Efficacy and safety of sofosbuvir-based regimens in chronic hepatitis C patients on dialysis

Introduction

Patients with end-stage renal disease (ESRD) have poor treatment tolerance and outcome to interferon-based regimens. Sofosbuvir-based regimens have improved treatment success in chronic hepatitis C. There is limited data in ESRD patients as sofosbuvir is excreted by the kidney. Several small studies have shown good results.

Methods

Sixteen consecutive patients of ESRD (on dialysis) and chronic hepatitis C were treated with sofosbuvir-based regimens as they were prospective kidney transplantation recipients, at a tertiary care center in north India. Sofosbuvir was given 400 mg on alternate days. Data is shown as number, mean (SD), and median (range).

Results

Sixteen patients (12 males) aged 45±12 years received sofosbuvir-based treatment. These patients were on hemodialysis from 10 (2–48) months. Eleven of these patients had genotype 1, four had genotype 3, and one had genotype 4 infection; baseline RNA was 7 (5–8) log. The following treatment regimens were used: sofosbuvir, ribavirin, and low dose peginterferon (n = 8; 6 genotype 1 and one each had genotype 3 and 4); sofosbuvir and daclatasvir (n = 7); sofosbuvir, ribavirin, and daclatasvir (n = 1). Ten patients achieved end of treatment response and 8 (80%) of these achieved sustained virological response at 12 weeks (SVR12); six are on treatment. Two patients with genotype one (including one with cirrhosis) had relapse. Seven patients needed blood transfusion; interferon was stopped in one due to thrombocytopenia. Fatigue was present in 4 patients.

Conclusion

Sofosbuvir-based regimens can be used in ESRD patients on dialysis with good efficacy.

     

Sertraline hydrochloride treatment for patients with hemodialysis hypotension

BACKGROUND: Recently some pathogenetic parallels have been drawn between dialysis-induced hypotension and disorders characterized by hemodynamic instability due to autonomic dysfunction, such as neurocardiogenic syncope and idiopathic orthostatic hypotension. Several studies have shown that central serotonergic pathways participate in the abnormal response, and selective serotonin reuptake inhibitors improve the symptoms of patients with neurocardiogenic syncope or idiopathic orthostatic hypotension. In order to evaluate the effectiveness of sertraline on dialysis-induced hypotension a prospective study was designed. METHODS: The data of 9 patients from a 4-week pre-sertraline period were compared with the data of a 4-week sertraline (100 mg daily) period. The therapeutic effect of sertraline requires 4 weeks. Therefore the sertraline period was begun 4 weeks after starting the drug. RESULTS: Post-hemodialysis weights and ultrafiltration volumes were similar in the pre-sertraline and sertraline periods. There were also no changes in hematocrit and serum albumin. Both systolic and diastolic blood pressure before dialysis remained unchanged during sertraline treatment. The nadir systolic blood pressure and systolic blood pressure after dialysis increased significantly in the sertraline period. The nadir diastolic pressure was also increased significantly but the increase in post-dialysis diastolic blood pressure did not reach statistical significance. The necessity of therapeutic interventions per dialysis session decreased significantly in the sertraline period compared with pre-sertraline period. CONCLUSIONS: This pilot study has shown that sertraline has the potential to be a safe and effective therapy for dialysis hypotension. Long-term clinical and pathophysiological studies are currently in progress.     

Safe and effective sofosbuvir-based therapy in patients with mental health disease on hepatitis C virus treatment

AIM To study impact of baseline mental health disease on hepatitis C virus(HCV) treatment; and Beck's Depression Inventory(BDI) changes with sofosbuvir- andinterferon-based therapy.METHODS This is a retrospective cohort study of participants from 5 studies enrolled from single center trials conducted at the Clinical Research Center of the National Institutes of Health, Bethesda, MD, United States. All participants were adults with chronic HCV genotype 1 infection and na?ve to HCV therapy. Two of the studies included HCV mono-infected participants only(SPARE, SYNERGY-A), and 3 included human immunodeficiency virus(HIV)/HCV co-infected participants only(ERADICATE, PFINPK, and ALBIN). Patients were treated for HCV with 3 different regimens: Sofosbuvir and ribavirin in the SPARE trial, ledipasvir and sofosbuvir in SYNERGY-A and ERADICATE trials, and pegylated interferon(IFN) and ribavirin for 48 wk in the PIFNPK and ALBIN trials. Participants with baseline mental health disease(MHD) were identified(defined as either a DSM Ⅳ diagnosis of major depression, bipolar disorder, schizophrenia, generalized anxiety, and post-traumatic stress disorder or requiring anti-depressants, antipsychotics, mood stabilizers or psychotropics prescribed by a psychiatrist). For our first aim, we compared sustained virologic response(SVR) and adherence(pill counts, study visits, and in 25 patients, blood levels of the sofosbuvir metabolite, GS-331007) within each study. For our second aim, only patients with HIV coinfection were evaluated. BDI scores were obtained pre-treatment, during treatment, and post-treatment among participants treated with sofosbuvir-based therapy, and compared to scores from participants treated with interferon-based therapy. Statistical differences for both aims were analyzed by Fisher's Exact, and t-test with significance defined as a P value less than 0.05.RESULTS Baseline characteristics did not differ significantly between all participants with and without MHD groups treated with sofosbuvir-based therapy. Among patients treated with sofosbuvir-based therapy, the percentage of patients with MHD who achieved SVR was the same as those without(SPARE: 60.9% of those MHD compared to 67.6% in those without, P = 0.78; SYNERGY-A: 100% of both groups; ERADICATE: 100% compared to 97.1%). There was no statistically significant difference in pill counts, adherence to study visits between groups, nor mean serum concentrations of GS-331007 for each group at week 2 of treatment(P = 0.72). Among patients with HIV co-infection, pre-treatment BDI scores were similar among patients treated with sofosbuvir, and those treated with interferon(sofosbuvir-based 5.24, IFN-based 6.96; P = 0.14); however, a dichotomous effect on was observed during treatment. Among participants treated with directly acting antiviral(DAA)-based therapy, mean BDI scores decreased from 5.24(pre-treatment) to 3.28 during treatment(1.96 decrease, P = 0.0034) and 2.82 post-treatment. The decrease in mean score from pre- to post-treatment was statistically significant(-2.42, P = 0.0012). Among participants treated with IFN-based therapy, mean BDIscore increased from 6.96 at pre-treatment to 9.19 during treatment(an increase of 2.46 points, P = 0.1), and then decreased back to baseline post-treatment(mean BDI score 6.3, P = 0.54). Overall change in mean BDI scores from pre-treatment to during treatment among participants treated with DAA-based and IFN-therapy was statistically significant(-1.96 and +2.23, respectively; P = 0.0032). This change remained statistically significant when analysis was restricted to participants who achieved SVR(-2.0 and +4.36, respectively; P = 0.0004).CONCLUSION Sofosbuvir-based therapy is safe and well tolerated in patients with MHD. A decline in BDI associated with sofosbuvir-based HCV treatment suggests additional MHD benefits, although the duration of these effects is unknown.     

维持性血液透析患者他汀类调脂治疗

脂代谢紊乱是诱发心脑血管事件的重要危险因素,已有大量研究证实,应用他汀类药物调脂治疗对心脑血管的保护作用.维持性血液透析(MHD)患者常伴严重的脂代谢异常,心脑血管疾病亦是MHD患者的主要死亡原因.因此,他汀类药物能否降低MHD患者心脑血管事件的发生率及相关死亡率已成为近来研究热点之一.本文对他汀类药物应用于MHD患者的临床研究进展作一综述.     

Multidrug regimens for treatment of older patients with metastatic pancreatic cancer

Background and AimsOlder patients with metastatic pancreatic adenocarcinoma (MPDAC) are under-represented in clinical trials.MethodsOur single-center, retrospective study enrolled MPDAC patients ≥ 70 treated with chemotherapyResults105 patients were divided in groups based on the received treatments: 44 gemcitabine or capecitabine monotherapy (A), 34 nabpaclitaxel-gemcitabine (B) 27 4-drugs combinations (gemcitabine, cisplatin, capecitabine plus either nab-paclitaxel or epirubicin or docetaxel) (C). Group A: median age was 78 (70–87) and Karnofsky performance status (KPS) ≥80 was found in 84% of patients; Group B: median age 77 (71–84) and KPS ≥ 80 in 88% of patients; Group C: median age 73 (70–78) and KPS ≥ 80 in 93% of patients. Median OS was 7.9, 11.7 and 14.2 months in group A, B and C respectively; 1 and 2-year OS were 27% and 8% in group A; 44% and 5% in group B; 52% and 22% in group C. When lung metastatic only patients were excluded, patients <75 and ≥ 75 had similar OS in group A (6.4 vs 5.6 months) and in group B (12.3 vs 11.1 months). In group B grade 3 thrombocytopenia, fatigue and peripheral neuropathy were more frequent in patients ≥ 75.ConclusionsIn older patients, combination chemotherapy shows acceptable feasibility and promising efficacy.     

血管内带膜支架置入术在主动脉夹层治疗中的初步应用

目的 :探讨血管内带膜支架置入术治疗主动脉夹层的疗效。方法 :采用MedtronicTalentTM带膜支架置入治疗 5例StanfordB型亚急性期主动脉夹层患者 ,在全麻、数字减影血管造影术 (DSA)监控下 ,切开股动脉 ,将带膜支架系统置入降主动脉内膜破裂口处 ,封闭破口。结果 :所有患者带膜支架置入后破口完全封闭 ,真腔血流恢复正常 ,技术成功率 10 0 %。无急诊开胸手术、截瘫、瘤体破裂等严重并发症 ,无围手术期死亡。 1例术中发生新的StanfordA型夹层 ,所有患者在 1～ 8[平均 (4 .5 5± 2 .1) ]个月的随访期内经螺旋CT证实无内漏及支架移位等并发症发生。结论 :血管内带膜支架置入术治疗亚急性降主动脉夹层具有技术可靠、安全性高、术后恢复快、手术成功率高等优点 ,可望部分替代外科开胸手术     

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糖尿病肾病(DN)发展到终末期的过程是可以延缓但却是不可逆的。近年国内外报道,肾脏替代治疗人群源于DN逐年增多,美国DN在透析患者中占40%,以2型糖尿病居多[1]。目前我国DN发病率也呈上升趋势,已占透析患者的13.5%,我院统计为8.2%[2]。1充分血液透析延缓糖尿病肾病进展糖尿病导致DN的主要机制是高血糖、高血压、高血脂、内分泌紊乱、血流动力学异常以及微血管结构损害,还包括透析相关因素、遗传因素等[3]。DN早期干预的目的是减慢肾病进展速度,预防高血压和血脂代谢紊乱等导致的心血管并发症。干预重点是在充分透析的基础上控制血糖和…     

重视维持性血液透析患者的整体治疗

临床实践表明 ,在充分透析的基础上 ,重视对透析患者的整体治疗 ,则有助于提高透析效率 ,延长维持性透析患者的存活期和改善生存质量。一、对尿毒症毒素的新认知及透析的治疗作用据悉 ,各种肾病的终末期 (尿毒症 )体内有 2 0 0多种代谢产物水平增高 ,其中绝大多数对人体有害 ,例如已确认的毒素有尿素、尿酸、肌酐、胍类等 ;重新认识的毒素有甲状旁腺激素[1] 、β2 微球蛋白(β2 ＭＧ)等 ;近年新确认的毒素有马尿素、吲跺酚硫酸酯 (ｉｎｄｏｘｙｌｓｕｌｆａｔｅ)、对 甲酚 (Ｐ ｃｒｅｓｏｌ)、抑制免疫细胞活性的抑制蛋白 (ＧＩＰ、ＣＩ…     

Split-drug regimens for the treatment of patients with sputum smear-positive pulmonary tuberculosis--a unique approach

OBJECTIVE: To evaluate the efficacy of split-drug regimens for treatment of patients with sputum smear-positive pulmonary tuberculosis in south India. DESIGN: Randomized controlled clinical trial where eligible patients were randomly allocated to: (i) 2RE(3)HZ(3)(alt)/4RH(2) (split I): rifampicin plus ethambutol given on one day and isoniazid plus pyrazinamide the next day for first 2 months followed by rifampicin plus isoniazid twice weekly for 4 months, or (ii) 3RE(3)HZ(3)(alt)/3RH(2) (split II): similar to regimen 1, except duration was 3 months in each phase, or (iii) 2REHZ(3)/4RH(2) (control): rifampicin, isoniazid, ethambutol and pyrazinamide, given thrice weekly for 2 months followed by isoniazid and rifampicin twice weekly for 4 months. All patients were followed up clinically and bacteriologically every month up to 2 years and every 6 months for up to 5 years. RESULTS: A favourable response (cultures negative for Mycobacterium tuberculosis during the last 2 months of treatment) was observed in 91% of 407 patients in split I, 94% of 415 in split II and 89% of 418 in the control regimen. Ninety-one per cent of 370 patients in split I, 93% of 389 in split II and 90% of 370 in control regimens had quiescent disease at the end of 60 months. Gastrointestinal symptoms were more frequent under the control regimen (P = 0.01). CONCLUSION: Split-drug regimens were as effective as the control regimen in terms of favourable response at the end of treatment and quiescent disease at 5 years, and caused fewer gastrointestinal side-effects.     

Approach to treatment of patients with virologic failure to multiple regimens

Second-line and rescue antiretrovirals regimens have a poor success record only 30-45% achieves viral suppression. This rate will be improved if salvage therapy is individualized with a better understanding what causes previous failures, establishing reasonable goals of therapy for the patient and speaking with him about the pros and the cons of the new regimens.Before deciding the change we must have available the first and the present HIV RNA levels, absolute CD4 T cell count and changes in these counts, prior antiretroviral therapies, resistance test, assessment of adherence to medications, and preparation of the patient for the implications of the new regimens. Carrying out drug salvage levels and the inhibitory quotient probably can be important.In patients on therapy with detectable but low (< 5,000 copies/ml) stable HIV RNA levels the risk of clinical or immunologic failure is low. Recent reports provide support for a conservative strategy, particularly for those patients with limited therapeutic options.In-patients who are failing their second regimen it is important to use at least two new susceptible drugs, with a high potency and using combinations that assure high drug levels. In this population treatment interruption as a strategy for managing drug resistance is in study.New therapies such as DAPD, tenofovir, TMC 120, lopinavir, tipranavir and T-20 offer significant promise for the treatment of drug-experienced patients.     

Treatment regimens for patients with chronic hepatitis C

Infection by the hepatitis C virus (HCV) is a major public health problem, with more than 170 million people infected throughout the world. The infection prevalence, with small regional differences, is estimated in 1-3% of the global population. HCV is the most frequent cause of chronic liver disease and 20-30% of patients develop cirrhosis with a risk of hepatocellular carcinoma. Nowadays, pegylated interferon-a (PEG-IFN) in combination with ribavirin, a nucleoside analogue, is the current treatment for chronic hepatitis C (CHC), with less adverse effects and better compliance. Dosage and duration depend on some factors as weight, genotype, viral load and a rapid virological response presented by the patient. One of the most relevant aspects in the treatment of CHC is how to manage the group of non-responder or relapser patients to previous treatments. As such, a substantial proportion of patients had already been unsuccessfully treated with interferon-based therapies and these patients claim for an optimal therapeutic option. The future treatment of CHC walk along through the association of two or three drugs, including nucleoside/nucleotide analogues, higher PEG-IFN initial dosages (induction) or longer treatments duration, or combination of helicase and protease inhibitors.     

Preliminary experience with anterior interbody titanium cage fusion for treatment of cervical disc disease

This study evaluated the efficacy and safety of titanium cage implants in cervical reconstruction to treat cervical spondylosis. Surgical data covered a 4-year period from January 1999 to December 2002 and included 34 consecutive patients, 20 men and 14 women, with ages ranging from 27 to 84 years (mean, 57 years). Patients underwent anterior cervical microdiscectomy followed by interbody fusion with a titanium cage implant (rather than an autogenous iliac crest bone graft) at a single level ranging from C3 to C7. Twenty-one patients had a herniated intervertebral disc, nine had degenerative disc disease, and four had previous failed autograft fusion surgery that required revision. At clinical presentation, 26 patients had neck pain, 23 had radiculopathy, and nine had myelopathy. Diagnostic imaging studies included spinal dynamic roentgenography, computerized tomography, and magnetic resonance imaging. Lesions were located at C3-4 in seven cases, C4-5 in 14 cases, C5-6 in nine cases, and C6-7 in four cases. The follow-up period ranged from 7 to 48 months (mean, 26 months). Results revealed that the procedure was technically feasible. There were no intra- or postoperative complications. The most commonly used cage was 9 mm high. Imaging studies showed no cage instability, migration, or pseudarthrosis. Although mild subsidence (< 5 mm) was observed in three cases, these patients preserved adequate postoperative cervical lordosis and the subsidence did not preclude a good clinical result. The advantages of this procedure over a similar operation using traditional tricorticate bone graft are: no graft morbidity; shorter operation time (mean time saved, 35 minutes); reduced blood loss (average blood loss, 75 mL); and early postoperative ambulation (mean, 4.7 hospital days). Nearly all patients rapidly lost their neck pain (92%, 24/26) and radicular symptoms (87%, 20/23) after surgery. The recovery rate from myelopathy was 44% (4/9). Progressive bony shield formation over the anterior/posterior cortex (sentinel sign) indicated fusion in five cases.     

Nonresponses and treatment failures with conventional empiric regimens in patients with community-acquired pneumonia

Although most patients with suspected CAP respond to empiric therapy,a small number of patients do not respond in the expected fashion. Age and underlying comorbid conditions have a strong influence on the course of illness. Less common causes of treatment failures include overwhelming infection, antimicrobial resistance, and misdiagnosis. It is a common practice for empiric antimicrobial treatment of CAP to be initiated without microbiologic studies. Clinicians carefully should observe these patients for unusual or slow responses and should be ready to pursue a more extensive search for the cause of treatment failure.