A Postmarketing Clinical Experience Study of Metadate® CD

Summary

Objective:The objective of the study was to investigate the effectiveness and safety of Metadate® CD (methylphenidate HCl, USP) Extended Release Capsules in the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD), in actual clinical practice.

Method:This was a multicenter, open-label, postmarketing study. Eligible patients were aged 6-17 with a diagnosis of ADHD and receiving either no treatment or maintenance treatment with another approved methylphenidate (MPH) product. Metadate® CD was administered once daily for 3 weeks, titrated against reported and observed symptoms. Clinical Global Impression (CGI) scores at Week 3 were used for the primary efficacy evaluation. Patient treatment satisfaction was determined by questionnaire at the final evaluation visit. Safety was assessed through adverse event reporting, laboratory tests and vital sign measurements.

Results: Overall, of the 308 patients in the Intent-To-Treat population, the majority (65%) demonstrated a positive response to Metadate® CD (defined as CGI Global Improvement rating of very much or much improved). In addition, patients previously treated with immediate-release or extended-release tablet formulations of MPH were successfully converted to Metadate® CD at a comparable dose. Most patients (87%) were very satisfied or moderately satisfied with study treatment, and among previously treated patients, 71% rated Metadate® CD as much better or better than their previous MPH treatment. Adverse events were consistent with current FDA-approved product labeling for Metadate® CD.

Conclusions: Metadate® CD is effective and well-tolerated in actual clinical use for ADHD.     

血清可溶性CD44检测对急性髓系白血病的诊断分型价值研究

目的探讨血清可溶性CD44(solCD44)检测对于急性髓系白血病(AML)的临床诊断分型价值。方法选取2014年1月至2016年1月该院血液科收治的AML患者80例,包括初诊31例、复发24例、缓解25例。同期健康体检者40例为对照组。检测比较各组患者的血清solCD44std、solCD44v5、solCD44v6水平变化。结果 AML患者的血清solCD44s、solCD44v5、solCD44v6水平在初诊、复发组中显著高于缓解组及对照组(P0.05),而缓解组与对照组比较差异无统计学意义(P0.05);不同FAB分型(M1+M2)、M3、M4、M5的血清solCD44std、solCD44v5、solCD44v6水平比较差异有统计学意义,且M3型显著高于非M3型(P0.05)。结论血清solCD44尤其是solCD44std水平与AML患者病情活动变化密切相关,可作为AML的诊断分型、预后判断及复发预测的血清学参考指标。     

Apoptosis of Peripheral CD4+ T-Lymphocytes in End-Stage Renal Disease Patients Under Hemodialysis and rhEPO Therapies

End-stage renal disease (ESRD) under hemodialyses (HD) is related with a higher propensity to infections, essentially due to T-cell lymphopenia. We postulated that HD procedure affects CD4⁺ T cells, especially by inducing apoptotic death and that recombinant human erythropoietin (rhEPO) therapy may also play an important role in the modulation of the immune system in these patients. T-cell phenotype and apoptosis of HD patients and healthy controls were evaluated by flow cytometry using anticoagulated whole-blood samples. In 12 HD patients, these parameters were also analyzed before and immediately after HD procedure. HD patients showed a decrease in total circulating CD3⁺ lymphocytes, especially in CD4⁺ T cells (0.747 ± 0.410 vs. 0.941 ± 0.216 × 10⁹/L, p < 0.05), which could be a consequence of the higher proportion of CD3⁺ and CD4⁺ lymphocytes in the latest stage of apoptosis (or death) and of the higher proportion of apoptotic CD4⁺ T cells observed in the patients immediately after HD procedure (2.91 ± 0.780 vs. 3.90 ± 1.96, p < 0.05). A positive and statistically significant correlation between CD3⁺ and CD4⁺ lymphocytes in latest stage of apoptosis (or death) with HD time was found (CD3⁺: r = 0.592, p < 0.01; CD4⁺: r = 0.501, p < 0.01). We also found a negative and significant correlation between weekly rhEPO doses and the number of CD4⁺ T cells (r = –0.358, p < 0.05). In conclusion, HD procedure still contributes to the development of T-cell lymphopenia, at least in part, by apoptosis induction. It was also shown that rhEPO therapy is associated with the CD4⁺ T-cell decline, possibly by immune modulation, eliminating atypical cells and helping to restore the CD4⁺ T-cell subset.     

Motor speed and reaction time in HIV/AIDS patients: a case-control study

HIV infection can produce a range of cognitive and behavioural symptoms that become more frequent and severe as the immune system deteriorates. This case-control study assessed the reaction time and the motor speed of Nigerian Africans with HIV or AIDS using the simple reaction time and finger-tapping tasks, and correlated their performances with their CD4 levels. A total of 288 age-, sex-, and level of education-matched subjects, comprising 96 HIV-positive patients with symptomatic illness, 96 HIV-positive patients with asymptomatic infection, and 96 HIV-negative controls, participated in the study. The mean CD4 cell counts of the controls, HIV-positive asymptomatic subjects, and HIV-positive symptomatic subjects were 682 ±44, 284 ±62 and 142 ±36, respectively (p < 0.05). There was no significant difference in the reaction time and motor speeds of the asymptomatic HIV-positive subjects and the controls (p > 0.05), but there was significant prolongation of reaction time and reduced finger taps among the symptomatic HIV-positive subjects (p < 0.01). The cognitive performance was worse in subjects with CD4 cell counts less than 200/μl as compared with subjects with CD4 cell counts greater than 200/μl. We conclude that there is no significant prolongation of reaction time and reduced motor speed in asymptomatic HIV-positive individuals but there is a definite cognitive deterioration with progressive reduction in CD4 levels.     

Pollen shells and soluble factors play non-redundant roles in the development of allergic conjunctivitis in mice

PurposeWe aimed to clarify the role of particulate allergen exposure to the conjunctiva in the development of allergic conjunctivitis.MethodsWe administered ragweed pollen suspension, pollen extract, pollen shell, particulate air pollutants, and their combinations to the mouse conjunctiva five days a week without prior sensitization. Clinical signs were scored. Histological changes, cellular infiltrations, mRNA expressions, lymph node cell recall responses, and serum immunoglobulin levels were assessed. Immune cell-depleting antibodies and ST2 knockout mice were used to investigate the cellular and molecular requirements.ResultsPollen suspension, but not the extract or shell alone, induced robust eosinophilic conjunctivitis, accompanied by a proliferative response of epithelial cells. A combination of pollen extract and shell completely restored eosinophil accumulation. In addition, eosinophilic conjunctivitis was induced by a mixture of particulate air pollutants and pollen extract. Mechanistically, eosinophil accumulation was ameliorated by deficiency of the IL-33 receptor ST2 and abolished by depleting CD4⁺ T cells. Pollen shells, but not the extract, induced IL-33 release from conjunctival epithelial cells in vivo.ConclusionsOur results indicate the non-redundant roles for the allergens’ particulate properties and soluble factors in the development of allergic conjunctivitis.