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APSRTC planning to apply all the existing 11,000 diesel buses with the AC exposed bus. Olectra allowed 10 e-buses to the APSRTC on Rich in the Alipiri deport. This news is not announced by the CM of Andhra Pradesh. The APSRTC is much eco-friendly air-conditioning asses on the Tirupati-Tirumala ghat road for the first time.
In the first application, ten electric AC credits were put into systemic between Tirupati and Tirumala.
Equivalent anti-inflammatory doses Summary Have I got the right topic? How up-to-date is this topic? Goals and outcome measures Background information Definition Properties of corticosteroids Types of oral corticosteroids Equivalent anti-inflammatory doses Management Supporting evidence How this topic was developed References. Equivalent anti-inflammatory doses of oral corticosteroids A comparison of the anti-inflammatory doses of corticosteroids, equivalent to 5 mg of prednisolone, are shown in Table 1.
Table 1. Equivalent anti-inflammatory doses of oral corticosteroids. Drug Dose equivalent to 5 mg of prednisolone Betamethasone micrograms Cortisone acetate 25 mg Deflazacort 6 mg Dexamethasone micrograms Hydrocortisone 20 mg Methylprednisolone 4 mg Prednisone 5 mg Triamcinolone 4 mg This table does not take into account mineralocorticoid effects or variations in duration of action of the corticosteroids. Data from [ Joint Formulary Committee, ; Brayfield, ].
Back to top. This table does not take into account mineralocorticoid effects or variations in duration of action of the corticosteroids.
mg. Dexamethasone (long-acting) ; 8 mg. Methylprednisolone (intermediate-acting) ; 8 mg. Triamcinolone (intermediate-acting) ; 10 mg. PrednisoLONE (PO). PredniSONE (PO). Triamcinolone (IV). Drug Dosage in mg. mg. Converting To: Betamethasone (IV). Cortisone (PO). Dexamethasone (IV or PO). Dose conversion of prednisone to dexamethasone is also a controversial issue. In most published studies, the dose ratio of dexamethasone to. Corticosteroids conversion calculator hydrocortisone, dexamethasone, prednisone, methylprednisolone, betamethasone antiinflammatory potency. Dexamethasone has a six- to sevenfold higher efficacy than prednisone in terms of antiinflammatory effects,3 which traditionally led to dexamethasone/prednisone. Compared to prednisone, dexamethasone was reported to be associated with more bone toxicities, proximal myopathy, mood and behavior changes, neuro-cognitive impairment and life threatening infections 9. Significant relapse reduction and improvement in event-free survival without significant improvement in overall survival has also been experienced in other studies 3132 and will be a relevant matter of debate in modern trials in pediatric oncology. Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. The trial design also included second randomization to Capizzi regimen with lower, escalating doses of intravenous methotrexate C-MTX vs.Blood ; 17 : — Dexamethasone vs prednisone in induction of pediatric ALL led to significant relapse reduction and increased treatment-related mortality. No overall survival benefit was achieved with dexamethasone except in the subset of patients with T-cell ALL and good early treatment response.
Induction therapy for childhood acute lymphoblastic leukemia ALL traditionally includes prednisone; yet, dexamethasone may have higher antileukemic potency, leading to fewer relapses and improved survival. The benefit of dexamethasone was partially counterbalanced by a significantly higher induction-related death rate 2.
No difference was seen in 5-year overall survival OS in the total cohort dexamethasone, Retrospective analyses of predefined subgroups revealed a significant survival benefit from dexamethasone only for patients with T-cell ALL and good response to the prednisone prephase prednisone good-response [PGR] dexamethasone, In patients with precursor B-cell ALL and PGR, survival after relapse was found to be significantly worse if patients were previously assigned to the dexamethasone arm.
We conclude that, for patients with PGR in the large subgroup of precursor B-cell ALL, dexamethasone especially reduced the incidence of better salvageable relapses, resulting in inferior survival after relapse.
This explains the lack of benefit from dexamethasone in overall survival that we observed in the total cohort except in the subset of T-cell ALL patients with PGR. This trial was registered at www. Since the early era of treating patients with acute lymphoblastic leukemia ALL , glucocorticoids have been an essential component of therapy regimens.
Additional factors may contribute to a greater efficacy of dexamethasone in vivo, namely a longer plasma half-life and a lower protein-bound fraction in combination with a longer half-life in the cerebral spinal fluid CSF , leading to better CSF penetration and higher CSF concentrations. Results of this trial regarding the prognostic impact of minimal residual disease MRD have already been reported. Children and adolescent patients from the ages of 1 to 17 years were diagnosed with ALL in one of the participating study centers in Austria, Germany, Italy, and Switzerland details are provided in the supplemental Appendix, available on the Blood Web site and registered in the AIEOP-BFM ALL randomized trial after obtaining written informed consent from their guardians.
Tests were performed according to standard procedures as published before. Nonresponse was defined as not having achieved CR after the third pulsatile high-dose block. Risk group assignment was based on cytologic and molecular response to treatment and on genetic features of ALL blasts. The study protocol was approved by the competent ethics committees of the national coordinating centers Hannover Medical School, Hannover; St.
Gerardo Hospital, Monza. In this open-label study, patients were randomly assigned to receive the standard glucocorticoid therapy with prednisone or the experimental therapy with dexamethasone as part of the 4-drug induction therapy phase Protocol IA.
Randomization was performed by day 8 in a ratio. It used permuted blocks of 4 patients and was stratified by country and in Italy and Germany in addition by center.
All patients started therapy with a 7-day prephase with prednisone and one intrathecal dose of methotrexate. The treatment outline is provided in Figure 1. Criteria for eligibility for allogeneic stem cell transplantation and cranial irradiation are shown in supplemental Tables 1 and 2 in the supplemental Appendix. Full treatment details and drug doses were published earlier 9 , 10 and are also listed in supplemental Table 3 in the supplemental Appendix.
The primary outcome in this study was event-free survival. Event-free survival was defined as the time from diagnosis to the date of last follow-up or first event. Events were nonresponse, relapse, secondary neoplasm, or death from any cause. Failure to achieve remission as a result of early death or nonresponse was considered as event at time zero. Secondary outcomes were overall survival, short- and long-term toxicity, treatment-related death in induction or in remission, and MRD levels at end of induction and after consolidation.
Overall survival was defined as the time from diagnosis to death from any cause or last follow-up. The Kaplan-Meier method was used to estimate survival rates; differences between groups were compared with the log-rank test.
Cumulative incidence functions for competing events were constructed by the method of Kalbfleisch and Prentice and were compared with the Gray test. Differences in the distribution of categorical variables were analyzed using the Fisher exact test. The sample size for randomization of induction treatment was calculated in the light of the estimations for the primary endpoint ie, event-free survival.
A Data Safety and Monitoring Committee periodically supervised the study progress. In view of safety concerns, the Committee suggested in October halting the randomization for patients aged 10 years or older. The trial was registered at www. Of these patients, Of the remaining patients randomly placed, were assigned to the dexamethasone arm and patients to the prednisone arm Figure 2. Initial patient characteristics were equally distributed between the 2 randomization groups Table 1.
The proportion of patients who did not reach CR on day 33 was similar in the 2 randomization groups Table 2. In pB-ALL patients, a more rapid MRD response with a significant shift to lower MRD results on day 33 could be shown in the dexamethasone group; the difference was no longer obvious on day MRD data are shown for patients who could successfully be classified by MRD according to the protocol criteria.
Events are shown in Table 3. The overall relapse incidence was reduced by one third in the dexamethasone arm Figure 3Ai. Relapse reduction was more pronounced for extramedullary relapses than for isolated bone marrow relapses.
Death rates before achievement of CR and in first CR related to induction treatment were significantly higher in patients assigned to receive dexamethasone. No difference between the randomization groups was seen with regard to the rate of nonresponse, postinduction deaths, and the incidence of secondary neoplasms. Event-free survival was significantly better for patients randomly assigned to the dexamethasone arm compared with patients assigned to receive prednisone hazard ratio [HR], 0.
No difference between the randomization groups could be demonstrated for overall survival HR, 1. Fisher exact test was used for deaths and resistant disease and Gray test was used for relapses and secondary neoplasms. Relapse incidence, mortality rate, event-free survival, and overall survival according to the assigned randomization arms. Subpanels show i the incidence of relapse and mortality rate, ii the event-free survival, and iii overall survival. Numbers of patients at risk in the event-free survival graphs also apply to the relapse incidence graph.
Retrospective analyses were performed for clinical subgroups. Patients with prednisone poor-response had comparable relapse incidence, event-free survival, and overall survival in the 2 randomization groups Figure 3Bi-iii , which was also valid when analyzing B- and T-lineage ALL separately supplemental Table 5 or stratified by treatment with chemotherapy only or chemotherapy with additional hematopoietic allogeneic stem cell transplantation data not shown.
Among the patients with prednisone good-response, a significantly lower incidence of relapse and better event-free survival could be demonstrated in the dexamethasone arm compared with the prednisone arm for patients with B-lineage Figure 3Ci-ii and T-lineage ALL Figure 3Di-ii. In patients with prednisone good-response and T-ALL, the better event-free survival of the dexamethasone group also translated into significantly better survival Figure 3Diii. This was in contrast to the patients with prednisone good-response and pB-ALL, who had an even inferior—though statistically insignificant—survival rate in the dexamethasone group Figure 3Ciii.
Detailed outcome data of further clinical and biological subgroups are presented in supplemental Table 5 of the supplemental Appendix. Survival after relapse was significantly better in the pB-ALL patients with prednisone good-response previously assigned to the prednisone arm compared with the corresponding patients of the dexamethasone arm 5-year probability of survival [5 y-pSUR] after relapse: dexamethasone Patients with relapsed ALL previously assigned to dexamethasone had a higher proportion of features predicting poor survival after relapse Table 4.
In a multivariate Cox analysis including these factors as covariates, the type of glucocorticoid in induction completely lost its significance Table 4. Despite the worse risk profile of the relapses in the dexamethasone arm, the proportion of patients who underwent allogeneic stem cell transplantation in second CR was not higher in this group compared with the patients who had relapsed in the prednisone arm dexamethasone Results of the univariate and multivariate Cox regression analyses on survival after relapse in patients with pB-ALL and prednisone good-response according to randomization arm as assigned and other characteristics.
No significant difference in survival after relapse was seen in the small group of patients with T-ALL and prednisone good-response 5 y-pSUR after relapse: prednisone Incidences of life-threatening and fatal adverse events related to the induction phase Protocol IA according to the randomized treatment arm and age are shown in Table 5. The incidence of life-threatening and fatal infections was significantly higher in patients treated with dexamethasone compared with those who received prednisone, which was attributed to more bacterial and fungal infections as well as more infections of unknown origin Table 5.
The table includes all life-threatening events that were related to therapy and occurred during or after induction Protocol IA before start of consolidation element Protocol IB. An adverse event was considered as life-threatening if its occurrence placed the patient at immediate risk of death. An adverse event that might have caused death, if it had occurred in a more severe form, was not considered as life-threatening.
Percentages are related to the total number of randomized patients treated in the respective arm. A higher incidence in the dexamethasone-treated patients could also be found for the noninfectious treatment complications, which could in particular be shown for events of neurologic and gastrointestinal etiology Table 5. Only patients from the BFM group were included in the analyses of osteonecroses because collection of these data was not prospectively done in the AIEOP group.
Because randomization was stopped for patients at the age of 10 years or older in October of , only patients with ALL diagnosis before this date were included in those analyses that were performed across age groups, to avoid a bias as a result of the nonrepresentative age distribution in the entire randomized cohort.
The age-stratified analyses were done including all randomized BFM patients. Five-year cumulative incidence of osteonecrosis was 4. Incidence was higher in patients 10 years of age or older and increased with age Figure 4A.
There was no difference in 5-year cumulative osteonecrosis incidence between the randomization groups, neither in the total group dexamethasone 4.
Cumulative incidence of osteonecrosis in patients of the BFM group. In the era of ALL-BFM protocols, no other intervention had a comparable impact on relapse reduction since the implementation of reinduction treatment in the s. Dexamethasone proved to be most effective in the prevention of extramedullary relapses, which is consistent with more even tissue distribution in general and better penetration of the blood-brain barrier compared with prednisone.
At the interim analysis, adolescent patients appeared to be at particular risk of serious treatment complications. Thus, 4 years into the trial, this led to the decision to stop the randomization for patients 10 years of age and older, based on the recommendation of an external data and safety monitoring committee.
Despite the remarkable overall relapse reduction observed in the dexamethasone group, no relevant effect could be shown for patients with prednisone poor-response.
This might reflect a general glucocorticoid and multidrug resistance of the leukemic cells of these patients, which cannot be overcome even by dexamethasone. In addition, a positive effect of dexamethasone might be obscured by the more intensive therapy administered to patients with prednisone poor-response.
No relapse reduction by the use of dexamethasone could be shown in these trials, with the exception of a marginally significant lower incidence of CNS relapse in the EORTC trial. The higher incidence of induction-related death in the dexamethasone arm of our trial was also reflected by a higher rate of life-threatening toxicity.
Among the life-threatening infections, we observed an excess of bacterial primarily gram-negative rods as well as fungal primarily molds infections in the dexamethasone arm. A higher incidence in dexamethasone-treated patients could also be shown for life-threatening neurologic and gastrointestinal complications.
The gastrointestinal toxicity mainly manifested as gastric bleedings and perforations without clearly different patterns in the 2 treatment arms. Etiologies of the neurologic events were more heterogeneous, and specific patterns that differed between the 2 arms were also not evident.
No significant difference in early treatment deaths could be demonstrated between the randomization arms in the CCG and MRC-ALL97 trials, a finding that at first sight seems to be in contrast to our results. Furthermore, for direct comparison of our results with those of the CCG trial, we assessed the difference in death rates before CR between the randomization arms in NCI standard-risk patients and also found no statistically significant difference in this subgroup in our trial supplemental Table 5.
In the Japanese L trial, a trend toward a higher rate of induction-related infectious deaths was observed in the dexamethasone arm, 22 whereas no difference in early treatment-related deaths was seen in the EORTC CLG trial.
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