The relationship between headache-attributed disability and lost productivity: 2. Empirical evidence from population-based studies in nine disparate countries

BackgroundHeadache disorders are disabling, with major consequences for productivity, yet the literature is silent on the relationship between headache-attributed disability and lost productivity, often erroneously regarding the two as synonymous. We evaluated the relationship empirically, having earlier found that investment in structured headache services would be cost saving, not merely cost-effective, if reductions in headache-attributed disability led to > 20% pro rata recovery of lost productivity.MethodsWe used individual participant data from Global Campaign population-based studies conducted in China, Ethiopia, India, Nepal, Pakistan and Russia, and from Eurolight in Lithuania, Luxembourg and Spain. We assessed relationships in migraine and probable medication-overuse headache (pMOH), the most disabling common headache disorders. Available symptom data included headache frequency, usual duration and usual intensity. We used frequency and duration to estimate proportion of time in ictal state (pTIS). Disability, in the sense used by the Global Burden of Disease study, was measured as the product of pTIS and disability weight for the ictal state. Impairment was measured as pTIS * intensity. Lost productivity was measured as lost days (absence or < 50% productivity) from paid work and corresponding losses from household work over the preceding 3 months. We used Spearman correlation and linear regression analyses.ResultsFor migraine, in a linear model, we found positive associations with lost paid worktime, significant (p < 0.05) in many countries and highly significant (p < 0.001) in some despite low values of R² (0–0.16) due to high variance. With lost household worktime and total lost productivity (paid + household), associations were highly significant in almost all countries, although still with low R² (0.04–0.22). Applying the regression equations for each country to the population mean migraine-attributed disability, we found pro rata recoveries of lost productivity in the range 16–56% (> 20% in all countries but Pakistan). Analysing impairment rather than disability increased variability. For pMOH, with smaller numbers, associations were generally weaker, occasionally negative and mostly not significant.ConclusionRelief of disability through effective treatment of migraine is expected, in most countries, to recover > 20% pro rata of lost productivity, above the threshold for investment in structured headache services to be cost saving.     

Association of D-dimer with Plaque Characteristics and Plasma Biomarkers of Oxidation-Specific Epitopes in Stable Subjects with Coronary Artery Disease

D-dimer has emerged as a biomarker of cardiovascular event risk, yet pathophysiological factors associated with plasma D-dimer levels in stable coronary artery disease (CAD) subjects are poorly understood. In 106 stable CAD subjects undergoing intravascular ultrasound with virtual histology (IVUS-VH), we measured D-dimer, lipoprotein(a) (Lp(a)), plasminogen, biomarkers reflecting oxidation-specific epitopes (OSE) such as oxidized phospholipids on apolipoprotein B-100 (OxPL-apoB), OxPL on plasminogen (OxPL-PLG), and autoantibodies to phosphorylcholine-BSA [PC-BSA] and a malondialdehyde [MDA] mimotope. In univariate analysis, D-dimer was positively associated with Lp(a), OxPL-apoB, OxPL-PLG, and coronary artery calcium, and inversely associated with autoantibodies to OSE and plaque fibrosis. D-dimer levels >?500 ng/ml also showed positive association with plaque necrosis. After multivariate analysis, D-dimer remained significantly associated with Lp(a) and plaque calcium. While further studies are needed, results provide evidence that plasma D-dimer levels are associated with levels of OxPLs and IVUS-VH indices linked to plaque erosion and rupture.     

急性心肌梗死后CD34+干细胞自体动员的意义

目的:已有理论提出急性心肌梗死后骨髓和外周血中的CD34 干细胞具有自身动员的潜能,观察这一潜能的变化特征及其对心肌梗死组织再生能力的影响。方法:实验于2004-09/2005-02在阜外心血管病医院完成。①实验动物:雄性SD大鼠40只,随机数字表法分为心肌梗死组、假手术组,20只/组。②实验方法:心肌梗死组大鼠采用冠状动脉结扎法建立心肌梗死模型。心电图ST段抬高或有室性心律出现,前壁心肌呈苍白色为造模成功。假手术组仅作开胸手术,前降支不予结扎。③实验评估:于心肌梗死后3,7,14,28d,流式细胞仪检测骨髓和外周血中CD34 干细胞的含量。用免疫组化方法检测梗死心肌组织中的Ki67细胞和毛细血管数量。结果:①外周血及骨髓CD34 干细胞含量的变化:心肌梗死组外周血中的CD34 干细胞数量于造模后3d开始上升,7d后明显高于假手术组(P<0.01),至14,28d时逐渐回落至假手术组水平(P>0.05)。心肌梗死组骨髓中的CD34 干细胞数量于造模后各时间点始终无明显变化(P>0.05)。②组织学评定:心肌梗死组梗死区Ki67细胞和毛细血管数量于造模后3d开始增多,7d时明显多于非梗死区(P<0.05);至14,28d梗死区Ki67细胞数量明显少于造模后7d(P<0.05),毛细血管数量的减少不明显(P>0.05)。免疫组化染色显示少数Ki67细胞分化为血管内皮细胞,未见向心肌细胞分化。③相关性分析:梗死区Ki67细胞、毛细血管数量于造模后7d与外周血中CD34 干细胞数量呈显著正相关(r=0.913,P=0.021;r=0.887,P=0.035)。结论:机体CD34 干细胞的自体动员、增殖反应的潜能随急性心肌梗死时间的延长而逐渐减弱,自体动员的干细胞功能尚不足以达到修复梗死心肌组织的效果。     

Evaluation of atypical human immunodeficiency virus immunoblot reactivity in blood donors

Blood donors reactive by enzyme-linked immunosorbent assay for antibody to the human immunodeficiency virus (HIV) who showed atypical patterns of viral core protein reactivity on Western blot were monitored for several months. Characterization of their antibodies was performed by 1) use of recombinant HIV proteins; 2) determination of cross-reactivity to HTLV-I, HTLV-II, and HTLV-IV: 3) assessment of immune status; and 4) identification of potentially interfering autoantibodies. Nineteen of 20 donors maintained the same HIV antibody reactivity throughout the follow-up period; the other donor became fully antibody-positive. Eighteen of 20 donors' sera showed clear reactivity with HIV recombinant core proteins. Ten of 19 donor samples demonstrated cross-reactivity to HTLV-IV; 3 of these 10 also cross-reacted with HTLV-I. The immune status of all donors was normal, although the medical histories and HLA antibody screens suggested possible autoimmune reactivity in 9 of 18 donors. During follow-up interviews, three donors reported possible risk factors for HIV infection that had not been acknowledged at the time of blood donation. We conclude that exclusion of donors with these atypical serologic test results is warranted while further studies to determine significance are being conducted.     

耐一线药物及注射药物对耐多药结核病治疗效果的影响

背景和目的:最近的研究结果表明,对其他一线药物和注射类药物(如卡那霉素、卷曲霉素)等耐药是影响耐多药结核病(MDR-TB)患者治疗效果的独立危险因素.本研究旨在明确耐其他一线药物和注射类药物对韩国不合并人免疫缺陷病毒(HIV)感染的MDR-TB患者临床疗效的影响.方法:采用回顾性队列研究分析1996年1月至2005年12月首尔国家大学附属医院治疗的211例MDR-TB患者治疗效果,排除7例丢失和7例迁出,对197例患者进行了最终分析.     

Embracing complexity and uncertainty to create impact: exploring the processes and transformative potential of co-produced research through development of a social impact model

The potential use, influence and impact of health research is seldom fully realised. This stubborn problem has caused burgeoning global interest in research aiming to address the implementation ‘gap’ and factors inhibiting the uptake of scientific evidence. Scholars and practitioners have questioned the nature of evidence used and required for healthcare, highlighting the complex ways in which knowledge is formed, shared and modified in practice and policy. This has led to rapid expansion, expertise and innovation in the field of knowledge mobilisation and funding for experimentation into the effectiveness of different knowledge mobilisation models. One approach gaining prominence involves stakeholders (e.g. researchers, practitioners, service users, policy-makers, managers and carers) in the co-production, and application, of knowledge for practice, policy and research (frequently termed integrated knowledge translation in Canada). Its popularity stems largely from its potential to address dilemmas inherent in the implementation of knowledge generated using more reductionist methods. However, despite increasing recognition, demands for co-produced research to illustrate its worth are becoming pressing while the means to do so remain challenging. This is due not only to the diversity of approaches to co-production and their application, but also to the ways through which different stakeholders conceptualise, measure, reward and use research. While research co-production can lead to demonstrable benefits such as policy or practice change, it may also have more diffuse and subtle impact on relationships, knowledge sharing, and in engendering culture shifts and research capacity-building. These relatively intangible outcomes are harder to measure and require new emphases and tools. This opinion paper uses six Canadian and United Kingdom case studies to explore the principles and practice of co-production and illustrate how it can influence interactions between research, policy and practice, and benefit diverse stakeholders. In doing so, we identify a continuum of co-production processes. We propose and illustrate the use of a new ‘social model of impact’ and framework to capture multi-layered and potentially transformative impacts of co-produced research. We make recommendations for future directions in research co-production and impact measurement.     

Supracardiac total anomalous pulmonary venous connection with cor triatriatum sinister: A rare diagnosis confirmed by saline contrast echocardiography

In cor triatriatum sinister, the left atrium is divided by a membrane into a proximal and a distal chamber. Usually proximal chamber receives all the pulmonary veins and drains through an opening in the dividing membrane into distal chamber, which empties into left ventricle through the mitral valve. Rarely, the two chambers lack a communication and there is associated total anomalous pulmonary venous connection (TAPVC). We report a 1-month-old infant with cyanosis and heart failure, who had cor triatriatum sinister associated with supracardiac TAPVC. The case is reported for rarity of the association with a focus on contrast echocardiographic imaging.     

Benzathine penicillin, metronidazole and benzyl penicillin in the treatment of tetanus: a randomized, controlled trial

Penicillin, the drug of choice in tetanus, may potentiate the effect of tetanus toxin by inhibiting the type-A (GABAA) receptor for gamma-amino-n-butyric acid. Metronidazole has therefore been suggested as an alternative. Intramuscular benzathine penicillin (1.2 million units as a single dose; N=56), enteral metronidazole (600 mg every 6 h for 10 days; N=55) and intravenous benzyl penicillin (2 million units every 4 h for 10 days; N=50) were therefore compared, in a randomized, controlled trial, among patients with all grades of tetanus. On presentation, the three treatment groups were similar in terms of age and sex distributions, immune statuses, durations of illness, and their APACHE-II scores and Ablett's grades of tetanus. Of the patients given benzathine penicillin, 36 required tracheostomy, 10 neuromuscular blockade, and 23 mechanical ventilation; the corresponding numbers for the metronidazole (34, 12 and 18, respectively) and benzyl-penicillin groups (39, 12 and 25, respectively) were similar (P>0.10). The incidences of dysautonomia and nosocomial pneumonia and the numbers of in-hospital deaths (26 with benzathine penicillin, 19 with metronidazole and 22 with benzyl penicillin; P=0.392) were also similar in each treatment arm. The length of the hospital stay was longer in the patients receiving benzyl penicillin than in the benzathine-penicillin or metronidazole groups, with means (S.D.) of 21.9 (15), 16.9 (11) and 19.9 (15) days, respectively, but the difference was not statistically significant (P=0.09). Although the three antibiotic regimens investigated appear equally effective, benzathine penicillin offers the convenience of a single, intramuscular injection instead of the 10 days of therapy needed with the other two drugs.