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Dose Reduction (dose + reduction)
Selected AbstractsPhantom measurements and computed estimates of breast dose with radiotherapy for Hodgkin's lymphoma: Dose reduction with the use of the involved field,JOURNAL OF MEDICAL IMAGING AND RADIATION ONCOLOGY, Issue 4 2008A Wirth Summary The risk of breast cancer following radiotherapy for Hodgkin's lymphoma appears to be dose related. In this study we compared breast dose in an anthropomorphic phantom for conventional ,mantle'; upper mediastinal/bilateral neck (minimantle) and unilateral neck fields, and evaluated the accuracy of computer planned dose estimates for out-of-field doses. For each field, computer-planned breast dose (CPD) estimates were compared with thermoluminescence dosimetry measurements in five locations within ,breast tissue'. CPD were also compared with ion chamber measurements in a slab phantom. Measured dose and CPD were within 20% of each other up to approximately 10 cm from the field edge. Beyond 10 cm, the CPD underestimated dose by a factor of 2 or more. The mini-mantle reduced the breast dose by a factor of approximately 10 compared with the mantle treatment. Treating the neck field lowered the breast dose by a further 50% or more. Modern involved-field radiotherapy for lymphoma substantially reduces breast dose compared with mantle fields. Computer dosimetery underestimated dose at larger distances from the field. This needs to be considered if computer dosimetery is used to estimate breast dose and, by extrapolation, breast cancer risk. [source] Systemic toxicity of tacrolimus given by various routes and the response to dose reductionCLINICAL & EXPERIMENTAL OPHTHALMOLOGY, Issue 1 2005Laboratory Science Abstract Purpose:,To evaluate the long-term systemic toxicity of tacrolimus (FK-506) administered by various routes, and to assess the effect of dose reduction on toxicity. Methods:,The study animals were 120 experimentally naïve adult female Wistar rats weighing 200,250 g each. The rats were randomly divided into 10 equal groups (n = 12 in each) and treated with tacrolimus administered topically (in drops, 0.3%, q.i.d.), intravitreally (0.5 mg/kg bodyweight/week), intramuscularly (1 mg/kg bodyweight/week), low-dose intravenously (1 mg/kg bodyweight/week) and in high-dose intravenously (2 mg/kg bodyweight/week) for 3 months. The rats in the control groups (one for each different route of administration) were treated with 0.9% NaCl. The blood concentration of tacrolimus, complete blood count and biochemistry parameters were measured each month for the 3-month study period. Results:,The rats in the control groups and experimental groups administered topical and intravitreal tacrolimus did not demonstrate any systemic toxic effects. The rats that developed certain toxic effects (hyperglycaemia, hyperkalaemia and nephrotoxicity) in the groups given low-dose or high-dose i.v. tacrolimus responded well to dose reduction. Following dose reduction, blood glucose concentrations decreased from 247.4 ± 42.3 mg/dL to 189.6 ± 37.9 mg/dL (P < 0.05), and from 237.4 ± 41.1 mg/dL to 182.3 ± 22.7 mg/dL (P < 0.05) in the low- and high-dose i.v. tacrolimus-treated rats, respectively. The rats that developed impaired hepatic function after high-dose tacrolimus did not respond to dose reduction. Baseline cholesterol concentrations for the intramuscular and low- and high-dose i.v. tacrolimus-treated groups, demonstrated decreases, respectively, from 87.4 ± 14.0 mg/dL, 86.4 ± 14.0 mg/dL and 90.4 ± 14.3 mg/dL to 53.6 ± 9.8 mg/dL, 52.1 ± 12.5 mg/dL and 63.5 ± 11.7 mg/dL by the end of the second month. The differences were found to be statistically significant (P < 0.05 for each result). Conclusion:,Topical or intravitreal administration of tacrolimus seems to be systemically safe whereas parenteral administration can cause some systemic haematological changes such as dose-dependent decreased serum cholesterol concentrations. Dose reduction may prevent such adverse effects. [source] Risk factors for infection during treatment with peginterferon alfa and ribavirin for chronic hepatitis C,HEPATOLOGY, Issue 4 2010Robert Roomer Neutropenia during treatment with peginterferon alfa and ribavirin for chronic hepatitis C virus (HCV) infection is a common cause of dose reductions of peginterferon alfa. These reductions are performed to prevent bacterial and fungal infections, which are common during HCV treatment and can be attributed to neutropenia. The aims of this study were to investigate the occurrence of infections and their relation to neutropenia and to identify potential risk factors for infections during HCV treatment. In this single-center cohort study, 2,876 visits of 321 patients treated with peginterferon alfa and ribavirin were evaluated for neutropenia, infections, dose reductions, and potential risk factors for infection during HCV treatment. The baseline mean absolute neutrophil count (ANC) was 3,420 cells/,L, and 16 patients had a baseline ANC of <1,500 cells/,L. During treatment, neutropenia, which was defined as ANC <750 cells/,L, was observed in 95 patients (29.7%) and ANC <375/,L was observed in 16 patients (5%). Ninety-six infections were observed in 70 patients (21.8%). Thirteen infections (13.5%) were defined as severe. Infections were not correlated with neutropenia during treatment. Dose reductions did not lead to a decrease in infection rate. Multivariate logistic regression analysis revealed that age >55 years (odds ratio [OR] 2.06, 95% confidence interval [CI] 1.19-3.56, P = 0.01) and baseline hyperglycemia (OR 2.17, 95% CI 1.15-4.10, P = 0.016) were associated with an increased risk of infection during HCV treatment. Cirrhosis and chronic obstructive pulmonary disease were not risk factors for infection. Conclusion: Bacterial infections during treatment with peginterferon alfa and ribavirin are not associated with neutropenia. Older patients and patients with poorly controlled diabetes mellitus have a greater risk of developing infections during HCV treatment. (HEPATOLOGY 2010) [source] A Phase II trial of the oral mTOR inhibitor everolimus in relapsed Hodgkin lymphoma,AMERICAN JOURNAL OF HEMATOLOGY, Issue 5 2010Patrick B. Johnston Everolimus is an oral antineoplastic agent that targets the raptor mammalian target of rapamycin (mTORC1). The phosphatidylinositol 3-kinase/mTOR signal transduction pathway has been demonstrated to be activated in tumor samples from patients with Hodgkin lymphoma (HL). The goal of this trial was to learn the antitumor activity and toxicity of everolimus in patients with relapsed/refractory HL. Patients were eligible if they had measurable disease, a platelet count >75,000, and an absolute neutrophil count >1,000. Patients received everolimus 10 mg PO daily. Dose reductions were allowed. Response was assessed after two and six cycles and then every three cycles until progression. Patients could remain on drug until progression or toxicity. Nineteen patients were enrolled. Median age was 37 years (range, 27,68). Patients had received a median of six prior therapies (range, 3,14) and 84% had undergone prior autologous stem cell transplant. The ORR was 47% (95% CI: 24,71%) with eight patients achieving a PR and one patient achieving a CR. The median TTP was 7.2 months. Four responders remained progression free at 12 months. Patients received a median of seven cycles of therapy. Of the 19 patients, one remains on therapy at 36 months; the others went off study because of progressive disease (16), toxicity (1), and death from infection (1). Four patients experienced a Grade 3 or higher pulmonary toxicity. Everolimus has single-agent activity in relapsed/refractory HL and provides proof-of-concept that targeting the mTOR pathway in HL is clinically relevant. Am. J. Hematol., 2010. © 2010 Wiley-Liss, Inc. [source] Due to low infection rates no routine anti-infective prophylaxis is required in younger patients with chronic lymphocytic leukaemia during fludarabine-based first line therapyBRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2007Barbara F. Eichhorst Summary The impact of the combination therapy fludarabine plus cyclophosphamide (FC) in comparison with fludarabine alone regarding the incidence and severity of infections among previously untreated patients with chronic lymphocytic leukaemia (CLL) was evaluated within a multicentre phase III study. A total of 375 patients, up to 65 years old, were randomised between fludarabine or FC for first line therapy. No routine anti-infective prophylaxis was provided. A total of 196 infectious episodes, including 33 severe infections, were documented. In the fludarabine arm, 32·9% of the patients developed an infectious complication compared with 39·9% in the FC arm (P = 0·2). No difference was observed in the rate of severe infections (Common Toxicity Crtieria grades III and IV) between both treatment arms. Dose reductions were performed more frequently in FC-treated patients. Granulocyte colony-stimulating factor (G-CSF) was administered due to leucopenia in 5% of all patients. A multivariate regression model identified only elevated thymidine kinase, but not the treatment arm, as a statistically independent risk factor for infections. In summary, FC was not associated with a higher rate of infections compared with fludarabine alone. No routine antibiotic or virostatic prophylaxis, or pre-emptive treatment with G-CSF, is necessary in first line therapy with fludarabine-based regimens in younger patients with CLL, if adequate dose reduction is performed. The combination therapy FC is not associated with a higher rate of infections compared with fludarabine alone. No routine antibiotic or virostatic prophylaxis as well as pre-emptive treatment with G-CSF is necessary in first line therapy with fludarabine-based regimen in younger patients with CLL, if adequate dose reductions due to cytopenia or previous infections are performed. [source] THERAPEUTIC HOTLINE: Alefacept in the treatment of hyperkeratotic palmoplantar psoriasisDERMATOLOGIC THERAPY, Issue 5 2010Sagi Lior ABSTRACT Plaque-type palmoplantar psoriasis (PPP) is associated with marked morbidity and frequently resistant to conventional therapies. Patients with long-standing plaque-type PPP failing previous treatments were included and treated with a 12-week intramuscular alefacept. The biweekly evaluation included hyperkeratosis, itching, and pain grading. In all of the seven treated patients significant to complete improvement in hyperkeratosis, pruritus and pain were observed, along with dose reduction or complete discontinuation of additional systemic treatments and without any recorded side effects. Alefacept should be considered as a therapeutic option for plaque-type PPP. [source] Inhibitors of purine and pyrimidine synthesis: mycophenolate, azathioprine, and leflunomideDERMATOLOGIC THERAPY, Issue 4 2002Daniel Mimouni The major goal in the treatment of autoimmune blistering diseases has changed from simply keeping the patient alive to suppressing disease while maintaining quality of life and minimizing drug side effects. Researchers and clinicians are constantly seeking steroid-sparing agents that would allow a dose reduction in corticosteroids with no loss of benefit. Purine and pyrimidine base inhibitors are commonly used for this purpose. These drugs act by inhibiting cell division and inducing cell death. The pharmacologic and clinical aspects of azathioprine, mycophenolate mofetil, and leflunomide are discussed in this review. [source] A double-blind, randomized, parallel group study to compare the efficacy, safety and tolerability of slow-release oral morphine versus methadone in opioid-dependent in-patients willing to undergo detoxificationADDICTION, Issue 9 2009Ekkehard Madlung-Kratzer ABSTRACT Aims Evaluation of the efficacy and safety of slow-release oral morphine (SROM) compared with methadone for detoxification from methadone and SROM maintenance treatment. Design Randomized, double-blind, double-dummy, comparative multi-centre study with parallel groups. Setting Three psychiatric hospitals in Austria specializing in in-patient detoxification. Participants Male and female opioid dependents (age > 18 years) willing to undergo detoxification from maintenance therapy in order to reach abstinence. Interventions Abstinence was reached from maintenance treatment by tapered dose reduction of either SROM or methadone over a period of 16 days. Measurements Efficacy analyses were based on the number of patients per treatment group completing the study, as well as on the control of signs and symptoms of withdrawal [measured using Short Opioid Withdrawal Scale (SOWS)] and suppression of opiate craving. In addition, self-reported somatic and psychic symptoms (measured using Symptom Checklist SCL-90-R) were monitored. Findings Of the 208 patients enrolled into the study, 202 were eligible for analysis (SROM: n = 102, methadone: n = 100). Completion rates were 51% in the SROM group and 49% in the methadone group [difference between groups: 2%; 95% confidence interval (CI): ,12% to 16%]. The rate of discontinuation in the study was high mainly because of patients voluntarily withdrawing from treatment. No statistically significant differences between treatment groups were found in terms of signs and symptoms of opiate withdrawal, craving for opiates or self-reported symptoms. SROM and methadone were both well tolerated. Conclusions Detoxification from maintenance treatment with tapered dose reduction of SROM is non-inferior to methadone. [source] Effectiveness of current treatment approaches for benzodiazepine discontinuation: a meta-analysisADDICTION, Issue 1 2009Jannette M. Parr ABSTRACT Aims To assess the effectiveness of current treatment approaches to assist benzodiazepine discontinuation. Methods A systematic review of approaches to benzodiazepine discontinuation in general practice and out-patient settings was undertaken. Routine care was compared with three treatment approaches: brief interventions, gradual dose reduction (GDR) and psychological interventions. GDR was compared with GDR plus psychological interventions or substitutive pharmacotherapies. Results Inclusion criteria were met by 24 studies, and a further eight were identified by future search. GDR [odds ratio (OR) = 5.96, confidence interval (CI) = 2.08,17.11] and brief interventions (OR = 4.37, CI = 2.28,8.40) provided superior cessation rates at post-treatment to routine care. Psychological treatment plus GDR were superior to both routine care (OR = 3.38, CI = 1.86,6.12) and GDR alone (OR = 1.82, CI = 1.25,2.67). However, substitutive pharmacotherapies did not add to the impact of GDR (OR = 1.30, CI = 0.97,1.73), and abrupt substitution of benzodiazepines by other pharmacotherapy was less effective than GDR alone (OR = 0.30, CI = 0.14,0.64). Few studies on any technique had significantly greater benzodiazepine discontinuation than controls at follow-up. Conclusions Providing an intervention is more effective than routine care. Psychological interventions may improve discontinuation above GDR alone. While some substitutive pharmacotherapies may have promise, current evidence is insufficient to support their use. [source] Once-per-cycle pegfilgrastim in breast cancer patients treated with docetaxel/epidoxorubicin/cyclophosphamideEUROPEAN JOURNAL OF CANCER CARE, Issue 2 2010L. MONTELLA md MONTELLA L., ADDEO R., GUARRASI R., CENNAMO G., FAIOLA V., CAPASSO E., CARAGLIA M. & DEL PRETE S. (2010) European Journal of Cancer Care19, 200,204 Once-per-cycle pegfilgrastim in breast cancer patients treated with docetaxel/epidoxorubicin/cyclophosphamide The incidence of neutropenia following combination chemotherapy is significant in breast cancer and impairs patients' quality of life. Colony-stimulating factors significantly decrease the risk of febrile neutropenia (FN). Aim of the present study was to assess the efficacy and safety profile of once-per-cycle pegfilgrastim in reducing FN in breast cancer patients treated with docetaxel (75 mg/m2), epidoxorubicin (75 mg/m2), cyclophosphamide (500 mg/m2) administered every 3 weeks. Thirty-five breast cancer patients were enrolled. Chemotherapy was administered in adjuvant, neoadjuvant and metastatic setting respectively in 26, 4 and 5 patients. Toxicity was monitored with programmed clinical evaluation and blood sampling. All patients completed the therapeutic programme consisting of six cycles for overall 210 cycles. The FN appeared in 6 out of 35 patients (17%), requiring dose reduction in 3 patients. Hypertransaminasemia was registered in two patients. In one patient pegfilgrastim administration was stopped because of skin hypersensititivity reaction. In conclusion, pegfilgrastim was able to maintain doses and timing of docetaxel/epidoxorubicin/cyclophosphamide in almost all breast cancer patients treated in this series. The reduced need for daily administration of colony-stimulating factors, blood sampling, antibiotic therapy and hospitalization has a significant impact in terms of both quality of life and pharmaco-economic evaluations. [source] Dialysate concentration and pharmacokinetics of 2F-Ara-A in a patient with acute renal failureEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2005Jan T. Kielstein Abstract:, Fludarabine is frequently used for treatment of B-cell chronic lymphocytic leukemia and in conditioning regimes for hematopoietic cell transplantations. The total body clearance of the principal metabolite 2-fluoro-ara-A (2F-Ara-A) correlates with the creatinine clearance. We report data on total dialysate concentration as well as pharmacokinetics of 2F-Ara-A in a patient with anuric acute renal failure. On three consecutive days the patient received a daily dose of 80 mg (40 mg/m2) fludarabine and underwent three consecutive extended (daily) dialysis (ED) sessions. ED removed a considerable amount of the drug. The average dialysis clearance was 33.85 ml/min which is about 25% of the clearance in patients without renal failure. No toxic side effects of the treatment were observed. This case suggests that fludarabine treatment can be considered in patients requiring dialysis if dose reduction and adequate removal of the drug by hemodialysis is provided. [source] Low dose erythropoietin-beta improves anemia and maintains ribavirin dose in chronic hepatitis C patients receiving combination therapy with ribavirin plus pegylated interferon Alfa-2bHEPATOLOGY RESEARCH, Issue 6 2009Kuo-Chih Tseng Aim:, Anemia during combination therapy with pegylated interferon alfa-2b plus ribavirin (RBV) for chronic hepatitis C virus (HCV) patients usually leads to RBV dose reduction or discontinuation. This study evaluated the effect of erythropoietin-beta (EPO-,) to maintain RBV dose and hemoglobin (Hb) level in chronic HCV patients treated with antiviral combination therapy. Methods:, Eighty-eight chronic HCV patients who developed anemia during therapy were enrolled into this retrospective study: 55 in the EPO-, group and 33 in the untreated group. The study endpoints were to assess the RBV maintenance and the changes in Hb. Results:, A higher percentage of patients with RBV maintenance was observed in the EPO-, group compared with the untreated group (nadir Hb level <10.5 g/dL; 70% vs. 38%, P = 0.020; nadir Hb < 10 g/dL; 62% vs. 27%, P = 0.046). The mean Hb change from week 12 to week 20 was higher in the EPO-, group when compared with the untreated group, especially for patients receiving a total EPO-, dose of more than 16 000 U (+0.70 g/dL vs. ,0.32 g/dL, P = 0.023) and of 10 000 U-14 000 U (+0.60 g/dL vs. ,0.32 g/dL, P = 0.023). Conclusions:, Low-dose EPO-, can maintain RBV dose and increase Hb levels in anemic chronic HCV patients receiving combination therapy. [source] Response of refractory colitis to intravenous or oral tacrolimus (FK506)INFLAMMATORY BOWEL DISEASES, Issue 5 2002Dr. Klaus Fellermann Abstract Intravenous cyclosporine has proven to be an alternative to emergency colectomy in steroid-refractory ulcerative colitis, whereas the experience with FK506 is limited. In this report we compare intravenous to oral FK506 treatment in 38 patients with refractory ulcerative (n = 33) or indeterminate (n = 5) colitis. FK506 was started intravenously in the first group (n = 18) at a dose of 0.01 to 0.02 mg/kg up to 14 days, followed by 0.1 to 0.2 mg/kg orally, or was started orally at this dose in a second group (n = 20). Additional azathioprine/6-mercaptopurine was given and steroids were tapered in responding patients, followed by a dose reduction of FK506. Clinical disease activity and laboratory parameters were assessed to evaluate efficacy and safety. Primary objectives were the induction of remission (Truelove index of mild) and colectomy-free survival. Treatment lasted for a mean of 7.6 months, and the mean observation period was 16.2 months. Eighteen of 38 patients improved within 14 days, and a complete remission was achieved in 13 patients after 1 month. A colectomy within 1 month was performed in 3 of 38 patients. The overall colectomy rate was 34%. One-half of the patients with a minimum follow-up of 2 years required a colectomy. Intravenous and per oral administration were equally safe and effective. The most frequent adverse events included tremor, hyperglycemia, hypertension, and infection, but none were severe. Renal impairment was rare and subsided upon drug withdrawal. In conclusion, FK506 is effective in the treatment of refractory colitis with per oral dosing being equivalent to intravenous administration. [source] Effect of an interdisciplinary educational program on antipsychotic prescribing among nursing home residents with dementiaINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 6 2008Johanne Monette Abstract Objective To assess the effect of an interdisciplinary educational program in reducing the use of antipsychotics in nursing home residents with dementia. Methods We conducted a longitudinal pilot study to test the implementation of a 7-month interdisciplinary educational program in a fixed cohort of residents with dementia receiving antipsychotics. The program included consciousness-raising, educational sessions, and clinical follow-up. Administrators, physicians, pharmacists, nursing staff, and personal care attendants were involved. The effect of the program was assessed over a 6-month period, in terms of the proportion of discontinuations and dose reductions of antipsychotics. Repeated measures for use of other psychotropics and restraints, frequency of disruptive behaviors, and stressful events experienced by nursing staff and personal care attendants were simultaneously assessed. Results Among the 81 residents still present at the end of the program, there were 40 (49.4%) discontinuations and 11 (13.6%) dose reductions. No significant changes were found in the use of other psychotropics, the use of restraints, or in the number of stressful events experienced by nursing staff and personal care attendants. The frequency of disruptive behaviors decreased significantly over the 6-month period (p,<,0.001). Conclusions Our interdisciplinary educational program led to a substantial reduction in the number of residents receiving antipsychotics and to a decrease in the frequency of disruptive behaviors. Our findings suggest that implementation of recognized practice guidelines could be an effective way to target residents who might not benefit from antipsychotics or who may tolerate a dose reduction. Copyright © 2007 John Wiley & Sons, Ltd. [source] Withdrawal of Fall-Risk-Increasing Drugs in Older Persons: Effect on Tilt-Table Test OutcomesJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 5 2007Nathalie Van Der Velde MD OBJECTIVES: To determine whether outcomes of tilt-table tests improved after withdrawal of fall-risk-increasing drugs (FRIDs). DESIGN: Prospective cohort study. SETTING: Geriatric outpatient clinic. PARTICIPANTS: Two hundred eleven new, consecutive outpatients, recruited from April 2003 until December 2004. MEASUREMENTS: Tilt-table testing was performed on all participants at baseline. Subsequently, FRIDs were withdrawn in all fallers in whom it was safely possible. At a mean follow-up of 6.7 months, tilt-table testing was repeated in 137 participants. Tilt-table testing addressed carotid sinus hypersensitivity (CSH), orthostatic hypotension (OH), and vasovagal collapse (VVC). Odds ratios (ORs) of tilt-table-test normalization according to withdrawal (discontinuation or dose reduction) of FRIDs were calculated using multivariate logistic regression analysis. RESULTS: After adjustment for confounders, the reduction of abnormal test outcomes (ORs) according to overall FRID withdrawal was 0.34 (95% confidence interval (CI)=0.06,1.86) for CSH, 0.35 (95% CI=0.13,0.99) for OH, and 0.27 (95% CI=0.02,3.31) for VVC. For the subgroup of cardiovascular FRIDs, the adjusted OR was 0.13 (95% CI=0.03,0.59) for CSH, 0.44 (95% CI=0.18,1.0) for OH, and 0.21 (95% CI=0.03,1.51) for VVC. CONCLUSION: OH improved significantly after withdrawal of FRIDs. Subgroup analysis of cardiovascular FRID withdrawal showed a significant reduction in OH and CSH. These results imply that FRID withdrawal can cause substantial improvement in cardiovascular homeostasis. Derangement of cardiovascular homeostasis may be an important mechanism by which FRID use results in falls. [source] Prospective study of short-term peginterferon-,-2a monotherapy in patients who had a virological response at 2 weeks after initiation of interferon therapyJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 4 2008Soocheol Jeong Abstract Background and Aims:, Long-term interferon (IFN) therapy is effective in eliminating hepatitis C virus (HCV). However, it carries the risk of adverse effects and reduced quality of life. To assess whether short-term IFN therapy effectively eliminates HCV, we performed a prospective pilot study of pegylated (peg)IFN-,-2a therapy for 8 or 24 weeks. Methods:, After excluding patients with high titers of genotype-1, 55 HCV patients received pegIFN-,-2a. Patients who became negative for HCV-RNA at week 2 were allocated to either an 8-week (n = 19) or 24-week (n = 15) course of IFN. We evaluated the efficacy of and tolerance to IFN therapy. Results:, The sustained virological response rate was excellent in the two groups (8 weeks, 89.5% [17/19]; 24 weeks, 100% [15/15], respectively,). IFN dose reduction was required in one patient of the 8-week group, but in six patients of the 24-week group (P = 0.028). Treatment was completed by all patients of the 8-week group, but discontinued in five patients of the 24-week group (P = 0.011). Conclusions:, The 8-week IFN therapy is more tolerable than the 24-week therapy and had similar outcomes. Excluding the patients with high titers of genotype-1, we recommend switching to an 8-week course of pegIFN-, monotherapy once patients show an ultra rapid virological response at week 2 from the start of IFN therapy. [source] Sustained low-dose growth hormone therapy optimizes bioactive insulin-like growth factor-I level and may enhance CD4 T-cell number in HIV infectionJOURNAL OF MEDICAL VIROLOGY, Issue 2 2010Ove Andersen Abstract High-dose recombinant human growth hormone (rhGH) (2,6,mg/day) regimes may facilitate T-cell restoration in patients infected with human immunodeficiency virus (HIV) on highly active antiretroviral therapy (HAART). However, high-dose rhGH regimens increase insulin-like growth factor-I (IGF-I) to supra-physiological levels associated with severe side effects. The present study investigated whether lower doses of rhGH may improve T-cell restoration in patients infected with HIV following an expedient response of total and bioactive (i.e., free) IGF-I. A previous 16-week pilot-study included six HIV-infected patients on stable HAART to receive rhGH 0.7,mg/day, which increased total (+117%, P,<,0.01) and free (+155%, P,<,0.01) IGF-I levels. The study was extended to examine whether continuous use of low-dose rhGH (0.7,mg/day until week 60; 0.4,mg/day from week 60 to week 140) would maintain expedient IGF-I levels and improve CD4 T-cell response. Total and free IGF-I increased at week 36 (+97%, P,<,0.01 and +125%, P,<,0.01, respectively) and week 60 (+77%, P,=,0.01 and +125%, P,<,0.01) compared to baseline levels (161,±,15 and 0.75,±,0.11,µg/L). CD4 T-cell number increased at week 36 (+15%, P,<,0.05) and week 60 (+31%, P,=,0.01) compared to baseline levels (456,±,55,cells/µL). Following rhGH dose reduction, total IGF-I and CD4 T-cell number remained increased at week 88 (+44%, P,=,0.01 and +33%, P,<,0.01) and week 140 (+46%, P,=,0.07 and +36%, P,=,0.02) compared to baseline levels. These data support the notion that low-dose rhGH regimens may increase expediently total and bioactive IGF-I and improve T-cell restoration in patients infected with HIV on HAART. J. Med. Virol. 82:197,205, 2010. © 2009 Wiley-Liss, Inc. [source] Tolerability of Gemcitabine and Carboplatin Doublet Therapy in Cats with CarcinomasJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 3 2009I. Martinez-Ruzafa Background: This study was performed to determine the toxicity of gemcitabine-carboplatin doublet therapy in cats with carcinomas. Hypothesis: Gemcitabine and carboplatin are safe in tumor-bearing cats. Animals: Twenty cats with spontaneously occurring carcinomas. Methods: A cohort of 6 cats received gemcitabine (2 mg/kg IV) on days 1, 8, and 15 and carboplatin (10 mg/kg IV) immediately after gemcitabine on day 1 of a 21-day cycle. A 2nd cohort of 14 cats received carboplatin 4 hours after gemcitabine on day 1 and gemcitabine on day 8 but not day 15. The cycles were repeated every 21 days. Results: Cats in the 1st cohort received a median of 3.75 cycles per animal (range, 1,6). Two cats (33.3%) developed grade 3 or 4 neutropenia, 1 (16.7%) grade 4 thrombocytopenia, and 1 (16.7%) grade 3 gastrointestinal toxicity. Gemcitabine dose reductions and treatment delays occurred in 1 and 4 cats, respectively. Cats in the 2nd cohort received a median of 2 cycles per animal (range, 0.5,10). Two cats (14.3%) had grade 3 or 4 neutropenia and 1 (7.1%) had grade 3 and 4 gastrointestinal toxicity. One cat required gemcitabine dose reduction and 6 had treatment delays. In the 2nd cohort, of 11 cats with measurable tumors, there was 1 complete response (pancreatic carcinoma) and 1 partial response (squamous cell carcinoma, receiving concurrent nonsteroidal anti-inflammatory drugs). Conclusions and Clinical Importance: Gemcitabine-carboplatin combination appears moderately well tolerated in tumor-bearing cats. Minimal patient benefit suggests that alternative schedules or combinations of gemcitabine with other agents should be explored. [source] Recombinant Human Thyrotropin Administration Enhances Thyroid Uptake of Radioactive Iodine in Hyperthyroid CatsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 6 2008I. Van Hoek Background: Hyperthyroidism is the most diagnosed endocrine disorder in cats and radioiodine (131I) is the treatment of choice. The dose emission rate and radioactivity in urine, saliva, and on hair and paws are determined by the dose of administered 131I. A dose reduction of therapeutic 131I could possibly be achieved after recombinant human thyrotropin (rhTSH) administration as in humans with nodular goiter. Hypothesis: rhTSH will increase radioiodine uptake in hyperthyroid cats. Animals: Five hyperthyroid cats. Methods: Twenty-five micrograms rhTSH (day 1) or 2 mL 0.9% sodium chloride (NaCl) (day 9) was injected IV. One hour later, 11.4 ± 4.1 (mean ± SD) MBq 123I was injected IV. Radioactive iodine uptake (RAIU) was measured 6, 12, and 24 hours after rhTSH (RAIU-rhTSH) or NaCl (RAIU-blanco) injection. Blood samples for measurement of TT4 were taken before injection of rhTSH or NaCl (TT40) and at the time of imaging. Results: Percentages of RAIU-rhTSH (and RAIU-blanco) at 6, 12, and 24 hours after administration of rhTSH were 34 ± 18 (31 ± 21), 46 ± 20 (38 ± 18), and 47 ± 15 (36 ± 14). There was a statistically significant effect of rhTSH administration on RAIU (P= .043) but not on serum TT4 concentration. Baseline serum TT40 concentration influenced RAIU-rhTSH significantly at 6 hours (P= .037). Conclusion and Clinical Importance: The increased RAIU observed after rhTSH administration in hyperthyroid cats could lead to a lower therapeutic dose of 131I after rhTSH administration in hyperthyroid cats and decreased risk of environmental and owner contamination during and after hospitalization. [source] Efficacy and Toxicosis of VELCAP-C Treatment of Lymphoma in CatsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 1 2008A.G. Hadden Background: Lymphoma is the most common malignancy affecting cats. A protocol employing vincristine, l -asparaginase, cyclophosphamide, doxorubicin, and prednisone (VELCAP-S) is effective and well tolerated in dogs with lymphoma. A 24-week variation of this protocol (VELCAP-C) was developed for treatment of cats. Hypothesis: That VELCAP-C will result in survival times for cats with lymphoma that are similar to those obtained when cats are treated with a protocol that includes fewer chemotherapy agents. Animals: Sixty-one cats with lymphoma. Methods: Retrospective study. Outcomes evaluated were response to VELCAP-C therapy, toxicosis, and survival time. The effect of signalment, staging, CBC, and serum chemistry profile and dosage on these outcomes was examined. Results: Six cats (10%) completed the protocol with a median survival of 1189 days. Forty-three percent (23 of 61) of the cats achieved complete response (CR) with a median survival time of 62 days. Cats that required a dose reduction of any drug during induction were more likely to achieve CR. Weight loss and hepatomegaly at diagnosis were negatively associated with response to treatment. Increased lactate dehydrogenase (LDH) serum activity at the time of initial treatment correlated with decreased survival times. Conclusions and Clinical Importance: This multi agent protocol did not provide improved survival over historical data using protocols with fewer agents. Serum LDH activity levels might provide useful prognostic information for cats with lymphoma. [source] Definition and management of anemia in patients infected with hepatitis C virusLIVER INTERNATIONAL, Issue 4 2006John G. McHutchison Abstract: Chronic infection with hepatitis C virus (HCV) can progress to cirrhosis, hepatocellular carcinoma, and end-stage liver disease. The current best treatment for HCV infection is combination therapy with pegylated interferon and ribavirin. Although this regimen produces sustained virologic responses (SVRs) in approximately 50% of patients, it can be associated with a potentially dose-limiting hemolytic anemia. Hemoglobin concentrations decrease mainly as a result of ribavirin-induced hemolysis, and this anemia can be problematic in patients with HCV infection, especially those who have comorbid renal or cardiovascular disorders. In general, anemia can increase the risk of morbidity and mortality, and may have negative effects on cerebral function and quality of life. Although ribavirin-associated anemia can be reversed by dose reduction or discontinuation, this approach compromises outcomes by significantly decreasing SVR rates. Recombinant human erythropoietin has been used to manage ribavirin-associated anemia but has other potential disadvantages. Viramidine, a liver-targeting prodrug of ribavirin, has the potential to maintain the virologic efficacy of ribavirin while decreasing the risk of hemolytic anemia in patients with chronic hepatitis C. [source] C2 monitoring of cyclosporine in de novo liver transplant recipients: The clinician's perspectiveLIVER TRANSPLANTATION, Issue 5 2004Federico Villamil Adjusting cyclosporine (CsA) dose based on blood concentration at 2 hours after dose (C2) has been shown in prospective clinical trials to reduce the risk of rejection compared with conventional trough monitoring. In addition, it provides equivalent efficacy to tacrolimus in liver transplant patients, with a favorable safety profile. Target C2 should be defined on an individual basis depending on adjunctive therapy and the level of exposure required. It appears less critical to achieve target C2 in the first few days after liver transplantation than was previously believed. Achieving target C2 exposure in the initial period after transplant requires that changes in the proportion of cyclosporine absorbed from the gut be taken into account to avoid risk of overexposure. In addition, if a starting dose of 10,15 mg/day is used, it is advisable to delay increasing the dose until a trend in C2 level indicates this to be necessary. Immediate dose reduction is required if C2 exceeds target range. In patients with low C2 values, cyclosporine concentration at a later time point should be measured to establish whether the patient is a poor absorber or a delayed absorber of C2, and dose adjustments should be undertaken accordingly. In conclusion, this more flexible approach to C2 monitoring allows the dose of cyclosporine to be individualized effectively for each patient, which results in significant efficacy benefits while minimizing the risk of toxicity. (Liver Transpl 2004;10:577,583.) [source] Changes in arterial oxygen tension when weaning neonates from inhaled nitric oxide,,PEDIATRIC PULMONOLOGY, Issue 1 2001Gregory M. Sokol MD Abstract We set out to evaluate changes in arterial oxygen tension (PaO2) when weaning neonates from inhaled nitric oxide (INO). We reviewed the records of 505 prospectively collected INO weaning attempts on 84 neonates with hypoxic respiratory failure. PaO2 values before and 30 min after weaning attempts were recorded. Relationships between change in PaO2 and decreases in INO concentrations were investigated using regression analysis and ANOVA. PaO2 decreased (,18.7,±,1.8 torr; P,<,0.001); when weaning INO. A stepwise decline in PaO2 was observed weaning INO from 40 ppm. The greatest decline occurred when INO was discontinued (,42.1,±,4.1 torr). Forward stepwise multiple regression using variables with significant relationships to the decline in PaO2 identified the specific dose reduction 7(P,<,0.001), the prewean PaO2 (P,<,0.001), and surfactant therapy (P,=,0.018) as the variables best describing the change in PaO2(P,=,0.004, r,=,0.51). In conclusion, a graded decline in PaO2 occurs when reducing INO. INO should be weaned to less than 1 ppm before discontinuing its use. Prior surfactant treatment appears to enhance the oxygenation reserve when weaning INO. Pediatr Pulmonol. 2001; 32:14,19. © 2001 Wiley-Liss,Inc. [source] Cardiac tamponade in a pediatric renal transplant recipient on sirolimus therapyPEDIATRIC TRANSPLANTATION, Issue 4 2005Uyen Truong Abstract:, Because of its lack of nephrotoxicity, the use of sirolimus, as an immunosuppressive agent, has increased considerably in solid-organ transplant (Tx) recipients. With its increased use, Tx professionals are encountering a variety of previously unreported side-effects such as angioedema and interstitial pneumonitis. We describe here the case of a pediatric renal Tx recipient who, while receiving sirolimus, developed a large pericardial effusion requiring pericardiocentesis. An extensive workup for an infectious etiology was performed; the only positive result was isolation of adenovirus type 2 from the patient's stool specimen. Following sirolimus dose reduction this child's effusion stabilized and has not recurred. The purpose of this report is to advise health-care professionals caring for Tx recipients about this potentially life-threatening complication associated with sirolimus. The role of adenovirus, if any, in contributing to the development of our patient's pericardial effusion is discussed herein. [source] Increased risk of hip fracture in the elderly associated with prochlorperazine: is a prescribing cascade contributing?,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 9 2010Gillian E. Caughey Abstract Purpose To examine the prescribing of prochlorperazine secondary to the prescribing of a medicine which could lead to symptoms for which prochlorperazine is indicated and commonly used. Given the range of potential hypotensive, sedative, dystonic and other extra-pyramidal side effects associated with prochlorperazine, its association with hip fracture was also examined. Methods Prescription/event sequence symmetry analyses were undertaken from 1st January 2003 to 31st December 2006, using administrative claims data from the Department of Veterans' Affairs, Australia. This method assesses asymmetry in the distribution of an incident event (either prescription of another medicine or hospitalization) before and after the initiation of prochlorperazine. Crude and adjusted sequence ratios (ASR) with 95% confidence intervals (CI) were calculated. Results A total of 34,235 persons with incident use of prochlorperazine were identified during the study period. Statistically significant positive associations were found for a number of commonly used medicines, including cardiovascular medicines, NSAIDs, opioids and sedatives and the subsequent initiation of prochlorperazine that ranged from 1.07 (95%CI 1.01,1.14) for diuretics to 1.50 (95%CI 1.40,1.61) for statins. Prescription event analysis showed a 49% (95%CI 1.19,1.86) increased risk of hospitalisation for hip fracture following dispensing of prochlorperazine. Conclusions Prescribers should consider the possible contributing role of newly initiated medicines with the potential to cause of dizziness, and where possible address this through dose reduction or cessation of the medicine, rather than prescribing prochlorperazine. Copyright © 2010 John Wiley & Sons, Ltd. [source] Impact of Cyclosporine Reduction With MMF: A Randomized Trial in Chronic Allograft Dysfunction.AMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2006Reference' Study Long-term use of calcineurine inhibitors (CNIs) may contribute to the development of chronic allograft dysfunction (CAD). We investigate the impact of the introduction of MMF combined with cyclosporine (CsA) 50% dose reduction. An open, randomized, controlled, multicenter, prospective study was conducted in 103 patients, receiving a CsA-based therapy with a serum creatinine between 1.7,3.4 mg/dL, more than 1 year after transplantation. They were randomized to receive MMF with half dose of CsA (MMF group) or to continue their maintenance CsA dose (control group). A total of 96 weeks after randomization, the evolution of renal function assessed by regression line analysis of 1/SeCr improved in the MMF group (positive slope) vs. the control group (negative slope), 4.2 × 10,4 vs. ,3.0 × 10,4, respectively (p < 0.001). Concurrently, the absolute renal function improved significantly in the MMF group. No episode of biopsy-proven acute rejection occurred. One patient in each group lost his graft because of biopsy-proven chronic allograft nephropathy. There was a significant decrease of triglycerides level in the MMF group. Anemia and diarrhea were statistically more frequent in the MMF group. In CAD, the reduction of CsA in the presence of MMF results in significant improvement in renal function during a 2-year follow-up. [source] Dose rounding of chemotherapy in colorectal cancer: An analysis of clinician attitudes and the potential impact on treatment costsASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 3 2010Kathryn FIELD Abstract Aim: The aims of this study were to calculate theoretical cost savings of oxaliplatin dose rounding in colorectal cancer (CRC), and to assess clinician attitudes to chemotherapy dose rounding. Methods: Data were obtained from a prospective data repository (BioGrid Australia) from four hospitals regarding the use of oxaliplatin, given at a standard dose of 85 mg/m2. We examined potential cost savings for patients with a body surface area (BSA) between 1.77 m2 and 1.94 m2, resulting in a calculated dose up to 10% above 150 mg (a 100 mg and 50 mg vial). The attitudes of oncologists at these hospitals toward minor dose reductions were assessed. Results: From January 2003 to June 2008, of 676 patients with Stages III or IV CRC, 227 (33.58%) received oxaliplatin. Overall 66 patients (29%) had a calculated BSA between 1.77 m2 and 1.94 m2. The potential cost saving for these hospitals in one year, if oxaliplatin doses were rounded down to 150 mg, is $AU51 898. Extrapolated to the Australian population, estimated savings are over $AU2.5 million per year. Three of nine (33.3%) oncologists were comfortable with an initial dose reduction of up to 10% in the adjuvant disease setting, and seven of nine (77.8%) in the setting of metastatic disease. Conclusion: Minor dose reductions for CRC to accommodate vial sizes would lead to significant cost savings. Oncologists are more comfortable with minor dose reductions when treatment is given in a palliative setting. [source] Reversible encephalopathy following 5-fluorouracil-based chemotherapy in patients with dihydropyrimidine dehyrogenase deficiencyASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 3 2009Dong Wook KIM 5-fluorouracil (5-FU) is one of the most frequently used chemotherapy agents for the treatment of a number of solid cancers. We report two patients with advanced gastric cancer who developed acute encephalopathy after receiving chemotherapy composed of 5-FU and oxaliplatin. One patient presented with altered consciousness and the other with generalized tonic clonic seizure. 5-FU-induced encephalopathy was suspected by clinical, radiological and electroencephalographic findings, and both patients had reduced expression of dihyropyrimidine dehydrogenase, the rate-limiting enzyme responsible for the catabolism of 5-FU. The neurological symptoms improved spontaneously, and did not recur in the following cycle of chemotherapy with the administration of a reduced dose of 5-FU. We suggest that the early recognition of this adverse event can reverse 5-FU-induced neurological symptoms and a dose reduction of the offending drug can prevent the recurrence of 5-FU induced encephalopathy. [source] Low molecular weight heparin (dalteparin) for the treatment of venous thromboembolism in pregnancyBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 2 2003Anne Flem Jacobsen Objective To evaluate the effect and dose of dalteparin given to pregnant women with acute venous thromboembolism. Design An observational study of pregnant women in Norway. Setting Delivery and haematological departments in Norway. Population Twenty women, aged 22,41 years, with acute venous thromboembolism verified by objective means. Methods Patients were treated with dalteparin from diagnosis until delivery. Treatment was monitored with anti-activated factor Xa (anti-Xa) activity, and the dose was adjusted to achieve target 0.5,1.0 U/mL 2,3 hours post-injection. Main outcome measure Anti-Xa activity and side effects. Result None of the patients suffered recurrent venous thromboembolism or major bleeding complications. In 9 of 13 women starting with conventional dose of dalteparin (100 iu/kg bd), dose escalation was necessary to reach target anti-Xa activity. None of the six women who started with 105,118 iu/kg bd required dose escalation. One woman who started with 133 iu/kg bd required dose reduction. Bioaccumulation of dalteparin was not observed. Conclusion Our study suggests that dalteparin may be used for the treatment of acute venous thromboembolism in pregnancy. Approximately 10,20% higher doses of dalteparin may be needed as compared with non-pregnant individuals. [source] Population pharmacokinetic analysis of varenicline in adult smokersBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 5 2009Patanjali Ravva WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT? , Several clinical pharmacology studies have characterized the pharmacokinetics of varenicline in young adult and elderly smokers and subjects with impaired renal function. , Varenicline pharmacokinetics is linear over the recommended dose range. , Varenicline total clearance is linearly related to its renal clearance. , Both are progressively reduced as renal function declines, which results in a progressive increase in varenicline systemic exposure and prolonged half-life. WHAT THIS STUDY ADDS? , This work provides an integrated model-based analysis of varenicline pharmacokinetics across multiple studies in the target patient population. , The model describes the impact of patient-specific covariates, such as renal function, and provides a rationale for dose adjustment. , The resulting model also provides a means to predict individual-specific drug exposures to clinical responses in subsequent analyses. AIMS To characterize the population pharmacokinetics of varenicline and identify factors leading to its exposure variability in adult smokers. METHODS Data were pooled from nine clinical studies consisting of 1878 subjects. Models were developed to describe concentration,time profiles across individuals. Covariates were assessed using a full model approach; parameters and bootstrap 95% confidence intervals (CI) were estimated using nonlinear mixed effects modelling. RESULTS A two-compartment model with first-order absorption and elimination best described varenicline pharmacokinetics. The final population parameter estimates (95% CI) were: CL/F, 10.4 l h,1 (10.2, 10.6); V2/F, 337 l (309, 364); V3/F, 78.1 l (61.9, 98.9); Q/F, 2.08 l h,1 (1.39, 3.79); Ka, 1.69 h,1 (1.27, 2.00); and Alag, 0.43 h (0.37, 0.46). Random interindividual variances were estimated for Ka[70% coefficient of variation (CV)], CL/F (25% CV), and V2/F (50% CV) using a block covariance matrix. Fixed effect parameters were precisely estimated [most with % relative standard error < 10 and all with % relative standard error < 25], and a visual predictive check indicated adequate model performance. CL/F decreased from 10.4 l h,1 for a typical subject with normal renal function (CLcr = 100 ml min,1) to 4.4 l h,1 for a typical subject with severe renal impairment (CLcr = 20 ml min,1), which corresponds to a 2.4-fold increase in daily steady-state exposure. Bodyweight was the primary predictor of variability in volume of distribution. After accounting for renal function, there was no apparent effect of age, gender or race on varenicline pharmacokinetics. CONCLUSIONS Renal function is the clinically important factor leading to interindividual variability in varenicline exposure. A dose reduction to 1 mg day,1, which is half the recommended dose, is indicated for subjects with severe renal impairment. [source] | |||||||||||||||||||||||||||||||||||||