基因变异功能学研究在不典型长QT综合征诊断中的作用

目的探讨基因变异功能学研究在临床不典型长QT综合征（LQTS）诊断中的作用。方法先证者有晕厥事件,心电图无QTc延长,临床疑诊LQTS;基因检测显示KCNH2基因M756V变异;家系中变异携带者QT正常,无心脏事件。分别使用含有野生型（WT）和突变M756V HERG基因的pcDNA3.1重组质粒进行转染,设WT＋M756V共转染组。转染后进行膜片钳和免疫组化研究明确临床诊断。结果 HERG M756V组电流较WT组明显减低,提示M756V变异为具有病理意义的LQTS突变;HERG M756V与WT共转染并无明显负显性机制。免疫组化研究表明HERG M756V蛋白存在转运障碍。结论体外功能学研究证实KCNH2基因M756V变异为LQTS突变,为临床疑诊患者提供确诊依据。     

Does anxiety predict the use of urgent care by people with long term conditions? A systematic review with meta-analysis

Objective

The role of anxiety in the use of urgent care in people with long term conditions is not fully understood. A systematic review was conducted with meta-analysis to examine the relationship between anxiety and future use of urgent healthcare among individuals with one of four long term conditions: diabetes; coronary heart disease, chronic obstructive pulmonary disease and asthma.

Methods

Electronic searches of MEDLINE, EMBASE, PSYCINFO, CINAHL, the British Nursing Library and the Cochrane Library were conducted These searches were supplemented by hand-searching bibliographies, citation tracing eligible studies and asking experts within the field about relevant studies. Studies were eligible for inclusion if they: a) used a standardised measure of anxiety, b) used prospective cohort design, c) included adult patients diagnosed with coronary heart disease (CHD), asthma, diabetes or chronic obstructive pulmonary disease (COPD), d) assessed urgent healthcare use prospectively. Data regarding participants, methodology, and association between anxiety and urgent care use was extracted from studies eligible for inclusion. Odds ratios were calculated for each study and pooled using random effects models.

Results

8 independent studies were identified for inclusion in the meta-analysis, with a total of 28,823 individual patients. Pooled effects indicate that anxiety is not associated with an increase in the use of urgent care (OR = 1.078, p = 0.476), regardless of the type of service, or type of medical condition.

Conclusions

Anxiety is not associated with increased use of urgent care. This finding is in contrast to similar studies which have investigated the role of depression as a risk factor for use of urgent care.     

Perampanel,a selective,noncompetitive α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor antagonist,as adjunctive therapy for refractory partial‐onset seizures: Interim results from phase III,extension study 307

Purpose: To evaluate safety, tolerability, and seizure outcome data during long‐term treatment with once‐daily adjunctive perampanel (up to 12 mg/day) in patients with refractory partial‐onset seizures. Methods: Study 307 was an extension study for patients completing the double‐blind phase of three pivotal phase III trials (studies 304, 305, and 306). The study consisted of two phases: an open‐label treatment phase (including a 16‐week blinded conversion period and a planned 256‐week maintenance period) and a 4‐week follow‐up phase. Patients were blindly titrated during the conversion period to their individual maximum tolerated dose (maximum 12 mg/day). Adverse events (AEs) were monitored throughout the study and seizure frequency recorded. The interim data cutoff date for analyses was December 1, 2010. Key Findings: In total, 1,218 patients were enrolled in the study. At the interim cutoff date, 1,186 patients were in the safety analysis set; 1,089 (91.8%) patients had >16 weeks of exposure to perampanel, 580 (48.9%) patients had >1 year of exposure, and 19 (1.6%) patients had >2 years of exposure. At the interim analysis, 840 (70.8%) patients remained on perampanel treatment. The large majority of patients (n = 1,084 [91%]) were titrated to 10 mg or 12 mg/day. Median (range) duration of exposure was 51.4 (1.1–128.1) weeks. Treatment‐emergent AEs were reported in 87.4% of patients. The most frequent were dizziness (43.9%), somnolence (20.2%), headache (16.7%), and fatigue (12.1%). Serious AEs were reported in 13.2% of patients. In the intent‐to‐treat analysis set (n = 1,207), the frequency of all seizures decreased over the first 26 weeks of perampanel treatment in patients with at least 26 weeks of exposure to perampanel (n = 1,006 [83.3%]); this reduction was maintained in patients with at least 1 year of exposure (n = 588 [48.7%]). The overall median percent changes in seizure frequency in patients included in each 13‐week interval of perampanel treatment were ?39.2% for weeks 14–26 (n = 1,114), ?46.5% for weeks 40–52 (n = 731), and ?58.1% for weeks 92–104 (n = 59). Overall responder rates in patients included in each 13‐week interval of perampanel treatment were 41.4% for weeks 14–26 (n = 1,114), 46.9% for weeks 40–52 (n = 731), and 62.7% for weeks 92–104 (n = 59). During the blinded conversion period, the reduction in seizure frequency in patients previously randomized to placebo (?42.4%, n = 369) was similar to that in patients previously randomized to perampanel (?41.5%, n = 817). Significance: Consistent with pivotal phase III trials, these interim results demonstrated that perampanel had a favorable tolerability profile in patients with refractory partial‐onset seizures over the longer term. The decrease in seizure frequency was consistent and maintained in those patients over at least 1 year of perampanel exposure.     

Intramural injection with botulinum toxin significantly elongates the pig esophagus

Background/Purpose

Surgical treatment of long-gap esophageal atresia (LGEA) is challenging. Methods which facilitate stretching of the esophageal pouches may allow primary anastomosis. Botulinum toxin type A (BTX-A) blocks acetylcholine release in neuromuscular junctions, thereby causing muscle relaxation. We hypothesized that intramural injections with BTX-A into the esophageal wall of piglets would significantly elongate the tissue upon stretch.

Methods

Twenty-four piglets were randomized to receive BTX-A of placebo (saline). After one hour, the esophagus was removed en bloc and tested in a stretch-tension device.

Results

The mean esophageal elongation was 84% (range 83–101) in the BTX-A-group and 65% (50–78) in the control group. The mean difference between the two groups was 18%, which was significant (p < 0.001).

Conclusion

Intramural injections with botulinum toxin type A elongate the esophagus significantly. Clinically, this could be a potential method to achieve primary anastomosis in LGEA. Additional clinical studies are necessary to evaluate the method before it can be generally recommended.     

Diversification of care policy measures supporting older people: towards greater flexibility for carers?

Originally part of the private domain of families, care of the older people is now the concern of public policy. Yet, in the European context of cost containment, it is not easy to make a case for increasing public support and the caring function of families remains prominent in social policy. In this paper, the authors question public policies around care of the older people in relation to both the needs of old people, but also those of adult children, mainly women, who work and provide care for their old parents. We investigate the interactions between public support in long-term care and the caring function of families. The paper presents some results of a comparative research study based on the identification of the policy measures which have been implemented in different European countries in the sector of care of the older people, and on the detailed analysis of care arrangements set up by a sample of 86 family carers in these various national contexts. We argue that in a context of cost containment, whatever the usual patterns of care and the role given to the family and public authorities, the policy measures which have been introduced since the 90s aim to support family carers in various ways with the common objective of giving them the flexibility they need in the organisation of care arrangements, combining various resources (formal professional care, unpaid informal care, semi-formal care). Different patterns of flexibility can be identified according to the regulation of the policy measures.     

改良长方案的控制性超促排卵方案在体外受精-胚胎移植中的应用

目的探讨延长促性腺激素释放激素激动剂（GnRH—a）使用时间的控制性超促排卵（COH）方案对体外受精一胚胎移植（IVF-ET）助孕临床结局的影响。方法回顾性分析改良长方案336个周期和常规长方案358个周期,比较两种COH方案的促排卵药使用情况、激素变化及助孕结局。结果两组患者的年龄、不育年限、体重指数（BMI）无统计学差异（P〉0．05）。改良长方案组促性腺激素（Gn）使用天数与常规长方案无显著差异（P〉0．05）,但Gn使用剂量较常规长方案组多,药费却显著低（P〈0．001）。改良长方案组基础和启动日的卵泡刺激素（FSH）和雌二醇（E2）高于常规长方案组（P〈0．01）,启动日和人绒毛膜促性腺激素（HCG）日的黄体生成素（LH）则显著低于常规长方案组（P〈0．01）,两组HCG日E2无统计学差异（P〉0．05）。改良长方案组启动日窦卵泡数、获卵数、受精数、胚胎数均少于常规长方案,但临床妊娠率、胚胎种植率及活产率高于常规长方案组（P〈0．05）,两组间优质胚胎数、移植胚胎数、早期流产率无统计学差异（P〉0．05）。结论延长GnRH—a使用时间方案（改良长方案）较常规长方案更有利于提高IVF-ET临床妊娠率、胚胎种植率及活产率,并减少促排卵药物的费用。     

重组人生长激素对高龄妇女不同超促排卵方案IVF—ET结局的影响

目的观察高龄妇女（≥35岁）患者不同促排卵方案体外受精-胚胎移植（IVF-ET）治疗周期中添加重组人生长激素（GH）辅助超排卵的临床应用效果。方法对2010年1月至2012年12月在我中心行微量长方案及长方案促排卵的IVF—ET高龄患者,随机分为两组,其中研究组加用GH,对照组未用GH,两组患者启动剂量均为福特蒙300U,分析两组获卯数、人绒毛膜促性腺激素（HCG）日内膜厚度、HCG日内膜形态、受精率、卵裂率、优胚率及妊娠率的差异。结果两种促排卵方案中研究组与对照组相比较受精率均明显增高,有显著差异（P〈0．05）,妊娠率有增高趋势,但无显著差异,其中长方案促排卯研究组优质胚胎率较对照组明显升高,微量长方案促排卵研究组优质胚胎率无此趋势,两种促排卵方案中研究组与对照组中获卯率、卵裂率、HCG日内膜厚度、HCG日内膜形态、优质胚胎率均无明显差异。结论对高龄患者行IVF—ET治疗中使用GH可以显著提高受精率,并有增加优质胚胎率及妊娠率的趋势;针对不同年龄或卵巢功能状态,个体化调整GH剂量可能更可行。