Home About us Contact
|
Home About us Contact | ||
|
|
||
Treatment Duration (treatment + duration)
Kinds of Treatment Duration Selected AbstractsEstimating Mean Response as a Function of Treatment Duration in an Observational Study, Where Duration May Be Informatively CensoredBIOMETRICS, Issue 2 2004Brent A. Johnson Summary. After a treatment is found to be effective in a clinical study, attention often focuses on the effect of treatment duration on outcome. Such an analysis facilitates recommendations on the most beneficial treatment duration. In many studies, the treatment duration, within certain limits, is left to the discretion of the investigators. It is often the case that treatment must be terminated prematurely due to an adverse event, in which case a recommended treatment duration is part of a policy that treats patients for a specified length of time or until a treatment-censoring event occurs, whichever comes first. Evaluating mean response for a particular treatment-duration policy from observational data is difficult due to censoring and the fact that it may not be reasonable to assume patients are prognostically similar across all treatment strategies. We propose an estimator for mean response as a function of treatment-duration policy under these conditions. The method uses potential outcomes and embodies assumptions that allow consistent estimation of the mean response. The estimator is evaluated through simulation studies and demonstrated by application to the ESPRIT infusion trial coordinated at Duke University Medical Center. [source] Treatment duration in acute hepatitis C: The issue is not solved yet,HEPATOLOGY, Issue 4 2006Heiner Wedemeyer M.D. No abstract is available for this article. [source] MMPI Profile as an Outcome "Predictor" in the Treatment of Noncancer Pain Patients Utilizing Intraspinal Opioid TherapyNEUROMODULATION, Issue 3 2001Daniel M. Doleys PhD Objective. To evaluate changes in Minnesota Multiphasic Personality Inventory (MMPI) profiles pre- and post-treatment involving intrathecal opioid therapy. Patients and Methods. This study reports on 30 patients that were evaluated pre- and post-intraspinal opioid therapy. Treatment duration was slightly more than four years. Each patient experienced chronic non-cancer pain deemed suitable for trialing and subsequent implantation of a drug administration system (DAS). On average the patients had experienced pain for 8.4 years and had a mean of 3.2 pain-related surgeries. Results. The patients could be divided into "positive change group" and "negative change group" based upon pre- and post-treatment MMPI profiles. Those patients in the negative change group had more "normal profiles" pretreatment. This group evidenced less reduction in pain and was found to be using slightly higher levels of intraspinal opioids. Conclusions. These results would suggest that the MMPI profile may not be a good "predictor" of long-term outcome utilizing intraspinal opioid therapy. Indeed, patients with the more normal profile pretreatment did not fare as well as those with the more elevated profile. A positive change in MMPI profile from pre- to post-treatment was associated with a higher level of pain reduction. Patient selection therefore should be based not on a single test such as the MMPI, but on consistency across multiple sources of information including physical examination, complaints of pain and disability, behavioral observations, and psychological testing. [source] Initial testing of the aurora kinase a inhibitor MLN8237 by the Pediatric Preclinical Testing Program (PPTP),PEDIATRIC BLOOD & CANCER, Issue 1 2010John M. Maris MD Abstract Background MLN8237 is a small molecule inhibitor of Aurora Kinase A (AURKA) that is currently in early phase clinical testing. AURKA plays a pivotal role in centrosome maturation and spindle formation during mitosis. Procedures MLN8237 was tested against the Pediatric Preclinical Testing Program (PPTP) in vitro panel at concentrations ranging from 1.0,nM to 10,µM and was tested against the PPTP in vivo panels at a dose of 20,mg/kg administered orally twice daily,×,5 days. Treatment duration was 6 weeks for solid tumor xenografts and 3 weeks for ALL xenografts. Results MLN8237 had a median IC50 of 61,nM against the PPTP in vitro panel. The ALL cell lines were more sensitive and the rhabdomyosarcoma cell lines less sensitive than the remaining PPTP cell lines. In vivo, MLN8237 induced significant differences in event-free survival (EFS) distributions compared to controls in 32/40 (80%) solid tumor models and all (6/6) ALL models. Maintained complete responses (CRs) were observed in 3 of 7 neuroblastoma xenografts, and all 6 evaluable ALL xenografts achieved CR (n,=,4) or maintained CR (n,=,2) status. Maintained CRs were observed among single xenografts in other panels, including the Wilms tumor, rhabdoid tumor, rhabdomyosarcoma, Ewing sarcoma, osteosarcoma, and medulloblastoma. Conclusions The in vivo activity observed against the neuroblastoma panel far exceeds that observed for standard agents evaluated against the panel by the PPTP. High levels of in vivo activity were also observed against the ALL xenograft panel. These data support expedited clinical development of MLN8237 in childhood cancer. Pediatr Blood Cancer 2010;55:26,34. © 2010 Wiley-Liss, Inc. [source] Patients' help-seeking behaviours for health problems associated with methadone and buprenorphine treatmentDRUG AND ALCOHOL REVIEW, Issue 4 2008ADAM R. WINSTOCK Abstract Introduction and Aims. Clients in opioid substitution therapy often have considerable unmet health-care needs. The current study aimed to explore health problems related to opioid substitution therapy among clients on methadone and buprenorphine treatment. Design and Methods. A self-complete, cross-sectional survey conducted among 508 patients receiving methadone and buprenorphine treatment at community pharmacies in New South Wales (NSW), Australia. Results. The most common problems for which participants had ever sought help were dental (29.9%), constipation (25.0%) and headache (24.0%). The most common problems for which participants would currently like help were dental (41.1%), sweating (26.4%) and reduced sexual enjoyment (24.2%). There were no significant differences between those currently on methadone and those currently on buprenorphine for any of the health problems explored, nor differences for gender or treatment duration. Participants on methadone doses 100 mg or above were significantly more likely to want help currently for sedation. Discussion and Conclusions. The considerable unmet health care needs among participants in this study suggest that treatment providers should consider improving the detection and response to common health problems related to opioid substitution therapy. [source] Pregabalin, tiapride and lorazepam in alcohol withdrawal syndrome: a multi-centre, randomized, single-blind comparison trialADDICTION, Issue 2 2010Giovanni Martinotti ABSTRACT Introduction The aim of this trial was to compare lorazepam with non-benzodiazepine medications such as pregabalin and tiapride in the treatment of alcohol withdrawal syndrome (AWS). These drugs were chosen for their inhibitorial effects on the hypersecretion of neurotransmitters usually observed in AWS. Craving reduction and improvement of psychiatric symptoms were the secondary end-points. Methods One hundred and ninety subjects affected by current alcohol dependence were considered consecutively: 111 were enrolled and divided into three groups of 37 subjects each. Within a treatment duration of 14 days, medication was given up to the following maximum doses (pregabalin 450 mg/day; tiapride 800 mg/day; lorazepam 10 mg/day). Withdrawal (CIWA-Ar), craving [visual analogue scale (VAS); Obsessive and Compulsive Drinking Scale (OCDS)], psychiatric symptoms [Symptom Check List 90 Revised (SCL-90-R)] and quality of life (QL-index) rating scales were applied. Results On the CIWA-Ar score, all the groups showed a significant reduction between times (P < 0.001) with a higher reduction for the pregabalin group (P < 0.01) on items regarding headache and orientation. Retention in treatment was lower in the tiapride group (P < 0.05), while the number of subjects remaining alcohol free was higher in the pregabalin group (P < 0.05). Significant reduction between baseline and the end of the treatment was found in all the groups at the OCDS and the VAS for craving, at the SCL-90-R and QL-index (P < 0.001). Discussion All the medications in the trial showed evidence of safety and efficacy in the treatment of uncomplicated forms of AWS, with some particular differences. The efficacy of pregabalin was superior to that of tiapride, used largely in research trials and, for some measures, to that of the ,gold standard', lorazepam. Accordingly, pregabalin may be considered as a potentially useful new drug for treatment of AWS, deserving further investigation. [source] A Dutch day treatment program for anorexia and bulimia nervosa in comparison with internationally described programsEUROPEAN EATING DISORDERS REVIEW, Issue 2 2007M. W. Lammers Abstract A Dutch day treatment program for patients with anorexia and bulimia nervosa is described and compared to intensive day treatment programs for patients with eating disorders outlined in international literature. The 5-day program is described in terms of its general characteristics, intended outcome and specific treatment interventions. Along these parameters it is compared to the programs found in a systematic literature search of day hospitalization programs for eating disorders. Global inspection shows a lot of similarities between all the programs. Looking more closely, also many important differences exist (concerning, e.g. treatment duration, intensity of treatment, theoretical orientation, goals of treatment and weight gain regime). Because of the differences, it is hard to compare outcome data between centres. Besides, on many of these dimensions, the literature does not yet tell us unambiguously what is best for our patients. Therefore, it is necessary to keep the dialogue between treatment centres going. Copyright © 2007 John Wiley & Sons, Ltd and Eating Disorders Association. [source] Individualized treatment strategy according to early viral kinetics in hepatitis C virus type 1,infected patients,,HEPATOLOGY, Issue 2 2009Thomas Berg Individualized treatment on the basis of early viral kinetics has been discussed to optimize antiviral therapy in chronic hepatitis C virus (HCV) infection. Individually tailored reduction in treatment duration in HCV type 1,infected patients represents one possible strategy. Four hundred thirty-three patients were randomly assigned to receive either 1.5 ,g/kg peginterferon alfa-2b weekly plus 800-1,400 mg ribavirin daily for 48 weeks (n = 225, group A) or an individually tailored treatment duration (18-48 weeks; n = 208, group B). In the latter group, treatment duration was calculated using the time required to induce HCV RNA negativity (branched DNA [bDNA] assay; sensitivity limit, 615 IU/mL) multiplied by the factor 6. All bDNA negative samples were retested with the more sensitive transcription-mediated amplification (TMA) assay (sensitivity limit, 5.3 IU/mL). Sustained virologic response (SVR) rates were significantly lower in group B (34.6% versus 48.0% [P = 0.005]) due to higher relapse rates (32.7% versus 14.2% [P< 0.0005]). Important predictors of response were the levels of baseline viremia as well as the time to TMA negativity on treatment. Taking the simultaneous presence of low baseline viral load (<800,000 IU/mL) and a negative TMA test within the first 4 weeks as predictors for treatment response, SVR rates were comparable between both treatment schedules with an SVR probability of >80% obtained in patients treated for only 18 or 24 weeks. Conclusion: The individualized treatment strategy according to time to bDNA negativity failed to provide comparable efficacy compared with the standard of care. The inferiority of the individualized protocol may be explained by the use of a less sensitive HCV RNA assay, and also by underestimation of the importance of baseline viremia. (HEPATOLOGY 2009.) [source] Benefits and risks of interferon therapy for hepatitis B,HEPATOLOGY, Issue S5 2009Robert Perrillo Alpha interferon is the only licensed drug for hepatitis B with immunomodulatory as well as viral inhibitory properties. Potential advantages of interferon compared to nucleoside analogs include a lack of drug resistance, a finite and defined treatment course, and a higher likelihood for hepatitis B surface antigen (HBsAg) clearance. Approximately 30% of hepatitis B e antigen (HBeAg)-positive and 40% of HBeAg-negative cases have a sustained virological response (when defined as HBeAg seroconversion and/or hepatitis B virus (HBV) DNA levels below 20,000 copies/mL, respectively) 6 months after completion of a 48-week course of peginterferon alfa-2a These responses remain durable in 80% and 50% of cases, respectively, when evaluated several years later. Recent studies have shown that changes in HBsAg and HBeAg concentration during treatment predict sustained virological response and serial monitoring of HBsAg is helpful in predicting HBsAg clearance. HBeAg-positive patients with genotype A have higher rates of HBeAg and HBsAg clearance, whereas HBeAg-negative patients with genotype D have the lowest rate of response to interferon therapy. Long-term follow-up of virological responders to either standard alpha interferon or peginterferon has demonstrated a progressive increase in the rate of HBsAg clearance, particularly in patients who were initially HBeAg-positive. Future studies need to address if specific virological benchmarks during therapy can be used to tailor treatment duration. Conclusion: Peginterferon alfa has a place as first-line therapy of hepatitis B in patients who are carefully selected on the basis of pretreatment serum HBV DNA and aminotransferase levels, safety considerations, and viral genotype. (HEPATOLOGY 2009;49:S103,S111.) [source] Determinants of relapse after a short (12 weeks) course of antiviral therapy and re-treatment efficacy of a prolonged course in patients with chronic hepatitis C virus genotype 2 or 3 infection,HEPATOLOGY, Issue 2 2009Alessandra Mangia In hepatitis C virus (HCV) genotypes 2 and 3 patients, the high rate of relapse after 12 to 16 weeks of antiviral therapy is the main concern for shortening treatment duration. This study was undertaken to delineate predictors of relapse after short treatment in patients with undetectable HCV RNA at treatment week 4 (RVR), and to report in RVR patients with relapse the sustained virological response (SVR) after a second 24-week course of therapy. RVR patients received pegylated interferon (Peg-IFN) alfa-2b (1.5 ,g/kg) and ribavirin (1000-1200 mg/day) for 12 weeks; those who relapsed were re-treated with the same drug doses but for the extended standard duration of 24 weeks. Logistic regression analysis was applied to delineate predictors of relapse by using age, sex, route of transmission, body mass index (BMI), serum alanine aminotransferase (ALT), HCV genotypes, serum HCV RNA levels, and platelet counts as covariates. Of 718 patients with genotypes 2 and 3 who were started on therapy, 496 (69.1%) had undetectable HCV RNA at week 4. Of them, 409 patients (82.5%, CI 79.1-85.8) attained SVR, and 67 (14.1%, CI 10.4-16.5) relapsed. At regression analysis, only platelet count less than 140,000 mm3 [odds ratio, 2.51; confidence interval (CI), 1.49-4.20] and BMI 30 or higher (odds ratio, 1.7; CI, 1.03-2.70) were independently associated with relapse. Forty-three of 67 patients with relapse agreed to be re-treated, and an SVR was achieved in 30 (70.0%) of them. Conclusion: We recommend 12 weeks course of therapy for patients with undetectable HCV RNA at treatment week 4, providing they present with no advanced fibrosis and low BMI. (HEPATOLOGY 2008.) [source] Two week induction of interferon-beta followed by pegylated interferon alpha-2b and ribavirin for chronic infection with hepatitis CHEPATOLOGY RESEARCH, Issue 8 2010Keiji Matsui Objectives:, To elucidate the efficacy of interferon (IFN)-beta induction therapy followed by pegylated IFN alpha and ribavirin for chronic infection with hepatitis C virus (HCV). Methods:, Patients chronically infected with HCV genotype 1, high titer were enrolled. Twice daily bolus injections of 3 million units IFN-beta were administered for 14 days. Thereafter, weekly injection of pegylated IFN alpha 2b and daily intake of ribavirin were followed. Therapy duration was adjusted according to the response to the therapy. When time to an undetectable HCV-RNA was 1, 2, 4, 8, and 12 weeks, total duration of therapy was 12, 24, 36, 48 and 60 weeks, respectively. Patients who failed to achieve an undetectable HCV-RNA within 12 weeks discontinued therapy on 12 week. Results:, Among the 101 patients treated, 56 (55.4%) achieved sustained virological response (SVR). SVR rate for each treatment duration was 10/10 for 12 weeks, 12/14 for 24 weeks, 18/19 for 36 weeks, 15/26 for 48 weeks, 1/4 for 60 weeks and 0/28 for patients who discontinued therapy at 12 weeks. Mean time to an undetectable HCV-RNA was 35.5 ± 2.7 days. Mean therapy duration was 27.3 ± 1.4 weeks. Using a cut off value of 21.5 fmol/L of HCV core-antigen in the first week, SVR could be predicted by sensitivity of 0.91 and specificity of 0.78. Conclusion:, IFN-beta induction therapy resulted in acceptable SVR rates despite short therapy duration. Steep reduction of HCV by IFN-beta enables us to predict SVR in the first week of therapy. [source] Quetiapine versus olanzapine for the treatment of negative symptoms in patients with schizophreniaHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 4 2006Pinkhas Sirota Abstract Negative symptoms are considered the most debilitating and refractory aspect of schizophrenia, being associated with poor social, occupational and global outcomes. Conventional antipsychotics have limited efficacy against these symptoms and poor tolerability profiles. Atypical antipsychotics are an alternative treatment, and this 12-week, randomised, flexibly dosed study compared the efficacy, safety and tolerability of quetiapine and olanzapine in this regard. Of the 40 patients who entered the study (32 male; 8 female), 19 were randomised to quetiapine (mean dose 637,mg/day, mean treatment duration 80 days) and 21 to olanzapine (mean dose 16,mg/day, mean treatment duration 78 days). Quetiapine and olanzapine were similarly effective: in each treatment group significant improvements at Week 12 were observed for negative symptom scores on the SANS and the PANSS, and for subscale scores of affective flattening and alogia on the SANS. Both treatments were well tolerated in this patient population, with no worsening of extrapyramidal symptoms in either case. Anxiety and insomnia were the most common adverse events (,7% of patients in each group), but were not drug-related. Although this is a small study with limited power, the results support the effectiveness of quetiapine and olanzapine in treating the negative symptoms of schizophrenia. Copyright © 2006 John Wiley & Sons, Ltd. [source] Safety and efficacy of ezetimibe monotherapy in 1624 primary hypercholesterolaemic patients for up to 2 yearsINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 9 2008C. A. Dujovne Summary Aims:, This report examined the safety and efficacy of treatment for up to 2 years with the cholesterol absorption inhibitor, ezetimibe (EZE). Methods:, Two identical, randomised, double-blind trials (starting with 827 and 892 patients), evaluated the efficacy and safety of EZE 10 mg/day vs. placebo for 12 weeks in patients with primary hypercholesterolaemia [low-density lipoprotein cholesterol (LDL-C) 3.3,5.1 mmol/l]. Upon completion of these base studies, patients were offered a 2-year, open-label extension study. Adverse event (AE) reports for EZE monotherapy-treated patients were summarised for 3-month intervals to allow for comparison with the placebo group of the 3-month base studies. The primary end-point for this analysis was the evaluation of the long-term safety and tolerability of EZE 10 mg monotherapy dosed daily for up to 24 months. Results:, The incidences of new AEs, treatment-related (TR) AEs, serious AEs (SAEs), TRSAEs and discontinuations as a result of AEs during any 3-month interval were comparable with the respective observations in the placebo group of the base studies. The incidences of AEs, TRAEs, SAEs, TRSAEs and discontinuations as a result of AEs decreased in almost every interval compared with earlier intervals throughout the 2-year study. In addition, the incidences of , 3-fold consecutive elevations of liver transaminases (0.7%) or , 10-fold increases in creatine phosphokinase (0.4%) for the entire 2-year treatment period were comparable with those of the placebo group (0.7% and 0.2% respectively). LDL-C reductions of ,18% were maintained throughout the study. Conclusions:, Compared with placebo, treatment with EZE for up to 2 years in 1624 patients showed no evidence of increased incidence of AEs with increased treatment duration, while showing sustained effects on LDL-C reduction. [source] A Short-Term, Randomized, Double-Blind, Parallel-Group Study to Evaluate the Efficacy and Safety of Dronedarone versus Amiodarone in Patients with Persistent Atrial Fibrillation: The DIONYSOS StudyJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 6 2010JEAN-YVES LE HEUZEY M.D. Dronedarone versus Amiodarone in Patients with AF.,,Introduction: We compared the efficacy and safety of amiodarone and dronedarone in patients with persistent atrial fibrillation (AF). Methods: Five hundred and four amiodarone-naïve patients were randomized to receive dronedarone 400 mg bid (n = 249) or amiodarone 600 mg qd for 28 days then 200 mg qd (n = 255) for at least 6 months. Primary composite endpoint was recurrence of AF (including unsuccessful electrical cardioversion, no spontaneous conversion and no electrical cardioversion) or premature study discontinuation. Main safety endpoint (MSE) was occurrence of thyroid-, hepatic-, pulmonary-, neurologic-, skin-, eye-, or gastrointestinal-specific events, or premature study drug discontinuation following an adverse event. Results: Median treatment duration was 7 months. The primary composite endpoint was 75.1 and 58.8% with dronedarone and amiodarone, respectively, at 12 months (hazard ratio [HR] 1.59; 95% confidence interval [CI] 1.28,1.98; P < 0.0001), mainly driven by AF recurrence with dronedarone compared with amiodarone (63.5 vs 42.0%). AF recurrence after successful cardioversion was 36.5 and 24.3% with dronedarone and amiodarone, respectively. Premature drug discontinuation tended to be less frequent with dronedarone (10.4 vs 13.3%). MSE was 39.3 and 44.5% with dronedarone and amiodarone, respectively, at 12 months (HR = 0.80; 95% CI 0.60,1.07; P = 0.129), and mainly driven by fewer thyroid, neurologic, skin, and ocular events in the dronedarone group. Conclusion: In this short-term study, dronedarone was less effective than amiodarone in decreasing AF recurrence, but had a better safety profile, specifically with regard to thyroid and neurologic events and a lack of interaction with oral anticoagulants. (J Cardiovasc Electrophysiol, Vol. 21, pp. 597-605, June 2010) [source] Patients' preference for radiotherapy fractionation schedule in the palliation of symptomatic unresectable lung cancer,JOURNAL OF MEDICAL IMAGING AND RADIATION ONCOLOGY, Issue 5 2008JI Tang Summary The palliative radiotherapeutic management of unresectable non-small-cell lung cancer is controversial, with various fractionation (Fx) schedules available. We aimed to determine patient's choice of Fx schedule after involvement in a decision-making process using a decision board. A decision board outlining the various advantages and disadvantages apparent in the Medical Research Council study of Fx schedules (17 Gy in two fractions vs 39 Gy in 13 fractions) was discussed with patients who met Medical Research Council eligibility criteria. Patients were then asked to indicate their preferred Fx schedules, reasons and their level of satisfaction with being involved in the decision-making process. Radiation oncologists (RO) could prescribe radiotherapy schedules irrespective of patients' preferences. Of 92 patients enrolled, 55% chose the longer schedule. English-speaking patients were significantly more likely to choose the longer schedule (P = 0.02, 95% confidence interval: 1.2,7.6). Longer Fx was chosen because of longer survival (90%) and better local control (12%). Shorter Fx was chosen for shorter overall treatment duration (80%), cost (61%) and better symptom control (20%). In all, 56% of patients choosing the shorter schedule had their treatment altered by the treating RO, whereas only 4% of patients choosing longer Fx had their treatment altered (P < 0.001). Despite this, all (100%) patients were satisfied with being involved in the decision-making process. The decision board was useful in aiding decision-making, with both Fx schedules being acceptable to patients. Interestingly, despite the longer average survival associated with longer Fx, nearly half of the patients believed that this was not as important as a shorter duration of treatment and lower cost. Despite patients' preferences, there were significant alterations of preferred schedules because of RO's own biases. [source] The Efficacy of Acamprosate in the Maintenance of Abstinence in Alcohol-Dependent Individuals: Results of a Meta-AnalysisALCOHOLISM, Issue 1 2004Karl Mann Abstract: Background: A number of clinical trials have been undertaken to determine the efficacy of acamprosate in the maintenance of abstinence in alcohol-dependent individuals. However, the reported differences in patient populations, treatment duration, and study endpoints make comparisons difficult. An assessment of the efficacy of treatment with acamprosate was, therefore, undertaken using meta-analytical techniques. Methods: All randomized, placebo-controlled trials (RCTs) that fulfilled predetermined criteria were identified using (1) a language unrestricted search of 10 electronic databases; (2) a manual search of relevant journals, symposia, and conference proceedings; (3) cross-referencing of all identified publications; (4) personal communications with investigators; and (5) scrutiny of Merck-Santé's internal reports of all European trials. Study quality was assessed, independently, by three blinded workers. Key outcome data were identified; some outcome variables were recalculated to ensure consistency across trials. The primary outcome measure was continuous abstinence at 6 months; abstinence rates were determined by estimating Relative Benefit (RB). Results: A total of 19 published 1 unpublished RCTs were identified that fulfilled the selection criteria; 3 were excluded because the documentation available was insufficient to allow adequate assessment. The remaining 17 studies, which included 4087 individuals, 53% of whom received active drug, were of good quality and were otherwise reasonably comparable. There was no evidence of publication bias. Continuous abstinence rates at 6 months were significantly higher in the acamprosate-treated patients (acamprosate, 36.1%; placebo, 23.4%; RB, 1.47; [95% confidence intervals (CI): 1.29,1.69]; p < 0.001). This effect was observed independently of the method used for assigning missing data. The effect sizes in abstinent rates at 3, 6, and 12 months were 1.33, 1.50, and 1.95, respectively. At 12 months, the overall pooled difference in success rates between acamprosate and placebo was 13.3% (95% CI, 7.8,18.7%; number needed to treat, 7.5). Acamprosate also had a modest but significant beneficial effect on retention (6.01%; [95% CI, 2.90,8.82]; p= 0.0106). Conclusion:: Acamprosate has a significant beneficial effect in enhancing abstinence in recently detoxified, alcohol-dependent individuals. [source] Review article: the role of rapid virological response in determining treatment duration for chronic hepatitis CALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 12 2010F. F. POORDAD Aliment Pharmacol Ther,31, 1251,1267 Summary Background, For patients with chronic hepatitis C, attaining rapid virological response (RVR) is highly predictive of attaining SVR. Aim, To consider the predictive value of RVR in terms of SVR and relapse. Methods, Data were collected from published clinical trials to define the predictive value of RVR for SVR and evaluate the proposed continuum linking RVR to relapse. Results, These data support a 24-week regimen among genotype (G)1 patients who attain RVR with positive predictive values (PPVs) of 77.8% and 85.7% in patients with G1 infection treated for 24 and 48 weeks. Conversely, failure to attain RVR among G1 patients should not be viewed as a criterion for extending treatment duration beyond 48 weeks: negative predictive values (NPVs) were 60.9% and 52.7% in G1 patients without RVR treated for 48 and 72 weeks. Among G2/3 patients, RVR has a high PPV; however, the NPV varied with treatment duration indicating that a 24-week treatment regimen is warranted in G2/3 patients who fail to attain RVR. Conclusions, The present analysis confirms RVR as a strong predictor of SVR that can be used to tailor treatment duration, but which also should be appreciated in the context of treatment duration and regimen. [source] Thalidomide-associated neuropathy in multiple myelomaJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 2 2004S Morino Thalidomide is a neurotoxic immunomodulating agent currently used in Multiple Myeloma (MM). We prospectively evaluated the frequency and characteristics of peripheral neuropathy in a continuous series of 25 patients (13 M, 12 F; age 38,60, median 55 yrs) treated with thalidomide for MM. Patients underwent a neurological and neurophysiological evaluation before starting thalidomide therapy and monthly throughout duration of treatment. Sixteen patients (5 M, 11 F) developed neurophysiological characteristics of axonal sensitive damage and/or clinical peripheral neuropathy with distal sensory symptoms; treatment duration ranged between 95 and 572 days (median 298) in patients with neuropathy, and 49,264 days (median 162) in patients without neuropathy; the total amount of thalidomide taken ranged between 26 and 169 g (median 83 g) for patients with neuropathy and 13,170 g (median 51 g) for those without. In four patients, ENG alterations appeared before clinical symptoms, while in two patients they were not followed by clinical symptoms. In the remaining three patients, clinical symptoms preceded neurophysiological alterations. Age at onset of MM, disease duration before thalidomide therapy was started, total dose, duration of therapy and previous treatments were not correlated with neuropathy (multivariate logistic regression analysis). Female gender was a risk factor for developing neuropathy (OR 7.7). [source] Impact of hot water treatment on sprouting, membrane permeability, sugar content and chip colour of reconditioned potato tubers following long-term cold storageJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 15 2008Marios C Kyriacou Abstract BACKGROUND: The efficacy of hot water treatment in facilitating successful reconditioning of processing potato (Solanum tuberosum L.) cultivar Hermes following 6 months cold storage at 4.5 °C was examined. Tubers were subjected to hot water treatments (HWTs) at 52.5, 55.0, 57.5 and 60.0 °C for 0,60, 0,50, 0,40 and 0,20 min, respectively, and then reconditioned for 20 days at 16 °C before evaluated for sprouting, fresh weight loss, membrane permeability, sugar content and processing quality. RESULTS: The study demonstrates that in order to achieve complete inhibition of sprouting during potato reconditioning HWTs must exceed the thermal tolerance threshold of the tubers. Short-duration HWT was effective in retarding sprout growth and tuber dehydration without significantly affecting storage parenchyma membrane permeability, tuber sugar content or processing quality. On the contrary, prolonged HWT caused extensive heat damage, loss of membrane integrity and induced an increase in tuber sucrose and reducing sugar content resulting in deterioration of chip colour in proportion to treatment duration. CONCLUSION: Although HWT at 52.5,60 °C following long-term cold storage did not improve the processing quality of potato tubers after 20 days of reconditioning, future work is needed to evaluate the effect of short-duration HWT on the permissible extent of reconditioning and subsequent processing quality. Copyright © 2008 Society of Chemical Industry [source] Can oral vitamin K before elective surgery substitute for preoperative heparin bridging in patients on vitamin K antagonists?JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 3 2010A. STEIB See also Douketis JD, Spyropoulos AC. Vitamin K to reverse the anticoagulant effect of vitamin K antagonists: can you teach an old dog new tricks? This issue, pp 496,8. Summary.,Background: After a vitamin K antagonist (VKA) overdose, 1,2 mg of oral vitamin K can lower the International Normalized Ratio (INR) to the therapeutic range. Objective: To establish whether oral vitamin K can substitute for heparin bridging and decrease the INR to , 1.5 before elective surgery. Methods: Patients on long-term VKAs were randomized either to heparin bridging after the last VKA dose on day , 5 before surgery (group H) or to VKA treatment until day , 2, followed by 1 mg of oral vitamin K on the day before surgery (group K). Blood clotting variables were assessed on days ,5/,2, 1 and 0, and postoperatively. If the target INR was not achieved 2 h before incision, surgery was deferred or performed after injection of prothrombin complex concentrate (PCC). Results: In 30 of 94 included patients, baseline INR was outside the chosen range (18, INR < 2; 12, INR > 3.5), leaving 34 eligible patients in group H and 30 in group K. The groups were balanced in terms of body mass index, VKA treatment duration and indication, scheduled surgery, preoperative and postoperative hemoglobin, and blood loss. The INR was significantly higher in group K on days , 1 and 0 than in group H. An INR , 1.5 was not achieved in 20 group K patients (66%). Surgery was postponed or performed after PCC injection in 12 of these 20 patients. Conclusions: Oral vitamin K (1 mg) cannot substitute for heparin bridging before surgery. In addition, one-third of patients on VKAs were exposed to a risk of bleeding (overdose) or thrombosis (underdose), thus highlighting the need for new oral anticoagulants. [source] Interferon-induced retinopathy and its risk in patients with diabetes and hypertension undergoing treatment for chronic hepatitis C virus infectionALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2009J. D. PANETTA Summary Background, Ocular complications are amongst many side-effects of interferon based therapy for hepatitis C virus (HCV) infection. Some suggest that diabetic and hypertensive patients are at increased risk of these complications. Aim, To determine the frequency of ophthalmological complications related to interferon use. Methods, Retrospective analysis of patients undergoing HCV treatment with pegylated interferon ,-2a, ,-2b or consensus interferon plus ribavirin between 2005 and 2007. All patients underwent a baseline eye examination and any visual complaints during treatment prompted a repeat examination. Data recorded included HCV genotype, treatment duration, interferon type, pre-treatment and on treatment visual complaints, known ocular pathology, and retinal findings at baseline and at follow-up. Results, Of 183 patients, 29 (16%) had diabetes and 85 (46%) had hypertension. Seventy-one (38%) received interferon ,-2a, 100 (55%) ,-2b, and 12 (7%) consensus interferon. Seven (3.8%) had retinal changes on follow-up and treatment was discontinued in 3 (1.6%). Of seven with ocular changes two had hypertension and one had both hypertension and diabetes. Conclusion, The incidence of symptomatic retinopathy in HCV patients undergoing interferon therapy appears low and treatment cessation is rarely needed. Furthermore, patients with hypertension and diabetes may not be at higher risk for interferon-induced retinopathy. [source] Individualized duration of oral anticoagulant therapy for deep vein thrombosis based on a decision modelJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 12 2003R. Vink Summary.,Background:,The optimal duration of oral anticoagulant therapy for patients with a first episode of deep vein thrombosis (DVT) is still a matter of debate. However, according to the ACCP consensus strategy a limited stratification in treatment duration is advocated, i.e. 3 months for patients with a transient risk factor and 1 year or longer for patients with recurrent disease or a consistent risk factor such as thrombophilia or cancer. This consensus strategy is founded on the mean optimal duration of therapy obtained in large cohorts of patients and is mainly based on the risk of recurrent venous thromboembolism (VTE), with only minimal consideration for the patient's bleeding risk. Objective:,The aim of this study is to optimize the anticoagulant treatment strategy with vitamin K antagonists for the individual patient with DVT. Methods:,Based on an extensive literature study, a mathematical model was constructed to balance the risk of recurrent VTE against the risk of major hemorrhagic complications. The following parameters are incorporated in the model: baseline estimates and risk factors for recurrent VTE and bleeding, clinical course of DVT, and efficacy of treatment with vitamin K antagonists. With the use of these parameters, the risk for a recurrent VTE and a bleeding episode can be calculated for the individual patient. The optimal duration of anticoagulant therapy can be defined as the timepoint at which the benefit of treatment (prevention of VTE) is counterbalanced by its risk (bleeding). Results/conclusions:,How long a patient should receive anticoagulant treatment is a matter of balancing the benefits and risks of treatment. The model shows that the optimal treatment duration varies greatly from patient to patient according to the patient's unique bleeding and recurrence risk. [source] Clinical trial: extended treatment duration of peginterferon-alpha2b plus ribavirin for 72 and 96 weeks in hepatitis C genotype 1-infected late respondersALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2009M. NAGAKI Summary Background, The benefits of prolonging peginterferon and ribavirin after 48 weeks of treatment to maximize sustained virological responses (SVR) in hepatitis C virus (HCV) genotype 1-infected patients remain to be understood. Aim, To investigate whether extended treatment longer than 72 weeks may be superior to 72-week treatment. Methods, A total of 120 treatment-naïve or retreated patients with HCV genotype 1 were treated with peginterferon-alpha-2b (1.5 ,g/kg/week) plus weight-based ribavirin. We had 34 late responders, in whom HCV RNA first became undetectable at week 12,48, and randomized them into three groups receiving standard-dose peginterferon-alpha-2b plus low-dose ribavirin (200 mg/day) for extended 24 weeks (group A), receiving low-dose peginterferon-alpha-2b (0.75 ,g/kg/week) plus low-dose ribavirin for extended 48 weeks (group B) or no extended treatment (group C), and evaluated the outcome according to their virological response. Results, Multivariate analysis showed that the treatment for 96 weeks was identified as a significant, independent factor associated with SVR in HCV genotype 1-infected late responders in comparison with group A [odds ratio (OR), 10.002; P = 0.080] and group C (OR, 17.748; P = 0.025). Conclusion, Extending the treatment duration from 48 weeks to 96 weeks improves SVR rates in genotype 1-infected patients with late virological response to peginterferon-alpha-2b and ribavirin. [source] Cost-effectiveness of biological therapy for Crohn's disease: Markov cohort analyses incorporating United Kingdom patient-level cost dataALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2009K. BODGER Summary Background, Anti-TNF-alpha agents for Crohn's disease (CD) have good clinical efficacy but high acquisition cost compared to rival drugs. Aim, To assess the cost-effectiveness of infliximab and adalimumab for Crohn's disease from the perspective of the UK NHS, incorporating recent trial and observational data. Methods, Lifetime Markov analyses constructed to simulate quality-adjusted life-years (QALYs) and costs. CD was represented by four health-states representing: Full response, partial response, nonresponse, surgery and death. The course of CD under standard care was based on the Olmsted county cohort. Systematic review identified ACCENT I (infliximab) and CHARM (adalimumab) as sources for efficacy data. We modelled an intention-to-treat strategy for biologics including surgical rates based on observational data, cost estimates from our UK dataset and utilities from an algorithm converting CDAI to EQ-5D utilities. Results, The incremental cost-effectiveness ratios (ICERs) compared to standard care for 1-year of treatment with infliximab or adalimumab were £19 050 and £7190 per QALY gained, respectively. Lifetime therapy was dominated by standard care. Analyses over shorter time horizons, matched to treatment duration, resulted in unfavourable ICERs. Conclusion, The model suggests acceptable ICERs for biological agents when considering a lifetime horizon with periods of up to 4 years continuous therapy. As with all economic evaluations, the results may not be generalizable beyond the perspective of analysis. [source] Stringent cessation criterion results in better durability of lamivudine treatment: a prospective clinical study in hepatitis B e antigen-positive chronic hepatitis B patientsJOURNAL OF VIRAL HEPATITIS, Issue 4 2010L. Wang Summary., The cessation criteria for lamivudine treatment vary in published articles and their results are contradictory, especially factors predicting relapse. To clarify these contradictions, this long-term follow-up study of 125 Chinese hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients was designed with stringent cessation criterion. All patients received lamivudine and achieved HBeAg seroconversion (group A, n = 82) or loss (group B, n = 43) with undetectable hepatitis B virus (HBV) DNA by PCR assay during the treatment. Lamivudine was withdrawn ,6 months after HBeAg seroconversion/loss occurred. The median treatment durations were 24 (12,54) months and 36 (18,89) months in group A and group B, respectively. Patients were followed up for median 24 (2,84) months. The cumulative relapse (defined as serum HBV DNA ,104 copies/mL) rates in the two groups at months 12, 24, 36 and 48 were 23.4%vs 35.0%, 25.0%vs 37.7%, 25.0%vs 41.1% and 29.4%vs 41.1%, respectively (log-rank test, P = 0.119). For patients whose total treatment duration ,18 months in group A, the cumulative relapse rates at months 12, 24, 36 and 48 were 18.3%, 20.1%, 20.1% and 25.1%, which was significantly lower than those with a shorter duration (log-rank test, P = 0.002). The mean age and median total duration were statistically different between relapsers and nonrelapsers in group A (33.9 ± 13.6 vs 23.1 ± 11.0 years, P < 0.001 and 24 vs 26 months, P = 0.003). Cox regression revealed that age was the only predictive factor for relapse (RR, 1.069; 95% CI, 1.032,1.106, P < 0.001). Patients aged <30 years relapsed less frequently in 5 years (12.3%vs 53.5%, P = 0.001). In conclusion, for patients who maintained HBeAg seroconversion for ,6 months and total duration for ,18 months, lamivudine withdrawal is a reasonable option. Prolonged treatment may be required for patients aged greater than 30 years to reduce relapse. [source] Role of rapid virological response in prediction of sustained virological response to Peg-IFN plus ribavirin in HCV,/,,HIV co-infected individualsJOURNAL OF VIRAL HEPATITIS, Issue 7 2008D. O. Shea Summary., The objective of the study was to evaluate the role of rapid virological response (RVR) in predicting sustained virological response (SVR) rates to hepatitis C virus (HCV) therapy. 65 HIV,/,HCV co-infected patients commenced HCV treatment per protocol. HIV,/,HCV patients with a mean CD4 count of 502 were treated for 24,48 weeks depending on genotype. Virological response was assessed at weeks 4 (RVR), 12 [early virological response (EVR)], 24, at end of treatment (EOTR) and 24 weeks post-completion of treatment (SVR). Primary end-point was defined as undetectable HCV RNA at 24 weeks post-treatment completion. Fifty-five per cent of co-infected patients were on highly active anti-retroviral therapy. A majority of patient group were male. 60% of HIV,/,HCV patients achieved SVR (35% genotype 1,/,4; 77% genotype 2,/,3). 24 HIV,/,HCV patients achieved undetectable HCV levels compared with baseline by week 4. The positive predictive value (PPV) of RVR at week 4 for subsequent SVR in HIV,HCV co-infected patients was 100%; the negative predictive value (NPV) was 57%. Significant variables associated with SVR were: (i) lower median pre-treatment HCV viral load, (ii) genotype 2,/,3 disease and (iii) achievement of RVR. Independent variables associated with RVR were low pre-treatment HCV viral load and genotype 2,/,3 disease. Achievement of RVR, a negative HCV-PCR, at week 4 of treatment is predictive of SVR in this cohort of patients. This may be used to guide optimal treatment duration in patient groups. More significantly, the data serve to highlight the subgroup of patients who, on achieving RVR, should be actively supported to complete HCV treatment with full dose therapy, especially patients co-infected with G2,/,3 disease for whom 6 months' full dose therapy may be sufficient to obtain a SVR. [source] Practical use of hepatitis C virus kinetics monitoring in the treatment of chronic hepatitis CJOURNAL OF VIRAL HEPATITIS, Issue 2007S. Chevaliez Summary., Prevention of hepatitis C virus (HCV) infection complications can be achieved by antiviral therapy based on the use of a combination of pegylated interferon (IFN)-, and ribavirin. The steady-state kinetics of HCV infection represents the treatment target. The goal is cure, which is achieved when all infected cells have been cleared from the body. Because of their intrinsic properties, real-time polymerase chain reaction (PCR) methods are rapidly replacing other technologies for routine quantification of HCV-RNA during antiviral therapy. The virological response at week 12 of therapy is currently used to tailor treatment duration in HCV genotype 1 infection only. Recent reports suggest that the virological response at week 4 could be used to tailor treatment duration, whatever the HCV genotype. [source] Peginterferon alpha-2b plus ribavirin vs interferon alpha-2b plus ribavirin for chronic hepatitis C in HIV-coinfected patientsJOURNAL OF VIRAL HEPATITIS, Issue 4 2007M. Crespo Summary., Treatment of chronic hepatitis C in human immunodeficiency virus (HIV)-infected patients is associated with low response rates and high incidence of side effects. One hundred twenty-one hepatitis C virus (HCV),HIV-coinfected patients were randomized to receive interferon alpha-2b (3 MU thrice weekly; n = 61) or peginterferon alpha-2b (1.5 ,g/kg/week; n = 60), plus ribavirin (800 mg daily), for 24 (genotype 2 or 3) or 48 weeks (genotype 1 or 4). We assessed early virological response at 4, 8 and 12 weeks to predict sustained virological response (SVR). Safety assessment included frequent blood lactate measurement and relative quantitation of mitochondrial DNA (mtDNA) content in peripheral blood mononuclear cells. In intention-to-treat analysis, the SVR rate was higher in the peginterferon group (55%vs 26%; P = 0.002). The difference for HCV genotypes 1 and 4 was 45%vs 14% (P = 0.009) and 50%vs 27% (P = 0.387), respectively, and for genotype 2 or 3, 71%vs 43% (P = 0.12) Viral response at 4, 8 and 12 weeks of treatment was highly predictive of SVR. Among genotype 3 patients, 17 of 20 (85%) whose HCV RNA was already undetectable at 4 weeks had an SVR after 24 weeks of treatment. Hyperlactataemia occurred in 22 patients and was clinically significant in six, two of whom died. mtDNA decreased significantly 4,12 weeks after the start of treatment in patients developing clinically significant hyperlactataemia. Peginterferon alpha-2b plus ribavirin was more effective than interferon alpha-2b plus ribavirin in HIV-coinfected patients. Frequent monitoring of virological response may be very helpful to optimize treatment compliance, to tailor treatment duration and to minimize side effects. [source] Long-term effect of tacrolimus therapy in patients with refractory ulcerative colitisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2008S. YAMAMOTO Summary Background, Little is known about long-term outcome of tacrolimus therapy for ulcerative colitis. Aim, To evaluate long-term efficacy and safety of tacrolimus in Japanese patients with refractory ulcerative colitis. Methods, Twenty-seven patients with UC refractory to conventional therapy were administered tacrolimus with trough whole-blood levels of 10,15 ng/mL to induce remission and 5,10 ng/mL to maintain remission. Median treatment duration was 11 months (1,39 months) and median follow-up duration was 17 months (2,65 months). Evaluation of the clinical response was based on a modified Truelove,Witts severity index (MTWSI). Results, Tacrolimus produced a clinical response in 21 patients (77.8%), and remission was achieved in 19 of these 21 (70.4%) within 30 days. Overall cumulative colectomy-free survival was estimated as 62.3% at 65 months. In 18 of 19 patients treated with corticosteroids at the initiation of tacrolimus therapy, corticosteroids were discontinued or tapered. Adverse events were tremor (25.9%), renal function impairment (18.5%), infectious disease (14.8%), hot flashes (11.1%), hyperkalaemia (7.4%), headache (7.4%), epigastralgia (7.4%) and nausea (3.7%). No mortality occurred. Conclusion, Long-term administration of tacrolimus appears to be an effective and well-tolerated treatment for Japanese patients with refractory ulcerative colitis. [source] Meta-analysis: Helicobacter pylori eradication treatment efficacy in childrenALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2007R. KHURANA Summary Background, Several meta-analyses assessing the efficacy of anti- Helicobacter pylori treatment in adults have been published but a comparable meta-analysis in children is lacking. Aims, To summarize the efficacy of treatments aimed at eradicating H. pylori in children and to identify sources of variation in treatment efficacy across studies. Methods, We searched Medline, reference lists from published study reports, and conference proceedings for anti- H. pylori treatment trials in children. Weighted meta-regression models were used to find sources of variation in efficacy. Results, Eighty studies (127 treatment arms) with 4436 children were included. Overall, methodological quality of these studies was poor with small sample sizes and few randomized-controlled trials. The efficacy of therapies varied across treatment arms, treatment duration, method of post-treatment assessment and geographic location. Among the regimens tested, 2,6 weeks of nitroimidazole and amoxicillin, 1,2 weeks of clarithromycin, amoxicillin and a proton pump inhibitor, and 2 weeks of a macrolide, a nitroimidazole and a proton pump inhibitor or bismuth, amoxicillin and metronidazole were the most efficacious in developed countries. Conclusions, Before worldwide treatment recommendations are given for eradication of H. pylori, additional well-designed randomized placebo-controlled paediatric trials are needed, especially in developing countries where both drug resistance and disease burden is high. [source] | ||||||||||||||||||||||||||||||||||||||||