Digital pathology and image analysis augment biospecimen annotation and biobank quality assurance harmonization

Standardization of biorepository best practices will enhance the quality of translational biomedical research utilizing patient-derived biobank specimens. Harmonization of pathology quality assurance procedures for biobank accessions has lagged behind other avenues of biospecimen research and biobank development. Comprehension of the cellular content of biorepository specimens is important for discovery of tissue-specific clinically relevant biomarkers for diagnosis and treatment. While rapidly emerging technologies in molecular analyses and data mining create focus on appropriate measures for minimizing pre-analytic artifact-inducing variables, less attention gets paid to annotating the constituent makeup of biospecimens for more effective specimen selection by biobank clients. Both pre-analytic tissue processing and specimen composition influence acquisition of relevant macromolecules for downstream assays. Pathologist review of biorepository submissions, particularly tissues as part of quality assurance procedures, helps to ensure that the intended target cells are present and in sufficient quantity in accessioned specimens. This manual procedure can be tedious and subjective. Incorporating digital pathology into biobank quality assurance procedures, using automated pattern recognition morphometric image analysis to quantify tissue feature areas in digital whole slide images of tissue sections, can minimize variability and subjectivity associated with routine pathologic evaluations in biorepositories. Whole-slide images and pathologist-reviewed morphometric analyses can be provided to researchers to guide specimen selection. Harmonization of pathology quality assurance methods that minimize subjectivity and improve reproducibility among collections would facilitate research-relevant specimen selection by investigators and could facilitate information sharing in an integrated network approach to biobanking.     

The quality assurance of antiglobulin reactions with Fab-sensitized reagent red blood cells

The production, function, and use of a new antiglobulin control cell is described. The cells are sensitized with monovalent Fab (fragment, antigen-binding) fragments and can be agglutinated by active antiglobulin serum only. In contrast to commercial antiglobulin control cells, which are frequently associated with false-positive results, the reactivity of the Fab-sensitized cells is entirely specific. It is concluded that Fab-sensitized cells provide greater quality assurance than currently available reagents.     

Minimally processed fresh frozen human reference sera: preparation, testing, and application to international external quality assurance

The preparation of unmodified or minimally processed fresh frozen human sera is described, as well as the previous use of such sera, e.g. in Nordic and international external quality assurance (EQA) activities. The unmodified serum is prepared from fresh donors' blood collected in dry bags and allowed to coagulate. The serum is collected "on the clot", pooled, filtered, mixed, dispensed in polypropylene vials and frozen at -80 degrees C without further processing. Some batches were slightly modified by spiking or dilution. Critical steps of the production and use of the sera are described and improvements are discussed. A total of 34 different batches have been prepared since 1985. Results from homogeneity and stability studies are presented. The studies cover 18 routine components in serum stored at +4 degrees C to 37 degrees C for up to 34 days. Good stability was observed for storage of all components, with the exception of triglyceride. Amylase, creatininium, glucose, gamma-glutamyltransferase, urate (and perhaps carbamide) showed deterioration after 13 days of incubation at 37 degrees C. The long-term stability at -80 degrees C is reviewed and new data are presented, e.g. as consensus values from EQA schemes, where the same serum has been sent out three times over 5 years, and from reference measurement procedure values that have been assigned twice with an interval of 5 years. Furthermore, a 10-year stability study has been started.     

ACL200型血凝仪在应用中的质量保证

目的 了解仪器性能和干扰指标,保证检测质量.方法 按美国临床实验室标准化委员会EP文件评价仪器,利用高脂、高胆红素、溶血等乏因子血清对仪器进行检测.结果 批内CV＜3%,总CV5%,回收率99.99%;纤维蛋白原(FIB)线性范围0.31～14.62 g/L,r=0.999 8,r2=0.999 6;总胆红素＞142.9 μmol/L,总胆固醇＞12.6 mmol/L,三酰甘油＞6.9 mmol/L,Hb＞42 g/L时,仪器不能检测结果;交叉污染率＜0.5%,批间试剂、新反应盘间无统计学意义(P＞0.05);而新旧反应盘间有统计学意义(P＜0.05);攀枝花地区参考范围凝血酶原时间(PT):10.1～16.1 s,活化部分凝血活酶时间:24.2～40.4 s,FIB:2.22～4.02 g/L.结论 ACL200型血凝仪自动化程度高,操作简单,结果准确可靠,线性范围宽,抗干扰性较强,互染率低,能保证检测质量.但ACL200型血凝仪存在批量样本检测少、成本高,适于急诊和基层医院使用;检测项目配置不合理,没有PT单项检测;受人为因素和严重乳糜血、溶血、黄疸干扰.因此,控制和解除干扰因素的影响,才能确保质量.     

血细胞分析网络实验室的初建与质量保证

目的建立血细胞分析网络实验室，拟解决本地区血液分析仪校准存在的困难。方法依据GB／T15481《检测和校准实验室能力通用要求》（等同ISO／IEC17025）建立血细胞分析溯源体系网络实验室；向卫生部临床检验中心校准实验室进行全血细胞计数的溯源；使用与校准实验室同型号二级标准血液分析仪和同批号比对物进行长期比对；使用健康人新鲜血对多台血液分析仪进行校准。结果逐步完善了实验室管理体系，实验室检测的精密度和准确度逐步达到血细胞分析比对实验室的技术要求；使用同一仪器定值的新鲜血校准的本院内4台血液分析仪，校准后各仪器测定结果与定值仪可比性良好，各试验参数相关系数在0．99以上，WBC、RBC、红细胞压积（HCT）、Hb、PLT的相对偏差分别在±7％、±3．5％、±4％、±3％、±15％以内。结论二级标准检测系统与校准实验室检测结果可比性良好，其溯源模式和质量控制方案保证了该系统全血细胞计数结果具有良好的溯源性和准确性；利用经筛选的健康人新鲜血可进行血液分析仪的校准，使不同分析仪间检测结果具有较好的可比性。     

Practices and attitudes towards quality assurance, inspection and accreditation in blood collection establishments in the European community

In the framework of a European Community (EC)-supported project, a survey of practices and attitudes towards quality assurance, inspection and accreditation in Blood Collection Establishments (BCEs) in the EC member states was carried out. Analysis of 352 responses to a structured questionnaire revealed a preference for national standards over international, and an introspective and reactive view to quality management. Four broad categories of operational performance in relation to safety were formed: initial, repeatable, managed and optimising, with the majority of responses (209) being characterized as initial. Although a direct relationship between the size of the BCE and the range and level of quality management practices is apparent in the data, further analysis shows that small BCEs have much higher ratio of personnel per blood unit collected/processed than large BCEs and thus seem to have an inherent potential for improvement. Overall, a clear preference for inspection and accreditation by professional peers at the national level was indicated.     

Population-level seasonality in cardiovascular mortality,blood pressure,BMI and inflammatory cells in UK biobank

Introduction: The risk of mortality from cardiovascular disease (CVD) is higher in wintertime throughout the world, but it is not known if this reflects annual changes in diet or lifestyle, or an endogenous photoperiodic mechanism that is sensitive to changes in day length.

Methods: Phenotypic data on cardiometabolic and lifestyle factors were collected throughout a 4 year time period from 502,642 middle-aged participants in UK Biobank. To assess the impact of seasonal environmental changes on cardiovascular risk factors, we linked these data to the outdoor temperature and day length at the time of assessment. Self-reported information on physical activity, diet and disease status were used to adjust for confounding factors related to health and lifestyle.

Results: Mortality related to CVD was higher in winter, as were risk factors for this condition including blood pressure, markers of inflammation and body mass index (BMI). These seasonal rhythms were significantly related to day length after adjustment for other factors that might affect seasonality including physical activity, diet and outdoor temperature.

Conclusions: The risk of CVD may be modulated by day length at temperate latitudes, and the implications of seasonality should be considered in all studies of human cardiometabolic health.

• Key messages

• In this cross-sectional study in UK Biobank, we report annual variations in cardiovascular risk factors and mortality that were associated with day length independent of environmental and lifestyle factors.

• These seasonal changes in day length might contribute to annual patterns in cardiovascular disease and mortality.

     

Clinical research, evaluation of care and quality assurance

This paper aims to clarify the concepts and terminology of clinical research, evaluation, and quality. Clinical research or clinical epidemiology aims to demonstrate the efficacy of medical care. The optimal methodology is a randomized, double-blind trial that allows a causal inference in respect of efficacy. This should be the first stage before generalization of all medical practice. Evaluation of quality of care aims to verify the effectiveness of medical care by comparing practice with references. The optimal methodology is clinical audit that allows fine-tuned diagnosis of the existence of deviant practices. The analysis of causes and correction of the care process are an integral part of the evaluation work. Thus quality assurance and quality management concepts and methods have been developed which tend to ensure solutions for better care and to maintain the level of quality of care to achieve patient satisfaction. Evaluation, clinical research and management quality could in fact be seen as the complementary facets of a comprehensive approach to quality of care.     

The role of quality assurance in future midwifery practice

Recent recommendations have been made which would give midwives a more central role in maternity care and a greater degree of independence than they currently enjoy This paper argues that midwives' current attitudes to quality assurance are incompatible with this enhanced role Research conducted in three health districts is described, which explored the perceptions of nurses, midwives and managers towards quality assurance The findings indicate that quality assurance (in whatever form that concept is operationalized) is a demonstration of accountability For managers this accountability is primarily for the service as a whole, whilst nurses and midwives view their accountability as being owed to patients/clients The main methodology which the study identified as being used for monitoring nursing care was the development and auditing of explicit standards This approach has been actively promoted by the Royal College of Nursing, enabling nurses to regain control of the purely professional aspects of the nursing profession Midwives in the study districts showed a marked reluctance to adopt such a strategy, taking the view that as independent practitioners consensus standards would be unacceptable It is argued that this attitude is inconsistent with the basic principle that professionals are accountable for both demonstrating and developing the quality of professional practice It is further suggested that midwives currently have an opportunity to regain professional control of midwifery practice, which will be lost unless they are prepared to take responsibility for evaluating the standards for which they are accountable     

The utilization of quality assurance methods in emergency medical services

Objective: The concept of the necessity of a good quality assurance (QA) plan for emergency medical services (EMS) is well-accepted; guidelines as how best to achieve this and how current systems operate have have not been defined. The purpose of this study was to survey EMS systems to discover current methods used to perform medical control and QA and to examine whether the existence of an emergency medicine residency affected these components. Methods: A survey was mailed in 1989 to the major teaching hospitals associated with all of the emergency medicine residency programs (n = 79) and all other hospitals with greater than 350 beds within the 50 largest United States metropolitan areas (n = 172). If no response was received, a second request was sent in 1990. The survey consisted of questions concerning four general EMS-QA categories: 1) general information; 2) prospective; 3) immediate; and 4) retrospective medical control. Results: Completed surveys were received from 78.5% of residency and 50% of non-residency programs. The majority had an emergency medicine physician as medical director (80.1% vs 61.5%, p = .03). While both residency and non-residency hospitals participated in initial public and prehospital personnel education, academic programs were more likely to be involved in continuing medical education (98.2% vs 82.3%, p = .009). On-line (direct) supervision was more likely to be provided by residency institutions (96.4% vs 81.0%, p = .017) which was provided by a physician in 88.3%.(ABSTRACT TRUNCATED AT 250 WORDS)     

The use of frozen blood in neonatal exchange transfusion

Because of inability to quickly locate donors to provide fresh heparinized blood, seven exchange transfusions were performed on four newborns with hemolytic disease due to Rhesus incompatibility using previously frozen erythrocytes suspended in albumin or heparinized, decitrated fresh frozen plasma. Platellets were added to one unit of previously frozen erythrocytes because of severe thrombocytopenia in one patient following an earlier exchange transfusion. The hematologic and bilirubin removing responses were comparable to those seen with fresh heparinized whole blood. Using this method, the safest red blood cells available, namely the mother's, can be drawn and frozen early in gestation for subsequent exchange transfusion.     

The manufacture and transfusion of deep frozen preserved blood

For the past ten years we have been evaluating the preservation of human red cells by freezing. A comparative study of several techniques revealed no major differences as far as clinical effectiveness is concerned. The recovery percentage varies from 90-95%. Due to the washing procedure, necessary for removing the intracellular cryophylactic substance glycerol, no side effects from these ghosts have been observed. The maximum storage time in the post-thaw period should not exceed 24 hours, because the so-called "closed system" is interrupted. Since the preparations and storage of these cells is laborious and expensive, frozen blood should be used in selected clinical situations, i.e. rare blood types, autologous transfusions.     

Regional quality assurance in medical rehabilitation. The Schleswig-Holstein medical rehabilitation quality community--initiative and testing

In light of the growing age of the population in Germany and worldwide as well as the increasing of chronic diseases, there can be no doubt about the importance of medical rehabilitation. Yet the unbalanced proportions of treatment (costs), effectiveness and efficiency have been discussed critically in the past. The Statutory Pension Insurance scheme responded to this imbalance with a comprehensive quality assurance programme. Furthermore, a nation-wide Rehabilitation Research Funding Programme was established. Still missing, however, are transfer of scientific results into practice and a quality assurance programme that focuses on outcomes and effectiveness. In 2001, in Schleswig-Holstein, a "Medical Rehabilitation Quality Community" was initiated. The Community aims are a higher level of transparency of rehabilitation treatment procedures, providing proof of effects on patient outcomes, and comparison of effects achieved in different rehabilitation clinics, based on patient surveys. After completion of funded pre- and main phases, the Medical Rehabilitation Quality Community will be continued on a self-initiative and self-financing basis. In this paper, procedures and feasibility of the project are described. The main empirical results (outcomes, patient satisfaction, treatment after rehabilitation, n = 2026, and indication related benchmarking) will be presented in a subsequent article.