Treatment Discontinuation (treatment + discontinuation)

Distribution by Scientific Domains
Distribution within Medical Sciences

Selected Abstracts

Open trial of nefazodone among Hispanics with major depression: Efficacy, tolerability, and adherence issues

J. Arturo Snchez-Lacay M.D., M.P.H.
Abstract The efficacy and tolerability of nefazodone in the treatment of major depression among Spanish-monolingual Hispanics was examined and compared to historical controls among English-speaking, predominantly non-Hispanic subjects. Fifty monolingual Hispanic outpatients with major depression and a HAM-D17 score ,18 were treated with nefazodone in a flexible-dose 8-week open-label protocol. Sixty-three percent of the intent-to-treat (ITT) sample with ,1 efficacy visit were considered responders according to CGI-I criteria, falling within the range of response rates (58,69%) reported in six prior nefazodone trials with non-Hispanic subjects. Significant improvement was found for the ITT and completer samples in HAM-D17, HAM-D28, and SCL-90 scores and in two measures of psychosocial functioning. Endpoint mean dose in the ITT sample was 379 mg/day (SD=170), also within the range of previous trials (321,472mg/day). Adverse effects were not elevated, with only dry mouth (8%) reported by >6% of subjects. However, 42% of the sample dropped out of treatment before study termination, usually because of side effects or due to family or work difficulties, a higher rate than previously reported for nefazodone (21,33%). This open trial finds nefazodone to be an efficacious treatment for major depression among monolingual Hispanics, with comparable efficacy to previous controlled trials among non-Hispanic subjects. Double-blind studies are required to confirm this comparable efficacy. Mean endpoint doses and adverse effect rates similar to previous trials do not support the need for reduced doses of nefazodone among Hispanics. However, an elevated rate of treatment discontinuation threatens treatment efficacy among this population. Causes for this elevated rate require explanation, given the apparently unremarkable pattern of adverse effect reports. Depression and Anxiety 13:118,124, 2001. 2001 Wiley-Liss, Inc. [source]

Imiquimod Treatment of Superficial and Nodular Basal Cell Carcinoma: 12-Week Open-Label Trial

Ketty Peris MD
Background Imiquimod is an immune response modifier shown to be effective in basal cell carcinoma (BCC). Objective To evaluate the efficacy, tolerability, and response durability of imiquimod 5% cream in selected patients with superficial and/or nodular BCCs. Methods Seventy-five superficial and 19 nodular BCCs in 49 patients were treated with imiquimod once daily three times a week for up to 12 weeks. Results Of the 49 enrolled patients, 1 discontinued the study and 1 was lost to follow-up. After 12 weeks of treatment, a complete response occurred in 70 of 75 (93.3%) superficial BCCs and a partial response in 4 of 75 (5.3%) superficial BCCs. Ten of 19 (52.6%) nodular BCCs cleared after 12 weeks, whereas 7 (36.8%) showed partial remission. Adverse side effects were limited to local skin reactions. Recurrence was observed in 2 of 70 (2.9%) successfully treated superficial BCCs 6 and 8 months after treatment discontinuation. No recurrence was detected in 68 of 70 (97.1%) superficial BCCs and in 10 successfully treated nodular BCCs after 12 to 34 months of follow-up (mean 23 months). Conclusions In our patient population, treatment of superficial BCCs with topical imiquimod for 12 weeks produced an excellent clinical response overall, with complete remission maintained after a mean of 23 months. KETTY PERIS, MD, ELENA CAMPIONE, MD, TAMARA MICANTONIO, MD, GEORGIANA CLARE MARULLI, MD, MARIA CONCETTA FARGNOLI, MD, AND SERGIO CHIMENTI, MD, HAVE INDICATED NO SIGNIFICANT INTEREST WITH COMMERCIAL SUPPORTERS. [source]

Outcomes for 236 patients from a 2-year early intervention in psychosis service

M. A. Turner
Objective:, To examine: i) changes in key outcome measures over time in treatment in a representative first-episode psychosis treatment cohort and ii) baseline predictors of service disengagement. Method:, Baseline characteristics of 236 patients were examined for associations with outcomes over time using generalized estimating equation models. The data on disengagement were analysed using logistic regression. Results:, After controlling for admission scores, patients showed consistently improved outcomes while in treatment on functional recovery (unemployment, P < 0.01; HoNOS, P < 0.001; the Quality of Life Scale, P < 0.001; GAF, P < 0.05) but not symptomatology (as assessed by the PANSS and substance abuse). The 64 (33%) who disengaged were more likely to be unemployed (P < 0.01) and have higher HoNOS (P < 0.01) and GAF (P < 0.05) scores at baseline. Conclusion:, This evaluation has shown significant improvements in psychosocial functioning but not psychopathology during treatment at an Early Intervention for Psychosis Service. Despite attempts to retain patients, there is a high rate of treatment discontinuation. [source]

Prophylactic use of anti-emetic medications reduced nausea and vomiting associated with exenatide treatment: a retrospective analysis of an open-label, parallel-group, single-dose study in healthy subjects

C. Ellero
Diabet. Med. 27, 1168,1173 (2010) Abstract Aims, Transient nausea and, to a lesser extent, vomiting are common adverse effects of exenatide that can be mitigated by dose titration and usually do not result in treatment discontinuation. This retrospective analysis of data from a phase 1, open-label, parallel-group, single-dose study in healthy subjects evaluated the effect of oral anti-emetics on exenatide-associated nausea and vomiting and on the pharmacokinetics of exenatide. Methods, A single subcutaneous dose (10 ,g) of exenatide was administered to 120 healthy subjects (19,65 years, BMI 23,35 kg/m2). Incidences of nausea and vomiting were compared between 60 subjects premedicated with two oral anti-emetics 30 min before the exenatide dose and 60 non-premedicated subjects. Similarly, the area under the concentration-time curve (AUC) and the maximum observed concentration (Cmax) of plasma exenatide concentrations over 8 h post-dose were compared. Results, Among all subjects [61% male, 32 12 years, body mass index (BMI) 29.1 3.4 kg/m2 (mean sd)], mild to moderate nausea was the most frequent adverse event after exenatide dosing. Vomiting was also observed. Subjects premedicated with anti-emetics experienced significantly less nausea and vomiting (16.7 and 6.7%, respectively) vs. non-premedicated subjects (61.7 and 38.3%, respectively; P -value < 0.0001 for both nausea and vomiting). The mean area under the concentration-time curve and the maximum observed concentration AUC and Cmax of plasma exenatide concentrations during 8 h post-dose were not significantly different between groups. Conclusion, Administration of oral anti-emetics before a single 10-,g exenatide dose was associated with significant reductions in treatment-emergent nausea and vomiting, with no discernible effect on the pharmacokinetics of exenatide. Use of anti-emetic therapy may provide a short-term strategy to minimize the nausea and vomiting associated with exenatide treatment. [source]

Time Course of Adverse Events in Patients with Localization-related Epilepsy Receiving Topiramate Added to Carbamazepine

EPILEPSIA, Issue 5 2005
Jerzy Majkowski
Summary:,Purpose: To explore the time course of treatment-emergent adverse events (AEs) during topiramate (TPM) adjunctive therapy. Methods: Post hoc analyses were performed by using data from a large (264 subjects) multicenter, double-blind, placebo-controlled trial in which 200 mg/day TPM was added to carbamazepine (CBZ) with or without another antiepileptic drug (AED) in adults with treatment-resistant partial-onset seizures. The daily incidence and mean duration of the most common (,5% incidence) AEs were calculated for patients completing the 12-week study. Results: The daily incidence of somnolence, headache, loss of appetite, nervousness, fatigue, dizziness, upper respiratory tract infection, and vertigo peaked during titration and declined to rates similar to that of placebo after the target TPM dose had been reached. In contrast, the daily incidence of paresthesia increased during titration and was maintained for the study duration. Relatively few patients had cognitive symptoms (9% with TPM, 5% with placebo), but these were the most common AEs associated with treatment discontinuation. Patient/investigator reports of weight loss increased gradually over the course of the trial, corresponding with the pattern of change in weight measured at study visits. Conclusions: This study demonstrates that most of the more common AEs with TPM adjunctive therapy are transient. Patients can be counseled that most AEs emerging when TPM is initially added to CBZ can be expected to diminish with continued therapy. [source]

Prognostic Factors Affecting Long-Term Retention of Topiramate in Patients with Chronic Epilepsy

EPILEPSIA, Issue 3 2000
S. D. Lhatoo
Summary: Purpose: To determine the long-term retention rate of topiramate (TPM) therapy in patients with chronic epilepsy and to identify the relevant prognostic factors that influence retention. Methods: All patients with chronic epilepsy (n = 393) prescribed TPM between October 1, 1995, and December 31, 1998, at a tertiary referral centre for epilepsy were analysed. The retention rate for TPM was calculated by using Kaplan-Meier survival analysis, and the prognostic factors influencing retention were analysed by using Cox regression. Results: Of patients prescribed TPM, 30% continued taking the drug beyond 3 years. Discontinuation was mainly due to adverse events and lack of efficacy. Use of more than one new concurrent antiepileptic drug (AED) and lower maximal daily doses were more likely to result in treatment discontinuation due to adverse events. Older age at onset of epilepsy, a history of having previously taken more than one new AED [lamotrigine (LTG), gabapentin (GBP), or vigabatrin (VGB)], and lower maximal daily doses were more likely to lead to discontinuation due to lack of efficacy. Conclusions: A third of patients with chronic epilepsy started on TPM therapy will continue on treatment for >3 years. Absence of learning disabilities, late age at onset of seizures, previous use of more than one new AED, two or more concurrent AED use, and low maximal daily doses of TPM are more likely to result in discontinuation of medication. These factors should be taken into account when considering the use of TPM for the treatment of chronic epilepsy. [source]

Sustained virologic response prevents the development of esophageal varices in compensated, Child-Pugh class A hepatitis C virus,induced cirrhosis.

HEPATOLOGY, Issue 6 2010
A 12-year prospective follow-up study
The incidence of de novo development of esophageal varices (EV) in patients with compensated liver cirrhosis has been determined by few studies in the short term and never in the long term. The aims of the present study were to determine the incidence and the risk factors associated with the development of EV and to assess whether antiviral treatment and achievement of sustained virologic response (SVR) may prevent de novo EV development in patients with HCV-induced cirrhosis. We studied 218 patients with compensated EV-free, HCV-induced cirrhosis consecutively enrolled between 1989 and 1992 at three referral centers in Milan, Italy. Endoscopic surveillance was performed at 3-year intervals according to international guidelines. SVR was defined as undetectable serum HCV-RNA 24 weeks after treatment discontinuation. During a median follow-up of 11.4 years, 149/218 (68%) patients received antiviral treatment and 34 (22.8%) achieved SVR. None of the SVR patients developed EV compared with 22 (31.8%) of the 69 untreated subjects (P < 0.0001) and 45 (39.1%) of the 115 non-SVR patients (P < 0.0001). On multivariate analysis, HCV genotype 1b (hazard ratio [HR] 2.40; 95% confidence interval [CI] 1.17-4.90) and baseline model for end-stage liver disease (MELD) score (HR 1.20; 95% CI 1.07-1.35 for 1 point increase) were independent predictors of EV. Conclusion: In the long term, the achievement of SVR prevents the development of EV in patients with compensated HCV-induced cirrhosis. Therefore, in these patients, endoscopic surveillance can be safely delayed or avoided. Genotype 1b infection and MELD score identify the subset of patients at higher risk of EV development who need tailored endoscopic surveillance. Hepatology 2010 [source]

Relationship of health-related quality of life to treatment adherence and sustained response in chronic hepatitis C patients

HEPATOLOGY, Issue 3 2002
David Bernstein
Interferon therapy may exacerbate health-related quality of life (HRQL) deficits associated with hepatitis C virus (HCV) early in the course of therapy. Treatment with polyethylene glycol,modified interferon (peginterferon) alfa-2a (40 kd) provides improved sustained response over interferon alfa-2a, but its effect on HRQL is unknown. The objective of this study was to (1) evaluate the effect of sustained virologic response on HRQL in patients with HCV and (2) determine whether impairment of HRQL during treatment contributes to early treatment discontinuation. Data consisted of a pooled secondary analysis of patients (n = 1,441) across 3 international, multicenter, open-label, randomized studies that compared peginterferon alfa-2a (40 kd) with interferon alfa-2a. ANCOVA was used to examine the effect of sustained virologic response on HRQL. Repeated-measures mixed-models ANCOVA was used to compare Fatigue Severity Scale (FSS) and SF-36 scores during treatment by treatment group. Logistic regression analysis was used to examine the association between changes at baseline in on-treatment HRQL and early treatment discontinuation. Sustained virologic response was associated with marked improvements from baseline to end of follow-up in all subjects, including patients with cirrhosis. During treatment, patients receiving peginterferon alfa-2a (40 kd) had statistically significantly better scores on both the SF-36 and FSS. Baseline to 24-week changes in fatigue and SF-36 mental and physical summary scores significantly predicted treatment discontinuation. In conclusion, sustained virologic response is associated with improvements in quality of life in patients with or without advanced liver disease. This parameter may be an important consideration in maximizing treatment adherence. [source]

Antiviral maintenance treatment with interferon and ribavirin for recurrent hepatitis C after liver transplantation: Pilot study

Arno Kornberg
Abstract Background:, The aim of this pilot study was to evaluate efficacy of a long-term antiviral maintenance therapy (AMT) with interferon-,2b and ribavirin in liver transplant recipients with recurrent hepatitis C. Methods:, Twenty-one patients with recurrent hepatitis C after liver transplantation received AMT with interferon and ribavirin, following 12 months of a basic antiviral combination treatment. Allograft function, viremia loads and allograft morphology were evaluated continuously. Results:, After 12 months of basic antiviral therapy, 14 patients (66.6%) had achieved initial clearance of viremia levels, and 17 recipients (81%) demonstrated normalization of allograft function, respectively. Inflammation score declined significantly (6.0 vs 3.9; P = 0.002), while stage of fibrosis remained unchanged. In virological responders maintenance therapy led to further regression of inflammation score (4.0 at baseline vs 3.1 at 24 months AMT) and fibrosis score (1.6 at baseline vs 1.1 at 24 months AMT). Despite persistence of viremia levels, continued antiviral therapy prevented progression to severe allograft inflammation in virological non-responders. Hematologic adverse effects resulted in treatment discontinuation in seven patients (33.3%). Conclusion:, Long-term AMT, if tolerable, might be an effective approach for preventing progression to severe allograft fibrosis and thereby improving long-term survival in liver transplant recipients with recurrent hepatitis C. [source]

Mercaptopurine rescue after azathioprine-induced liver injury in inflammatory bowel disease

Summary Background, Azathioprine (AZA) liver toxicity arises in approximately 3% of inflammatory bowel disease patients and may result in treatment discontinuation. Aim, To describe the tolerance to mercaptopurine (MP) in patients with previous AZA-related liver injury. Methods, Retrospective description of 31 patients (14 Crohn's, 17 ulcerative colitis), in which AZA therapy was interrupted because of liver injury, with MP started as alternative therapy. Results, Mean AZA dose was 2.2 0.4 mgkg/day. Median (interquartile range) of AZA exposure when liver injury was detected was 2 months (1,5.2). The type of AZA-related injury was cytolitic in 32%, cholestatic in 39% and mixed in 29%. After a median of 2.5 months (0.7,5.2), the therapy was switched to MP at a mean dose of 1.3 0.2 mgkg/day. Median of follow-up of MP therapy was 32 months (8,54). In 87.1% of patients (95%CI: 70,96%), MP was tolerated without further liver injury; of these, 77.4% tolerated full MP doses and 9.7% tolerated lower doses. In a further cohort of 12.9% of patients, (95%CI: 3,29%), liver injury reappeared (two cholestasis, two mixed), 1,3 months after the onset of MP exposure. Conclusion, The administration of MP is a good alternative in patients with AZA-related liver injury, before thiopurines are definitely discarded. [source]

Review article: adherence to medication for chronic hepatitis C , building on the model of human immunodeficiency virus antiretroviral adherence research

Summary Background, Treatment of hepatitis C virus (HCV) infection with pegylated interferon/ribavirin achieves sustained virological response in up to 56% of HCV mono-infected patients and 40% of HCV/human immunodeficiency virus (HIV)-co-infected patients. The relationship of patient adherence to outcome warrants study. Aim, To review comprehensively research on patient-missed doses to HCV treatment and discuss applicable research from adherence to HIV antiretroviral therapy. Methods, Publications were identified by PubMed searches using the keywords: adherence, compliance, hepatitis C virus, interferon and ribavirin. Results, The term ,non-adherence' differs in how it is used in the HCV from the HIV literature. In HCV, ,non-adherence' refers primarily to dose reductions by the clinician and early treatment discontinuation. In contrast, in HIV, ,non-adherence' refers primarily to patient-missed doses. Few data have been published on the rates of missed dose adherence to pegylated interferon/ribavirin and its relationship to virological response. Conclusions, As HCV treatment becomes more complex with new classes of agents, adherence will be increasingly important to treatment success as resistance mutations may develop with suboptimal dosing of HCV enzyme inhibitors. HIV adherence research can be applied to that on HCV to establish accurate methods to assess adherence, investigate determinants of non-adherence and develop strategies to optimize adherence. [source]

Impact on adherence and sustained virological response of psychiatric side effects during peginterferon and ribavirin therapy for chronic hepatitis C

Summary Background The psychiatric side effects of interferon, often responsible for dose reduction or treatment discontinuation, represent a major limitation in the treatment of chronic hepatitis C (CHC). Aim To prospectively assess the impact on adherence and sustained virological response (SVR) of the occurrence of psychiatric side effects during peginterferon and ribavirin therapy for CHC. Methods Ninety-eight consecutive treatment-nave CHC patients receiving a standard course of peginterferon plus ribavirin were systematically screened for psychiatric side effects, using DSM-IV, at baseline and both during and after treatment. Results Psychiatric side effects occurred in 38 patients (39%), mostly within the first 12 weeks (87%), and always consisted of mood disorders. Overall, 68% of patients achieved an SVR (71% of patients with mood disorders and 68% of those without; P = N.S.). Peginterferon and ribavirin dose reductions did not differ between patients with mood disorders and those without (46% vs. 37%, respectively; P = N.S. and 13% vs. 22%, respectively; P = N.S.). Anti-viral therapy had to be discontinued in four patients (nonresponse: two, hyperthyroidism: one, psychiatric event: one). Conclusion Early detection and appropriate management of psychiatric side effects during peginterferon and ribavirin therapy for CHC allow optimizing adherence and virological efficacy. [source]

Managing chronic hepatitis C in the difficult-to-treat patient

Nyingi Kemmer
Abstract Patients with chronic hepatitis C virus (HCV) infection and disease-related complications , among them cirrhosis and liver failure , pose a particular management challenge. Some of these patients may fail to respond to current therapy (non-responders), and some are affected so severely that treatment puts them at an unacceptable risk for complications. Treatment with pegylated interferon (peg-IFN) plus ribavirin improves hepatic enzyme levels and eradicates the virus in ,50% of patients; however, a significant number of patients do not respond to therapy or relapse following treatment discontinuation. Several viral, hepatic and patient-related factors influence response to IFN therapy; many of these factors cannot be modified to improve long-term outcomes. Identifying risk factors and measuring viral load early in the treatment can help to predict response to IFN therapy and determine the need to modify or discontinue treatment. Retreatment options for patients who have failed therapy are limited. Retreatment with peg-IFN has been successful in some patients who exhibit an inadequate response to conventional IFN treatment, particularly those who have relapsed. Consensus IFN, another option in treatment-resistant patients, has demonstrated efficacy in the retreatment of non-responders and relapsers. Although the optimal duration of retreatment and the benefits and safety of maintenance therapy have not been determined, an extended duration is likely needed. This article reviews the risk factors for HCV treatment resistance and discusses the assessment and management of difficult-to-treat patients. [source]

Lansoprazole in children: pharmacokinetics and efficacy in reflux oesophagitis

C. Faure
Background: Data on the proton pump inhibitor lansoprazole in paediatric patients are limited. Aim: To investigate the pharmacokinetics, optimal dosage and efficacy of lansoprazole in paediatric patients. Methods: A 24-h gastric pH recording and a pharmacokinetic study were performed after 7 days of lansoprazole, 17 mg/m2, in 23 patients with reflux oesophagitis (median age, 3.5 years). Response was defined as pH > 3 for > 65% of the recording. The dosage was doubled in non-responders. Patients with no response on day 14 were excluded. Responders underwent endoscopy after 4 weeks on the response-inducing dosage; abnormal findings led to a repeat endoscopy after four additional weeks. Results: Nine patients responded to 17 mg/m2 and six to 30.3 mg/m2. On day 7, time with pH > 3 was significantly correlated with the area under the plasma concentration,time curve (P=0.003). The area under the plasma concentration,time curve was significantly greater in the nine responders to 17 mg/m2 than in the 14 other patients. Pharmacokinetic parameters were similar in responders and non-responders to the higher dose. After 4 weeks, oesophagitis was healed in 80% of responders. Adverse events occurred in three patients and required treatment discontinuation in one. Conclusions: Lansoprazole is effective and safe in children. The optimal starting dosage is 30 mg/m2 or 1.4 mg/kg. [source]

Gender Differences in Predictors of Treatment Attrition with High Dose Naltrexone in Cocaine and Alcohol Dependence

Jesse J. Suh PsyD
Recently, we reported that naltrexone at 150 mg/day significantly decreased cocaine and alcohol use for men but not women with co-occurring cocaine and alcohol dependence. The present study is an exploratory investigation of predictors that explain the different gender responses to naltrexone, with a particular focus on differential predictors of treatment attrition. No significant predictors were associated with treatment discontinuation in men. Women, however, were more likely to discontinue treatment when reporting severe pre-treatment psychiatric problems or nausea while in treatment. Further research on the impact of pre-treatment and in-treatment gender differences with naltrexone is warranted. [source]

Sunitinib malate in the treatment of renal cell carcinoma and gastrointestinal stromal tumor: Recommendations for patient management,

Jayesh DESAI
Abstract Sunitinib malate (SU011248, Sutent[Pfizer]) is an oral multitargeted tyrosine kinase inhibitor with efficacy against renal cell carcinoma (RCC) and gastrointestinal stromal tumor (GIST). Sunitinib has been approved by various regulatory authorities for treatment of advanced RCC and unresectable and/or malignant GIST following failure of imatinib mesylate treatment due to resistance or intolerance. Sunitinib is generally well tolerated, with most side-effects being mild to moderate. The most common adverse events are lethargy, diarrhea, stomatitis, hand,foot syndrome and hypertension. Uncommon but important adverse effects are hypothyroidism and hematological toxicity (neutropenia and thrombocytopenia), which require monitoring. Caution is recommended when using concurrent inhibitors or inducers of CYP3A4. The frequency and severity of side-effects often correlates with increased drug exposure. In clinical trials, side-effects seldom led to treatment discontinuation. This paper summarizes the published literature and provides recommendations for patient assessments and management of treatment-related side-effects. [source]

Terazosin for treating symptomatic benign prostatic obstruction: a systematic review of efficacy and adverse effects

T.J. Wilt
Objective To systematically review and evaluate the effectiveness and adverse effects of the ,-antagonist, terazosin, for treating urinary symptoms associated with benign prostatic obstruction (BPO). Methods Studies were sought and included in the review if they were randomized trials of at least 1 month duration, involved men with symptomatic BPO and compared terazosin with placebo or active controls. The study, patient characteristics and outcome data were extracted in duplicate onto standardized forms using a prospectively developed protocol. Results Seventeen studies involving 5151 men met the inclusion criteria, i.e. placebo-controlled (10), ,-blockers (seven), finasteride alone or combined with terazosin and placebo (one), and microwave therapy (one). The study duration was 4,52 weeks; the mean age of the men was 65 years and 82% were white. Baseline urological symptom scale scores and flow rates showed that men had moderate BPO. Efficacy outcomes were rarely reported in a way that allowed for data pooling, but indicated that terazosin improved symptom scores and flow rates more than did placebo or finasteride, and similarly to other ,-antagonists. The pooled mean percentage improvement for the Boyarsky symptom score was 37% for terazosin and 15% for placebo (four studies). The mean percentage improvement for the American Urological Association symptom score was 38%, compared with 17% and 20% for placebo and finasteride, respectively (two studies). The pooled mean improvement in the International Prostate Symptom Score of 40% was similar to that with tamsulosin (43%). Peak urinary flow rates improved more with terazosin (22%) than with placebo (11%) and finasteride (15%), but did not differ significantly from the other ,-antagonists. The percentage of men discontinuing terazosin was comparable with those receiving placebo and finasteride, but greater than with other ,-antagonists. Adverse effects were greater than with placebo and included dizziness, asthenia, headache and postural hypotension. Conclusions The available evidence indicates that terazosin improves the symptoms and flow rates associated with BPO; it was more effective than placebo or finasteride and similar to other ,-antagonists. Adverse effects were generally mild but more frequent than with other ,-antagonists and associated with a two- to four-fold increase in treatment discontinuation. [source]

A prospective study of aromatase inhibitor-associated musculoskeletal symptoms and abnormalities on serial high-resolution wrist ultrasonography

CANCER, Issue 18 2010
N. Lynn Henry MD
Abstract BACKGROUND: Nearly half of women treated with aromatase inhibitors (AI) develop AI-associated musculoskeletal symptoms (AIMSS) such as arthralgias, but to the authors' knowledge the etiology is unclear. The upper extremities are frequently affected, especially the wrists, hands, and fingers. AI use may also increase the risk of developing carpal tunnel syndrome. Tendon sheath fluid and tenosynovial changes have been demonstrated by imaging symptomatic patients who were treated with AIs. The authors hypothesized that these abnormalities are correlated with AIMSS. METHODS: Thirty consecutive patients in whom adjuvant therapy with letrozole or exemestane was initiated on a prospective clinical trial enrolled in a pilot study evaluating tendon and joint abnormalities at baseline and after 3 months of AI therapy. Patients underwent high-resolution ultrasonography of the wrists bilaterally and completed the Health Assessment Questionnaire (HAQ) and pain Visual Analog Scale (VAS). AIMSS were defined as an increase in the HAQ or VAS score during AI therapy that exceeded a predefined cutoff. RESULTS: Twenty-five patients completed both the baseline and 3-month assessments. During the first 12 months of AI therapy, 15 patients developed AIMSS, and 13 discontinued therapy because of musculoskeletal symptoms. There was a trend toward an association between the presence of tendon sheath abnormalities on wrist ultrasound at baseline and the development of AIMSS (P = .06). CONCLUSIONS: Clinically relevant musculoskeletal symptoms develop in women treated with AIs, leading to treatment discontinuation in a substantial percentage of these patients. However, in the current study, patient-reported symptoms were not found to be associated with changes visible on wrist ultrasonography. Cancer 2010. 2010 American Cancer Society. [source]

Insights into reasons for discontinuation according to year of starting first regimen of highly active antiretroviral therapy in a cohort of antiretroviral-nave patients

HIV MEDICINE, Issue 2 2010
P Cicconi
Objectives The aim of the study was to determine whether the incidence of first-line treatment discontinuations and their causes changed according to the time of starting highly active antiretroviral therapy (HAART) in an Italian cohort. Methods We included in the study patients from the Italian COhort Nave Antiretrovirals (ICoNA) who initiated HAART when nave to antiretroviral therapy (ART). The endpoints were discontinuation within the first year of ,1 drug in the first HAART regimen for any reason, intolerance/toxicity, poor adherence, immunovirological/clinical failure and simplification. We investigated whether the time of starting HAART (stratified as ,early', 1997,1999; ,intermediate', 2000,2002; ,recent', 2003,2007) was associated with the probability of reaching the endpoints by a survival analysis. Results Overall, the 1-year probability of discontinuation of ,1 drug in the first regimen was 36.1%. The main causes of discontinuation were intolerance/toxicity (696 of 1189 patients; 58.5%) and poor adherence (285 of 1189 patients; 24%). The hazards for all-reason change were comparable according to calendar period [2000,2002, adjusted relative hazard (ARH) 0.82, 95% confidence interval (CI) 0.69,0.98; 2003,2007, ARH 0.94, 95% CI 0.76,1.16, vs. 1997,1999; global P -value=0.08]. Patients who started HAART during the ,recent' period were less likely to change their initial regimen because of intolerance/toxicity (ARH 0.67, 95% CI 0.51,0.89 vs. ,early' period). Patients who started in the ,intermediate' and ,recent' periods had a higher risk of discontinuation because of simplification (ARH 15.26, 95% CI 3.21,72.45, and ARH 37.97, 95% CI 7.56,190.64, vs. ,early' period, respectively). Conclusions It seems important to evaluate reason-specific trends in the incidence of discontinuation in order to better understand the determinants of changes over time. The incidence of discontinuation because of intolerance/toxicity has declined over time while simplification strategies have become more frequent in recent years. Intolerance/toxicity remains the major cause of drug discontinuation. [source]

Safety and efficacy of peginterferon plus ribavirin in patients with chronic hepatitis C and bridging fibrosis or cirrhosis

F. Marrache
Summary., The combination of pegylated interferon and ribavirin is the most effective therapy in patients with chronic hepatitis C. We evaluated this combination in unselected patients with bridging fibrosis or cirrhosis. Eighty patients were treated with peginterferon alpha-2b plus ribavirin. Hepatitis C virus serum RNA was monitored. Tolerance and safety were evaluated by the rate of treatment's discontinuation for any reason, and occurrence of serious clinical adverse events, respectively. Sustained virologic response (SVR) rate was 36.3% overall, and was observed in every group of patients except those who had previously failed to respond to the combination of interferon and ribavirin. No serious clinical adverse event occurred. Treatment was withdrawn in 18.7% of patients. Variables associated with discontinuation of treatment were low prothrombin index [OR: 1.16 (1.05;1.27)] and low body mass index [OR: 1.47 (1.12;1.92)]. Initial blood count abnormalities were not associated with cessation of treatment. Furthermore, early virologic response at week 8 and week 12 of treatment had similar predictive value for SVR. Combination therapy with peginterferon plus ribavirin seems effective in this group of patients, except in those who had previously failed to respond to the combination of interferon and ribavirin. This therapy is safe with appropriate monitoring, but tolerance seems worse in patients with the most advanced liver disease. [source]