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Multiple Courses (multiple + course)
Selected AbstractsThe effect of single or multiple courses of antenatal corticosteroid therapy on neonatal respiratory distress syndrome in singleton versus twin pregnanciesAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 2 2009Suk-Joo CHOI Background: Antenatal corticosteroid (ACS) treatment is widely used for the prevention of respiratory distress syndrome (RDS) in preterm infants. However, the efficacy and safety of ACS treatment remains controversial in twin pregnancies. Aims: To investigate the effect of ACS therapy, single or multiple courses, on the incidence of neonatal RDS in singleton and twin pregnancies. Methods: We retrospectively evaluated the pregnancy and neonatal outcomes of 450 singleton and 117 twin pregnancies delivered at 24,34 weeks of gestation due to preterm labour or preterm premature rupture of membranes. The subjects were categorised into four groups according to ACS exposure: 0, 1, 2 and , 3 courses. Results: Overall, RDS occurred more frequently in twins compared to singletons (41.0% vs 25.3%, P < 0.001). In singleton pregnancy, the incidence of RDS was significantly lower in the ACS user groups than in the non-user group, with the lowest incidence in the multiple course groups. An increase in the number of courses of ACS was associated with a reduction in the incidence of RDS (odds ratio 0.349, 95% confidence interval 0.226, 0.537, P < 0.001) independent of confounding variables. In twin pregnancies, however, the incidence of RDS was not significantly different in comparisons among the four groups. Conclusion: Multiple courses of ACS were associated with a significantly decreased risk of RDS in singleton pregnancies. However, the current standard dose or interval for ACS administration in singleton pregnancy, as either a single or multiple courses, did not reduce RDS in twins. [source] Positioning biologic agents in the treatment of Crohn's disease,INFLAMMATORY BOWEL DISEASES, Issue 10 2009Stephen B. Hanauer MD Abstract One decade after the emergence of biologic therapy for Crohn's disease (CD), our treatment algorithms are beginning to change. Once reserved for patients with refractory disease, disease unresponsive to conventional therapies, or those requiring multiple courses of corticosteroids, there is increasing evidence that early, aggressive interventions with immunosuppressants or biologic therapies targeting tumor necrosis factor-, or ,-4 integrins can alter the natural history of CD by reducing the transmural complications of structuring and fistulization and the nearly inevitable requisite for surgical resections. More recent trials are beginning to suggest that intervention with combination therapy for selected patients with a poor prognosis may modify the long-term course of CD. Selection of patients with features predicting a complex or progressive course and early, combined intervention is now possible. Future studies are still needed to best identify predictors of response to individual agents with differing mechanisms of action, as well as to optimize the risk-benefit of long-term maintenance therapy. (Inflamm Bowel Dis 2009) [source] Inference for two-stage adaptive treatment strategies using mixture distributionsJOURNAL OF THE ROYAL STATISTICAL SOCIETY: SERIES C (APPLIED STATISTICS), Issue 1 2010Abdus S. Wahed Summary., Treatment of complex diseases such as cancer, leukaemia, acquired immune deficiency syndrome and depression usually follows complex treatment regimes consisting of time varying multiple courses of the same or different treatments. The goal is to achieve the largest overall benefit defined by a common end point such as survival. Adaptive treatment strategy refers to a sequence of treatments that are applied at different stages of therapy based on the individual's history of covariates and intermediate responses to the earlier treatments. However, in many cases treatment assignment depends only on intermediate response and prior treatments. Clinical trials are often designed to compare two or more adaptive treatment strategies. A common approach that is used in these trials is sequential randomization. Patients are randomized on entry into available first-stage treatments and then on the basis of the response to the initial treatments are randomized to second-stage treatments, and so on. The analysis often ignores this feature of randomization and frequently conducts separate analysis for each stage. Recent literature suggested several semiparametric and Bayesian methods for inference related to adaptive treatment strategies from sequentially randomized trials. We develop a parametric approach using mixture distributions to model the survival times under different adaptive treatment strategies. We show that the estimators proposed are asymptotically unbiased and can be easily implemented by using existing routines in statistical software packages. [source] Extended phase I evaluation of vincristine, irinotecan, temozolomide, and antibiotic in children with refractory solid tumors,PEDIATRIC BLOOD & CANCER, Issue 7 2010René Y. McNall-Knapp MD Abstract Background The combination of irinotecan, temozolomide, and vincristine is appealing because of potentially synergistic mechanisms of action and non-overlapping toxicities. This phase I study was designed to determine the toxicity and maximum tolerated dose (MTD) of escalating daily protracted doses of irinotecan given in this combination. With extended accrual, we more fully explored the toxicity of multiple courses at the MTD. Procedure Patients under 22 years with recurrent or refractory solid tumors were eligible. A course of chemotherapy was given every 28 days. Cefpodoxime was given for diarrhea prophylaxis. Vincristine (1.5,mg/m2, max 2,mg) was given intravenously (IV) on days 1 and 8. Temozolomide (100,mg/m2/day) was given orally on days 1,5. Irinotecan was given IV over 1,hr on days 1,5 and 8,12. Dose escalation was done in the standard 3,+,3 cohort design, starting at 15,mg/m2/day. Results Twenty-five of 26 eligible patients were evaluable for toxicity and response. They received 111 courses (1,13, median 4). Dose limiting toxicity (DLT,pancreatitis, transaminitis) was seen in two of three patients at dose level 2 (20,mg/m2). No patients at level 1 had DLT during the first two cycles. Thus, the MTD of irinotecan in this combination is 15,mg/m2/day,×,10 doses. Hematologic toxicity was mild and not prolonged. Grade 3 diarrhea was seen in five courses. Responses included two complete and two partial with 12 stable disease (SD) (median 6 months). Conclusions This combination is safe and shows activity in pediatric patients with recurrent malignancy. Pediatr Blood Cancer 2010;54:909,915 © 2010 Wiley-Liss, Inc. [source] Prenatal synthetic glucocorticoid exposure alters hypothalamic,pituitary,adrenal regulation and pregnancy outcomes in mature female guinea pigsTHE JOURNAL OF PHYSIOLOGY, Issue 5 2010Elizabeth Dunn Preterm delivery occurs in approximately 10% of all pregnancies. Prenatal exposure to synthetic glucocorticoids (sGCs) reduces the incidence of respiratory distress syndrome (RDS) in these babies. Therefore, administration of multiple courses of sGCs became common practice. Animal and human studies have demonstrated that multiple courses of sGCs can have long-term effects. While the majority of animal studies have been undertaken in male offspring, it is emerging that there are profound sex differences in the consequences of prenatal sGC exposure. To our knowledge, no studies have determined the effects of prenatal sGC exposure on hypothalamic,pituitary,adrenal (HPA) axis function in female offspring while accounting for reproductive cycle status, or determined if there are effects on pregnancy parameters. Pregnant guinea pigs were administered three courses of betamethasone (Beta), dexamethasone (Dex) or vehicle on gestational days 40/41, 50/51 and 60/61. In adulthood (age range: postnatal days 126,165), basal and activated HPA axis function were assessed at various stages of the reproductive cycle. The female offspring were then mated and underwent an undisturbed pregnancy. Females were killed in the luteal phase of the reproductive cycle following litter weaning, and molecular analysis undertaken. In the luteal phase, Beta-exposed females exhibited significantly lower basal salivary cortisol levels (P < 0.05). Dex-exposed females also exhibited significantly lower basal salivary cortisol levels during the luteal phase (P < 0.05), but increased basal salivary cortisol levels during the ostrous phase (P < 0.01). The Beta-exposed females exhibited increased glucocorticoid receptor (GR) mRNA expression in the CA1/2 region of the hippocampus (P < 0.05) and MC2R mRNA in the adrenal cortex (P < 0.05). The Dex-exposed animals exhibited higher hippocampal GR and mineralocorticoid receptor (MR) mRNA levels (P < 0.05). Beta-exposed females showed reduced fecundity (P < 0.05). In Dex-exposed females there was a lower male to female sex ratio. In conclusion, prenatal sGC exposure affects HPA axis activity, in a cycle-dependent manner, and long-term reproductive success. The clinical implications of the findings on endocrine function and pregnancy in females are profound and further follow-up is warranted in human cohorts. Furthermore, we have shown there are considerable difference in phenotypes between the Beta- and Dex-exposed females and the specific endocrine and maternal outcome is contingent on the specific sGCs administered during pregnancy. [source] Merkel cell carcinoma and multiple cutaneous squamous cell carcinomas in a patient with pityriasis rubra pilarisAUSTRALASIAN JOURNAL OF DERMATOLOGY, Issue 1 2002Nghi T Huynh SUMMARY A 79-year-old female was diagnosed with Merkel cell carcinoma (MCC) and multiple cutaneous squamous cell carcinomas (SCC) occurring on a background of pityriasis rubra pilaris. At the time of initial diagnosis and treatment for upper limb MCC, axillary nodal metastases were clinically evident. In the ensuing months, she developed multiple rapidly progressing SCC and eventually a left arm soft tissue deposit of metastatic MCC. Treatment involved multiple courses of fractionated radiotherapy. The salient clinical features and supporting evidence for this case are presented. [source] The effect of single or multiple courses of antenatal corticosteroid therapy on neonatal respiratory distress syndrome in singleton versus twin pregnanciesAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 2 2009Suk-Joo CHOI Background: Antenatal corticosteroid (ACS) treatment is widely used for the prevention of respiratory distress syndrome (RDS) in preterm infants. However, the efficacy and safety of ACS treatment remains controversial in twin pregnancies. Aims: To investigate the effect of ACS therapy, single or multiple courses, on the incidence of neonatal RDS in singleton and twin pregnancies. Methods: We retrospectively evaluated the pregnancy and neonatal outcomes of 450 singleton and 117 twin pregnancies delivered at 24,34 weeks of gestation due to preterm labour or preterm premature rupture of membranes. The subjects were categorised into four groups according to ACS exposure: 0, 1, 2 and , 3 courses. Results: Overall, RDS occurred more frequently in twins compared to singletons (41.0% vs 25.3%, P < 0.001). In singleton pregnancy, the incidence of RDS was significantly lower in the ACS user groups than in the non-user group, with the lowest incidence in the multiple course groups. An increase in the number of courses of ACS was associated with a reduction in the incidence of RDS (odds ratio 0.349, 95% confidence interval 0.226, 0.537, P < 0.001) independent of confounding variables. In twin pregnancies, however, the incidence of RDS was not significantly different in comparisons among the four groups. Conclusion: Multiple courses of ACS were associated with a significantly decreased risk of RDS in singleton pregnancies. However, the current standard dose or interval for ACS administration in singleton pregnancy, as either a single or multiple courses, did not reduce RDS in twins. [source] Obstetric risk factors and persistent increases in brain parenchymal echogenicity in preterm infantsBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 9 2004Arsenio Spinillo Objective To assess the risk of persistent (>7 days) increases in brain parenchymal echogenicity in preterm infants and their association with known obstetric risk factors. Design Case,control study of prospectively collected data. Setting A University hospital in Northern Italy. Population Eighty-five singleton infants between 24 and 34 weeks of gestation with a cranial ultrasonographic diagnosis of persistently increased parenchymal echogenicity without development of cystic degeneration, and 170 control infants with negative cranial ultrasonographic findings. Methods A comparison of the prevalence of selected obstetric risk factors between infants with persistent echo-dense lesions and negative controls. Main outcome measures Odds ratios of persistent echo-dense lesions including first-degree interactions between variables. Results After adjusting for birthweight, logistic regression analysis showed that the only factor associated with an increased risk of persistent brain echo-dense lesions in infants was multiple courses of antenatal steroids (OR = 2.14, 95% CI = 1.11,4.15, P= 0.024). In this group, the risk of persistent echo-dense lesions was particularly high in: (i) mothers receiving dexamethasone rather than betamethasone (P value for interaction = 0.015) and (ii) after expectant management of pre-eclampsia or intrauterine growth retardation (P value for interaction = 0.03). Conclusions Multiple doses of antenatal steroids, especially dexamethasone, could influence the prevalence of persistent increases in brain parenchymal echogenicity in preterm infants. [source] Are we prescribing multiple courses of antenatal corticosteroids?BJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 4 2000A survey of practice in the UK No abstract is available for this article. [source] Blood pressure support in extremely premature infants is affected by different courses of antenatal steroidsACTA PAEDIATRICA, Issue 9 2009GV Nair Abstract Objective:, To examine the effects of partial, single and multiple courses of antenatal corticosteroids (ANS) on the need for blood pressure support in extremely premature infants. Methods:, Extremely premature infants with gestational age of 24 to 28 weeks were included in this study during a 5-year period. The main outcome measure of the study was the amount of blood pressure support during the first 3 days of life. Results:, The study infants (n = 163) were divided into: infants not exposed (ANS; n = 27) and exposed to ANS (ANS; n = 136). Blood pressure support was significantly lower in ANS compared with No ANS (65% vs 96%; p = 0.003) and in single course (SANS; n = 73) and ,2 courses (MANS; n = 34) compared with partial course of ANS (PANS; n = 29) (62%, 56% vs 86%; p = 0.03). The number of infants who received volume support and the amount of volume support were significantly lower in ANS compared with that in No ANS (p < 0.001) and in SANS and MANS compared with that in PANS (p < 0.02). Conclusion:, Exposure to multiple courses of ANS was as beneficial as single course of ANS in decreasing the need for blood pressure support in extremely premature infants. [source] |