Association of stressful life events with accelerated bone loss in older men: the osteoporotic fractures in men (MrOS) study

Summary

Prior studies suggest an association between stressful life events and fractures that may be mediated by BMD. In the current study, risk of accelerated hip BMD loss was higher in older men with any type of stressful life event and increased with the number of types of stressful life events.

Introduction

Prior studies suggest that stressful life events may increase adverse health outcomes, including falls and possibly fractures. The current study builds on these findings and examines whether stressful life events are associated with increased bone loss.

Methods

Four thousand three hundred eighty-eight men aged ≥65 years in the Osteoporotic Fractures in Men study completed total hip bone mineral density (BMD) measures at baseline and visit 2, approximately 4.6 years later, and self-reported stressful life events data mid-way between baseline and visit 2, and at visit 2. We used linear regression to model the association of stressful life events with concurrent annualized total hip BMD loss, and log binomial regression or Poisson regression to model risk of concurrent accelerated BMD loss (>1 SD more than mean annualized change).

Results

Men (75.3 %) reported ≥1 type of stressful life event, including 43.3 % with ≥2 types of stressful life events. Mean annualized BMD loss was ?0.36 % (SD 0.88), and 13.9 % of men were categorized with accelerated BMD loss (about 5.7 % or more total loss). Rate of annualized BMD loss increased with the number of types of stressful life events after adjustment for age (p?p?=?0.07). Multivariable-adjusted risk of accelerated BMD loss increased with the number of types of stressful life events (RR, 1.10 [95 % confidence interval (CI), 1.04–1.16]) per increase of one type of stressful life event). Fracture risk was not significantly different between stressful life event-accelerated bone loss subgroups (p?=?0.08).

Conclusions

In these older men, stressful life events were associated with a small, dose-related increase in risk of concurrent accelerated hip bone loss. Low frequency of fractures limited assessment of whether rapid bone loss mediates any association of stressful life events with incident fractures. Future studies are needed to confirm these findings and to investigate the mechanism that may underlie this association.     

Development of appropriateness criteria for the surgical treatment of symptomatic lumbar degenerative spondylolisthesis (LDS)

Purpose

Spine surgery rates are increasing worldwide. Treatment failures are often attributed to poor patient selection and inappropriate treatment, but for many spinal disorders there is little consensus on the precise indications for surgery. With an aging population, more patients with lumbar degenerative spondylolisthesis (LDS) will present for surgery. The aim of this study was to develop criteria for the appropriateness of surgery in symptomatic LDS.

Methods

A systematic review was carried out to summarize the current level of evidence for the treatment of LDS. Clinical scenarios were generated comprising combinations of signs and symptoms in LDS and other relevant variables. Based on the systematic review and their own clinical experience, twelve multidisciplinary international experts rated each scenario on a 9-point scale (1 highly inappropriate, 9 highly appropriate) with respect to performing decompression only, fusion, and instrumented fusion. Surgery for each theoretical scenario was classified as appropriate, inappropriate, or uncertain based on the median ratings and disagreement in the ratings.

Results

744 hypothetical scenarios were generated; overall, surgery (of some type) was rated appropriate in 27 %, uncertain in 41 % and inappropriate in 31 %. Frank panel disagreement was low (7 % scenarios). Face validity was shown by the logical relationship between each variable’s subcategories and the appropriateness ratings, e.g., no/mild disability had a mean appropriateness rating of 2.3 ± 1.5, whereas the rating for moderate disability was 5.0 ± 1.6 and for severe disability, 6.6 ± 1.6. Similarly, the average rating for no/minimal neurological abnormality was 2.3 ± 1.5, increasing to 4.3 ± 2.4 for moderate and 5.9 ± 1.7 for severe abnormality. The three variables most likely (p < 0.0001) to be components of scenarios rated “appropriate” were: severe disability, no yellow flags, and severe neurological deficit.

Conclusion

This is the first study to report criteria for determining candidacy for surgery in LDS developed by a multidisciplinary international panel using a validated method (RAM). The panel ratings followed logical clinical rationale, indicating good face validity. The work refines clinical classification and the phenotype of degenerative spondylolisthesis. The predictive validity of the criteria should be evaluated prospectively to examine whether patients treated “appropriately” have better clinical outcomes.     

【特刊综述】性腺功能低下在克氏综合征中的角色

克氏综合症（47,XXY）（KS）是最常见的性染色体异常,也是男性不育和性腺功能低下的常见原因。大部分KS患者终其一生都不知道自己患有这个疾病,只有25％的患者得到诊断,而在青春期前被诊断的更是少数。除了性腺功能低下和无精子症,大多数KS患者都有一定程度的学习障碍,并且可能有多种精神问题。长期性腺功能低下的影响可能使其难以与额外的x染色体引起的基因剂量效应相辨别。不管是什么原因,KS患者常出现身体成分的改变,包括脂肪增加、肌肉减少和骨矿物质流失,同时发生代谢障碍的风险也增加,例如患2型糖尿病和代谢综合征。这些发现应该引起我们的重视,因为他们不仅仅是简单的化验结果,流行病学调查表明KS患者因不同的疾病住院和死亡的风险均增加。KS患者应该在青春期早期就被给予睾丸激素治疗,尽管目前证据不足,因为至今仍未有随机对照试验的文章发表过。在这篇文章里,我们回顾了近期关于KS患者性腺功能低下症的研究进展和睾丸激素治疗的合理性,希望能为这个常见但往往被忽视的综合征提出我们的最佳建议。     

【原创论文】应关注男性不育的药物治疗——睾酮：用还是不用？

在男性不育的治疗中是否使用睾酮是一个重要问题。2013年欧洲泌尿外科学会（EAU）在其最新版的男性不育治疗指南中明确指出“睾酮替代治疗是男性不育治疗的严格禁忌证”,这个论断引起了广泛的关注和争议。尽管目前还缺乏设计良好的临床对照研究来提供足够证据支持男性不育症的药物治疗,用来证明这些药物的有效性的研究机会不能被剥夺,药物治疗的研究应该被鼓励和加强（而不是简单地禁止）。无论从基本的医学原则、医学发展、医学专业知识方面,以及人文医学角度,包括睾酮在内的药物治疗都应该作为一线的治疗方法或基础治疗。因此,我认为EAU指南中于注男性不育治疗严格禁忌使用睾酮的论断考虑有欠周全,使用睾酮治疗男性不育的主要理由在本文中进行了充分的讨论。     

【特刊综述】睾酮和雌二醇检测方法面临的挑战和取得的进展

在患者护理、公共卫生、科学研究过程中类固醇激素的检测方法需要正确而精准,因为这些检测的标准可以保证所有的临床机构和研究机构的结果具有可比性。本文陈述了目前有关检验结果易变的主要问题以及最近美国疾病预防控制中心（CDc）针对提升检验效果所做的工作。目前,睾酮和雌二醇的检测方法还无法达到高度的正确性和精准性。虽然类固醇激素检测方法已经有了长足的进步,但是实验室内部和实验室之间的检测差异仍然未能得到相应的改善。检测标准和特异性的差异被认为是测量精度变异性的来源。最终认为,类固醇激素检测的不准确性似乎是由综合因素造成的,其中不一致的检验标准和缺乏特异性被认为是产生结果变异的两个主要因素。目前,同一批次内的化验结果也变异较大,特别是在样本浓度低的情况下。2007至2011年间的质谱分析法和CDC参考方法之间的平均绝对偏差下降了50％,由此可以看出CDC激素标准化测试程序正在提高临床化验的准确性。这种测试程序可以为CDC参考方法提供追朔源头的途径,从而减少产生测量结果变异的因素。     

【特刊综述】利用雄激素受体敲除（ARKO）小鼠模型认识人类雄激素缺乏

雄激素的作用机理很复杂。最近,使用转基因修饰小鼠模型进行的雄激素受体研究使我们对雄激素作用机理有了更进一步的理解。Cre-loxP系统能够完成组织和／或细胞特异性的敲除。通过使用Cre—loxP系统已经获得了大量整体性或组织特异性雄激素受体（ARK0）敲除模型。这些ARKO模型的多个雄激素作用位点,包括心血管系统、免疫和造血系统、骨骼、肌肉、脂肪组织、前列腺和脑,均已被检测。本篇综述着重阐述了通过针对这些雄激素作用位点的ARKO小鼠模型而取得的人类雄激素缺乏的研究成果,并且指出充分理解Cre-loxPdx鼠模型的优缺点才能正确认识其表型。     

Resistance to macrolides, clindamycin and telithromycin in Streptococcus pyogenes isolated in Spain during 2004

OBJECTIVES: To study the antimicrobial susceptibility and prevalence of the different phenotypes and genotypes of macrolide resistance in group A streptococci isolated in Spain in 2004, and to compare the results with those obtained in 1998 and 2001 using the same methodology and centres. METHODS: A total of 530 unique isolates of Streptococcus pyogenes collected in 21 laboratories from 16 geographic areas (regions) in Spain were used. Antimicrobial susceptibility testing was performed using the agar dilution method. Discs containing erythromycin or clindamycin were used to recognize the phenotypes of macrolide-lincosamide-streptogramin (MLS) resistance. Genes encoding macrolide-lincosamide resistance were detected by PCR. RESULTS: Resistance to erythromycin was 21.7% [95% confidence interval (CI) 16.5-26.3]. The resistance to azithromycin was 21.5%, whereas the resistance to miocamycin and to clindamycin was 6.6% (95% CI 3.0-8.9). Thirty-one (5.8%) of the isolates were resistant to telithromycin. Of the 115 erythromycin-resistant isolates, 67.8% had the M phenotype, representing 14.7% of all the isolates tested. Thirty-five isolates (30.5% of the erythromycin-resistant strains and 6.6% of all the isolates) had the MLS(B) constitutive phenotype. There was a high prevalence of resistance to telithromycin (88.6%) among the 35 strains with the MLS(B) constitutive phenotype. When we compared these results with those from previous studies (1998 and 2001), we found a significant increase in the MLS(B) constitutive phenotype (P < 0.001), and a significant decrease in the M phenotype (P < 0.005) was noted. CONCLUSIONS: The significant increase in the prevalence of resistance to clindamycin and miocamycin, and the prevalence of resistance to telithromycin reached in a short period of time from the introduction of its use, underscore the need for continuous surveillance of antimicrobial resistance in S. pyogenes in Spain.     

中度低温体外循环对大鼠海马c-fos,bcl-2及bax mRNA表达的影响

目的:观察中度低温体外循环(CPB)对大鼠海马即刻基因c-fos、凋亡相关基因bcl-2和baxmRNA表达的影响。方法:雄性SD大鼠随机分为CPB组(n=6)及假手术对照组(Sham组,n=6)。所有动物在咪唑安定、芬太尼麻醉后经口插管控制呼吸,置入颈静脉流出管和尾动脉输入管,肝素抗凝(500U/kg)。CPB组采用中度低温CPB(26℃—28℃),经尾动脉灌注、颈静脉右心房-腔静脉引流,灌流量160mL·kg-1·min-1,总转流时间2h,Sham组除不经历CPB外,其余操作同CPB组相同。实验中进行动脉压、ECG及动脉血气监测。术后1h处死动物,立即断头取脑分离海马组织,放入-70℃液氮罐保存。基因mRNA检测采用逆转录多聚酶联反应(RT-PCR)方法。结果:海马c-fos、bcl-2和baxmRNA表达CPB组显著高于Sham组;bax与bcl-2mRNA表达比值CPB组显著高于Sham组。结论:中度低温体外循环可引起海马即刻基因c-fos、凋亡相关基因bcl-2和baxmRNA的表达增加。     

注意缺陷多动障碍血小板单胺氧化酶活性测定的初步研究

本文测定了注意缺陷多动障碍(ADHD)患者血小板单胺氧化酶活性,结果显示ADHD时该酶活性明显低于对照组,而在经哌醋甲酯治疗后无明显改变,与Conners量表也未显示出明显相关。文中还对单胺氧化酶与治疗的关系进行了讨论。