Weight-based high- and low-dose ribavirin in combination with peginterferon α-2b therapy for genotype 2 chronic hepatitis C: A randomized trial

Aim: The optimal ribavirin dose in the treatment of patients infected with hepatitis C virus (HCV) genotype 2 remains to be elucidated. We aimed to seek the optimal ribavirin dose required for this genotype in a randomized trial. Methods: We compared the efficacy and tolerability of the 24‐week peginterferon α‐2b (1.5 µg/kg/week) therapy in combination with a weight‐based higher dose (600–1000 mg) and lower dose (400–800 mg) of ribavirin for genotype 2 patients. Noninferior margin was set at 10%. Results: A total of 120 patients were randomized to a higher‐dose or a lower‐dose group. Sustained virological response (SVR) by intention‐to‐treat analysis was achieved in 47/58 (81.0%, 90% confidential interval [CI]: 72.6–89.5) patients in the higher‐dose group and 41/60 (68.3%, 90% CI: 58.5–78.2) patients in the lower‐dose group (difference, ?12.7%; 90% CI, ?25.7 to 0.3). Relapse rates were 10% and 21.6% in the higher‐dose and the lower‐dose groups, respectively. Multiple logistic regression analysis showed that ribavirin dose/kg body weight was the only significant predictor of SVR (≥9.5 mg/kg per day vs <9.5 mg/kg per day; odds ratio = 3.34; 95% CI, 1.41–7.92; P = 0.006). Twenty‐one (36.2%) in the higher‐dose group required ribavirin dose reduction because of anemia, whereas seven patients (11.7%) did in the lower‐dose group (P < 0.01). Three of the higher‐dose group and two of the lower‐dose group required premature termination of therapy. Conclusions: Weight‐based lower‐dose ribavirin regimen was not equivalent to the higher‐dose counterpart in the treatment of HCV genotype 2. We discourage treating these patients with low‐dose ribavirin regimens. The peginterferon therapy in combination with ribavirin at a weight‐based higher dose (600–1000 mg) remains the standard‐of‐care treatment for this genotype.     

Treatment outcome for systemic chemotherapy for recurrent pancreatic cancer after postoperative adjuvant chemotherapy

ObjectivesA global consensus on how to treat recurrent pancreatic cancer after adjuvant chemotherapy with gemcitabine (ADJ-GEM) does not exist.MethodsWe retrospectively reviewed the clinical data of 41 patients with recurrences who were subsequently treated with chemotherapy.ResultsThe patients were divided into two groups according to the time until recurrence after the completion of ADJ-GEM (ADJ-Rec): patients with an ADJ-Rec < 6 months (n = 25) and those with an ADJ-Rec ≥ 6 months (n = 16). The disease control rate, the progression-free survival after treatment for recurrence and the overall survival after recurrence for these two groups were 68 and 94% (P = 0.066), 5.5 and 8.2 months (P = 0.186), and 13.7 and 19.8 months (P = 0.009), respectively. Furthermore, we divided the patients with an ADJ-Rec < 6 months into two groups: patients treated with gemcitabine (n = 6) and those treated with alternative regimens including fluoropyrimidine-containing regimens (n = 19) for recurrent disease. Patients treated with the alternative regimens had a better outcome than those treated with gemcitabine.ConclusionsFluoropyrimidine-containing regimens may be a reasonable strategy for recurrent disease after ADJ-GEM and an ADJ-Rec < 6 months.     

Comparison of characteristics and therapeutic efficacy in rheumatoid arthritis patients treated by rheumatologists and those treated by orthopedic surgeons under a team medicine approach at the same institute

The treatment of rheumatoid arthritis (RA) has improved dramatically with the advent of the latest generation of disease-modifying antirheumatic drugs. Despite these advances, in some patients inflammation is not diminished sufficiently to prevent irreversible musculoskeletal damage, thereby necessitating surgical intervention to reduce pain and improve function. For RA treatment, Japanese orthopedic surgeons also prescribe medication. In this study, we examined whether this Japanese system is effective for RA treatment. We analyzed the clinical condition of RA patients treated by rheumatologists and those treated by orthopedists in a linked registry study using information from a large observational cohort of RA patients followed every half year from 2000 to 2010 (the IORRA cohort). Two groups of patients were compared: patients treated by rheumatologists (rheumatologic group) and patients treated by orthopedists (orthopedic group). The results revealed that patients in the orthopedic group were older, more likely to be female, and had a longer disease duration than patients in the rheumatologic group. The proportion of patients with a history of joint surgery was also much higher in the orthopedic group than in the rheumatologic group. The average scores on the Japanese version of the Health Assessment Questionnaire, and the remission ratio determined using a Boolean-based definition gradually increased from 2000 until 2010, and these findings were consistently better in the rheumatologic group than in the orthopedic group. These data suggest that patients treated primarily by orthopedists are more likely to have long-standing RA compared to patients treated by rheumatologists. Therefore, it is critical for rheumatologists and orthopedists to complement each other medically in the treatment of RA patients.     

Serum from minimal change patients in relapse increases CD80 expression in cultured podocytes

Background

Minimal change disease (MCD) is the most common cause of nephrotic syndrome in children and is associated with the expression of CD80 in podocytes and the increased excretion of CD80 in urine. We hypothesized that serum from patients with MCD might stimulate CD80 expression in cultured podocytes.

Methods

Sera and peripheral blood mononuclear cells (PBMCs) were collected from subjects with MCD in relapse and remission and from normal controls. Immortalized human podocytes were incubated with culture media containing patient sera or supernatants from patient and control PBMC cultures. CD80 expression was measured by quantitative PCR and western blot analysis.

Results

Sera collected from patients with MCD in relapse, but not in remission, significantly increased CD80 expression (mean ± standard deviation: 1.8?±?0.7 vs. 0.8?±?0.2; p?<?0.004) and CD80 protein secretion by podocytes (p?<?0.05 between relapse and normal controls). No such CD80 increase was observed when podocytes were incubated with supernatants of PBMC cultures from patients in relapse.

Conclusions

Sera from MCD patients in relapse, but not in remission, stimulated CD80 expression in cultured podocytes. Identifying this factor in sera could provide insights into the pathogenesis of this disorder. No role in CD80 expression by podocytes was found for cytokines released by PBMCs.     

Safety and efficacy of azilsartan in paediatric patients with hypertension: a phase 3, single-arm,open-label,prospective study

Clinical and Experimental Nephrology - Azilsartan is an angiotensin II receptor blocker indicated for the treatment of adult hypertension. A previous single-dose study suggested that azilsartan may...     

Sex differences in clinical outcomes in Japanese incident dialysis patients: a prospective observational multicenter study

Clinical and Experimental Nephrology - A Dialysis Outcomes and Practice Patterns Study (DOPPS) has shown a one-to-one male-to-female mortality ratio, notwithstanding the statistically longer life...     

Impact of immunohistological subtypes on the long-term prognosis of patients with metastatic breast cancer

Purpose

Although improved long-term prognoses for patients with metastatic breast cancer (MBC) have been demonstrated, few reports address overall survival (OS) with sufficient follow-up. Furthermore, the relevance of immunohistological subtypes to OS in MBC has not been clarified.

Methods

We evaluated, retrospectively, the OS of patients who had been initiated on systemic therapy for MBC between 2000 and 2008.

Results

The subjects of this study were 527 patients with MBC treated by systemic therapy. The median survival time (MST) was 55.5 months. The MST for each immunohistological subtype was as follows: luminal, 59.9 months; luminal-HER2, not reached; triple-negative, 18.6 months; and HER2-enriched, 49.9 months. According to multivariate analysis, metastasis-free intervals of ≥2 years and treatment with anthracycline for MBC were predictive of better OS. The predictors of shorter OS included disease progression after first-line treatment for MBC, triple-negative, and all histological factors, except papillotubular carcinoma, with liver metastasis, and having three or more initial metastatic sites.

Conclusions

The prognosis of the patients with MBC in this series was better than that reported before 2000, which is probably attributable to the use of novel, improved pharmacological agents. For example, luminal-HER2 tumors can be treated using both aromatase inhibitors and trastuzumab. Because of the lower toxicities, it is now possible to administer these agents for longer periods, resulting in better prognoses.

     

Population pharmacokinetics of mizoribine in pediatric patients with kidney disease

Background

The present study aimed to obtain information enabling optimisation of the clinical effect of mizoribine (MZR) in pediatric patients with kidney disease.

Methods

A total of 105 pediatric patients with kidney disease treated at our institutions were enrolled. Kidney transplant patients were excluded. Population pharmacokinetic analysis of MZR was performed based on serum concentration data. Area under the curve from time zero to infinity (AUC_∞) and maximal concentration (C _max) were calculated by Bayesian analysis.

Results

In children, the appearance of MZR in the blood tended to be slower and the subsequent rise in blood concentration tended to be more sluggish, compared to healthy adults. Apparent volume of distribution and oral clearance were also higher in children compared to adults. A significant positive correlation was observed between patient age and AUC_∞. There were significant differences of AUC_∞ and C _max by age group. No relationship was observed between the administration method of MZR and serum concentration.

Conclusion

The pharmacokinetics of MZR was different in children compared to adults. To obtain the expected clinical efficacy, the regular MZR dosage schedule (2–3 mg/kg/day) might be insufficient for pediatric patients. In particular, younger patients might require a higher dosage of MZR per unit body weight.