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Treatment Withdrawal (treatment + withdrawal)
Selected AbstractsTime to Cardiac Death After Withdrawal of Life-Sustaining Treatment in Potential Organ DonorsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2009C. Suntharalingam Organ donation after cardiac death (DCD) is increasing markedly, allowing more patients to benefit from transplantation. The time to cardiac death following withdrawal of life-supporting treatment varies widely and is an important determinant of whether organ donation occurs. A prospective multicenter study of potential DCD donors was undertaken to evaluate the time to death and identify associated factors. One hundred and ninety-one potential adult DCD donors at nine UK centers were studied. Treatment withdrawal comprised stopping ventilator support and inotropes. Demographics and physiological variables at the time of death were recorded. Following treatment withdrawal, all potential donors died, with median time to death of 36 min (range 5 min to 3.3 days). Eighty-three potential donors (43.5%) remained alive 1 h after treatment withdrawal, and 69 (36.1%) and 54 (28.3%) at 2 and 4 h, respectively. Univariate analysis revealed that age, cause of death, ventilation mode, inotrope use, systolic blood pressure, FiO2 and arterial pH at treatment withdrawal were all associated with time to death. Multivariable analysis showed that younger age, higher FiO2 and mode of ventilation were independently associated with shorter time to death. This information may aid planning and resourcing of DCD organ recovery and help maximize DCD donor numbers. [source] Overview: End-Stage Renal Disease in the Developing WorldARTIFICIAL ORGANS, Issue 9 2002Rashad S. Barsoum Abstract: Although the vast majority of patients with end-stage renal disease (ESRD) worldwide live in what is called the developing world, little is known about its epidemiology and management. With the current paucity of credible and adequately representative registries, it is justified to resort to innovative means of obtaining information. In this attempt, world-renowned leading nephrologists in 10 developing countries collaborated in filling a 103-item questionnaire addressing epidemiology, etiology, and management of ESRD in their respective countries on the basis of integrating available data from different sources. Through this joint effort, it was possible to identify a number of important trends. These include the expected high prevalence of ESRD, despite the limited access to renal replacement therapy, and the dependence of prevalence on wealth. Glomerulonephritis, rather than diabetes, remains as the main cause of ESRD with significant geographical variations in the prevailing histopathological types. The implementation of different modalities of renal replacement therapy (RRT) is inhibited by the lack of funding, although governments, insurance companies, and donations usually constitute the major sponsors. Hemodialysis is the preferred modality in most countries with the exception of Mexico where chronic ambulatory peritoneal dialysis (CAPD) takes the lead. In several other countries, dialysis is available only for those on the transplant waiting list. Dialysis is associated with a high frequency of complications particularly HBV and HCV infections. Data on HIV are lacking. Aluminum intoxication remains as a major problem in a number of countries. Treatment withdrawal is common for socioeconomic reasons. Transplantation is offered to an average of 4 per million population (pmp). Recipient exclusion criteria are minimal. Donor selection criteria are generally loose regarding tissue typing, remote viral infection, and, in some countries, blood-relation to the recipient in live-donor transplants. Cadaver donors are accepted in many countries participating in this survey. Treatment outcomes with different RRT modalities are, on the average, inferior to the internationally acknowledged standards largely due to infective and cardiovascular complications. [source] A randomized trial of classical and medium-chain triglyceride ketogenic diets in the treatment of childhood epilepsyEPILEPSIA, Issue 5 2009Elizabeth G. Neal Summary Purpose:, To conduct the first randomized trial on classical and medium-chain triglyceride (MCT) versions of the ketogenic diet, examining efficacy and tolerability after 3, 6, and 12 months. Methods:, One hundred forty-five children with intractable epilepsy were randomized to receive a classical or an MCT diet. Seizure frequency was assessed after 3, 6, and 12 months. Treatment withdrawals were documented. Tolerability was assessed by questionnaire, and blood ketone levels were measured. Results:, Of the 61 children who started a classical diet and the 64 who started an MCT diet, data from 94 were available for analysis: 45 classical and 49 MCT. After 3, 6, and 12 months there were no statistically significant differences in mean percentage of baseline seizures between the two groups (3 months: classical 66.5%, MCT 68.9%; 6 months: classical 48.5%, MCT 67.6%; 12 months: classical 40.8%, MCT 53.2%; all p > 0.05). There were no significant differences between groups in numbers achieving greater than 50% or 90% seizure reduction. Serum acetoacetate and ,-hydroxybutyrate levels at 3 and 6 months were significantly higher in children on the classical diet (p < 0.01); this was the case at 12 months for acetoacetate. There were no significant differences in tolerability except increased reports in the classical group of lack of energy after 3 months and vomiting after 12 months. Discussion:, This study has shown classical and MCT ketogenic diet protocols to be comparable in efficacy and tolerability; both ways of implementing the diet have their place in the treatment of childhood epilepsy. [source] A pilot study of interferon alfa and ribavirin combination in liver transplant recipients with recurrent hepatitis CHEPATOLOGY, Issue 5 2002A. Obaid Shakil Although interferon alfa (IFN-,) and ribavirin are widely used in the treatment of hepatitis C, their role in the transplant recipient is unclear. We conducted a pilot study to determine the efficacy and safety of this therapy in transplant recipients with recurrent hepatitis C. Patients at least 6 months posttransplantation were treated with IFN-, 3 million units 3 times a week subcutaneously and ribavirin 800 mg daily by mouth for 48 weeks followed by ribavirin monotherapy for 24 weeks. The primary end point was sustained virologic response, and secondary end points included biochemical, virologic, and histologic responses at the end of combination treatment. Thirty-eight patients initiated therapy but 16 withdrew due to adverse effects, including 2 with myocardial infarction. Median age was 50 years; 74% were men, and 91% had genotype 1. The median interval between transplantation and enrollment was 23 months. On an intention-to-treat basis, 7 patients (18%) had a biochemical and 5 (13%) had a virologic response at the end of combination treatment. Inflammatory activity did not change, but fibrosis worsened in virologic nonresponders. Ribavirin maintenance caused a further decrease in serum alanine aminotransferase levels, but hepatitis C virus (HCV) RNA levels increased. Only 2 of the 38 patients (5%) had a sustained virologic response. Several patients required treatment with erythropoietin for anemia. In conclusion, IFN-, and ribavirin are effective in a small proportion of liver allograft recipients with recurrent hepatitis C. Adverse effects occur commonly, requiring dose reductions and treatment withdrawal. [source] Terlipressin therapy with and without albumin for patients with hepatorenal syndrome: Results of a prospective, nonrandomized studyHEPATOLOGY, Issue 4 2002Rolando Ortega Vasopressin analogues associated with albumin improve renal function in hepatorenal syndrome (HRS). The current study was aimed at assessing the efficacy of the treatment, predictive factors of response, recurrence of HRS, and survival after therapy. Twenty-one consecutive patients with HRS (16 with type 1 HRS, 5 with type 2 HRS) received terlipressin (0.5-2 mg/4 hours intravenously) until complete response was achieved (serum creatinine level < 1.5 mg/dL) or for 15 days; 13 patients received intravenous albumin together with terlipressin. Twelve of the 21 patients (57%) showed complete response. Albumin administration was the only predictive factor of complete response (77% in patients receiving terlipressin and albumin vs. 25% in those receiving terlipressin alone, P = .03). Treatment with terlipressin and albumin was associated with a remarkable decrease in serum creatinine level, increase in arterial pressure, and suppression of the renin-aldosterone system. By contrast, no significant changes in these parameters were found in patients treated with terlipressin alone. Only 1 patient showed ischemic adverse effects. Recurrence of HRS occurred in 17% of patients with complete response. The occurrence of complete response was associated with an improved survival. In conclusion, terlipressin therapy reverses HRS in a high proportion of patients. Recurrence rate after treatment withdrawal is uncommon. Albumin appears to improve markedly the beneficial effects of terlipressin. [source] Recovery of Trabecular and Cortical Bone Turnover After Discontinuation of Risedronate and Alendronate Therapy in Ovariectomized RatsJOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2008Robyn K Fuchs Abstract Alendronate (ALN) and risedronate (RIS) are bisphosphonates effective in reducing bone loss and fractures associated with postmenopausal osteoporosis. However, it is uncertain how long it takes bone turnover to be re-established after treatment withdrawal, and whether this differs between the two drugs. The objective of this study was to determine the time required to re-establish normal bone turnover after the discontinuation of ALN and RIS treatment in an animal model of estrogen-deficiency osteoporosis. Two hundred ten, 6-mo-old female Sprague-Dawley rats were ovariectomized and 6 wk later were randomized into baseline controls (n = 10) and four treatment groups (n = 50/group): vehicle-treated controls (CON; 0.3 ml sterile water), ALN (2.4 ,g/kg), low-dose RIS (RIS low; 1.2 ,g/kg), and high-dose RIS (RIS high; 2.4 ,g/kg). Treatments were administered 3 times/wk by subcutaneous injection. Baseline controls were killed at the initiation of treatment. Other groups were treated for 8 wk, and subgroups (n = 10/ treatment group) were killed 0, 4, 8, 12, and 16 wk after treatment was withdrawn. Static and dynamic histological analyses were performed for cortical (tibial diaphysis) and trabecular (proximal tibia and L4 vertebrae) bone. DXA and mechanical testing was performed on the L5 vertebra. After 8 wk of treatment, trabecular bone turnover rates were significantly suppressed in all drug-treated animals. Trabecular bone formation rate (BFR/BS) remained significantly lower than vehicle in bisphosphonate-treated animals through 12 wk. Sixteen weeks after treatment withdrawal, trabecular BFR/BS in the proximal tibia was re-established in animals treated with RIS but not in animals treated with ALN compared with controls. BMD of the fifth lumbar vertebra remained significantly higher than controls 16 wk after treatment withdrawal in ALN-treated animals but not in RIS-treated animals. Despite reductions in BMD and increases in bone turnover, ultimate force of the fifth lumbar vertebra remained significantly higher in all drug-treated animals through 16 wk after withdrawal. [source] Autoimmune liver diseases in a paediatric population with coeliac disease , a 10-year single-centre experienceALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2010A. R. DI BIASE Summary Backgroud, Coeliac disease (CD) can be associated with liver disease. Gluten-free diet (GFD) normalizes cryptogenic forms, but most likely not autoimmune hepatitis (AIH). For this condition, immunosuppressants represent the treatment. However, when these are stopped, AIH generally relapses. Aim, To determine in CD children liver test abnormality frequency, the effect of GFD alone, or plus prolonged immunosuppressants on AIH course. Methods, Coeliac disease patients with abnormal transaminases were selected; if transaminases <5 × UNL (upper normal limits), GFD alone was administered; if >5 × UNL, liver examinations and biopsy were performed. In AIH, immunosuppressants were administered (5 years). Treatment was stopped only if patients remained in remission during the entire maintenance period and normalized liver histology. Results, A total of 140 out of 350 CD children had hypertransaminaemia: 133 cryptogenic disease, 7 AIH. GFD normalized only cryptogenic hepatitis. During treatment, all AIH persistently normalized clinical and biochemical parameters; after withdrawal, six patients maintained a sustained remission (follow-up range: 12,63 months), while one relapsed. Conclusions, In CD children with AIH, only GFD plus immunosuppressants determines a high remission rate. When clinical remission is reached, a prolonged immunosuppressive regimen induces a high sustained remission rate after treatment withdrawal, indicating that this regimen may prevent early relapse. Aliment Pharmacol Ther,31, 253,260 [source] Treatment of chronic hepatitis C in polytransfused thalassaemic patients: a meta-analysisJOURNAL OF VIRAL HEPATITIS, Issue 4 2010S.-M. Alavian Summary., Hepatitis C virus (HCV) infection is a major cause of liver-related morbidity and mortality among thalassaemic patients. In order to analyse the effect of the current anti-HCV treatment in this subset of HCV-infected patients, we conducted a systematic review with meta-analysis of the available literature. The outcome was sustained viral response. Both comparative [odds ratio (OR)] and non-comparative indeces (success rate) were used to run the meta-analytical procedure. Data encompassing 429 thalassaemic HCV-infected patients treated with conventional or pegylated interferon monotherapy or combination therapy with ribavirin were collected from 13 articles (10 prospective cohort studies, 1 randomized-controlled trial and 2 controlled trials). Pooled sustained viralogical response (SVR) was 44.7% (34.6,54.9). Pooled ORs of SVR for Genotype 1 vs non-Genotype 1 infected thalassaemic patients were 0.46 (95% CI: 0.22,0.95) in IFN monotherapy and 1.7 (95% CI: 0.46,6.04) in ribavirin combination therapy. Our meta-analysis shows that thalassaemic patients with Genotype 1 infection significantly benefit from the addition of ribavirin to their therapeutic regimen. It seems that using ribavirin in thalassaemic patients increases transfusion need by a median of 30,40%, but does not increase major adverse events or treatment withdrawal. Current literature is lacking sufficient evidence about the use of PEG-IFN as monotherapy or in combination with ribavirin in thalassaemic patients. [source] Consequences of treatment withdrawal in type 1 autoimmune hepatitisLIVER INTERNATIONAL, Issue 4 2007Aldo J. Montano-Loza Abstract Background and Aims: Drug-related side effects are considered the major consequences of relapse and re-treatment in patients with autoimmune hepatitis. Our goals were to determine whether relapse is associated with disease progression and whether treatment end points can be refined. Methods: The outcomes of 132 patients with definite type 1 autoimmune hepatitis who had been treated comparably until remission were assessed retrospectively after drug withdrawal. Results: Patients who had relapsed repeatedly after initial treatment withdrawal developed cirrhosis more commonly than patients who sustained remission (18/48 vs 1/22, P=0.004), and those who relapsed once (18/48 vs 2/21, P=0.02). Hepatic death or the need for liver transplantation was also more frequent in the patients who had multiple relapses than those who sustained remission (13/64 vs 0/30, P=0.008) and those who relapsed once (13/64 vs 1/38, P=0.02). Patients who sustained their remission had a higher frequency of normal laboratory indices at drug withdrawal than patients who relapsed (88% vs 46%, P=0.003). Adverse outcomes after relapse did not distinguish patients until after 5 years of observation. Conclusions: Multiple relapses are associated with a poorer prognosis than sustained remission or single relapse episodes. Initial treatment to resolution of laboratory abnormalities may afford the greatest opportunity to prevent relapse. [source] Time to Cardiac Death After Withdrawal of Life-Sustaining Treatment in Potential Organ DonorsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2009C. Suntharalingam Organ donation after cardiac death (DCD) is increasing markedly, allowing more patients to benefit from transplantation. The time to cardiac death following withdrawal of life-supporting treatment varies widely and is an important determinant of whether organ donation occurs. A prospective multicenter study of potential DCD donors was undertaken to evaluate the time to death and identify associated factors. One hundred and ninety-one potential adult DCD donors at nine UK centers were studied. Treatment withdrawal comprised stopping ventilator support and inotropes. Demographics and physiological variables at the time of death were recorded. Following treatment withdrawal, all potential donors died, with median time to death of 36 min (range 5 min to 3.3 days). Eighty-three potential donors (43.5%) remained alive 1 h after treatment withdrawal, and 69 (36.1%) and 54 (28.3%) at 2 and 4 h, respectively. Univariate analysis revealed that age, cause of death, ventilation mode, inotrope use, systolic blood pressure, FiO2 and arterial pH at treatment withdrawal were all associated with time to death. Multivariable analysis showed that younger age, higher FiO2 and mode of ventilation were independently associated with shorter time to death. This information may aid planning and resourcing of DCD organ recovery and help maximize DCD donor numbers. [source] A Multicenter Study of Valganciclovir Prophylaxis up to Day 120 in CMV-Seropositive Lung Transplant RecipientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2009V. Monforte Seventy-six cytomegalovirus (CMV)-seropositive lung transplant recipients receiving valganciclovir (900 mg/day) for CMV prophylaxis were compared with a group of 87 patients receiving oral ganciclovir (3000 mg/day). Prophylaxis was administered to day 120 post-transplantation and follow-up was 1 year. In addition, a study was conducted on risk factors for CMV infection/disease. CMV disease incidence was 7.9% and 16.1% for valganciclovir and oral ganciclovir, respectively (p = 0.11). Patients receiving valganciclovir had fewer viral syndromes (2.6% vs. 11.5%, p < 0.05), a similar rate of tissue-invasive disease (5.2% vs. 4.6%, p = ns), longer time-to-onset of CMV infection/disease (197.5 vs. 155.2 days, p < 0.05), and a lower probability of infection/disease while on prophylaxis (1.3% vs. 12.6%, p < 0.01). Nonetheless, leukopenia incidence was higher with valganciclovir (15.8% vs. 2.3%, p < 0.01), as was the need for treatment withdrawal due to adverse effects (11.8% vs. 1.1%, p < 0.01). CMV infection was similar in both groups (32.9% vs. 34.5%). Induction therapy with basiliximab and glucocorticosteroid treatment were independent risk factors for developing CMV infection/disease. In conclusion, valganciclovir prophylaxis results in a low incidence of CMV disease in lung transplant recipients and appears more effective than oral ganciclovir. Despite the comparatively higher incidence of adverse events with valganciclovir, the drug can be considered safe for prophylaxis. [source] Time course of serum inhibitory activity for facilitated allergen,IgE binding during bee venom immunotherapy in childrenCLINICAL & EXPERIMENTAL ALLERGY, Issue 9 2009E-M Varga Summary Background Immunotherapy for bee venom allergy is effective and provides long-term protection. Venom-specific IgG4 levels are increased but with no correlation with clinical improvement. Following grass pollen immunotherapy, elevation of antigen-specific IgG4 is accompanied by increases in IgG-dependent serum inhibitory activity for IgE-facilitated binding of allergen,IgE complexes to B cells. As this ,functional' assay of inhibitory antibodies may be more predictive of clinical efficacy, we investigated the time course of serum inhibitory activity for IgE-facilitated antigen binding during venom immunotherapy (VIT) in children and following 2 years of VIT withdrawal. Methods Ten bee venom-allergic children (mean age: 9.3 years; m/f, 7/3) with moderate to severe allergic reactions to bee stings received VIT. A separate group of seven children (mean age: 14 years; m/f, 5/2) were investigated 2 years after VIT withdrawal. Ten age- and gender-matched children served as non-allergic controls. Allergen-specific serum IgG4 and IgE levels were measured by ELISA at baseline, after 2 years of VIT and 2 years after VIT withdrawal. Serum inhibitory activity was assessed using the facilitated-allergen binding (FAB) assay. Results Sera obtained during VIT significantly inhibited allergen,IgE binding to B-cells (pre-treatment=104±23%; 2 years=46±15%; P<0.001) when compared with sera obtained after treatment withdrawal and sera from normal controls. In parallel to FAB inhibition during VIT, significantly higher IgG4 levels were noted after immunotherapy (pre-treatment=8.6±2.3 AU; 2 years=26.7±3.5 AU; P<0.001) compared with those observed after withdrawal and in the controls. In contrast, progressively lower IgE concentrations were observed compared with pre-treatment (44±7 AU) in sera obtained after 2 years of VIT (25±5 AU; P<0.01) and 2 years following the withdrawal of VIT (10±3 AU; P<0.05). Conclusions In contrast to grass pollen immunotherapy, the persistent decline in venom-specific IgE levels, rather than serum inhibitory activity for FAB, may be more relevant for long-term clinical efficacy of VIT. [source] Comparing the safety, tolerability and quality of life in patients with chronic hepatitis B vs chronic hepatitis C treated with peginterferon alpha-2aLIVER INTERNATIONAL, Issue 4 2008Patrick Marcellin Abstract Background/Aims: Hepatitis B and C viruses (HBV and HCV) are two clinically distinct but related diseases. Pooled data from five studies of peginterferon alpha-2a in patients with chronic HCV infection (CHC) were compared with two studies of the drug in patients with chronic HBV infection (CHB). Method: The HBV studies included both hepatitis B e antigen (HBeAg)-positive (n=271) and HBeAg-negative (n=177) patients; 791 patients took part in the HCV trials. In all studies, patients were treated with 180 ,g peginterferon alpha-2a monotherapy once weekly for 48 weeks. The number of adverse events (AEs), discontinuations and dose modifications were documented. Health-related quality of life (HRQL) was assessed using the Short-Form 36 questionnaire. Safety was assessed throughout the treatment period. A 24-week treatment-free follow-up period was also included. Results: Differences (HBV vs HCV) were observed in the incidence of AEs (88,89 vs 96,100%), serious AEs (4,5 vs 7,16%) and treatment withdrawals (6,8 vs 17,33%). The frequency of depression-related events was lower in CHB patients (4 vs 22%, P<0.001), as was the impact of treatment on HRQL. Conclusions: The safety and tolerability of peginterferon alpha-2a in patients with CHB compares favourably with that observed in CHC patients, with a lower incidence of common interferon-related AEs and a significantly lower incidence of depression. [source] An evaluation of the usefulness of mycophenolate mofetil in pemphigusBRITISH JOURNAL OF DERMATOLOGY, Issue 1 2003A.M. Powell SummaryBackground Pemphigus is a group of autoimmune blistering diseases of the skin and/or mucous membranes requiring management with immunosuppressive therapy. The optimal therapeutic regimen would rapidly induce remission and maintain effectiveness with minimal adverse effects in the long term. Objectives The present study describes our experience of the addition of mycophenolate mofetil (MMF) to prednisolone in the management of severe, refractory pemphigus. Methods Patients with active, refractory pemphigus were treated with MMF. Our series included 12 cases of pemphigus vulgaris, four cases of pemphigus foliaceous and one case of paraneoplastic pemphigus. All patients were monitored to assess disease control and mycophenolate toxicity. Results Of the 17 cases, MMF has been of benefit to 12. MMF was well tolerated and there were no treatment withdrawals because of safety concerns. Conclusions We found that MMF permitted a reduction in prednisolone dosage without disease relapse. [source] | ||||||||||||||||||||||