Benefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled despite best available therapy (GINA 2002 step 4 treatment): INNOVATE

BACKGROUND: Patients with severe persistent asthma who are inadequately controlled despite Global Initiative for Asthma (GINA) 2002 step 4 therapy are a challenging population with significant unmet medical need. We determined the effect of omalizumab on clinically significant asthma exacerbations (requiring systemic corticosteroids) in the first omalizumab study to exclusively enrol patients from this difficult-to-treat patient population. METHODS: Following a run-in phase, patients (12-75 years) inadequately controlled despite therapy with high-dose inhaled corticosteroids (ICS) and long-acting beta(2)-agonists (LABA) with reduced lung function and a recent history of clinically significant exacerbations were randomized to receive omalizumab or placebo for 28 weeks in a double-blind, parallel-group, multicentre study. RESULTS: A total of 419 patients were included in the efficacy analyses. The clinically significant asthma exacerbation rate (primary efficacy variable), adjusted for an observed relevant imbalance in history of clinically significant asthma exacerbations, was 0.68 with omalizumab and 0.91 with placebo (26% reduction) during the 28-week treatment phase (P = 0.042). Without adjustment, a similar magnitude of effect was seen (19% reduction), but this did not reach statistical significance. Omalizumab significantly reduced severe asthma exacerbation rate (0.24 vs 0.48, P = 0.002) and emergency visit rate (0.24 vs 0.43, P = 0.038). Omalizumab significantly improved asthma-related quality of life, morning peak expiratory flow and asthma symptom scores. The incidence of adverse events was similar between treatment groups. CONCLUSIONS: In patients with inadequately controlled severe persistent asthma, despite high-dose ICS and LABA therapy, and often additional therapy, omalizumab significantly reduced the rate of clinically significant asthma exacerbations, severe exacerbations and emergency visits. Omalizumab is effective and should be considered as add-on therapy for patients with inadequately controlled severe persistent asthma who have a significant unmet need despite best available therapy.     

Pregnancy-associated glycoprotein (PAG) family localized in chorionic cells within the epitheliochorial/diffuse placenta of the alpaca (Lama pacos)

Pregnancy-associated glycoproteins (PAGs) are abundant embryo-originated products expressed in the pre-placental trophoblast and later in the post-implantational chorionic epithelium of some ungulate species. This paper describes the cellular immunolocalization of the chorionic PAG family in the epitheliochorial placenta type of the alpaca (Lama pacos—Lp), in which the PAGs were named ‘LpPAGs’. Placental Lp sections (5 μm) of different females near mid-pregnancy (150 days post coitum; dpc), advanced pregnancy (244-263 dpc) and late pregnancy (347 dpc) were used for cross-species (heterologous—ht) double fluorescent immunohistochemistry (htdF-IHC). The htdF-IHC was performed with primary rabbit polyvalent anti-porcine PAG polyclonals. The LpPAG immuno-complexes were visualized with secondary goat anti-rabbit immunoglobulins-conjugated with Alexa 488 fluorophore (green), among all nuclei of placental cells stained with propidium iodide (red). This is the first study reporting the immunolocalization of the LpPAG family identified by htdF-IHC at the feto/maternal interface during different pregnancy stages of the alpaca. The most dominant and strongest immune-positive LpPAG signals were found in the well-developed chorionic cell layer. Our htdF-IHC indicated relatively high epitope resemblance to that of the PAGs in camelids and pigs. These data increase our general knowledge of chorionic PAG localization during pregnancy-stage dependent development of the epitheliochorial diffuse placenta type in the alpaca.     

Diurnal time course of heat pain perception in healthy humans

Rapid skin heating by infrared lasers can be used to investigate the integrity of the nociceptive system by activating A-delta and C fibers. The aim of our study was to analyze if healthy humans exhibit any clinically relevant diurnal variations in their heat pain sensitivity. Circadian A-delta fiber function was analyzed by studying N2 and P2 components of laser-evoked potentials (LEP) and pain thresholds evoked by laser stimulation of the foot every 2h from 8a.m. to 10p.m. in 15 healthy subjects. Heat stimuli were generated by an infrared Tm-YAG laser and were delivered to an area of 4 cm × 4.5 cm on the dorsum of the right or left foot in 3 runs of incremental and decremental intensities. After each stimulus subjects were asked to classify the intensity of pain with a numeric rating scale (NRS). LEPs were recorded with fixed stimulus intensities that were 1.5× of the pain threshold. Data were collected with the SynAmps System (Neuroscan, El Paso, USA) and averaged across 35-40 trials. Laser-induced heat pain thresholds and circadian latencies of LEP did not significantly vary during the day. Our results correspond with previous studies that did not detect any consistent significant diurnal variations in perception of heat pain perception using contact thermodes. The intensity of pain perception did not demonstrate any correlation with mood or sleep parameters as measured with the Beck Depression Inventory (BDI), the subjective sleep scales Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS).     

Immediate effects of foot orthoses on pain during functional tasks in people with patellofemoral osteoarthritis: A cross-over,proof-of-concept study

Background

The purpose of the study was to determine whether prefabricated foot orthoses immediately reduce pain during functional tasks in people with patellofemoral osteoarthritis, compared to flat insoles and shoes alone.

Botulinum toxin A is effective to treat tension-type headache caused by hemifacial spasm

ObjectiveWe examined the relationship between hemifacial spasm (HFS; a form of cranio-cervical dystonia) and chronic primary headache, including tension-type headache (TTH). We also examined whether botulinum toxin A (BoNT/A) therapy for HFS ameliorates concomitant TTH.MethodsFifty-one HFS patients receiving BoNT/A therapy were recruited. Patients’ characteristics (including age, gender, chronic headache history, exercise habits, stiff neck, cervical spondylolysis history), stress factors, worsening/new onset of headache associated with HFS, and dose of BoNT/A were examined. We diagnosed headache types according to The International Classification of Headache Disorders, 3rd edition, beta. Numerical Rating Scale (NRS) and Headache Impact Test-6 (HIT-6) scores for headache severity were compared between the 6-week baseline before BoNT/A therapy and 6-week follow-up after BoNT/A therapy.ResultsOf 51 patients with HFS, 17 (33.3%) reported worsening or new onset of headache (especially TTH) associated with HFS (Group-S), and 34 were not aware of headache (Group-N). Twelve patients (70.6%) in group-S reported improvement of headache after BoNT/A therapy. NRS (from 7 [5–9] to 0 [0–5], p < 0.01) and HIT-6 (from 55 [54–64] to 44 [36–52], p < 0.001) scores were significantly improved after BoNT/A therapy. Logistic regression analysis revealed significant interaction between TTH associated with HFS and the presence of stress factors (odds ratio 43.11: 2.95–629.39, p < 0.001) and history of chronic headache (odds ratio 28.53: 2.96–275.10, p < 0.001).ConclusionsPrimary headache, especially TTH, is associated with HFS. BoNT/A therapy for HFS may also be indirectly effective for treatment of TTH.     

广州地区住院患者NRS2002营养风险筛查的多中心研究

目的调查广州4所教学医院住院患者营养不足、营养风险发生率以及营养支持的应用状况,并明确营养风险发生率在性别或年龄间的差异。方法对2008年4月至2011年12月广州4所教学医院消化内科、呼吸内科、神经内科、肾内科、普外科、胸外科等6个专科符合NRS2002评定标准的2550例住院患者进行营养筛查,并调查其营养支持应用情况。结果共获取2142例（84％）的BMI值,营养不足和营养风险的发生率分别为17．8％和41．5％;6个专科中,呼吸内科患者的营养不足和营养风险发生率均最高,分别为28．2％和55．9％;≥70岁的患者营养风险发生率高于〈70岁者（64．2％US32．6％,P=0．000）;总的营养风险发生率没有性别差异。有营养风险者的营养支持率为47．6％,无营养风险者的营养支持率为19．4％。肠外营养占全部营养支持的88．7％。结论NRS2002是进行营养筛查的一个有效工具,可推荐用于新人院患者。广州住院患者中存在较高比例的营养风险或营养不足,≥70岁患者更易发生营养风险;营养治疗存在不恰当的营养干预及肠外营养的过度使用。应在精确评估患者营养状况的基础上制定合理的营养支持方案。     

NRS 2002营养风险筛查在胃肠道恶性肿瘤住院患者中的应用

目的 应用NRS 2002筛查胃肠道恶性肿瘤住院患者的营养风险及营养支持应用状况.方法 以110例胃肠道恶性肿瘤患者为研究对象,应用NRS 2002进行营养风险筛查,并测定营养支持前后血清白蛋白水平.结果 所有患者均完成营养风险筛查,营养风险的发生率为35.5％.在39例有营养风险的患者中,有31例（79.5％）接受了营养支持;在无营养风险的71例患者中,有24例（33.8％）接受了营养支持.有营养风险的患者接受营养支持后,血清白蛋白水平明显提高.结论 NRS 2002使用方便、适用性强,可有效用于胃肠道恶性肿瘤患者的营养风险筛查,指导患者的营养支持治疗.     

Hypersensitivity and hyperalgesia in somatoform pain disorders

Objective

In psychiatry, pain disorders not explained by structural lesions have been classified for decades as somatoform pain disorders, the underlying concept being somatization. In a parallel move, somatic medicine has defined an expanding group of similar pain disorders, known as functional pain syndromes. Functional pain syndromes are characterized by enhanced pain sensitivity. The aim of our study was to investigate the proportion of patients with somatoform pain disorders who also meet the criteria of functional pain syndromes and the extent to which patients with somatoform pain disorders also show enhanced pain sensitivity.

Methods

Data on pain sensitivity in 120 hospitalized patients were obtained by means of two algometric methods. The group of patients with somatoform pain disorders was further divided into two subsets: patients with and those without a co-diagnosis of a functional pain syndrome. Patients with nociceptive pain served as control group.

Results

Of the 120 in-patients selected, 67 fulfilled the criteria of a somatoform pain disorder of which 41 (61%) also met the co-diagnosis of a functional pain syndrome. Patients with somatoform pain disorder differed from controls in that they showed enhanced pain sensitivity, irrespective of whether a functional pain syndrome was concomitantly present (P< .001).

Conclusions

Somatoform pain disorders show considerable overlap with functional pain syndromes, including enhanced pain sensitivity. This suggests the relevance of integrating somatosensory aspects of pain into a modified understanding of somatoform pain disorders.     

三种术前营养评价方法对消化道恶性肿瘤患者术后并发症预测价值比较

目的比较欧洲营养风险筛查2002（NRS2002）、微型营养评价法（MNA）和主观全面评价法（SGA）3种术前营养评估方法对消化道恶性肿瘤患者术后并发症的预测价值。方法前瞻性入组2012年1月至2013年6月间南华大学附属第一医院普通外科和肿瘤外科收治的235例消化道恶性肿瘤患者,其中食管癌31例,胃癌82例,结直肠癌122例。分别采用NRS2002、MNA和SGA3种营养评价方法进行术前营养评估,分别比较这3种方法筛选出的存在营养不良（营养风险）患者与营养正常（无营养风险）患者术后并发症发生率。结果按照SGA评分,235例消化道恶性肿瘤患者术前重度营养不良、中度营养不良和无营养不良者术后并发症发生率分别为40．5％（17／42）、25．3％（22／87）和14．2％（15／106）,差异有统计学意义（P〈0．01）。按照iVINA评分,术前营养不良、潜在营养不良者和营养正常者术后并发症发生率分别为32．9％（23／70）、24．7％（18／73）和14．1％（13／92）,差异有统计学意义（P〈0．05）。按照NRS2002评分,术前存在营养风险和无营养风险者术后并发症发生率分别为27．6％（27／98）和19．7％（27／137）,差异无统计学意义（P〉0．05）。多因素逻辑回归分析证实,SGA评分和MNA评分均为术后并发症的独立预测因素（均P〈0．01）。SGA评分预测术后并发症的敏感性较MNA评分为高（90．7％比79．6％）,特异性相当（49．7％比50．8％）。结论SGA评分和MNA评分均能有效预测消化道恶性肿瘤患者术后并发症的发生情况;但相较之下,SGA的预测敏感性更高。术前制定营养支持方案时应重点参考SGA评估结果。