A型肉毒毒素治疗局限性肌张力障碍的临床研究

目的 探讨A型肉毒毒素(BTX—A)局部注射治疗局限性肌张力不全(偏侧面肌痉挛、眼睑痉挛、Meige综合症)的临床疗效及安全性。方法：对186例病人采用BTX—A局部多点注射痉挛肌肉，并进行治疗前后的病情分级及疗效对比。结果：治疗后随访至少半年，BTX—A治疗有效率为100％，疗效持续8W～28W，最好疗效维持2月左右。复发者重复注射治疗同样有效。注射后病人可出现轻度的局部肌无力，如眼睑闭合不良、轻度面瘫。但均在短期内恢复，副作用轻微可逆。结论：BTX—A治疗方法简单、安全、有效，可作为头面部肌张力障碍的首选治疗。     

Efficacy of statins in combination with interferon therapy in multiple sclerosis: A meta-analysis

Purpose The efficacy of statins in combination with interferon therapy in patients with multiple sclerosis (MS) is reviewed. Methods A systematic literature search was conducted through September 2011 to identify randomized controlled trials that evaluated the effect of combination statin-interferon therapy compared with interferon therapy alone in patients with MS. Trials had to report at least one of the following outcomes of interest: clinical relapse rate, disease progression, or Expanded Disability Status Scale (EDSS) score. A random-effects model was used to pool data. Trial quality was assessed using the Jadad score. Results Four unique trials were included in the analysis (n = 463 subjects; range of follow-up, 9-24 months), all with a Jadad score of ≥3. All trials evaluated patients with relapsing-remitting MS (RRMS). Most trials enrolled patients taking interferon beta therapy either twice or three times weekly. The mean baseline EDSS scores ranged from 1.2 to 3.4. Evaluated statins included simvastatin and atorvastatin. No significant difference was found between the statin and control groups in the incident rate ratio for clinical relapse (0.72; 95% confidence interval [CI], 0.17 to 3.11), risk of relapse (relative risk [RR], 0.99; 95% CI, 0.53 to 1.85], disease progression (RR, 1.31; 95% CI, 0.73 to 2.36), or difference in the change in the EDSS score from baseline (weighted mean difference, -0.06; 95% CI, -0.30 to 0.19). Conclusion A meta-analysis revealed that the addition of statins to interferon therapy did not significantly influence the relapse risk, disease progression, or EDSS scores in patients with RRMS.     

治疗纯合子型家族性高胆固醇血症新药:evinacumab

纯合子型家族性高胆固醇血症(HoFH)是一种罕见的低密度脂蛋白胆固醇(LDL-C)水平异常高的遗传性疾病.血管生成素样蛋白3(ANGPTL3)是治疗高脂血症的新靶点,evinacumab(Evi)是ANGPTL3抑制剂.Evi于2021年2月被美国食品和药物管理局批准上市,作为其他降低LDL-C疗法的辅助药物,用于治疗...     

他汀类药物能否减少谵妄发生的Meta分析

目的 评估他汀类药物的多效性能否减少谵妄的发生。方法 检索2000年1月至2016年6月PubMed、万方数据库、Cochrane library、EMBase、维普中文数据库、中国期刊全文数据库收录的关于他汀类药物使用能否减少谵妄发生的随机对照试验文献,以“谵妄,ICU谵妄,他汀,辛伐他汀,阿托伐他汀,西立伐他汀,氟伐他汀,洛伐他汀,美伐他汀,普伐他汀,罗素伐他汀,HMG-CoA还原酶阻滞剂”等为检索词检索,使用Jadad量表对纳入的文献进行严格的质量评价,主要评估指标为使用他汀类药物是否有效,次要评估指标包括住院时间,机械通气的例数,最后用RevMan5.2统计软件进行系统分析。结果 共纳入7项研究,290 274例患者。其中,显示服用他汀类药物不能减少谵妄的发生率（OR：1.01;95% CI：0.81~1.26）,也不能缩短住院时间（WMD：1.93;95% CI：-5.62~9.47）。但是,他汀类药物能够减少危重患者机械通气的发生率（OR：0.65;95% CI：0.47~0.90）。结论 使用他汀类不能减少谵妄的发生。     

血浆置换联合他汀类治疗肾病综合征严重高胆固醇血症

目的观察肾病综合征严重高胆固醇血症进行血浆置换(plasma exchange,PE)与他汀类药物联合治疗的临床效果。方法入选笔者所在医院2012年5月—2014年5月肾病综合征严重高胆固醇血症患者46例,根据随机数字表法分为联合组18例、他汀组22例、PE组6例,联合组在原有治疗基础上予服阿托伐他汀20 mg/d并同时予血浆置换治疗2周,共治疗2~5次;他汀组在原有治疗基础上服阿托伐他汀20 mg/d;PE组原有治疗基础上进行单纯血浆置换治疗2周,共治疗2~5次,各组均观察4周。结果三组患者治疗后血清肌酐、人血白蛋白、尿蛋白定量、Ig G等指标无明显改变;联合组治疗后的三酰甘油、总胆固醇下降程度显著优于他汀组及PE组(P<0.05);联合组治疗后Fib、Ig M、Ig A等血浆蛋白指标显著优于他汀组及PE组(P<0.01);联合组治疗后apo-E、apoB、apo-A1、HDL、LDL、TG、TC等血脂蛋白指标显著优于他汀组及PE组(P<0.01)。联合组治疗结束时TC、TG值最低,随访4周略有升高,仍明显低于治疗前;PE组治疗后TG、TC均明显下降,但随后出现明显反弹;他汀组血脂下降平稳,但下降幅度小。结论肾病综合征严重高胆固醇血症患者进行血浆置换与他汀类药物联合疗法虽不能改善肾病综合征(nephrotic syndrome,NS)患者原发病治疗的反应性,但可显著改善患者的高胆固醇血症。     

Use of statins and blood pressure control in treated hypertensive patients with hypercholesterolemia

High serum cholesterol has been frequently reported in patients with arterial hypertension in whom it might influence the blood pressure control. The aim of this study was to compare the extent of blood pressure changes in 41 patients with hypertension and hypercholesterolemia, taking antihypertensive drugs and treated for 3 months with statins (HC-S; pravastatin or simvastatin) and compared with matched controls with high (HC-D; 44) or normal serum cholesterol (NC-D; 45) undergoing antihypertensive treatment combined with dietary treatment alone. After 3 months of follow-up, a greater reduction of systolic (SBP) and diastolic (DBP) blood pressure values was observed in HC-S patients (ASBP/DBP, -11.3 +/-3/-10.6 +/- 2%) when compared with both HC-D (deltaSBP/DBP, -6.6 +/- 2/-6.1 +/- 2%; p < 0.05) and NC-D (deltaSBP/DBP, -6.9 +/- 2/-6.8 +/- 1.5%; p < 0.05). In statin-treated patients, a slight linear relation has been found between the percentage changes in DBP and those in plasma total cholesterol (R = 0.37, p = 0.043), whereas no relation was found with SBP changes (R =0.11; p = 0.35). In conclusion, the results of this study demonstrate that the use of statins in combination with antihypertensive drugs can improve blood pressure control in patients with uncontrolled hypertension and high serum cholesterol levels. The additional blood pressure reduction observed in patients treated with statins is clinically relevant and only partially related to the lipid-lowering effect.     

Mipomersen and its use in familial hypercholesterolemia

Introduction: Familial Hypercholesterolemia (FH) is an inherited disorder characterized by a defect in the binding and internalization of low-density lipoprotein (LDL) particles, resulting in markedly elevated LDL levels and premature atherosclerosis. It is one of the most common inherited disorders of lipid metabolism. Many FH patients, especially those with homozygous FH do not reach LDL goals with traditional LDL therapies and may require additional, less often used, therapies.

Areas covered: Mipomersen is an anti-sense oligonucleotide that prevents production of apolipoprotein B leading to decreased levels of very low-density lipoprotein (VLDL) and LDL. In this review the authors discuss the pharmacokinetics of the drug, the clinical trials evaluating its efficacy and safety, and risks and challenges associated with its clinical implementation. Its use as therapy for the treatment of FH is also discussed.

Expert opinion: Mipomersen is approved for use only in homozygous FH. It has frequent adverse effects, such as injection site reactions, flu-like symptoms, and hepatoxicity. It is useful only in patients who have failed other therapies, and it faces competition from other medications that have more tolerable side effect profiles.     

家族性高胆固醇血症的诊疗进展

家族性高胆固醇血症是一种脂蛋白代谢异常的常染色体显性遗传疾病,是早发动脉粥样硬化性心血管疾 病的一个常见遗传原因。尽管该病的终末不良事件发生于中老年人群,但是血管的损伤却开始于胎儿时期。大多 数患者是由于低密度脂蛋白受体（LDLR）、载脂蛋白B（APOB）和前蛋白转化酶枯草溶菌素9（PCSK9）基因突变所致。 对于儿童,间隔3个月的饮食控制2次低密度脂蛋白胆固醇（LDL-C）≥5 mmol/L高度提示该病。通过索引患者的瀑布 式筛查可以早期发现患者;从儿童时期开始给予他汀类药物治疗可以改善血管功能。因此,早期诊断和早期干预对 于改善预后至关重要。本文从病因、诊断、治疗和筛查等方面对该病进行综述。     

Developing implementation strategies to improve uptake of guideline-recommended treatments for individuals with familial hypercholesterolemia: A protocol

BackgroundFamilial hypercholesterolemia (FH) affects more than one million Americans, and most individuals have not been formally diagnosed with the condition. Individuals with FH have markedly elevated serum low-density lipoprotein cholesterol (LDL-C) levels from birth that substantially increase their risk for early-onset cardiovascular (CV) events. Guideline-recommended treatments exist to lower LDL-C and reduce the risk of CV events in individuals with FH and hypercholesterolemia. This study seeks to address a significant gap in the care of individuals with FH by systematically developing an effective approach to increase the adoption of guideline-recommended treatments for FH.MethodsThis developmental study will consist of three aims: 1) determine the barriers to and facilitators of treatment of FH; 2) develop a list of potential implementation strategies to promote the adoption of guideline-recommended treatment of individuals with FH, and 3) pilot one implementation strategy from Aim 2 in one health care system to evaluate implementation outcomes of the strategy. The Practical, Robust Implementation and Sustainability Model will guide this project, including the development of interview questions, implementation strategies, and evaluation of the implementation strategy. The implementation outcomes include: of individuals targeted by the implementation strategy, how many are impacted by it (reach), measure the change in knowledge, attitude, and behavior that is impacted by the implementation strategy (effectiveness), in settings targeted by the implementation strategy, how many adopt it (adoption), and fidelity and cost of the implementation strategy (implementation). Data sources will include electronic health records, administrative databases, surveys, and semi-structured interviews.DiscussionThe inclusion of patient and organizational stakeholder experiences is a critically important step in developing efficient and effective implementation strategies. Additionally, perspectives from a variety of geographic areas and cultural perspectives should increase feasibility and fidelity of the interventional approach to improve adoption of guideline-recommended practices for FH care.     

膝关节镜下治疗盘状半月板疗效分析

目的总结在膝关节镜下治疗盘状半月板临床应用效果。方法本组22例，男16例，女6例，年龄6—35岁。应用美国Stryker关节镜对22例膝关节盘状软骨进行了检查、确诊及手术。结果盘状半月板全切除术7例，部分切除术15例。随访2个月～5年，优19例，良2例，差1例，优良率95．5％。结论膝关节镜检查及手术在诊断和治疗膝关节盘状半月板是一种有效的方法。     

Meta-analysis of large randomized controlled trials to evaluate the impact of statins on cardiovascular outcomes

AIMS: Since 2002, there have been five major outcome trials of statins reporting findings from more than 47,000 subjects. As individual trial results differed, we performed a meta-analysis to ascertain the effectiveness and safety of statins overall and in subgroups. The aim of the study was to estimate the effect of statins on major coronary events and strokes, all-cause mortality and noncardiovascular mortality, and in different subgroups. METHODS: PubMed was searched for trials published in English. Randomized placebo-controlled statin trials with an average follow up of at least 3 years and at least 100 major coronary events were included. For each trial, the statin used, number and type of subjects, proportion of women, mean age and follow up, baseline and change in lipid profile, cardiovascular and non-cardiovascular outcomes were recorded. RESULTS: Ten trials involving 79,494 subjects were included in the meta-analysis. Due to heterogeneity, ALLHAT-LLT was excluded from some analyses. Statin therapy reduced major coronary events by 27% (95%CI 23, 30%), stroke by 18% (95%CI 10, 25%) and all-cause mortality by 15% (95%CI 8, 21%). There was a 4% (95%CI -10, 3%) nonsignificant reduction in noncardiovascular mortality. The reduction in major coronary events is independent of gender and presence of hypertension or diabetes. The risk reduction was greater in smokers (P < 0.05). Coronary events were reduced by 23% (95%CI 18, 29%) in pravastatin trials and 29% (95%CI 25, 33%) in five trials using other statins. Pravastatin reduced strokes by 12% (95%CI 1, 21%) whilst other statins reduced strokes by 24% (95%CI 16, 32%) (P = 0.04). CONCLUSIONS: Statins reduce coronary events, strokes and all-cause mortality without increasing noncoronary mortality. The benefits accrue in men and women, hypertensives and normotensives, diabetics and nondiabetics, and particularly in smokers. Pravastatin appears to have less impact on strokes.     

赖氨匹林治疗小儿高热疗效的Meta分析

目的系统评价赖氨匹林治疗小儿高热的疗效。方法检索维普(VIP)、中国知网(CNKI)、万方等数据库,检索时间建库至2016年,纳入赖氨匹林治疗(试验组)与复方氨林巴比妥(安痛定)(对照组)治疗小儿高热的随机对照试验(RCTs),独立评价纳入研究的质量并提取资料,采用Rev Man 5.3软件进行统计分析。结果共纳入9篇RCTs,包含患者3 659例,Meta分析结果显示:试验组用赖氨匹林治疗小儿高热,用药1 h后体温明显低于对照组(肌肉注射安痛定),差异有统计学意义[MD=-0.73,95%CI(-1.03,-0.44),P<0.01];用赖氨匹林治疗小儿高热,用药1 h有效率明显高于对照组,差异有统计学意义[RR=1.16,95%CI(1.07,1.27),P<0.01];用药1 h后显效率显著高于对照组,差异有统计学意义[RR=1.55,95%CI(1.35,1.79),P<0.01]。结论肌肉注射赖氨匹林治疗小儿高热疗效比肌肉注射安痛定效果显著。     

Formation of isoprostanes in children with type IIa hypercholesterolemia

F2-isoprostanes are stable lipid peroxidation products of arachidonic acid and their quantification provides a novel approach to the assessment of oxidative stress in vivo. F2-isoprostanes are present in increased amounts in adult hypercholesterolemia, but no data exist concerning children. We investigated urinary isoprostaglandin F2, type III production as an index of lipid peroxidation in 15 children presenting with type IIa hypercholesterolemia (serum total cholesterol, 290 [SD +/- 70] mg/dl; low-density lipoprotein cholesterol, 210 [SD +/- 90] mg/dl) compared with 15 sex- and age-paired control children (serum total cholesterol, 160 [SD +/- 20] mg/dl). Urinary levels of isoprostaglandin F2alpha type III were measured by gas chromatography mass spectrometry. Urinary concentrations did not differ significantly in hypercholesterolemic children compared with control children (84.7 [SD +/- 37] vs. 96 [SD +/- 35] pmol/mmol creatinine, respectively). No significant correlation was found with total cholesterol, low-density-lipoprotein and high-density-lipoprotein cholesterol, and apolipoprotein B and A1 serum levels. F2-isoprostane urinary levels in children with type IIa hypercholesterolemia do not differ from those of age- and sex-matched control children and are not correlated to blood lipid parameters, suggesting that hypercholesterolemia is not associated with increased lipid peroxidation in childhood.     

Novel treatment options for the management of heterozygous familial hypercholesterolemia

Introduction: Even though statins represent the mainstay of treatment of heterozygous familial hypercholesterolemia (FH), their low-density lipoprotein cholesterol (LDL-C) lowering efficacy is finite and most patients with FH will not achieve LDL-C targets with statin monotherapy. Addition of ezetimibe with or without bile acid sequestrants will also not lead to treatment goals in many of these patients, particularly in those with established cardiovascular disease. In this selected subgroup of the FH population, proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors provide substantial reductions in LDL-C levels, reduce cardiovascular morbidity and appear to be safe. Mipomersen, an antisense single-strand oligonucleotide that inhibits the production of apoB by binding to the mRNA that encodes the synthesis of apoB, and lomitapide, an inhibitor of microsomal triglyceride transfer protein, also reduce LDL-C levels but are currently indicated only for the management of homozygous FH.

Areas covered: In the present review, the role of PCSK9 inhibitors, mipomersen and lomitapide in the management of FH is briefly discussed. Other LDL-C-lowering agents under evaluation include inclisiran, a small interference RNA molecule that induces long-term inhibition of PSCK9 synthesis, anacetrapib, a cholesterol ester-transfer protein inhibitor, ETC-1002 (bempedoic acid), an inhibitor of adenosine triphosphate citrate lyase, and gemcabene, which reduces hepatic apolipoprotein C-III mRNA. The safety and efficacy of these agents are also reviewed.

Expert Commentary: Even though several novel treatment options for heterozygous FH are under development, it remains to be shown whether these treatments will also reduce cardiovascular morbidity in these high-risk patients.