Use Of Full Doses Research Articles

Clinical outcomes in patients with radioiodine refractory thyroid carcinoma treated with dose-reduced lenvatinib.

e18104 Background: In recent years, well-differentiated thyroid cancer (WDTC) accounted for over 40,000 new cancer diagnoses annually. For patients with metastatic, iodine-131-refractory thyroid cancer, systemic therapy is sometimes warranted. Lenvatinib was FDA approved in this setting at a starting dose of 24 mg orally daily based on the SELECT trial. Many patients required dose reductions on this trial, and the use of full dose (24 mg) lenvatinib is often not feasible in clinical practice. This study characterizes the clinical outcomes of lenvatinib for WDTC in a real-world setting. Methods: This study is a retrospective chart review of all patients over 18 years old diagnosed with radioiodine refractory thyroid carcinoma who received lenvatinib at a large academic center between 05/01/2016 and 01/01/2022. Demographic information, clinical data, and treatment outcomes were obtained. Results of our study were compared to historical controls from the SELECT trial. Results: There were 38 patients included in this study. Twenty-six of 38 patients had a dose reduction prior to start of treatment per judgement of the treating physician. Of the 12 patients who started at 24 mg, 11 required a dose reduction. Starting doses of lenvatinib ranged from 4 mg to 24 mg. The mean starting dose was 17 mg. Median progression free survival and overall survival were 35.2 months and 56.2 months, respectively. Eighteen patients remain on therapy. Overall response rate was 39.5% compared to 64.8% in historical controls. Disease control rate was 63.2%. Any grade weight loss was higher in this cohort versus historical control – 92.1% vs 46.4%, respectively. Systolic ( > 20 mmHg) and diastolic ( > 10 mmHg) blood pressure changes occurred in 13.2% of patients. 16.7% of patients had a peak increase in creatinine > 0.2 mg/dL above their baseline. Conclusions: Many patients were deemed ineligible for full dose lenvatinib by the treating physician. Despite an apparently lower response rate, lower doses of lenvatinib can still provide adequate disease control with an acceptable rate of blood pressure and serum creatinine elevation. Weight loss was an almost universal side effect of lenvatinib in this real-world population and was seen at a higher frequency than the historical population.

The effect of farmyard manure and urea on grain yield and agronomic characteristics of maize (Zea mays)

Combining organic and inorganic fertilizer has been proved to be an effective and sustainable soil management strategy for increased crop yield and safe environment. Field experiments were conducted in two locations in Nigeria namely Malete and Shao during 2018 and 2019 seasons. This was to find out the efficacy of organic and inorganic fertilizer (including prilled and granular urea) and their various combinations on grain yield and agronomic characteristics of maize. The use of full dose of P and K + 75% N through Granular Urea + 25 % N through farmyard manure improved most of the soil chemical properties with high economic returns. It was concluded from the experiment that a combination of organic and inorganic fertilizers is an environmentally friendly practice and could lead to high yields and improve farmers’ income and their livelihoods.

P269 LOCAL ULTRASOUND–FACILITATED THROMBOLYSIS IN ACUTE PULMONARY EMBOLISM: HAS A SPACE?

Abstract Acute pulmonary embolism (PE) has an annual incidence of 48 patients per 100,000 with a mortality rate of 10%, few hours after the onset of symptoms. The use of full dose of thrombolytic agent is currently the treatment of choice in acute PE at intermediate and high risk, although its contraindications are well known. An alternative choice is delivered, via percutaneous femoral or jugular venous access, infusion catheters in the pulmonary artery (PA), in order to perform a local thrombolysis (based on a map of thrombus distribution observed at pulmonary CT), with a lower dose of trobolytic agent (rTPA) in a limited time, with a core for emission of ultrasound waves capable of breaking the mesh of the thrombus. Data from the KNOCOUT PE registry show a reduced frequency of fatal intracranial hemorrhage (ICH 2.5%), compared with the full dose of rTPA. Since February 2021 we have treated 7 patients with PE, all with cTnI, D–dimer and high NT–ProBNP and with pulmonary CT finding of large thrombus burden with pruning of peripheral pulmonary branches compatible with the diagnosis of PE at high and intermediate risk in patients with complex comorbidities (significant PESI and simplified PESI). On admission to the ICU all patients were with BP < 100 mmHg, RR > 20/min, satO2 < 90% and HR > 100 bpm. In echocardiogram all were with impaired RV (RV/LF ratio >1 and TAPSE <15mm). All patients was treated with UHF, 1 in fondaparinux for thrombocytopenia. At time between 4h and 8gg from the onset of symptoms, all patients underwent placement of 1 or 2 catheters in right and/or left PA, 106 cm and 135 cm length with zone of interest between 18/32 cm. When possible, hemodynamic parameters were evaluated: PAPm, cardiac output, and stroke volume to characterize the associated hemodynamic deterioration. 12mg of rtPA per catheter was administered over 12 hours. In 3 patients an echocardiogram was performed at 6 hours. In all at 24 hours, vital and laboratory parameters were measured, and in one patient, right heart catheterization was repeated. In no patient was treatment discontinued early, nor were ICH or minor bleeding recorded. Low dose of rtPA allowed use of the technique in patients with severe comorbidities at the limit of thrombolysis use, in the presence of marked RV distress and severe hemodynamic instability. Trials are in progress to shorten the time and therefore reduce the dose of rTPA with equal effectiveness on the clinical course of acute PE.

English

The biomass productivity and wheat grains efficiency is determined by nitrogen dose adjustment (full or fractioned), environmental conditions, and cropping system. The aim of this study was to improve the efficiency of N-fertilizer usage on wheat to maximize the biomass productivity and grain yield by adjusting the full or fractioned nitrogen dose in favorable and unfavorable year conditions, in succession systems with high and reduced N-residual release. In this study, two experiments were conducted between 2012 and 2014. One was to quantify the biomass productivity rate and another to determine grain yield. The experimental design was a complete randomized block, with four replications, in a 4 × 3 factorial scheme to N fertilizer rates (0, 30, 60 and 120 kg ha-1) and supply forms of the nutrient [full dose (100%) in the V3 phenological stage (third expanded leaf); fractioned (70 and 30%) at the V3 and V6 phenological stages (third and sixth expanded leaf, respectively) and; fractionated (70 and 30%) at the V3 and E phenological stages (third expanded leaf and early grain filling), ] respectively, in soybean/wheat and maize/wheat cultivation systems. The nitrogen supply in wheat through single dose or fraction indicates linear tendency over the productivity biomass daily rate-1 with the increase of N-fertilizer, regardless of a favorable and unfavorable year and system of a succession of the high and reduced N-residual release. However, in favorable years, the use of full dose on V3 stage is indicated. In the maize/wheat system, the full dose at V3 stage is more efficient, especially with higher doses of the nutrient. For grain yield, the N-fertilizer fractioning was adjusted in intermediate cropping years, while the full dose became suitable at the V3 stage in favorable years. However, in unfavorable years, nitrogen investments should be minimized, regardless of the supply form and succession system. Key words: Triticum aestivum L., succession system, optimization, regression.

Hypomagnesemia because of kidney failure and rhabdomyolysis associated with sitagliptin and atorvastatin

Introduction: Sitagliptin is a dipeptidyl-dipeptidase-4 inhibitor used in the daily treatment of type 2 diabetes. The drug most frequent secondary effects are headache and pharyngitis. The association between sitagliptin and rhabdomyolysis and acute kidney failure has been exceptionally described. We present here a case of hypomagnesemia and acute kidney failure associated with the use of full-dose of sitagliptin and atorvastatin. Clinical case: An 80-year-old man with history of hypertension, diabetes treated with metformin (with poor metabolic control), dyslipidemia and generalized atherosclerosis (previous myocardial infarction and ictus, this last one, three weeks before), was attended in our hospital because of 3-week clinical profile of asthenia, acute confusional syndrome, myalgia and muscles cramps and fasciculations.

GRP-140 Pharmacist Involvement in Cytostatic Doses: in an Obese Population

BackgroundThe dosing of chemotherapy according to the body surface area (BSA) in obese adult patients, who present a BSA above 2 m2, is usually set to an established BSA maximum...

Toward a comprehensive approach to pharmacoinvasive therapy for patients with ST segment elevation acute myocardial infarction

What exactly is "pharmacoinvasive therapy" for treatment of patients with ST segment elevation myocardial infarction (STEMI)? When this term was introduced in 2003, it addressed the need for clinical trials besides those comparing fibrinolysis with primary percutaneous coronary intervention (PCI). Primary PCI is recognized as the best strategy for treatment of patients for whom it is applicable. However, use of fibrinolytic drugs initially is necessary in many patients for logistic reasons. Studies of pharmacoinvasive therapy addressed the question of what should be done after initial fibrinolysis. Confusion of the terms pharmacoinvasive therapy, facilitated PCI, rescue PCI, and delayed invasive approaches has obscured the principles that have emerged from such studies. In our view, a uniform conceptualization of pharmacoinvasive therapy emerges on the basis of three key considerations--transfer time, initial pharmacologic therapy, and time to PCI. We propose the following definition: Pharmacoinvasive therapy is the treatment of choice for patients with STEMI who require greater than a 60 min transfer time to a PCI center. It entails immediate use of full doses of fibrinolytic agents followed by prompt transfer to a PCI center and a plan to implement PCI within 2-12 h of the time of onset of initial therapy.

Optimización del tratamiento inmunomodulador con azatioprina o 6-mercaptopurina en pacientes con enfermedad inflamatoria intestinal

There is limited information on the optimal use of thiopurinic immunomodulators in inflammatory bowel disease (IBD) and the dosage, efficacy and toxicity of these drugs has not been clearly established. To evaluate clinical outcomes and the toxicity of thiopurinic immunomodulators in clinical practice (effectiveness), as well as possible associated variables. Data were obtained from a database of patients with ulcerative colitis and Crohn's disease who started treatment with azathioprine or 6-mercaptopurine with an identical predetermined schedule and follow-up. Remission, relapse and toxicity were defined and analyzed and their relationship with clinical, biologic and demographic variables was evaluated with multivariate analysis. We evaluated 150 courses of treatment in 126 patients. Treatment was given to induce clinical remission in 118 courses and 62% of the patients reached this outcome, which was maintained for a mean of 52 months. The only variable associated with poor response was perianal disease. Adverse events were detected in 34% of the courses and were the main cause of treatment withdrawal. Factors significantly associated with withdrawal due to adverse events were starting with full doses of thiopurinic drugs (OR, 4.26; 95% CI, 1.12-16.32) and cotreatment with infliximab (OR, 5.6; 95% CI, 1.17-27.1). Some clinical variables such as disease phenotype, the use of full doses of thiopurinic drugs from the start of treatment, and co-treatments can have a notable influence on adverse effects and thus on the effectiveness of this therapy in IBD.

Combination pharmacotherapy in hypertension

Combination pharmacotherapy with two or more drugs is required in order to reach the currently recommended blood pressure goals in the majority of hypertensive patients, particularly those with a goal of <130/80 mm Hg. Further to the potentiation of the antihypertensive effects, benefits of combination therapy include the potential of fewer adverse affects and of improvement of patients' compliance. Current guidelines recommend that combination pharmacotherapy might also be considered as initial treatment in patients with significant elevation of blood pressure and evidence of complications. Several effective and well-tolerated antihypertensive drug classes available today offer multiple options for combination therapy. The choice of antihypertensive agents should be made on the basis of current recommendations regarding first line drugs and compelling indications. Specific drug combinations might have additional beneficial or detrimental long-term metabolic effects, beyond their effects on blood pressure. However, more outcome data comparing antihypertensive drug combinations are required. The implementation of an intensive up-titration treatment strategy, together with a systematic use of full doses of multiple drug combinations, is expected to achieve optimal blood pressure control in the vast majority of hypertensive patients.

Full Dose Vincristine (V) Negatively Impacts Progression Free Survival in Newly Diagnosed or Relapsed/Refractory Multiple Myeloma Patients Treated with Pegylated Doxorubicin, Vincristine, Reduced-Dose Dexamethasone, and Thalidomide (DVd-T).

Background: The activity of V in myeloma was first described in the 1970's. Although Phase II data suggest that V demonstrates single agent activity, subsequent reports have questioned its role. Due to these conflicting results, we conducted a subanalysis investigating the effect of V dose in the phase II DVd-T regimen that we have previously reported (Agrawal et al ASH 2003). We evaluated the effects of V dose on progression free survival (PFS) and overall survival (OS) in newly diagnosed and relapsed/refractory patients treated with DVd-T.Patients and Methods: As previously reported, this Phase II study enrolled 102 patients with newly diagnosed or relapsed/refractory multiple myeloma with evidence of end organ damage. DVd-T was administered as previously reported. After best response, patients were maintained on prednisone 50mg every other day and the maximum tolerated dose of thalidomide until disease progression. For patients experiencing grade 1 neuropathy, V was reduced by 25%, and for grade 2, by 50%. Patients developing grade 3/4 neuropathy had V discontinued and thalidomide suspended until toxicity decreased by at least one grade. Univariate analyses were conducted to assess the effect of V dose reduction or elimination on PFS and OS. Multivariate analyses were performed to adjust for the impact of age, platelet count, stage, quality of response (CR or near CR versus SD or PR), and thalidomide dose.Results: Trial included 53 newly diagnosed and 49 relapsed/refractory patients. Median age was 62.9 years. 59% had stage 3 or 4 disease. 37% had abnormal cytogenetics. Median beta-2 microglobulin was 4.1. Overall response rate of 87% was seen in newly diagnosed patients (36% achieved CR; 13% near CR; 38% PR; 8% SD; 6% PD). In the relapsed/refractory patients, overall response rate of 87% was achieved (21% achieved CR; 26% near CR; 40% PR; 13% SD). Median follow up was 28.1 months. Median PFS for the newly diagnosed group was 28.2 months and 15.5 for the relapsed/refractory group. Median OS was 39.9 months for the relapsed/refractory group. After 50 months of follow-up for the newly diagnosed group, median OS has not been reached. In total, 464 cycles were administered, of which 225 were given with full dose V and 242 with reduced dose or eliminated V. Grade 3/4 neuropathy occurred in 22 patients. Univariate analysis revealed that reducing or eliminating V had a significant positive effect on PFS and OS (p = 0.0002 and 0.02 respectively). Multivariate analysis adjusting for age at start of study, platelet count, stage, quality of response [CR or near CR versus SD or PR], and thalidomide dose, similarly found that reducing or eliminating the dose of V had a significant positive effect (p = 0.0121) on PFS. However, multivariate analysis did not reveal the same effect on OS (p = 0.11).Conclusions: This subanalysis suggests that the use of full dose V in the DVd-T regimen may have a negative effect on PFS. The exact mechanism by which V affects PFS is not clear. Studies are now on-going investigating this regimen without V. [Display omitted]

Cost analysis of aprotinin for coronary artery bypass patients: analysis of the randomized trials

Background The full kallikrein-inhibiting dose of aprotinin has been shown to reduce blood loss, transfusion requirements, and the systemic inflammatory response associated with cardiopulmonary bypass graft surgery (CABG). A half-dose regimen, although having a reduced delivery cost, inhibits plasmin and fibrinolysis without substantially effecting kallikrein-mediated inflammation associated with bypass surgery. The differing pharmacologic effects of the two regimens impact the decision-making process. The current study assessed the medical cost offset of full-dose and half-dose aprotinin from short- and long-term perspectives to provide a rational decision-making framework for clinicians. Methods To estimate CABG admission costs, resource utilization and clinical data from aprotinin clinical trials were combined with unit costs estimated from a Duke University–based cost model. Lifetime medical costs of stroke and acute myocardial infarction were based on previous research. Results Relative to placebo, the differences in total perioperative cost for primary CABG patients receiving full-dose or half-dose aprotinin were not significant. When lifetime medical costs of complications were considered, total costs in full-dose and half-dose aprotinin-treated patients were not different relative to that of placebo. Total perioperative cost was significantly lower for repeat CABG patients treated with aprotinin, with savings of $2,058 for full-dose and $2,122 for half-dose patients when compared with placebo. Taking lifetime costs of stroke and acute myocardial infarction into consideration, the cost savings estimates were $6,044 for full-dose patients and $4,483 for half-dose patients, due to substantially higher lifetime stroke costs incurred by the placebo patients. Conclusions Using this cost model, use of full-dose and half-dose aprotinin in primary CABG patients was cost neutral during hospital admission, whereas both dosing regimens were significantly cost saving in reoperative CABG patients. Additional lifetime cost savings were realized relative to placebo due to reduced complication costs, particularly with the full-dose regimen. As the full kallikrein-inhibiting dose of aprotinin has been shown to be safe and effective, the current results support its use in both primary and repeat CABG surgery. No demonstrable economic advantage was observed with the half-dose aprotinin regimen.

FURTHER EXPERIENCE OF THE SPECIFIC CURATIVE ACTION IN AMOEBIC DISEASE OF HYPODERMIC INJECTIONS OF SOLUBLE SALTS OF EMETINE

In the British Medical Journal of June 22nd * last I recorded cases illustrative of acute and chronic amoebic dysentery and acute hepatitis respectively in patients who were unable to take ipecacuanha by the mouth, but were rapidly cured by subcutaneous injections of soluble salts of emetine, without the production of vomiting or marked nausea, which are such serious drawbacks to the use of full doses of ipecacuanha by the mouth. During the two months which have elapsed since that note was written I have had frequent opportunities of using the new treatment in suitable cases, thanks mainly to the kindness of my I.M.S. colleagues in the'different Calcutta hospitals, to whom I tender my best thanks. The results have boon more than confirmatory of my first very favourable im pressions, and leave no possible doubt as to the great practical importance of the discovery. Some of them are, indeed, so surprising that they must be seen to be fully appreciated, as words can convey but a feeble impression of the rapidity and completeness of the recoveries effected in very grave cases. In dealing with the more extensive material now available it will be well to classify the cases into different clinical groups.