Combination therapy with anabolic and antiresorptive agents

Combination therapy, the use of an anabolic agent with an antiresorptive agent in some sequence, has been evaluated in a number of clinical trials. There is no fracture data on combination therapy except for a small trial using PTH and estrogen. It appears that simultaneous use of a bisphosphonate (alendronate 10 mg per day) with PTH offers no advantage (and appears to blunt PTH's effect) compared with the use of PTH alone based on bone density gains. Previous therapy with alendronate also blunts gains in bone density with PTH therapy. Estrogen and raloxifene, whether given before or with PTH, do not blunt its anabolic effect. Sequential therapy with PTH followed by an antiresorptive agent (alendronate) offers the greatest gains in bone mass. It is possible that alendronate or other bisphosphonates given in a different dosing regimes may have different effects on PTH's anabolic effect. More trial data on combination therapy is needed.     

A rational approach to evidence gaps in the management of osteoporosis

Major advancements in the treatment of osteoporosis have occurred over the last decade. Therapies including the anti-resorptive drugs such as alendronate and risedronate have been shown in randomized placebo-controlled trials to increase bone mineral density and reduce fracture risk. Anabolic therapy in the form of parathyroid hormone has been introduced as the first treatment to build bone mass. However, gaps in our knowledge about specific management issues that arise frequently among primary care providers persist. In this paper, three common clinical scenarios are discussed: a postmenopausal woman with only slightly reduced bone mineral density; an osteoporotic woman on anti-resorptive therapy for more than 5 years; and a woman who continues to fracture despite treatment. Evidence gaps in each treatment scenario are presented, and rational approaches to management are suggested.     

植物雌激素的作用及安全性

植物雌激素可能通过调节雌激素受体、影响雌激素合成酶及非激素样作用机制缓解绝经期症状和防治骨质疏松症,对心血管系统和神经系统也有一定益处。此外,富含植物雌激素的饮食可能降低乳腺癌、子宫内膜癌、卵巢癌、前列腺癌及结肠癌的发病率。但同时有关植物雌激素的安全性仍有待深入研究,长期应用植物雌激素可能对子宫内膜、乳腺以及男性生殖系统存在一定的风险。     

检测尿Ⅰ型胶原交联氨基末端肽监测抗骨吸收药物疗效的特异性评价

目的 研究检测尿I型胶原交联基末端肽（NTx)监测抗骨吸收药物疗效的作用。方法 将46名绝经后妇女随机分成治疗组（阿仑磷酸钠10mg/d,6个月）和对照组（安慰剂，6个月）。用ELISA法检测尿NTx值，双能X线骨密度仪测定腰椎骨密度。结果 治疗组和对照组的NTx和骨密度的改变率 分别为－51．64％，5％和5．16％，－2．58％，治疗组的骨吸收指标均下降，以NTx下降最明显，近51．4％（P＜0．001），对照组的NTx值却有所上升。结论 NTx是监测抗骨吸收药物疗效的敏感指标。     

Long-term safety of antihypertensive therapy

Lowering blood pressure (BP) in hypertensive patients reduces morbidity and mortality. However the long-term safety of some antihypertensive agents was a matter of concern. Diuretic, the gold standard treatment in hypertension may impair glucose tolerance and thereby accelerate the development of diabetes mellitus. It was also associated with increased cardiovascular mortality in diabetic patients. However, recent evidence showed that low-medium dose of thiazide diuretic especially when given in combination with potassium sparing agent is effective in reducing BP and cardiovascular morbidity and mortality. Beta blockers are less effective than other antihypertensive agents in the elderly. Therefore they may be appropriate as a first choice in young and middle-age hypertensives, and in those with fast heart rate, but they should not be considered appropriate as the first-line therapy in the elderly with uncomplicated hypertension. Several years ago a plethora of publications showed that short-acting calcium antagonists may increase the risk for myocardial infarction and cancer. A few years ago two studies showed that calcium antagonists are less effective than angiotensin converting enzyme inhibitors in preventing cardiovascular events in diabetic hypertensive patients. However, recent results from large prospective randomized studies showed that calcium antagonists reduce cardiovascular morbidity and mortality in diabetic and non-diabetic hypertensive patients. Some investigators have suggested that angiotensin receptor blockers (ARBs) may increase the risk of myocardial infarction in hypertensive patients. However, recent meta analyses refuted this conclusions and showed that ARBs are probably as effective as other antihypertensive agents in prevention of myocardial infarction. Despite the concern that has been raised regarding the long-term safety of some antihypertensive agents, it is clear that lowering BP is safe and beneficial.     

三种胰岛素强化治疗方案的短期疗效和安全性比较

目的 比较三餐前注射预混胰岛素类似物(预混组),短效胰岛素类似物加睡前长效胰岛素类似物(类似物组)以及普通人胰岛素加睡前中效胰岛素(普通组)治疗2型糖尿病患者的短期疗效和安全性.方法 住院的2型糖尿病患者随机采用三种胰岛素强化治疗方案,在三餐前及睡前指间全血血糖达标后进行动态血糖监测,比较整体血糖控制水平、低血糖发生率,以及达标时间和胰岛素使用量等.结果 在三餐前及睡前全血血糖控制相同的情况下,预混组、类似物组和普通组达标时间分别为(8.3±2.5)、(9.1±3.8)和(8.4±1.7)天(P>0.05);胰岛素使用量分别为(0.63±0.13)、(0.69±0.20)和(0.68±0.24)U·ks-1·d-1(P>0.05);动态血糖监测的72 h平均血糖值分别为(8.3±2.1)、(7.5±1.9)和(6.8±0.8)mmol/L(P>0.05);早餐后3 h血糖曲线下面积分别为(27.7±11.5)、(27.6±8.3)和(24.0±3.1)mmol·L-1·h(P>0.05);血糖CV分别为(3.1±2.1)、(2.9±1.6)和(2.1±1.6)mmoL/L(P>0.05);低血糖(≤3.9 mmol/L)发生率分别为67%、87%和80%(P>0.05),多出现在凌晨0:00～4:00(55%),而且没有患者出现低血糖症状.结论 三种胰岛素强化治疗方案控制血糖的短期临床疗效和安全性没有明显差别,但需要更加关注监测夜间血糖.     

超长疗程阿米卡星在治疗耐多药肺结核中的疗效与药物安全风险分析

目的：分析超长疗程阿米卡星治疗耐多药肺结核的疗效及安全性。方法选择2010年1月至2014年3月共纳入符合研究条件的86例耐多药肺结核患者,按就诊顺序编号,均分为对照组与观察组2组,每组43例。均采用吡嗪酰胺(PZA)+盐酸乙胺丁醇(EMB)+对氨基水杨酸钠(PAS)+左氧氟沙星(LVFX)+丙硫异烟胺(PTH)化疗24个月,对照组加用阿米卡星6个月,观察组则采用超长疗程阿米卡星治疗12个月,共治疗24个月,观察治疗不同时间两组病灶吸收情况,统计痰菌阴转率,监测血常规、肝肾功能,观察药物安全性。结果①治疗6个月,两组治疗痰菌阴转率、病灶吸收率、治疗有效率对比差异无统计学意义(P >0.05),治疗12个月、18个月,观察组痰菌阴转率分别为68.29%、73.17%,均高于对照组(P <0.05);病灶吸收率分别为73.17%、78.05%,明显高于对照组的50.00%、52.50%(P <0.05);且其有效率分别为87.80%、85.37%,明显高于对照组的70.00%、70.00%,但仅治疗12个月对比差异有统计学意义(P <0.05)。②观察组治疗期间耳毒性发生率高于对照组(P <0.05),其肾毒性、肝毒性发生率略高于对照组,但对比差异无统计学意义(P >0.05)。结论超长疗程阿米卡星可提高耐多药肺结核患者痰菌阴转率,促进病灶吸收,改善疗效,虽长程用药患者耳毒性、肾毒性发生率高,但大部分均可逆。     

Efficacy and safety of denosumab for the treatment of osteoporosis: A systematic review

Denosumab is an anti-RANK ligand (RANKL) monoclonal antibody approved for the treatment of postmenopausal osteoporosis and prevention of skeletal metastasis complications. Administered subcutaneously every 6 months, it reduces the risk of vertebral fracture by 70% and of hip fracture by 40%. Its safety profile is acceptable. Denosumab may be used to treat patients with moderate to severe renal insufficiency. It has anti-fracture activity equivalent to that of zoledronic acid, but no residual effect, and no action at all beyond 6 months. In France, denosumab is reimbursed as a second-line treatment after a first attempt with bisphosphonate.     

粪便微生物群移植在部分消化疾病治疗中的应用及安全性问题

肠道微生物是机体不可或缺的部分,与机体各种功能的正常发挥及多种疾病的发生有密切关系.粪便微生物群移植(faecal microbiota transplantation, FMT)是纠正肠道微生态失调的主要方法,目前食品与药品管理局已批准用于治疗难治/复发性艰难梭菌感染,大量的临床研究提示FMT或许对于其他多种疾病有一定疗效.本文对目前FMT临床应用研究较多的几种消化系统疾病如炎症性肠病、肝性脑病、肠易激综合征及肿瘤的研究状况进行了简要综述,总结了这些临床研究中发现的不良反应及并发症,结合对FMT的管理规范,对其安全性进行了讨论.     

Long-term safety and efficacy of rituximab in 7 Japanese patients with ANCA-associated vasculitis

Abstract

Objectives. The safety and efficacy of rituximab were examined in a multicenter open-label pilot study in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in Japan.

Methods. Patients with refractory AAV were administered a rituximab infusion at a weekly dose of 375 mg/m² for 4 weeks. All patients also received oral daily prednisolone. The primary outcome was complete remission, which was defined as a Birmingham Vasculitis Activity Score (BVAS) of 0 or 1.

Results. The mean age of the 7 patients was 57 (range, 34–71) years. The mean follow-up period after rituximab treatment was 62.9 (range, 4.8–81) months. The mean BVAS at entry was 16.7 (range, 2–34). Complete remission occurred in all cases, except in 1 case in which the patient died, with a significant decline in BVAS from baseline at 12 months after initiation of rituximab. Rituximab reduced granulomatous orbital involvement in a patient with granulomatosis with polyangiitis. Relapse occurred in five patients. Adverse events included de novo hepatitis B in one patient, cancer (hepatocellular carcinoma and prostate cancer) in two patients, and transient visual disturbance, atypical mycobacterial infection, urinary tract infection, sepsis, and cytomegalovirus infection. Two patients died due to recurrent infections and airway obstruction, caused by an AAV lesion.

Conclusions. Rituximab had a beneficial effect on refractory AAV in Japanese patients, but several adverse effects occurred during rituximab treatment.     

Long-term hydroxyurea therapy in beta-thalassaemia patients

OBJECTIVE: The study aimed to investigate the use of hydroxyurea (HU) for the treatment of beta-thalassaemia (beta-thal) patients. METHODS: We examined the haematological effects of orally administered HU (10-20 mg/kg/d) in 11 patients, including four beta-thal major and seven beta-thal intermedia patients. Complete blood count and levels of foetal haemoglobin (HbF), liver enzymes and serum creatinine were evaluated before and during HU. Response to therapy was evaluated at 6 months of treatment. RESULTS: A substantial increase in haemoglobin (Hb) level (4.1 g/dL), leading to complete withdrawal from a regular transfusion programme, was observed in one unique beta-thal major patient. In the beta-thal intermedia patients, increases in Hb level of 1.3, 1.9 and 2.0 g/dL were observed in three of seven (42.9%) patients during HU therapy. The mean values of Hb, mean corpuscular haemoglobin (MCH), and HbF were higher during HU treatment than baseline values (8.7 vs. 7.7 g/dL, P = 0.05; 26.7 vs. 22.9 pg, P = 0.05; 57.2 vs. 44.9%, P = 0.04; respectively). In contrast, the mean reticulocyte count measured during therapy decreased (97.0 x 10(9) vs. 632.0 x 10(9)/L, P = 0.03). No correlations were observed between levels of Hb and HbF (r = 0.77, P = 0.10), and levels of Hb and reticulocyte counts (r = 0.26, P = 0.31). No significant toxicity was observed in our patients. CONCLUSION: These results suggest that HU may improve Hb levels in beta-thal. Thus, we may conclude that a large trial concerning the response to HU in these patients should be carried out to clarify this issue.     

骨质疏松椎体骨折患者药物治疗现状调查

目的 调查骨质疏松椎体骨折患者骨质疏松相关评估和药物治疗情况.方法 对2006年5月至2009年12月期间在本院行椎体成形术的骨质疏松椎体骨折患者通过病例回顾及电话随访的方式进行调查,排除因外伤、肿瘤转移所致的椎体骨折患者.调查内容包括骨密度检查、钙和维生素D的补充、抗骨质疏松药物的使用情况.结果 253例患者中进行过骨密度检查的患者极少,仅为3.6%,补充钙剂患者占9.5%,补充维生素D者占6.7%.使用抗骨质疏松药物者占36%,在所使用抗骨质疏松药物中双膦酸盐占27.5%,降钙素者29.7%,静滴骨肽者2.2%,中药制剂如强骨胶囊等占3.3%,对所服用药物不详者约占37.4%.结论 大多数骨质疏松椎体骨折患者除了外科手术对症处理外并没有接受抗骨质疏松药物治疗和相应的检查,应重视骨质疏松骨折的综合处理,对高危人群进行筛查和适当的药物治疗,以防止再次骨折的发生.

Abstract：

Objective To evaluate the efficacy of medical therapy in the patients with osteoporotic vertebrae fracture. Methods The patients suffered from vertebrae fracture and had undergone percutaneous vertebroplasty operation were reviewed from May, 2006 to December, 2009. Informations were collected via case evaluation and telephone interview, regarding dual-energy X-ray absorptiometry(DXA), calcium and vitamin D supplementation,and anti-osteoporosis drugs treatment. Patients with fracture induced by trauma and tumor metastasis were excluded. Results Among 253 patients, DXA was performed only in 3.6% of patients. Calcium and vitamin D supplements were prescribed in 9.5% and 6.7% of patients, respectively. Anti-osteoporosis drugs were prescribed in 36% of patients, of them 27.5%, 29.7%, 2.2%, and 3.3% received bisphosphonate, calcitonin, ossotide, and traditional Chinese drugs respectively. 37. 4% of patients could not recall the name of the drug they had received. Conclusions Most patients with osteoporotic vertebrae fracture do not receive adequate anti-osteoporosis drugs or appropriate evaluation. More care should be given to the patients with vertebrae fracture, with regard to adequate drug treatment and appropriate evaluation in order to prevent future fractures.     

Gender differences in disclosure concerns and HIV-related quality of life

HIV-related disclosure concerns are associated with higher rates of concealment and poorer well-being, including poorer health related HIV quality of life (HIV-QOL). Little research, however, has examined whether gender differences exist in the links between HIV disclosure concerns and HIV-QOL. We expected that disclosure concerns and gender would be associated with HIV-QOL, such that the relationship between disclosure concerns and poorer HIV-QOL to be stronger in women living with HIV (WLWH) than in men living with HIV (MLWH). One hundred and forty MLWH (n?=?102) and WLWH (n?=?38) completed an online questionnaire consisting of measures regarding their demographics, disclosure concerns (HIV-stigma scale), and HIV-QOL (HIV-AIDS-Targeted Quality of Life Instrument). Results suggested that more disclosure concerns were associated with poorer HIV-QOL, but in general, men and women did not differ in their levels of HIV-QOL. As expected, interactions emerged between gender and disclosure concerns such that disclosure concerns were associated with increased health worries and poorer sexual functioning for WLWH but not for MLWH. Interventions should acknowledge the differing needs and experiences of WLWH in order to improve HIV-QOL and increase longevity.     

Long-term efficacy and safety of biphasic insulin aspart in patients with type 2 diabetes

BACKGROUND: In this study, we sought to compare the long-term safety and efficacy of biphasic insulin aspart 30 (BIAsp30) with that of biphasic human insulin 30 (BHI30) over a period of 24 months in patients with type 2 diabetes. METHODS: Patients with type 2 diabetes (n=125) were assigned to twice-daily BIAsp30 or BHI30 and participated in both a 3-month initial period and a 21-month extension of a randomized, controlled, multinational trial. RESULTS: No significant difference was found in mean HbA(1c) after 24 months [BIAsp30, 8.35+/-0.20%; BHI30 8.13+/-0.16%; adjusted mean difference (BIAsp30-BHI30) 0.03 (90% CI -0.29 to 0.34)%, P=0.89]. The proportion of patients experiencing major hypoglycaemia was also similar during the first year (BIAsp30, 5%; BHI30, 8%; P=0.72), but it was significantly lower with BIAsp30 than with BHI30 during the second year (BIAsp30, 0%; BHI30, 10%; P=0.04). The proportion experiencing minor hypoglycaemia was not significantly different. No significant difference was recorded in changes in nonspecific insulin antibody levels after 24 months (BIAsp30, 4.87+/-1.92%; BHI30; 1.00+/-1.66%; P=0.13). Body weight change was 0.05+/-0.81 kg in the BIAsp30 group and 2.00+/-0.69 kg in the BHI30 group (P=0.07). CONCLUSIONS: Reduced major hypoglycaemia compared with BHI30 during the second year of treatment and comparable HbA(1c) levels after 24 months appear to support the hypothesis that the improved pharmacokinetic profile of BIAsp30 may favourably affect the balance between hypoglycaemia and hyperglycaemia in insulin-treated type 2 diabetes.     

Long-term side effects of androgen deprivation therapy in men with non-metastatic prostate cancer: a systematic literature review

Increasing numbers of men with non-metastatic disease are receiving androgen deprivation therapy (ADT) for a variety of indications, some of which are supported by evidence from randomized trials. Balanced against possible survival benefits and better disease control are data that ADT adversely affects quality of life, particularly in the areas of sexual function, physical function, and energy. There is some evidence of worsening upper extremity physical strength but no clear evidence of decline in daily function with ADT. The impact of ADT on cognitive function is not clear at this time. ADT is associated with declines in bone mineral density within 6–12 months of commencing treatment, with increased fracture rates within 5 years of treatment. ADT use is also associated with a 10–15 g/L decline in hemoglobin, although the clinical significance of this drop appears to be limited for most patients. It is reasonable for physicians who are about to start men on ADT to obtain a baseline bone mineral density, to counsel them about the impact on sexual function and possible treatments for sexual dysfunction, and to encourage regular exercise. Further insight into adverse effects of ADT and strategies to minimize these adverse effects await data from ongoing studies.     

全程新辅助治疗局部进展期直肠癌疗效和安全性的Meta分析

目的 比较全程新辅助治疗(TNT)和新辅助放化疗(nCRT)治疗中低位局部进展期直肠癌的疗效和安全性.方法 全面检索中文数据库(中国知网、万方、中国生物医学文献数据库)和英文数据库(PubMed、Embase)公开发表的有关TNT和nCRT治疗局部进展期直肠癌疗效和安全性的临床研究.随机对照研究的质量评价采用Cochr...     

Improvement in spine bone density and reduction in risk of vertebral fractures during treatment with antiresorptive drugs

PURPOSE: To estimate how much the improvement in bone mass accounts for the reduction in risk of vertebral fracture that has been observed in randomized trials of antiresorptive treatments for osteoporosis. METHODS: After a systematic search, we conducted a meta-analysis of 12 trials to describe the relation between improvement in spine bone mineral density and reduction in risk of vertebral fracture in postmenopausal women. We also used logistic models to estimate the proportion of the reduction in risk of vertebral fracture observed with alendronate in the Fracture Intervention Trial that was due to improvement in bone mineral density. RESULTS: Across the 12 trials, a 1% improvement in spine bone mineral density was associated with a 0.03 decrease (95% confidence interval [CI]: 0.02 to 0.05) in the relative risk (RR) of vertebral fracture. The reductions in risk were greater than predicted from improvement in bone mineral density; for example, the model estimated that treatments predicted to reduce fracture risk by 20% (RR = 0.80), based on improvement in bone mineral density, actually reduce the risk of fracture by about 45% (RR = 0.55). In the Fracture Intervention Trial, improvement in spine bone mineral density explained 16% (95% CI: 11% to 27%) of the reduction in the risk of vertebral fracture with alendronate. CONCLUSION: Improvement in spine bone mineral density during treatment with antiresorptive drugs accounts for a predictable but small part of the observed reduction in the risk of vertebral fracture.