Advances in Therapy

Thiếu sắt và thiếu máu do thiếu sắt liên quan đến sự gia tăng tỷ lệ mắc bệnh và tử vong trong một loạt các tình trạng khác nhau. Ở nhiều nhóm bệnh nhân, tình trạng này có thể được điều trị hiệu quả bằng cách bổ sung sắt đường uống; nhưng ở những bệnh nhân không thể sử dụng hoặc không phản ứng với liệu pháp sắt đường uống, việc tiêm sắt tĩnh mạch được khuyến nghị. Hơn nữa, trong một số tình trạng nhất định, chẳng hạn như bệnh thận giai đoạn cuối, suy tim mạn tính và bệnh viêm ruột, việc tiêm sắt tĩnh mạch đã trở thành phương pháp điều trị hàng đầu. Một trong những chế phẩm sắt tĩnh mạch đầu tiên có sẵn là sắt sucrose (Venofer®), một loại nanomedicine đã được sử dụng trên lâm sàng từ năm 1949. Việc điều trị bằng sắt sucrose đặc biệt có lợi nhờ vào khả năng làm tăng nhanh chóng mức hemoglobin, ferritin và bão hòa transferrin, với hồ sơ an toàn chấp nhận được. Gần đây, nhiều dữ liệu mới quan trọng liên quan đến việc sử dụng sắt sucrose, bao gồm các phát hiện từ thử nghiệm PIVOTAL nổi bật ở các bệnh nhân mắc bệnh thận giai đoạn cuối, đã được công bố. Vài năm trước, một số chế phẩm tương tự sắt sucrose đã trở thành có sẵn, mặc dù có lo ngại về sự phù hợp lâm sàng khi thay thế sắt sucrose gốc bằng một chế phẩm tương tự do những khác biệt về hiệu quả và an toàn. Điều này là kết quả của các thuộc tính vật lý hóa học phức tạp và độc đáo của các nanomedicine như sắt sucrose, điều này làm cho việc sao chép phân tử trở nên khó khăn và gặp vấn đề. Trong bài tổng quan này, chúng tôi tổng hợp các bằng chứng đã tích lũy trong 70 năm kinh nghiệm lâm sàng với sắt sucrose về hiệu quả, độ an toàn và hiệu quả chi phí.

Pregabalin is a new anxiolytic that selectively binds to the alpha2-delta subunit of voltage-gated calcium channels, inhibiting release of excessive levels of excitatory neurotransmitters. In this open-label trial we aimed to investigate the efficacy of pregabalin on alcoholism indices in detoxified alcohol-dependent subjects. Reduction of cravings, psychiatric symptom improvements, and the evaluation of safety parameters were the secondary endpoints. Thirty-one alcohol-dependent patients were consecutively recruited and screened for the study. Twenty detoxified patients received pregabalin starting at 50 mg/day (orally) in the first week, gradually increasing to a flexible dose of 150–450 mg/day. Subjects were assessed at the beginning of the treatment, and after 2, 8 and 16 weeks. Craving (visual analogue scale, Obsessive and Compulsive Drinking Scale [OCDS]) and withdrawal (Clinical Institute Withdrawal Assessment for Alcohol [CIWA-Ar]) rating scales were applied; psychiatric symptoms were evaluated through the Symptom Check List-90-Revised (SCL-90-R). Out of the twenty patients who received the study drug, 15 completed the study procedures: 10 remained totally alcohol-free for the duration of the study, five relapsed. An additional four patients dropped out during the study, and one stopped taking medication due to adverse events. A significant progressive reduction of both craving and withdrawal symptomatology were observed. Safety parameters did not show any significant variation during treatment. Pregabalin shows promise as a treatment for alcohol dependence. Although limited by a low number of participants and by the open design, this is the first study concerning the efficacy and safety of pregabalin in current alcoholics. In these patients pregabalin was effective and well tolerated. Additional research is needed to explore the clinical relevance of these findings.

This double-blind, randomized, prospective study was conducted to compare the analgesic and sedative efficacy of fentanyl and meperidine in orthopedic closed reduction of fractures and dislocations undertaken in the emergency department. Seventy consecutive adult patients with fractures or dislocations suitable for reduction were randomized to receive fentanyl (1 mcg/kg; n=36) or meperidine (0.5 mg/kg; n=34) in combination with midazolam (0.02 mg/kg). Vital signs and alertness scale scores of the patients were monitored. The Visual Analog Scale (VAS) was used to determine the degree of pain. There was no statistically significant difference between the VAS mean scores of the fentanyl and meperidine groups (t test,P=.772). The need for additional analgesic drugs was significantly more frequent in patients receiving meperidine (P=.018). No adverse events, such as hypotension or respiratory depression, were noted. Euphoria occurred in one patient in the fentanyl group. Although dose requirements differ, fentanyl and meperidine provide effective and reliable analgesia in closed reduction of fractures and dislocations.

The role of vitamin D supplementation on muscle function and physical performance is still debated. Calcifediol is an available treatment for hypovitaminosis D, particularly for extra-skeletal effects. Aim of this prospective cohort study was to evaluate the effectiveness of calcifediol on serum levels of 25(OH)D3, appendicular muscle strength, physical performance, and prevention of falls in post-menopausal women. We recruited post-menopausal women aged ≥50 years, referring to an outpatient service for the management of osteoporosis over a 18-month period. We included women with a diagnosis of osteoporosis and/or vitamin D deficiency [serum levels of 25(OH)D3 <30 ng/ml]. All the participants received calcifediol (20 μg, 4 oral drops/day) for a 6-month period. We evaluated at the baseline and after 6 months the following outcomes: serum levels of 25(OH)D3, appendicular muscle strength, using the Isometric Hand Grip Strength Test and the Knee Isometric Extension Strength Test, physical performance, using the Short Physical Performance Battery (SPPB) and the 4-m gait speed (4MGS), and the risk of falls (percentage of fallers and recurrent fallers and mean number of falls). A sub-analysis was performed in patients with vitamin D deficiency. We enrolled 113 post-menopausal women, mean aged 68.01 ± 9.13 years. After 6 months of treatment, there was a significant increase in serum levels of 25(OH)D3 (p < 0.001), appendicular muscle strength (p < 0.001), and physical performance (p = 0.002 at SPPB and p = 0.010 at 4MGS, respectively). At 6 months, the percentage of fallers was lower, although not significantly (p = 0.078), whereas there was a significant reduction both in percentage of recurrent fallers and in the mean number of falls (p < 0.001 and p = 0.020, respectively). Calcifediol was significantly effective in improving serum levels of 25(OH)D3 and muscle function and in reducing the percentage of recurrent fallers and the mean number of falls in a cohort of post-menopausal women.

Insulation failure leading to conductor externalization (CE) of a Linox (Biotronik, Berlin, Germany) implantable cardioverter defibrillator (ICD) lead has recently been reported. The aim of this study was to assess prospectively all Linox family ICD leads implanted at our center for evidence of CE or an electrical abnormality. All patients with a Linox family ICD lead implanted at our center, between November 2007 and March 2015, were identified and all living patients were invited to attend for fluoroscopic screening and electrical assessment of the lead. A total of 183 patients had a Linox family ICD lead implanted at our center. Of these, 5 patients (2.7%) had the lead extracted because of electrical failure and 2 of these leads had evidence of CE. Out of 158 living patients with a Linox family ICD lead, 111 patients attended for screening (mean age 63.1 years, 22.5% female). In this group of patients, no cases of CE or electrical abnormalities of the lead were identified. In this study evaluating 183 patients with a Linox family ICD lead implanted at a single center, 5 leads (2.7%) were explanted because of electrical failure and 2 of these leads had evidence of CE. Prospective fluoroscopic assessment of 111 Linox family ICD leads, with a mean dwell time of 31.5 months, revealed no further cases of CE.

Adalimumab has been used successfully in the treatment of psoriasis. The objective of the study is to compare the efficacy, safety, and immunogenicity between HLX03, an adalimumab biosimilar, and adalimumab in Chinese patients with moderate-to-severe plaque psoriasis. In this double-blind, active-controlled, parallel-group study, 262 patients with moderate-to-severe plaque psoriasis were randomized (1:1) to receive HLX03 or adalimumab (80 mg at week 1, 40 mg at week 2, and then 40 mg every 2 weeks) for 48 weeks. The primary endpoint was improvement in Psoriasis Area and Severity Index (PASI) score at week 16 comparing to baseline. Equivalence was demonstrated if 95% confidence interval (CI) of the between group difference fell within the equivalence margins of ± 15%. Other efficacy endpoints, safety and immunogenicity were also evaluated. In the full analysis set, PASI improvements at week 16 was 83.5% (n = 131) in the HLX03 group and 82.0% (n = 130) in the adalimumab group, with a least-square-mean difference of 1.5% (95% CI − 3.9% to 6.8%). There were no significant between-group differences in all secondary efficacy analyses including proportion of patients achieving ≥ 75% improvement from baseline PASI (PASI 75), physician global assessment (PGA) 0/1 (clear or almost clear) and change in dermatology life quality index (DLQI) score. The incidences of adverse events and the proportion of patients with antidrug antibodies were also comparable between the two treatment groups. HLX03 demonstrated equivalent efficacy, similar safety and immunogenicity to reference adalimumab, supporting its development as an alternative treatment for patients with plaque psoriasis in China. Chinadrugtrials.org.cn, CTR20171123 (November 27, 2017); ClinicalTrials.gov, NCT03316781 (October 20, 2017). Plaque psoriasis is a chronic, autoimmune, inflammatory skin disease associated with significant morbidity and reduced quality of life. In China, the prevalence of plaque psoriasis increased four-fold between 1987 and 2012. Adalimumab is a biologic antibody used to treat plaque psoriasis globally. However, high treatment costs remain as a significant barrier to adalimumab therapy. Therefore, HLX03 has been developed as an adalimumab (Humira®) biosimilar, which is almost identical to the licensed reference adalimumab, but less expensive and more accessible to patients. In this randomized clinical trial, the efficacy (ability of a drug to produce the desired treatment effects), safety, and immunogenicity (ability of a drug to induce immune response which would affect its efficacy and safety) of HLX03 were compared with the reference adalimumab in Chinese patients with moderate-to-severe plaque psoriasis. Efficacy was evaluated by comparing the changes in severity and extent of disease using Psoriasis Area and Severity Index score between treatment initiation and week 16. Safety was monitored by adverse events, laboratory tests and vital signs. Immunogenicity was assessed by the incidence of antidrug antibodies. Among the 262 randomized patients, 131 received HLX03 and 130 received adalimumab. Both groups reported similar improvements in Psoriasis Area and Severity Index scores (between-group difference fell within the prespecified equivalence margins), and also in other efficacy evaluations. Additionally, the two treatment groups showed similar safety and immunogenicity profiles. In summary, HLX03 demonstrated equivalent efficacy to adalimumab, validating it as an alternative treatment for patients with plaque psoriasis in China.