ. We hypothesize that MTX can maintain remission in GCA patients, who have achieved stable remission after treatment with GC and TCZ, and prevent the occurrence of relapses. The study design is a monocentric, randomized, double-blind, placebo-controlled, parallel-group phase II trial randomizing 40 GCA patients 1:1 into a MTX or placebo arm. Patients will receive 17.5 mg MTX/matching placebo weekly by subcutaneous injection for 12 months, with the possibility of dose reduction if clinically needed. A 6-month follow-up will take place. The primary endpoint is the time to first relapse in the MTX group versus placebo during the 12-month treatment period. Secondary outcomes include patient- and investigator-reported outcomes and laboratory findings, as well as the prevalence of aortitis, number of vasculitic vessels, and change in intima-media thickness during the study.DiscussionThis is the first clinical trial evaluating remission maintenance of GCA with MTX after a previous treatment cycle with TCZ. Following the discontinuation of TCZ in GCA, MTX could be a safe and inexpensive drug.Trial registrationClinicalTrials.gov, NCT05623592. Registered on 21 November 2022.EU Clinical Trials Register, 2022-501058-12-00.German Clinical Trials Register DRKS00030571.

Possible Radiation Dose Reduction in Abdominal Plain CT Using Deep Learning Reconstruction

The purposes of this study were to evaluate the low-contrast detectability of CT images assuming hepatocellular carcinoma and to determine whether dose reduction in abdominal plain CT imaging is possible. A Catphan 600 was imaged at 350, 250, 150, and 50 mA using an Aquilion ONE PRISM Edition (Canon) and reconstructed using deep learning reconstruction (DLR) and model-based iterative reconstruction (MBIR). A low-contrast object-specific contrast-to-noise ratio (CNRLO) was measured and compared in a 5-mm module with a CT value difference of 10 HU, assuming hepatocellular carcinoma; a visual examination was also performed. Moreover, an NPS within a uniform module was measured. CNRLO was higher for DLR at all doses (1.12 at 150 mA for DLR and 1.07 at 250 mA for MBIR). On visual evaluation, DLR could detect up to 150 mA and MBIR up to 250 mA. The NPS was lower for DLR at 0.1 cycles/mm at 150 mA. The low-contrast detection performance was better with DLR than with MBIR, indicating the possibility of dose reduction.

Dosing Regimens of Immune Checkpoint Inhibitors: Attempts at Lower Dose, Less Frequency, Shorter Course.

Immune checkpoint inhibitors (ICIs) are a revolutionary breakthrough in the field of cancer by modulating patient’s own immune system to exert anti-tumor effects. The clinical application of ICIs is still in its infancy, and their dosing regimens need to be continuously adjusted. Pharmacokinetic/pharmacodynamic studies showed a significant plateau in the exposure-response curve, with high receptor occupancy and plasma concentrations achieved at low dose levels. Coupled with concerns about drug toxicity and heavy economic costs, there has been an ongoing quest to reevaluate the current ICI dosing regimens while preserving maximum clinical efficacy. Many clinical data showed remarkable anticancer effects with ICIs at the doses far below the approved regimens, indicating the possibility of dose reduction. Our review attempts to summarize the clinical evidence for ICIs regimens with lower-dose, less-frequency, shorter-course, and provide clues for further ICIs regimen optimization.

Effective cellular internalization, cell cycle arrest and improved pharmacokinetics of Tamoxifen by cholesterol based lipopolymeric nanoparticles

The present study aims at the development of cholesterol based lipopolymeric nanoparticles for improved entrapment, better cell penetration and improved pharmacokinetics of Tamoxifen (TMX). Self-assembling cholesterol grafted lipopolymer, mPEG-b-(CB-{g-chol}-co-LA) was synthesized from poly(ethyleneglycol)-block-2-methyl-2-carboxyl-propylenecarboxylic acid-co-poly (l-lactide) [mPEG-b-(CB-{g-COOH}-co-LA)] copolymer followed by carbodiimide coupling for attaching cholesterol. Lipopolymeric nanoparticles were prepared using o/w solvent evaporation technique, which were subsequently characterized to determine its particle size, entrapment efficiency, release pattern and compared with mPEG-PLA nanoparticles. Further, in order to assess the in vitro efficacy, cytotoxicity studies, uptake, apoptosis assay and cell cycle analysis were performed in breast cancer cell lines (MCF-7 and 4T1). Finally, the pharmacokinetic profile of TMX loaded mPEG-b-(CB-{g-chol}-co-LA) lipopolymeric nanoparticles was also performed. TMX loaded lipopolymeric nanoparticles of particle size 151.25 ± 3.74 (PDI 0.123) and entrapment efficiency of 73.62 ± 3.08% were formulated. The haemolytic index, protein binding and in vitro drug release of the optimized nanoparticles were found to be comparable to that of the TMX loaded mPEG-PLA nanoparticles. Lipopolymeric nanoparticles demonstrated improved IC50 values in breast cancer cells (22.2 μM in 4T1; 18.8 μM in MCF-7) than free TMX (27.6 μM and 23.5 μM respectively) and higher uptake efficiency. At IC50 values, TMX loaded lipopolymeric nanoparticles induced apoptosis and cell cycle arrest (G0/G1 phase) to similar extent as that of free drug. Pharmacokinetic studies indicated ∼2.5-fold increase in the half-life (t1/2) (p < 0.001) and ∼2.7-fold (p < 0.001) increase in the mean residence time (MRT) of TMX following incorporation into lipopolymeric nanoparticles. Thus, mPEG-b-(CB-{g-chol}-co-LA) lipopolymeric nanoparticles offer a more promising approach for delivery of Tamoxifen in breast cancer by improving drug internalization and prolonging the mean residence time of the drug indicating possibility of dose reduction and hence bypassing the adverse effects of TMX therapy.

Drug Potentiation with subsequent Extraction of Biomarker: A Case Study of Brahmi Ghrita

Introduction - To treat various neurological and psychological disorders, Ayurveda propounds use of lipids. One of the widely used internal lipoid dosage form is medicated ghee. It binds to various phytochemicals, minerals and effectively crosses blood brain barrier to make efficient drug delivery. However it’s high dose, greasy nature, strong smell and taste lead to poor drug compliance. Present study was aimed at the potentiation of ghee using Bacopa monnieri Linn, and standardization using the biomarker Bacoside-A. Methods - Ghee procured from Indian Geer breed cow was processed using fresh Bacopa juice in three different proportions 1x, 5x and 10x; combined with three processing cycles single, five and ten respectively. For each repetition, Standard Operating Procedure (SOP) was strictly adhered to. Finished products were analyzed using HPTLC to calculate concentrations of Bacoside A. Results were compared. Results - SOP was established for potentiation of medicated ghee. Values for all the physicochemical parameters as per Ayurvedic Pharmacopeia of India were established for the samples. Concentration of Bacoside A increased as the processing cycles increased in 1x, 5x and 10x samples, but exact quantification of the marker in each sample is yet to be evaluated. Discussion & Conclusion - Method of potentiation using higher quantity of drug along with more processing cycles increases concentration of active biomarker in medicated ghee. Thus it opens the possibility of dose reduction and thereby it’s encapsulation to increase drug compliance.

Biologics in rheumatoid arthritis: where are we going?

Biological disease-modifying antirheumatic drugs have significantly improved outcomes for patients with rheumatoid arthritis, but cost limits their use. This article assesses data on patients who have achieved remission or low disease activity with these drugs and the possibility of dose reduction or discontinuation in these patients.

Is insulin degludec a more effective treatment for patients using high doses of insulin glargine but not attaining euglycemia? Some case reports from India.

Insulin therapy is not without side effects. In patients with complications on complex regimens, failure to attain adequate glycemic control exposes the patient to high risks and the considerable mental distress associated with failed injectable therapy. As clinicians, we felt it necessary to undertake a trial of newer therapies like insulin degludec, which according to published literature, appears to be superior to earlier basal analogs by fewer hypoglycemic episodes, better glycemic predictability, and genuine 24-hour coverage. Here we report on three cases seen in our own clinical practice where insulin degludec was used in patients experiencing inadequacies with their current basal insulin therapy (insulin glargine). Switching to insulin degludec resulted in clinically meaningful reductions in hypoglycemia, along with reduced fasting plasma glucose and glycosylated hemoglobin and improved satisfaction with treatment. We also explored the use of long-acting insulin in renal failure and the possibility of dose reduction when switching from existing basal insulin therapy.

TH-C-18A-06: Combined CT Image Quality and Radiation Dose Monitoring Program Based On Patient Data to Assess Consistency of Clinical Imaging Across Scanner Models

Purpose: One of the principal challenges of clinical imaging is to achieve an ideal balance between image quality and radiation dose across multiple CT models. The number of scanners and protocols at large medical centers necessitates an automated quality assurance program to facilitate this objective. Therefore, the goal of this work was to implement an automated CT image quality and radiation dose monitoring program based on actual patient data and to use this program to assess consistency of protocols across CT scanner models. Methods: Patient CT scans are routed to a HIPPA compliant quality assurance server. CTDI, extracted using optical character recognition, and patient size, measured from the localizers, are used to calculate SSDE. A previously validated noise measurement algorithm determines the noise in uniform areas of the image across the scanned anatomy to generate a global noise level (GNL). Using this program, 2358 abdominopelvic scans acquired on three commercial CT scanners were analyzed. Median SSDE and GNL were compared across scanner models and trends in SSDE and GNL with patient size were used to determine the impact of differing automatic exposure control (AEC) algorithms. Results: There was a significant difference in both SSDE and GNL across scanner models (9–33% and 15–35% for SSDE and GNL, respectively). Adjusting all protocols to achieve the same image noise would reduce patient dose by 27–45% depending on scanner model. Additionally, differences in AEC methodologies across vendors resulted in disparate relationships of SSDE and GNL with patient size. Conclusion: The difference in noise across scanner models indicates that protocols are not optimally matched to achieve consistent image quality. Our results indicated substantial possibility for dose reduction while achieving more consistent image appearance. Finally, the difference in AEC methodologies suggests the need for size-specific CT protocols to minimize variability in image quality across CT vendors.

Dosisreduktion unter Betrachtung der erforderlichen Bildqualität - Wie viel Dosis braucht ein Bild?

Today, imaging of nose, paranasal sinuses and temporal bone by CT is standard in preoperative diagnostics. The need of reduction of applied dosage leads to the necessity of research in necessary imaging quality. Therefore this paper deals with new developed anatomical checklists and the analysis of imaging quality on anterior and lateral skull base. With 3 human complete heads over 400 examinations were performed on one cone beam CT device under varying x-ray-tube adjustments. 31 anatomic parameters were evaluated (Excellent, well, poor, not evaluable) for every data set. A summation score was built for every examination. As well for paranasal sinuses as for temporal bone a constant excellent imaging quality could be seen in high dosages. Certainly, in low dosages a reduction of imaging quality was detected. The optimal range (all parameters visualized well as average) could be evaluated for paranasal sinuses between 2,0 and 3,0 mGy and between 3,0 and 4,0 mGy for temporal bone. So, a reduction of 70-80% in comparison to highest adjustments of today is possible and realistic. In comparison to standard protocols, a reduction of about 50% can be reached. The possibility of dose reduction by discussion of the necessary imaging quality from clinical point of view could be shown.

Image-Guided Whole Abdominal Radiation Therapy in Gynecologic Cancers

The use of adjuvant Whole Abdominal Radiation Therapy (WART) in gynecologic cancers has not achieved widespread use for a variety of reasons. Several phase III trials comparing WART with adjuvant chemotherapy (CT) in both uterine and ovarian cancers have demonstrated marginal improvement in survival favoring CT over WART. However, the dose of conventionally delivered WART has been historically limited due in large part to the low threshold of normal organ tolerance in the upper abdomen associated with significant late effects of the bowel and kidneys in particular. Yet, with the advent of Image-Guided Radiation Therapy (IGRT), the possibility of dose reduction to nearby organs at risk along with the potential to increase target volume dose is now obtainable. This paper will review the current data related to IGRT WART for several different patient populations of gynecologic cancers.

SPECT/CT – Technische Aspekte und Optimierungsmöglichkeiten

In contrast to positron emission tomography/computed tomography (PET/CT), the currently available single photon emission computed tomography/computed tomography (SPECT/CT) systems are very heterogeneous. On the side of the gamma cameras, dual-head systems are established, which are not very different from one manufacturer to the other. For the CT component, there are low dose tubes on the one side and flat detector-based cone beam CT and multislice-CT on the other. The CT image data can be used for anatomic correlation of suspicious findings as well as for attenuation correction of SPECT data. Attenuation correction enables on the one hand enhancement of SPECT image quality and on the other hand quantification of the radioactivity concentration becomes possible. Modern iterative reconstruction algorithms allow scatter correction and attenuation correction of SPECT data using the density values from CT. It still has to be shown to what extent attenuation-corrected whole body SPECT/CT studies will be able to improve the sensitivity of scintigraphy studies. As SPECT/CT primarily aims at morphologic correlation and not detection of additional lesions, an attempt should be made to balance the necessary anatomic information and the additional radiation exposure. Besides SPECT-guided CT all technical possibilities for dose reduction should be exhausted.

Management der Polyneuropathie beim Multiplen Myelom unter der Therapie mit Bortezomib: Empfehlungen aus klinischen Erfahrungen

Bortezomib-induced peripheral neuropathy (PNP) in multiple myeloma (MM) can develop and progress rapidly. Rapid therapeutic intervention can possibly avoid the occurrence of neuropathic pain and the progression to higher grades of PNP. A group of experts consisting of haematologists and neurologists is issuing practice recommendations based on their experiences. The initial neurological assessment and neurological examinations during Bortezomib-therapy provide a basis for monitoring the patient. These examinations can be carried out by the haematologist. An important instrument is a questionnaire for the patients. If additional diagnostic workup is needed, consultation of a neurologist may be advantageous to fully evaluate the severity and type of PNP. If PNP develops, the therapy with Bortezomib has to be modified. International experts use different schemes, however, evidence based studies comparing these schemes are rare. In case of polyneuropathies caused by comorbidities, the possibility of dose reduction should be checked already prior to treatment initiation. Treatment of the PNP itself is discussed in the manuscript. Drug based as well as non-drug based therapies can often lead to significant improvement or even resolution of PNP symptoms.

SU-E-I-188: Potential for Dose Reduction in An Indirect Flat Panel Detector System Employing Irradiation Side Sampling

Purpose: To investigate possibility of dose reduction for a newly developed indirect flat panel detector(FPD)system employing irradiation side sampling (ISS), physical imaging properties were measured and compared with those of a conventional computed radiography(CR)system. Method and Materials:The FPDsystem employing ISS (CALNEO MT, Fuji Film) and the CRsystem (FCR PROFECT CS, Fuji Film) including the imaging plate (ST‐VI, Fuji Film) were used in this study. The Wiener spectrum (WS), the presampled modulation transfer function(MTF), and the detective quantum efficiency (DQE) for both systems were measured. To evaluate image quality of the detector for chest radiography, the RQA 9 in the International Electrotechnical Commission (IEC) 62220‐1 was used. Results: The WS of the FPDsystem showed considerably lower than that of the CRsystem at every spatial frequency. The WS of the FPDsystem with a 50 % dose reduction of the CRsystem was almost identical to that of the CRsystem. The presampled MTF of the FPDsystem was comparable to that of the CRsystem. The DQE of the FPDsystem obtained at zero spatial frequency was almost twice than that of the CRsystem. Conclusion: The radiographic noise property and the detection efficiency of the new ISS FPD were significantly superior to those of the conventional CRsystem. It is expected that the use of the new ISS FPDsystem for chest radiography can reduce the patient skin dose by 50 % compared with the conventional CRsystem.

Exploring the Effect on Asthma Control of Omalizumab Reduction After 28 Weeks Treatment

RATIONALE: In a 28-week, randomized, placebo-controlled trial (INNOVATE), the anti-IgE antibody omalizumab, significantly improved asthma control in patients with severe persistent allergic (IgE-mediated) asthma despite high-dose ICS plus LABA ± controller medication. The possibility of dose reduction was explored by observing clinical outcomes following omalizumab withdrawal.

Survey of posteroanterior chest radiography in The Netherlands: patient dose and image quality

Council Directive 97/43/Euratom (Medical Exposure Directive) states that member States of the European Union shall promote the establishment and use of diagnostic reference levels for radio-diagnostic examinations. Dose surveys can form the basis for the establishment of diagnostic reference levels. In view of the implementation of the Medical Exposure Directive in the Netherlands, a survey of dose and image quality has been performed for posteroanterior (PA) chest radiography in 2001. In this survey, 25 participants were selected from a list of 175 Dutch hospitals, whereas in a previous PA chest survey (about 10 years ago) participation was voluntary and participants came predominantly from the south-western part of the Netherlands. For conventional screen-film PA chest radiography, the present results for patient dose and image quality are quite similar to those results from the previous survey. The fraction of conventional X-ray systems utilizing lung compensation filters has remained approximately the same. For dedicated digital chest radiography systems, image quality is better than for conventional systems, but doses vary and can assume relatively high values. The results indicate that there are still possibilities for dose reduction, without loss of image quality. The 75 percentile value of the entrance surface dose distribution is approximately 0.13 mGy.

Patient exposures and radiation risks in Swedish diagnostic radiology.

Results are reported of measurements around 1974 on a thousand patient at 13 Swedish hospitals, and additionally at several photofluorographic and dental installations. Energy imparted as well as doses to the thyroid, breast, lung, bone marrow, ovary and testis have been calculated for many types of examination. Collective doses have been calculated and risk estimates made. The energy imparted corresponds to an annual mean body dose to the Swedish population of about 1 mGy (100 mrad), and the genetically significant dose was about the same as the 1955 total of 0.4 mGy; in both cases the uncertainty of the estimate is about +/- 50%. The possibility of dose reduction by a factor of 2 or more using available techniques is demonstrated. The risk of future serious injury is estimated to 0.0002 cases per joule of energy imparted to the patient.