阻断炎症部位5-HT2A受体对大鼠完全弗氏佐剂诱发炎性痛和脊髓背角神经肽Y表达的作用

炎症时组织释放5-羟色胺(5-hydroxytryptamine,5-HT),对炎性痛觉过敏的产生起重要作用。但炎症组织5-HT2A受体在其中的意义尚不明确。本文旨在研究外周组织5-HT2A受体在慢性炎性痛中的作用。大鼠后足底注射完全弗氏佐剂(complete Freund’s adjuvant,CFA),在局部炎性部位给予选择性5-HT2A受体阻断剂酮色林,用行为学检测后足底对热和机械刺激的撤足反射,用免疫组织化学方法检查脊髓背角和背根神经节(dorsal root ganglion,DRG)中神经肽Y(neuropeptide Y,NPY)表达变化。结果显示,炎症局部给予酮色林(20、40、80μg)能剂量依赖性地抑制CFA诱发的热痛觉过敏;每日给予80μg酮色林,在第三天即完全翻转CFA引起的热痛觉过敏,以及部分地减轻触觉超敏。CFA诱发脊髓背角I~II层NPY表达增加,炎症组织局部注射酮色林能抑制脊髓背角NPY的表达增加,但不改变DRG中NPY的表达。这些结果表明:外周炎症组织5-HT2A受体激活参与慢性痛觉过敏的发生;阻断炎症部位5-HT2A受体能缓解疼痛,矫正与病理疼痛密切关联的脊髓背角细胞异常改变。因此,外周5-HT2A受体,有望成为治疗慢性炎性痛觉敏感性增高、不产生中枢神经系统副作用的药物靶点。     

巴西绿蜂胶主要生物活性成分的研究进展

阿替匹林C(3,5-二异戊烯基4-羟基肉桂酸)是巴西绿蜂胶的主要生物活性成分之一,是目前巴西绿蜂胶定性检测及质量控制的主要评价指标.随着巴西绿蜂胶研究的深入,阿替匹林C也成为研究的热点.作者对阿替匹林C在蜂胶质量控制中的应用、分离纯化、人工合成、生物学活性等方面的研究进展进行了综述,为其在巴西绿蜂胶的质量控制及药理活性方面的深入研究提供参考.     

匹伐他汀临床应用的最新进展

匹伐他汀(pitavastatin)是新一代人工合成的降血脂类药物。该药是新一代HMG-COA还原酶抑制剂,用于治疗原发型高脂血症和混合型血脂障碍,能够显著降低LDL、TC、TG、及升高HDL-C。药物动力学性质优良,具有肝细胞选择性,并且毒性低,安全性好,具有抗动脉粥样硬化、促进血管生成和抗炎作用。本文就匹伐他汀的临床研究进展进行综述。     

莫匹罗星联合氦氖激光照射治疗新生儿脐炎的临床疗效研究

为探讨莫匹罗星联合氦氖激光照射治疗新生儿脐炎的临床疗效,本研究选取了2013至2018年新生儿脐炎患儿86例,通过对照研究,按治疗方法不同分为观察组(莫匹罗星+氦氖激光照射)与对照组(莫匹罗星)各43例,观察两组患儿新生儿脐炎愈合时间及不良反应发生情况。试验发现观察组平均愈合时间为(4. 186±0. 194) d,总有效率为100%;对照组平均愈合时间为(5. 189±0. 238) d,总有效率为86%;观察组愈合时间显著高于对照组(P 0. 05)。两组患儿在治疗期间均未发现皮肤红疹等不良事件。研究结果显示,莫匹罗星联合氦氖激光照射治疗新生儿脐炎的临床疗效确切,安全性高。     

复方氨林巴比妥与柴胡注射液肌注致过敏性休克1例

复方氨林巴比妥注射液及中药制剂单独使用出现过敏性休克罕见。我院收治1例两药合用出现过敏性休克的患者,现报告如下。1临床资料患者,男,58岁,因感冒发热(体温38.2℃)于个体诊所就诊,给予复方氨林巴比妥、柴胡注射液各2ml混合肌注,并给予口服药(具体药物不详,患者未服)。5min后患者出     

肾脏有机阳离子转运体2在急性肾损伤中病理生理调控的研究进展

有机阳离子转运体2(organic cation transporter 2,OCT2)是溶质转运体(solute carriers,SLC)超家族中SLC22A家族的重要成员之一。肾小管上皮细胞基底膜侧表达的OCT2在维持机体内环境平衡方面起着重要作用,是肾脏主动分泌众多内、外源性有机阳离子型化合物(包括环境毒素、药物以及内源性代谢产物等)的主要转运体。在急性肾损伤(acute kidney injury,AKI)期间,OCT2功能与表达的改变对其底物的清除具有巨大的影响,可导致药物的药代动力学过程发生改变,从而影响药物的安全性和有效性。现就OCT2的结构与分布、生理作用与调控机制以及在各种因素诱导的AKI中的功能与表达变化和病理生理调控等方面进行综述,旨在为临床合理用药提供参考。     

大熊猫粪源大肠杆菌耐药性及整合子研究

为了解大熊猫粪源大肠杆菌的耐药性、整合子-基因盒的分布特性,分析整合子对细菌耐药性的影响,采用Kirby-Bauer(K-B)纸片法进行了50株大肠杆菌对13种抗菌药物的药物敏感性试验;PCR-测序法检测了1、2、3型整合酶基因,进一步对阳性菌株可变区的基因盒序列鉴定分析。结果显示,菌株对13种抗菌药物表现出不同的耐药性,其中对氨苄西林、头孢唑林、四环素和复方新诺明表现出较高耐药性(耐药率为30%~68%),对其余药物耐药性较低(耐药率低于14%);50株菌中有15株(30%)含有1型整合子,未发现2型和3型整合子;15株1型整合子阳性菌中,有6株(40%)扩增出1200~2000 bp的基因盒,主要介导氨基糖苷类和磺胺-甲氧苄啶耐药的aad A和dfr A基因家族。以dfr A27+aad A2为主(检出率83.33%),1株为aac A4+aad A1+cat B2。以上说明本次检测的大熊猫粪源大肠杆菌对多种抗菌药物呈低水平耐药;1型整合子在大肠杆菌中广泛分布,整合子-基因盒是造成整合子阳性菌株耐氨基糖苷类、磺胺-甲氧苄啶类、氯霉素的主要原因。     

辽东低山区5种典型水源涵养林枯落物持水特性

对辽东低山区5种水源涵养林枯落物持水特性进行研究,可以为该区水源涵养林的营造、科学经营提供理论依据。2018年6月在辽宁省抚顺县国有温道林场选取纯林(落叶松林(Larix olgensis)、油松林(Pinus tabuliformis)、红松林(Pinus koraiensis)、刺槐林(Robinia pseudoacacia)和杂木林为研究对象,调查各林分枯落物厚度、蓄积量等,并用浸泡法测定最大持水量、最大持水率,建立持水量、吸水速率与浸水时间之间的关系。结果表明:(1)5种林分枯落物厚度3.6～7.8 cm,平均厚度6.2 cm;蓄积量15.40～50.38 t·hm-2,平均值30.42 t·hm-2。(2)枯落物最大持水量13.61～27.21 t·hm-2,大小排序为杂木林落叶松林刺槐林红松林油松林;最大持水率变化稍有不同,依次为刺槐林落叶松林杂木林红松林油松林。(3)枯落物有效拦蓄量19.60～142.67 t·hm-2,大小排序为落叶松林红松林杂木林刺槐林油松林。(4)回归分析表明,枯落物持水量与浸水时间符合关系式Q=alnt+b,相关系数R2均大于0.80;吸水速率与浸水时间符合关系式V=ctn,相关系数R2均大于0.99。综上,落叶松林、红松林枯落物蓄积量最大、持水能力和有效拦蓄能力均较强,刺槐林、杂木林次之,油松林较差。     

林窗尺度对马尾松人工林林下灌草层优势种生态位的早期影响北大核心CSCD

马尾松作为中国广泛栽植的乡土树种,其人工林群落结构简单和生物多样性低下是普遍存在的生态学问题。探究不同林窗尺度对马尾松人工林林下植被群落的影响,可为马尾松人工林近自然经营提供理论依据。该研究在45 a生马尾松人工林中分别设置A(50 m^(2))、B(100 m^(2))、C(200 m^(2))和D(667 m^(2))4种不同尺度的林窗,以不做任何处理的马尾松人工林作为对照(CK),探究采伐开窗后林窗内自然更新1 a后的灌草层植物组成、优势种生态位宽度和生态位重叠度分布特征。结果显示:(1)除100 m^(2)林窗下灌木层物种数与对照无显著差异外,其余林窗灌草层物种数均显著高于对照(P<0.05),且200 m^(2)林窗下灌草层物种数均最多,分别为35种和20种;4种林窗下灌草层物种丰富度指数较对照均显著增加(P<0.05),最大值均出现在200 m^(2)林窗下,其值分别为对照的1.5倍和2.6倍。(2)林窗增加了灌草层喜光植物种类,且在200 m^(2)林窗下种类最多,灌木层喜光植物有13种,草本层喜光植物有5种。(3)4种林窗下灌草层优势种中,喜光植物生态位宽度均较大,200 m^(2)林窗下灌草层生态位宽度平均值最小,其对资源利用程度低,重要值与生态位宽度之间无显著相关性(P>0.05)。(4)4种林窗下灌草层优势种间生态位重叠度指数均较小。667 m^(2)林窗下,灌草层优势种平均生态位重叠度指数最小,分别为0.029和0.024,200 m^(2)林窗下灌草层优势种高生态位重叠度占总数比例最大,分别为20%和23.8%。研究表明,采伐开窗促进了马尾松人工林林下植被发育,丰富了林下植物多样性,有利于马尾松林稳定持续发展,对精准提升马尾松人工林质量具有重要意义。     

大兴安岭兴安落叶松森林不同林型AMF分布特性

为了初步了解内蒙古大兴安岭兴安落叶松森林生态系统丛枝菌根真菌(AMF)多样性状况, 调查了5种落叶松林型和火烧迹地土壤中AMF状况。从90份土样中共分离到AMF 4属53种, 其中无梗囊霉属Acaulospora 25种(47.17%), 球囊霉属Glomus 23种(43.40%), 此二属为优势属, 内养囊霉属Entrophospora 4种(7.55%), 巨孢囊霉属Gigaspora 1种(1.89%)。杜香落叶松林的优势种为浅窝无梗囊霉A. lacunosa; 草地落叶松林没有优势种, 最常见种为浅窝无梗囊霉A. lacunosa; 柴桦落叶松林的优势种为一种无梗囊霉Acaulospora sp. 3和缩球囊霉G. constrictum; 落叶松皆伐林的优势种为刺无梗囊霉A. spinosa; 落叶松渐伐林的优势种为一种球囊霉Glomus sp. 3; 火烧迹地的优势种为刺无梗囊霉A. spinosa。5种林型中以柴桦落叶松林的孢子密度(41.00个/50 g 风干土)、物种丰富度(12.66种/土样)、多样性指数(H = 2.12, D = 0.85)都为最高。孢子密度与有机质含量呈明显正相关(r = 0.956*), 物种丰富度与速效磷含量呈明显的负相关(r = -0.899*)。     

On the Discovery and Development of Pimavanserin: A Novel Drug Candidate for Parkinson’s Psychosis

Parkinson’s disease psychosis (PDP) is a condition that may develop in up to 60 % of Parkinson’s patients, and is a major reason for nursing home placement for those affected. There are no FDA approved drugs for PDP but low doses of atypical anti-psychotic drugs (APDs) are commonly prescribed off-label. Only low-dose clozapine has shown efficacy in randomized controlled trials, but all APDs have black box warnings related to the increased mortality and morbidity when used in elderly demented patients. Using molecular pharmacological profiling of a large collection of marketed drugs, we discovered that potent inverse agonist activity against 5-HT_2A serotonin receptors was a common feature of atypical APDs, especially the atypical APDs used to treat PDP. Since low-dose clozapine therapy selectively blocks this receptor, it was hypothesized that a highly selective 5-HT_2A receptor inverse agonist might provide good symptom control in patients suffering from PDP, with a greatly improved safety and tolerability profile. A high throughput screening and subsequent chemical lead optimization campaign to develop potent, selective 5-HT_2A receptor inverse agonists was launched, eventually resulting in the discovery of pimavanserin. Pimavanserin displays nanomolar potency as a 5-HT_2A receptor inverse agonist, selectivity for 5-HT_2A over 5-HT_2C receptors, and no meaningful activity at any other G-protein coupled receptor. It demonstrated robust activity in preclinical models of schizophrenia and PDP, and did not worsen motoric symptoms, in contrast to the APDs tested. In a Phase III clinical trial, pimavanserin showed highly significant benefits in the primary endpoint, the scale for assessment of positive symptoms-PD, a scale adapted for use in PDP. In addition, improvements in all other efficacy endpoints, including physician’s clinical global impression, caregiver burden, night-time sleep quality and daytime wakefulness, were seen. Pimavanserin demonstrated good safety and tolerability and did not worsen motoric symptoms as assessed by the unified Parkinson’s disease rating scale parts II and III. An open-label extension study has further demonstrated that pimavanserin is safe and well-tolerated with long-term use. Pimavanserin may therefore offer a viable treatment option for patients suffering from PDP.     

Efficacy,tolerability, and upper gastrointestinal safety of celecoxib for treatment of osteoarthritis and rheumatoid arthritis: systematic review of randomised controlled trials

ObjectiveTo determine the efficacy, gastrointestinal safety, and tolerability of celecoxib (a cyclo-oxygenase 2 (COX 2) inhibitor) used in the treatment of osteoarthritis and rheumatoid arthritis.DesignSystematic review of randomised trials that compared at least 12 weeks'' celecoxib treatment with another non-steroidal anti-inflammatory drug (NSAID) or placebo and reported efficacy, tolerability, or safety. Trials identified from manufacturer and by searching electronic databases and evaluated according to predefined inclusion and quality criteria. Data combined through meta-analysis.Participants15 187 patients with osteoarthritis or rheumatoid arthritis.ResultsNine randomised controlled trials were included. Celecoxib and NSAIDS were equally effective for all efficacy outcomes. Compared with those taking other NSAIDs, in patients taking celecoxib the rate of withdrawals due to adverse gastrointestinal events was 46% lower (95% confidence interval 29% to 58%; NNT 35 at three months), the incidence of ulcers detectable by endoscopy was 71% lower (59% to 79%; NNT 6 at three months), and the incidence of symptoms of ulcers, perforations, bleeds, and obstructions was 39% lower (4% to 61%; NNT 208 at six months). Subgroup analysis of patients taking aspirin showed that the incidence of ulcers detected by endoscopy was reduced by 51% (14% to 72%) in those given celecoxib compared with other NSAIDs. The reduction was greater (73%, 52% to 84%) in those not taking aspirin.ConclusionCelecoxib is as effective as other NSAIDs for relief of symptoms of osteoarthritis and rheumatoid arthritis and has significantly improved gastrointestinal safety and tolerability.

What is already known on this topic

Long term NSAID use is associated with the development of peptic and duodenal ulcersCOX 2 specific inhibitors are claimed to cause fewer gastrointestinal complicationsThe National Institute for Clinical Excellence has recently recommended that COX 2 specific inhibitors are used in patients with arthritis who are at risk of gastrointestinal complications but not in those taking prophylactic aspirin

What this study adds

Systematic review of randomised trials shows that celecoxib is as effective as other NSAIDs for osteoarthritis and rheumatoid arthritisCelecoxib has significantly improved gastrointestinal safety and tolerability compared with standard NSAIDsAn improvement in gastrointestinal safety was still evident in patients who were also taking aspirin     

AACE/ACE Disease State Clinical Review: Medical Management of Cushing Disease

ObjectiveTo review available medical therapies for patients with Cushing disease and to provide a roadmap for their use in clinical practice.MethodsPubMed searches were performed to identify all of the available published data on medical management of Cushing disease.ResultsMedical therapy is usually not the firstline treatment for patients with Cushing disease but may be used to improve clinical manifestations of Cushing disease in patients who are not suitable candidates for surgery, following unsuccessful surgery or recurrence, or as a “bridge therapy” in those who have undergone radiotherapy. Medical therapy may also be used in preoperative preparation of patients with severe disease. Current available medical options for patients with Cushing disease include centrally acting agents, steroidogenesis inhibitors, and a glucocorticoid receptor antagonists. At present, there are no head-to-head studies comparing the efficacy, tolerability, and safety of different U.S. Food and Drug Administration (FDA)- and non-FDA-approved drugs in patients with Cushing disease. With the initiation of new studies and the completion of ongoing clinical trials, the number of FDA-approved drugs for medical treatment of Cushing disease is expected to increase.ConclusionMedical therapy has an important adjunctive role in the management of patients with Cushing disease. The decision to initiate medical treatment depends on many factors, including patient characteristics and preference. Long-term studies are needed to better define the clinical efficacy, safety, and tolerability of medical treatment of Cushing disease, including the role of combination therapies. (Endocr Pract. 2014;20:746-757)     

Oral Octreotide: A Review of Recent Clinical Trials and Practical Recommendations for Its Use in the Treatment of Patients With Acromegaly

ObjectiveAcromegaly is characterized by chronic growth hormone (GH) and insulin-like growth factor 1 (IGF-1) hypersecretion, often caused by a GH-secreting pituitary adenoma. Even though surgery remains the first line of treatment, medical therapy is essential if surgery is contraindicated, does not achieve remission, or does not prevent recurrence despite apparent surgical remission. Oral octreotide capsules (OOCs) that combine octreotide with a transient permeability enhancer technology are the first oral somatostatin receptor ligands (SRLs) approved in the United States for acromegaly.MethodsWe review the literature and clinical trial data on OOC therapy in patients with acromegaly and discuss the clinical assessment of OOC use, potential drug–drug interactions, drug initiation, dose titration, and monitoring of drug efficacy and tolerability.ResultsIn 4 pivotal clinical trials involving 238 patients with acromegaly treated with OOC, effective suppression of serum GH and IGF-1 levels, maintenance of disease control, decreased breakthrough symptoms and symptomatic improvement with non-inferiority of OOCs to injectable SRLs in maintaining biochemical response was seen. Additionally, the safety profile of OOC therapy is comparable to that of injectable SRLs. Most patients who completed the clinical trials of OOCs have also expressed preference for oral compared with injectable SRL administration.ConclusionOOCs are an effective treatment option for patients with acromegaly who previously responded to injectable SRLs, with the benefits of avoiding injection-related side effects. This article provides a review of the pharmacology, safety, and efficacy and offers practical recommendations on the use of OOCs to treat injectable SRL-responsive patients with acromegaly.     

Statin Intolerance: A Review and Update

ObjectiveTo review the evidence of existing literature on the management of statin intolerance.MethodsWe searched for literature pertaining to statin intolerance and treatments in PubMed. We reviewed articles published between 2005 and 2022.ResultsStatin-associated myalgia is the most common adverse effect of statin therapy and the most common reason for statin discontinuation. The risk factors for statin intolerance include unexplained muscle pain with other lipid-lowering therapy, unexplained cramps, a history of increased creatine kinase levels, a family history of muscle symptoms, and a family history of muscle symptoms with lipid therapy. Vitamin D repletion and coenzyme Q supplementation may help alleviate the musculoskeletal effects of statins. Trials of different types of statins and different dosing regimens are recommended to improve tolerability. The use of statins in individuals who perform regular exercise requires closer attention to muscular symptoms and creatine kinase levels; however, it does not preclude the use of statins.ConclusionManagement of the adverse effects of statin therapy and improving statin tolerability are key to achieving optimum cardiovascular benefits. Identifying statin-associated adverse effects and managing them appropriately can reduce unnecessary statin discontinuation and subsequently provide longer cardiovascular protection.     

Osilodrostat: A Review of Recent Clinical Studies and Practical Recommendations for its Use in the Treatment of Cushing Disease

ObjectiveCushing disease (CD) is characterized by chronic hypercortisolism caused by an adrenocorticotropic hormone-secreting pituitary adenoma. Surgery remains the first-line treatment option; however, medical therapy is essential if surgery is contraindicated or fails to achieve remission or when recurrence occurs after surgical remission. Osilodrostat (Isturisa), a novel steroidogenic inhibitor, is now approved for the treatment of CD in the United States and Cushing syndrome in Europe. Herein, we review pharmacology and data on the efficacy, safety, and clinical use of osilodrostat and provide guidance on its use in treating patients with CD.MethodsWe reviewed the literature and published clinical trial data of osilodrostat use in patients with Cushing syndrome. Detailed information related to the clinical assessment of osilodrostat use, potential drug-to-drug interactions, drug initiation, dose titration, and the monitoring of drug tolerability were discussed.ResultsClinical trial data demonstrated that osilodrostat, by virtue of inhibiting 11-β hydroxylase, potently and rapidly decreased the 24-hour urinary free cortisol levels and sustained these reductions, with improved glycemia, blood pressure, body weight, and quality of life as well as lessened depression. Osilodrostat may interact with certain drugs, resulting in QT prolongation, which requires careful assessment of concomitant medications and periodic monitoring using electrocardiogram, respectively. The common adverse effects include adrenal insufficiency, hypokalemia, edema, and hyperandrogenic symptoms, which can be minimized using a slower up-titration dosing regimen.ConclusionOsilodrostat is an effective, new treatment option for CD, with positive effects on cardiovascular and quality of life parameters as well as tolerable adverse effects. This article provides a review of the pharmacology of osilodrostat and offers practical recommendations on the use of osilodrostat to treat CD.     

Treatment of Osteoporosis and Prevention of New Fractures: Role of Intravenously Administered Bisphosphonates

ObjectiveTo evaluate the usefulness of intravenously administered bisphosphonates for improving absorption, tolerability, adherence, and outcomes in the treatment and prevention of osteoporosis.MethodsData published from 1996 to 2009 relevant to the treatment of osteoporosis, with emphasis on bisphosphonates, fracture risk, adherence to therapy, frequency of dosing, intravenous treatment, tolerability, cost-effectiveness, and quality of life, were reviewed.ResultsAlthough bisphosphonates are currently the standard of care for treatment of postmenopausal osteoporosis and osteoporosis in men, oral formulations are associated with poor absorption and potential irritation of the upper gastrointestinal tract. These issues necessitate complicated and restrictive dosing regimens, which in turn lead to poor compliance and persistence. Intravenous formulations such as 3 mg of ibandronate given quarterly and 5 mg of zoledronic acid administered once yearly avoid problems relating to absorption and tolerability by bypassing the gastrointestinal tract. Intravenously administered ibandronate is presumed (by virtue of similar or superior improvements in bone mineral density) to have antifracture efficacy similar to that of orally administered ibandronate given daily, which has been shown to produce significant reductions in vertebral fractures during a 3-year period in comparison with placebo. Zoledronic acid, 5 mg once yearly, has been shown to produce a significant reduction in the risk of morphometric vertebral fractures, clinical vertebral fractures, hip fractures, and nonvertebral fractures versus placebo during a 3-year interval in patients with postmenopausal osteoporosis and also to yield a significantly decreased risk for new clinical fractures versus placebo in patients with recent low-trauma hip fracture. Both agents have favorable safety and tolerability profiles.ConclusionIntravenously administered bisphosphonates have the potential to increase compliance and persistence with therapy in patients with osteoporosis and to improve patient outcomes. (Endocr Pract. 2009;15:483-493)     

Safety and tolerability of medicinal parasite ova (Trichuris suis) in healthy Japanese volunteers: A randomized,double-blind,placebo-controlled trial

BackgroundTrichuris suis ova (TSO), with the potential to modulate the human immune system, have been tested for therapeutic application in autoimmune and allergic diseases such as inflammatory bowel disease (IBD). Previous clinical studies were limited to European and American participants, whereas Asian populations have not been well documented. In this study, a clinical trial was conducted to examine the safety and tolerability of TSO administration among a healthy Japanese population.MethodsThe study was a randomized, double-blind, placebo-controlled trial held at Jikei University Hospital, Tokyo. Twelve volunteers were stratified into three groups receiving different doses of TSO (TSO 1000, 2500, and 7500) and another into the control group. These cases were limited to healthy Japanese men aged over 20 years old. Single doses of medicinal TSO or placebo were given to three participants of each group. All participants were followed up to 56 days after ingestion. During the follow-up period, clinical practitioners checked each participant at the clinic at 7, 14, 28, and 56 days post-ingestion (dpi). Clinical symptoms were evaluated using questionnaire-based self-reporting, which participants filled at every visit. Blood samples were drawn at 7, 14, 28, and 56 dpi. Fecal samples were collected at 28 and 56 dpi.ResultsDuring the study period, twelve healthy Japanese male volunteers were enrolled. All participants completed the follow-up period. No severe adverse events were observed during the study period in all groups. Three participants in the TSO 1000, 2500, and 7500 groups had mild to moderate abdominal symptoms, diarrhea, bloating, and appetite loss during the observation period. One participant in the placebo group presented with mild diarrhea. Microscopic examination identified no parasite ova in any fecal samples. Blood sample examination indicated elevated eosinophil count in several cases, especially in the groups with the higher dose of TSO. No extra-abdominal symptoms were present in all cases.ConclusionsHealthy Japanese people tolerated all doses of TSO without any severe adverse events. On the other hand, mild to moderate abdominal symptoms were observed in several participants. This study suggested that the medicinal use of TSO in Japan is relatively safe, and close follow-up is recommended for sustainable usage.     

Relative benefit-risk comparing diclofenac to other traditional non-steroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors in patients with osteoarthritis or rheumatoid arthritis: a network meta-analysis

IntroductionThere is argument over the benefits and risks of drugs for treating chronic musculoskeletal pain. This study compared the efficacy, safety, and tolerability of diclofenac, ibuprofen, naproxen, celecoxib, and etoricoxib for patients with pain caused by osteoarthritis (OA) or rheumatoid arthritis (RA).MethodsA systematic literature review used Medline and EMBASE to identify randomised controlled trials. Efficacy outcomes assessed included: pain relief measured by visual analogue scale (VAS); Western Ontario McMaster Universities Arthritis Index (WOMAC) VAS or WOMAC Likert scale; physical functioning measured by WOMAC VAS or Likert scale; and patient global assessment (PGA) of disease severity measured on VAS or 5-point Likert scale. Safety outcomes included: Antiplatelet Trialists’ Collaboration (APTC), major cardiovascular (CV) and major upper gastrointestinal (GI) events, and withdrawals. Data for each outcome were synthesized by a Bayesian network meta-analysis (NMA). For efficacy assessments, labelled doses for OA treatment were used for the base case while labelled doses for RA treatment were also included in the sensitivity analysis. Pooled data across dose ranges were used for safety.ResultsEfficacy, safety, and tolerability data were found for 146,524 patients in 176 studies included in the NMA. Diclofenac (150 mg/day) was likely to be more effective in alleviating pain than celecoxib (200 mg/day), naproxen (1000 mg/day), and ibuprofen (2400 mg/day), and similar to etoricoxib (60 mg/day); a lower dose of diclofenac (100 mg/day) was comparable to all other treatments in alleviating pain. Improved physical function with diclofenac (100 and 150 mg/day) was mostly comparable to all other treatments. PGA with diclofenac (100 and 150 mg/day) was likely to be more effective or comparable to all other treatments. All active treatments were similar for APTC and major CV events. Major upper GI events with diclofenac were lower compared to naproxen and ibuprofen, comparable to celecoxib, and higher than etoricoxib. Risk of withdrawal with diclofenac was lower compared to ibuprofen, similar to celecoxib and naproxen, and higher than etoricoxib.ConclusionsThe benefit-risk profile of diclofenac was comparable to other treatments used for pain relief in OA and RA; benefits and risks vary in individuals and need consideration when making treatment decisions.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0554-0) contains supplementary material, which is available to authorized users.     

Comparison Of The Efficacy,Adverse Effects,And Cost Of Zoledronic Acid And Denosumab In The Treatment Of Osteoporosis

ObjectiveInjectable osteoporosis drugs are increasing in popularity due to their efficacy and convenient administration. In this retrospective comparison of the two available treatments, denosumab (Prolia®) and zoledronic acid (ZA, Reclast®), we aimed to determine and compare the efficacy and tolerability of denosumab and ZA.MethodsThe charts of patients who received denosumab and ZA at Loyola Hospital were reviewed, and adverse events were noted. Of primary interest were myalgias, flu-like symptoms, back pain, and fractures. A questionnaire regarding the efficacy, tolerability, and treatment cost supplemented this chart review in a subset of study participants. Bone mineral density (BMD) changes, bone turnover markers, and questionnaire results were also compared.ResultsThe study cohort consisted of 107 patients (51 denosumab, 56 ZA). The denosumab group had a greater mean increase in spine BMD at 1 year (0.060 g/cm²) than the ZA group (0.021 g/cm²; P = .04). The change in femur and spine BMD at 1 year were not significantly different between the 2 groups. The ZA group had a significantly greater incidence of mild flu-like symptoms (29% ZA group vs. 0% denosumab group; P = .04).ConclusionThe denosumab group had a higher mean increase in spine BMD, and the ZA group had a higher incidence of flu-like symptoms, but the study groups were statistically similar in terms of patient satisfaction. As denosumab is still a relatively new therapy, there were a limited number of patients with posttreatment data available for comparison. As more posttherapy data become available, it can be further investigated. (Endocr Pract. 2015;21:275-279)