Dose For Treatment Of Patients Research Articles

A Simulated Dosimetric Study of Contribution to Radiotherapy Accuracy by Fractional Image Guidance Protocol of Halcyon System.

PurposeFrequency of conventional kV-image guidance is sometimes sacrificed to reduce concomitant risk, leaving deviations of unguided fractions unknown. MV-imaging and treatment dose can be collectively optimized on Halcyon, where fractional MVCBCT provides complete anatomic records for course-wide dose reconstruction. By retrospective dose accumulation, this work simulated the impact of imaging frequency on patient treatment dose on the platform of Halcyon.MethodsFour hundred and sixteen MVCBCT image sets from 16 patients of various tumor sites treated with radiotherapy on Halcyon were retrospectively selected. After applying the image-guided couch shifts of the clinical records, deformable image registration was performed using Velocity software, to deform the planning CTs to the corresponding MVCBCTs, generating pseudo CTs representing the actual anatomies on the treatment day. Fractional treatment dose was reconstructed on pseudo CTs for accumulation, representing the actual patient dose (Ddaily). To simulate weekly image guidance, fractional dose was reconstructed and accumulated by incorporating 1 CBCT-guided corrections and 4 laser-guided setups of each week (Dweekly). Limited by partially imaged volumes and different organs-at-risk of various sites, only target dose-volume parameters were evaluated across all patients.ResultsGTV_D98%, CTV_D98%, PTV_D90%, PTV_D95%, PGTV_D90%, and PGTV_D95% were evaluated, where Dx% means the minimal dose received by x% volume. Pairwise comparisons were made between plan dose and Ddaily, Ddaily and Dweekly respectively. PGTV_D95% of accumulated Dweekly were significantly lower than those of accumulated Ddaily by up to 32.90% of prescription dose, suggesting that weekly-guidance may result in unacceptable under dose to the target. The broad distribution of fractional differences between Ddaily and Dweekly suggested unreliable patient positioning based on aligning surface markers to laser beams, as a popular approach broadly used on conventional Linac systems. Slight target under-dose was observed on daily reconstructed results compared with planned dose, which provided quantitative data to guide clinical decisions such as the necessity of adaptive radiotherapy.ConclusionFractional image guided radiotherapy on Halcyon provides more reliable treatment accuracy than using sacrificed imaging frequency, which also provides complete anatomic records for deformable dose reconstruction supporting more informed clinical decisions.

IDegLira Versus Insulin Glargine U100: A Long-term Cost-effectiveness Analysis in the US Setting.

IntroductionTreatment with IDegLira has the potential to improve glycemic control in patients with type 2 diabetes mellitus (T2DM) without the weight gain and with a lower risk of hypoglycemia than with other therapies. The aim of the present analysis was to evaluate the long-term cost-effectiveness of IDegLira versus insulin glargine U100 with re-education and up-titration of the dose for treatment of patients with T2DM failing to achieve glycemic control on basal insulin in the US setting.MethodsData were obtained from the DUAL V randomized controlled trial in which adults with T2DM failing to achieve glycemic targets with insulin glargine U100 were randomly allocated to receive either IDegLira or insulin glargine U100. Long-term projections of clinical outcomes and direct costs were made using the IMS CORE Diabetes Model. Costs were accounted from a healthcare payer perspective. Future costs and clinical benefits were discounted at 3% annually.ResultsIDegLira was associated with improved discounted life expectancy (13.99 [standard deviation 0.19] versus 13.82 [standard deviation 0.20] years) and quality-adjusted life expectancy (9.14 [standard deviation 0.12] versus 8.87 [standard deviation 0.13] quality-adjusted life years [QALYs]) compared to insulin glargine U100. IDegLira was associated with increased direct costs of $16,970, yielding an incremental cost-effectiveness ratio (ICER) of $63,678 per QALY gained versus insulin glargine U100. Sensitivity analyses identified that the key driver of cost-effectiveness was the greater reduction in glycated hemoglobin with IDegLira compared with insulin glargine U100.ConclusionsBased on head-to-head clinical trial data, the present analysis suggests that IDegLira is likely to improve long-term clinical outcomes for patients with T2DM not achieving glycemic control on basal insulin compared to re-education and up-titration of the dose of insulin glargine U100, with these improvements coming at an increased cost from a healthcare payer perspective. An ICER within the range described as high care value was calculated, suggesting IDegLira is a cost-effective treatment option in the US. Funding: Novo Nordisk A/S and Novo Nordisk Inc.Electronic supplementary materialThe online version of this article (doi:10.1007/s13300-017-0251-x) contains supplementary material, which is available to authorized users.

Cyclophosphamide dose: how much is needed to win the war against paraquat poisoning?

Cyclophosphamide dose: how much is needed to win the war against paraquat poisoning?

フランカルボン酸モメタゾン点鼻液の通年性アレルギー性鼻炎における用法用量検討試験

A randomized, double-blind placebo-controlled, parallel-group, comparative study was conducted in 455 patients with perennial allergic rhinitis in order to examine the recommended dosage and administration of mometasone fuorate (MF) nasal spray for the treatment of allergic rhinitis in Japanese subjects over 2 weeks. Subjects were randomized to 6 treatment groups: (placebo: 77; 100 μg/day QD: 75; 200 μg/day QD: 74; 400 μg/day QD: 79; 200 μg/day BID: 75; and 400 μg/day BID: 75). All subjects were evaluated for safety and efficacy. The primary efficacy endpoint, decrease in individual nasal symptoms and overall improvement at week one and at the end of treatment for subjects treated with MF 200 μg/day or higher were significantly better than those of the placebo group (p<0.05). The incidence of adverse events was comparable among treatment groups. Based on the findings of safety and efficacy,200 μg/day QD was considered the most appropriate MF dose for treatment of patients with allergic rhinitis.

The lowest effective dose of botulinum A toxin in adult patients with upper limb spasticity

Objective: To define the lowest effective dose of botulinum toxin type A (Dysport®) and safety in the treatment of adult patients with upper limb spasticity. Design: This was a prospective, randomized, double-blind, dose-ranging study. Patients received either a placebo or one of three doses of Dysport® (350, 500, 1000 U) into five muscles of affected arm by anatomical and electromyography guidance. Efficacy was assessed periodically throughout the 6-month study period by the Modified Ashworth Scale (MAS), the Action Research Arm Test (ARA), the Barthel Index (BI) and the Visual Analogue Pain Scale (VAS). Results: Fifty patients were recruited. The four study groups were comparable at baseline with respect to their demographical characteristics and severity of spasticity. All doses of Dysport® studied showed a significant reduction from baseline of muscle tone and pain compared to placebo. However, the effect of functional disability was best at a dose of 500 U and the peak improvement was at week 8 after injection. A dose of 1000 U Dysport produced such an excess degree of muscle weakening that the number of randomized patients was reduced to five. BI and ARA of all patients were decrease after injection. No other adverse event was considered related to the study medication. Conclusion: This study suggests that treatment with Dysport® reduces muscle tone in adult patients with upper limb spasticity. The optimal dose for treatment of patients with residual voluntary movement in the upper limb appears to be 500 U.

Hereditary progressive dystonia with marked diurnal fluctuation (Segawa syndrome) in Taiwan

Since 1988, we have diagnosed 6 cases of hereditary progressive dystonia with marked diurnal fluctuation (HPD) in Taiwan. All cases presented with clinical features similar to those described by Segawa. They consisted of four sporadic and two familial cases. The age at onset ranged from 18 months to 8 years. There is a female predominance of 4:2. All of them showed mild postural tremor and postural dystonia manifested initially by flexion-inversion of a foot. However, unlike Segawa's description, side preference to the right (4:2) was noticed. Neck and axial muscles were not or were minimally involved, except a case presenting with retrocollis and tilting of the neck. These symptoms showed remarkable diurnal fluctuation which became aggravated towards the evening and alleviated in the morning or after rest. Response to l-dopa was dramatic, independent of the duration of illness, and no adverse effect of l-dopa has been observed. Our experience suggested that 10 mg/kg/day of l-dopa may be an optimally effective dose for treatment of patients with HPD. Neurophysiological, neuroradiological and biochemical studies were all normal except in one case who showed prolonged somatosensory potential latencies and white matter changes on MRI. Change of dopamine and its metabolites in CSF, plasma and urine had been investigated in one case.

5-Fluorourcil combined with the [6S]-stereoisomer of folinic acid in high doses for treatment of patients with advanced colorectal carcinoma: A phase I-II study of two consecutive regiments

Potentiation of the antitumor activity of 5-fluorouracil (5-FU) by folinic acid has been demonstrated in patients with colorectal adenocarcinoma. Modulation is due to the interaction of thymidylate synthase (TS), fluorodeoxyuridylate (FdUMP), and methylene tetrahydrofolate (5,10-CH2-FH4), which leads to the formation of a stable ternary complex with concomitant enzyme inactivation. Folinic acid consists of a mixture of equal parts of two stereoisomers differing in chirality at the C6 carbon of the pteridine ring. Only the levorotatory [6S]-folinic acid is transformed into active folate cofactors. However, the [6R]-stereoisomer is not inert; it was shown to interfere with the [6S] form at the cellular level. The possibility of a deleterious effect of the unnatural stereoisomer on the modulation of 5-FU led us to carry out 2 consecutive phase I-II studies of 5-FU combined with the [6S]-stereoisomer of folinic acid given in high doses for treatment of patients with advanced colorectal carcinoma. Treatment comprised 5-FU by i.v. infusion for 2 hours (the initial dose was 350 mg/m2/d; it was incremented by 25 mg/m2/d until a maximal dose of 550 mg/m2/d) and [6S]-folinic acid (100 mg/m2/d by rapid i.v. injection in Regimen 1, and 100 mg/m2 by rapid i.v. injection followed by a 2-hour infusion of 250 mg/m2 in Regimen 2) for 5 days, every 21 days. Twenty-five pts and 27 pts were assessed in Regimen 1 and in Regimen 2, respectively. They had had no prior chemotherapy. The median follow-up time was 9 months and 15.5 months for patients treated with Regimen 1 and Regimen 2, respectively. For pts treated with Regimen 1, the response rate was 52% (CR, 12%; PR, 40%). The median time to disease progression was 9.2 months. The probability of survival at 12 months was 73%. For pts treated with Regimen 2, the response rate was 37% (CR, 7%; PR, 30%). The median time to disease progression was 8.9 months. The probability of survival at 12 months was 67%. Improvement in quality of life was achieved in most patients who had symptoms due to the tumor before the start of treatment. The dose-limiting toxic effects (WHO grades > or = 3) were diarrhea, dermatitis, and mucositis. One single episode of grade 4 diarrhea occurred. After injection according to the schema in Regimen 1, [6S]-folinic acid was rapidly cleared from plasma (mean t 1/2 alpha and t 1/2 beta of 7.2 and 126 minutes, respectively). The mean concentration of the [6S]-stereoisomer two hours after injection was 5.8 mmol/L. After a rapid i.v. injection of 100 mg/m2 followed by a 2-hour infusion of 250 mg/m2, the mean concentration of [6S]-folinic acid two hours after the injection was 57.5 mmol/L. Pharmacokinetic data suggests saturation of the metabolic conversion of [6S]-folinic acid when large doses are administered. The [6S]-form of folinic acid potentiates the antitumor effect of 5-FU given concomitantly. However, increase of the daily dose of the folate did not result in a therapeutic improvement. The present results justify a more complete exploration of the pure active stereoisomer as a modulator of the fluoropyrimidines.

Fluorouracil Combined With the Pure (6S)-Stereoisomer of Folinic Acid in High Doses for Treatment of Patients With Advanced Colorectal Carcinoma: A Phase I-II Study

Potentiation of the antitumor activity of fluorouracil (5-FU) by folinic acid has been demonstrated in patients with colorectal adenocarcinoma. Modulation is due to the interaction of thymidylate synthase, fluorodeoxyuridine monophosphate, and methylene tetrahydrofolate, which leads to the formation of a stable ternary complex with concomitant enzyme inactivation. Folinic acid consists of a mixture of equal parts of two stereoisomers differing in chirality at the C-6 carbon of the pteridine ring. Only the levorotatory (6S)-stereoisomer of folinic acid is transformed into active folate cofactors. However, the (6R)-stereoisomer of folinic acid is not inert; it was shown to interfere with the (6S) form at the cellular level. The possibility of a deleterious effect of the unnatural stereoisomer on the modulation of 5-FU led us to carry out a phase I-II study of 5-FU combined with the (6S)-stereoisomer of folinic acid given in high doses for treatment of patients with advanced colorectal carcinoma. We also determined the plasma pharmacokinetics of folates after intravenous (IV) injection of (6S)-folinic acid at the dose used in this study. Treatment consisted of 5-FU (350-550 mg/m2 per day by IV infusion for 2 hours) and (6S)-folinic acid (100 mg/m2 per day by IV bolus injection) given for 5 consecutive days; the treatment was repeated every 21 days. Twenty-five patients with advanced colorectal carcinoma, who had had no prior chemotherapy, were evaluated for antitumor activity. The quantity of folates in plasma was measured using a microbiological assay. The median follow-up time was 9 months (range, 3.5-15.2 months). The response rate was 52% (complete response, 12%; partial response, 40%). The median time to disease progression for responding patients was 9.2 months (range, 5.9-15+ months). The estimated probability of survival at 12 months was 73%. Palliative improvement in quality of life was achieved in most patients who had symptoms due to the tumor before the start of treatment. The dose-limiting toxic effects were grade 3 diarrhea, dermatitis, and oral mucositis. Grade 4 toxicity did not occur. Myeloid toxicity was minor. After IV injection, (6S)-folinic acid was rapidly cleared from plasma (mean half-lives: alpha = 7.2 minutes and beta = 126 minutes). The mean concentration of the unchanged compound 2 hours after injection was 5.8 mumol/L. The (6S)-form of folinic acid potentiates the antitumor effect of 5-FU given concomitantly. Our results justify a more complete exploration of the pure active stereoisomer as a modulator of the fluoropyrimidines.