Comparative analgesic efficacy of pregabalin administered according to either a prevention protocol or an intervention protocol in rats with cisplatin‐induced peripheral neuropathy

Chemotherapy‐induced peripheral neuropathy (CIPN) is a type of peripheral neuropathic pain that may be dose‐limiting in patients administered potentially curative cancer chemotherapy dosing regimens. In cancer survivors, persistent CIPN adversely affects patient quality of life and so adjuvant drugs (anticonvulsants eg pregabalin or antidepressants eg amitriptyline) are recommended for the relief of CIPN. However, most studies in rodent models of CIPN involve administration of single bolus doses of adjuvant drugs to assess pain‐relieving efficacy. Hence this study was designed to assess the efficacy of pregabalin administered to CIPN‐rats according to either a prevention or an intervention protocol. Groups of male Sprague‐Dawley rats received four single intraperitoneal bolus doses of cisplatin at 3 mg/kg at once‐weekly intervals to induce CIPN. For the prevention protocol, oral pregabalin (or vehicle) was administered to CIPN‐rats once‐daily for 21 consecutive days from day 0 to day 20 inclusive. For the intervention protocol, oral pregabalin was administered once‐daily for 21 consecutive days from day 28 to day 48, inclusive. Mechanical allodynia and mechanical hyperalgesia in the bilateral hindpaws were assessed just prior to each dose of cisplatin and at least once weekly until study completion (day 27, prevention protocol; or day 48, intervention protocol). Mechanical allodynia and mechanical hyperalgesia were also determined at the time of peak effect at about 2 hours post pregabalin/vehicle administration, once weekly until study completion. For the prevention protocol in CIPN‐rats, pregabalin alleviated mechanical hyperalgesia but not mechanical allodynia. For the intervention protocol, pregabalin alleviated both mechanical allodynia and mechanical hyperalgesia in the hindpaws.     

On evaluation of consistency in multi-regional clinical trials

In recent years, multi-regional clinical trials (MRCT) that conduct clinical trials simultaneously in Asian Pacific region, Europe, and the United States have become very popular for global pharmaceutical development. The main purpose of multi-regional clinical trials is to shorten the time for pharmaceutical development and regulatory submission, and approval around the world. In practice, however, clinical results observed from some regions (sub-population) may not be consistent with the results from other regions and/or all regions combined (entire population). The inconsistency observed may be due to ethnic differences in different regions, differences in medical practice, time points of assessment, or by random chance due to small sample size for the region. Some regional regulatory agencies require consistency evaluation between local country results and overall results. However, the challenge is there is no detailed guidance on the definition of ‘consistency’ and methodology to evaluate it. Therefore, the questions are: how to evaluate consistency and what statistical methods are appropriate to be used for consistency evaluation? In this article, several statistical tests for consistency (similarity) between clinical results observed from a specific sub-population and the entire population are proposed. These methods are compared through extensive simulation. As most published articles discussed consistency evaluation for superiority situations, we have discussed consistency evaluation for non-inferiority situation in this article through a simulated example concerning consistency in some countries. Recommendations of the statistical methods to be used for consistency evaluation are given. Other aspects that should be considered for consistency evaluation are also provided.     

Mechanical Properties of the Human Tibial and Peroneal Nerves Following Stretch With Histological Correlations

Despite the extensive literature regarding peripheral nerve stretch injuries, there are few studies that compare the nerve histology with the mechanical properties in humans. There is clinical evidence suggesting that the peroneal nerve is at greater risk for injury compared to the tibial nerve following total hip arthroplasty and hip trauma. We examined the two nerves from fresh human cadavers with or without controlled stretch. The mechanical properties, stiffness, and strain were compared with light microscopic preparations in longitudinal sections stained by the trichrome method for collagen and showing the effects of structural deformation. The tibial nerve had an average failure load 1.7× that for the peroneal nerve (P = 0.0001). Although the corresponding average stiffness showed a trend toward being larger (4.39 vs. 3.81 N/mm), the difference was not significant (P = 0.126). Histologically, the perineurium along with the underlying nerve fascicle was undulated in the control specimens and straightened out in the stretched specimens. Peroneal nerves went on to failure at lower loads and exhibited a wavy pattern on pathologic slides after failure, which shows that peroneal nerves fail mechanically before they can unfold. The tibial nerve has a biomechanical and histological advantage compared to the peroneal nerve during tensile testing, which could be the reason why it is less commonly damaged. We conclude that the perineurium is especially protective against deformation changes in human nerves relative to the respective nerve size and number of fascicles. Anat Rec, 302:2030–2039, 2019. © 2019 American Association for Anatomy     

Ontogenetic changes of geometrical and mechanical characteristics of the avian femur: a comparison between precocial and altricial birds

The mechanical performance of limb bones is closely associated with an animal's locomotor capability and is thus important to our understanding of animal behaviour. This study combined a geometrical analysis and three‐point bending tests to address the question of how the mechanical performance of the femurs of Japanese quail (Coturnix coturnix japonica) and pigeon (Columba livia domestica) respond to changing functional demands during ontogeny. Results showed that hatchling quails had stiff bone tissues, and the femoral ultimate loads scaled negatively with body mass, corresponding to high functional demands during early growth. The hatchling pigeon femora had weak material properties but they showed a dramatic increase in Young's modulus during growth. Consequently, although femoral cross‐sectional geometry showed negative allometry, the ultimate loads scaled positively with body mass. Older pigeons had more circular bone cross‐sections than younger pigeons, probably due to load stimulation changes occurred shortly after the onset of locomotion. Negative allometry and isometry of the cross‐sectional geometry of hind limb bones were observed in flying birds and ground‐dwelling birds, respectively. The correspondence between geometrical change and locomotor pattern suggests that ontogenetic changes in cross‐sectional geometry may be an effective indicator of avian locomotor behaviour.     

Sphere梯度孔结构力学性能有限元分析

建立不同孔径分布的钛合金梯度多孔结构的三维有限元模型,对力学性能进行分析。使用Rhino 5.0和ABAQUS 6.1软件,分别建立sphere、sphere_line、sphere_plane、sphere_point等4种按不同梯度分布的多孔结构有限元模型。对模型分别加载200、400、600、800、1000 N的力,加载力作用于上表面,方向垂直于表面向下,选定下表面为固定约束,计算等效应力及最大主应力。在加载力相同的情况下,sphere_plane梯度孔模型的最大主应力及最大等效应力最大;其次为sphere_point梯度孔模型,较sphere_plane梯度孔模型小42.49%和23.61%;sphere_line梯度孔模型再次之,较sphere_plane梯度孔模型小47.60%和33.12%;sphere无梯度孔模型的最大主应力及最大等效应力最小,较sphere_plane梯度孔模型小68.44%和54.13%。在4种不同梯度孔径分布的多孔结构中,sphere无梯度孔结构的实际受力最小、承载能力最好,其次是sphere_line梯度孔结构,再次是sphere_point梯度孔结构次之,sphere_plane梯度孔结构实际受力最大,其承载能力相比前3种要差。最后通过快速原型对设计出的4种模型进行制备,得到多孔钛合金实体,并对实体进行力学性能测试实验,得出的结论可验证数值模拟分析结果的可靠性。该研究结果可为多孔钛合金植入体设计以及临床应用提供相关设计参考和理论依据。     

新型可降解锌合金支架的结构设计及其力学性能分析

目的对比分析一款新结构可降解支架和传统结构可降解支架力学性能和对狭窄血管的治疗效果。方法利用有限元数值模拟,将新结构支架和传统结构支架分别植入直径狭窄为30%的血管,对比分析两种支架的支撑性能及其对狭窄血管重构的影响。结果与传统结构支架相比,新结构支架的径向回弹率和狗骨头率分别降低了26.6%和34.7%。此外,植入新结构支架的狭窄血管回弹较小,拥有更平滑更大的管腔。结论对比传统结构支架,新结构支架具有更高的支撑性能,对狭窄血管的治疗效果更佳。具有高支撑性能的新结构支架有望成为临床介入治疗设备的新选择。     

Friction and Mechanical Properties of Highly Filled Polybenzoxazine Composites: Nanosilica Particle Size and Surface Treatment

Frictional and mechanical properties of highly filled polybenzoxazine [poly(BA‐a)] composites which are influenced by nanosilica contents, particle sizes, and surface treatments are investigated. The coefficient of friction and wear resistance, storage moduli, and microhardness of the nanosilica‐filled poly(BA‐a) composites systematically increase with an increase of nanosilica content, while those values of the nanocomposites are improved with decreasing particle sizes at the equivalent nanosilica content. The modulus can be predicted by the Kerner model with the maximum packing fraction, while the microhardness of the nanocomposites is in agreement with the Halpin–Tsai model. The nanocomposites fabricated with untreated nanosilica particles exhibit higher frictional and mechanical properties when compared with the surface‐treated nanocomposites at the equivalent particle sizes. The interfacial interactions via covalent bond formation between the nanosilica and the poly(BA‐a) are determinative factors for the nanocomposite properties. Highly filled nanosilica‐poly(BA‐a) composites can be employed in various applications where wear‐resistance plays an important role.     

呼吸机相关下呼吸道感染的病原菌调查

目的分析机械通气引发下呼吸道感染病原菌的构成及其耐药情况,指导早期经验性抗生素治疗. 方法对2001年1月～2004年9月间我院ICU收住的113例机械通气引发下呼吸道感染患者的病原菌及耐药情况进行回顾性调查分析. 结果检出病原菌138株,其中革兰阴性(G-)细菌87株(63.0%),革兰阳性细菌(G 菌)33株(23.9%),真菌18株(13.1%).大多数菌株多重耐药.结论机械通气引发下呼吸道感染院内感染病原菌以G-菌为主,其药敏实验呈多重耐药,临床早期经验性抗生素治疗应选择敏感广谱抗生素.     

伊潘立酮片有关物质一致性评价研究

目的 建立伊潘立酮片的有关物质测定方法,与参比制剂进行有关物质一致性评价研究。方法 建立高效液相色谱法（HPLC）测定伊潘立酮片有关物质,并考察方法的专属性、线性、精密度、准确性及耐用性等。采用Agela Venusil MP C₁₈（150 mm×4.6 mm,5 μm）色谱柱,以0.02 mol/L磷酸氢二铵缓冲液（磷酸调pH至7.0±0.1）为流动相A,以乙腈为流动相B,体积流量1.0 mL/min,检测波长为229 nm,柱温40℃。结果 在选定的色谱条件下,伊潘立酮与杂质分离良好,辅料无干扰。自研伊潘立酮片与参比制剂杂质谱相似。结论 该方法准确、可靠、耐用性好,自研伊潘立酮片与参比制剂具有有关物质一致性。     

Influenza vaccine effectiveness to prevent influenza-related hospitalizations and serious outcomes in Canadian adults over the 2011/12 through 2013/14 influenza seasons: A pooled analysis from the Canadian Immunization Research Network (CIRN) Serious Outcomes Surveillance (SOS Network)

BackgroundOngoing assessment of influenza vaccine effectiveness (VE) is critical to inform public health policy. This study aimed to determine the VE of trivalent influenza vaccine (TIV) for preventing influenza-related hospitalizations and other serious outcomes over three consecutive influenza seasons.MethodsThe Serious Outcomes Surveillance (SOS) Network of the Canadian Immunization Research Network (CIRN) conducted active surveillance for influenza in adults ≥16 years (y) of age during the 2011/2012, 2012/2013 and 2013/2014 seasons in hospitals across Canada. A test-negative design was employed: cases were polymerase chain reaction (PCR)-positive for influenza; controls were PCR-negative for influenza and were matched to cases by date, admission site, and age (≥65 y or <65 y). All cases and controls had demographic and clinical characteristics (including influenza immunization status) obtained from the medical record. VE was estimated as 1-OR (odds ratio) in vaccinated vs. unvaccinated patients × 100%. The primary outcome was VE of TIV for preventing laboratory-confirmed influenza-related hospitalization; secondary outcomes included VE of TIV for preventing influenza-related intensive care unit (ICU) admission/mechanical ventilation, and influenza-related death.ResultsOverall, 3394 cases and 4560 controls were enrolled; 2078 (61.2%) cases and 2939 (64.5%) controls were ≥65 y. Overall matched, adjusted VE was 41.7% (95% Confidence Interval (CI): 34.4–48.3%); corresponding VE in adults ≥65 y was 39.3% (95% CI: 29.4–47.8%) and 48.0% (95% CI: 37.5–56.7%) in adults <65 y, respectively. VE for preventing influenza-related ICU admission/mechanical ventilation in all ages was 54.1% (95% CI: 39.8–65.0%); in adults ≥65 y, VE for preventing influenza-related death was 74.5% (95% CI: 44.0–88.4%).ConclusionsWhile effectiveness of TIV to prevent serious outcomes varies year to year, we demonstrate a statistically significant and clinically important TIV VE for preventing hospitalization and other serious outcomes over three seasons. Public health messaging should highlight the overall benefit of influenza vaccines over time while acknowledging year to year variability.ClinicalTrials.gov Identifier: NCT01517191.