Clinical Evaluation of Point of Care Raman Analysis for Diagnosis of Gout

床旁拉曼分析诊断痛风的临床评价

基本信息

批准号：
9207158
负责人：
Sivaram P Gogineni
金额：
$ 22.32万
依托单位：
SPECTRAL ENERGIES, LLC
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-01 至 2018-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9207158
关键词：
Accident and Emergency department Acute Address Admission activity Affect Agreement Ambulatory Care Amendment American Arthralgia Arthritis Aspirate substance Bedside Testings Calcium Pyrophosphate Cardiovascular Diseases Caring Certification Charge Chronic Classification Clinic Clinical Clinical Research Clinical assessments Communication Community Healthcare Comorbidity Credentialing Development Device Designs Devices Diagnosis Diagnostic Digestion Disease Economic Burden Environment Filtration Future Gout Healthcare Hospitals Impaired health Inpatients Internal Medicine Investigation Joints Knowledge Laboratories Laboratory Finding Liquid substance Medical Metabolic syndrome Methods Microscope Microscopic Migraine Modification Molecular Profiling Morbidity - disease rate Optics Orthopedics Outcome Outpatients Pain Parkinson Disease Pathologist Patients Phase Physicians Polarization Microscopy Policies Population Preparation Procedures Professional Organizations Provider Pseudogout Quality of life Reagent Recurrence Regulation Reporting Research Research Personnel Rheumatology Sampling Schedule Sensitivity and Specificity Services Site Small Business Innovation Research Grant Spectrum Analysis Spottings Stress Swelling Symptoms Synovial Fluid Technology Testing Time Training Uncertainty United States Agency for Healthcare Research and Quality United States National Institutes of Health Universities Urate Work Writing arthropathies base care seeking college cost cost efficient design effective therapy experience follow-up functional disability improved innovation medical specialties phase 1 study phase 2 study point of care point-of-care diagnostics polarized light primary care setting programs prototype research clinical testing rheumatologist spectral energy standard of care urgent care user friendly software

项目摘要

Gout affects millions of people in the US and the economic burden due to the disease is comparable to other chronic conditions such as Parkinson's disease or migraine. Accurate identification of crystal identity is essential to pursue an appropriate form of treatment. Patients who have gout attacks seek care at hospitals, outpatient centers, urgent care or the ER with hot, swollen and painful joints; therefore, gout symptoms can be confused with other forms of arthritis. Conclusive diagnosis requires observation of synovial aspirates by polarized light microscopy (PLM) to confirm the presence of negatively or positively birefringent crystals. In practice, PLM analysis as a billable service requires a microscope equipped with compensated polarization optics and a Clinical Laboratory Improvement Amendments (CLIA) for the laboratory. Certification by pathologists or rheumatologists is done by professional organizations followed by credentialing and the hospital or lab that performs the analysis and subject to hospital policy about who may report PLM findings. For all intensive purposes, PLM is therefore only feasible in major healthcare centers and central laboratories in selected rheumatology practices. Therefore, clinicians on the front line may be unable to diagnose gout during their clinical encounter or they depend on presumptive diagnosis based on clinical symptoms that lack sensitivity and specificity. The new American College of Rheumatology gout classification criteria are an attempt to address this problem but truly, a facile and automated point of care testing for gout and pseudogout is needed in primary care settings to inform the diagnosis and treatment of these diseases. Point of care Raman device (POCR) is an existing prototype that is developed at Case Western Reserve University (CWRU) with past NIH R21 and R01 to identify MSU and CPPD crystals in synovial fluid. The method involves a simple and facile sample preparation to isolate crystals in a disposable cartridge that is then inserted in a compact, cost-efficient and automated device which identifies the crystal species based on fingerprint molecular spectroscopy. By design, the method should be able to be performed by the non-specialist with minimal training. POCR was evaluated using synovial fluid samples from symptomatic patients (N=174) and there was more than 90% agreement between the diagnoses of POCR and PLM conducted by a certified technician/pathologist. During a prior R01 (Akkus/Singer), clinical synovial sample analyses were performed by researchers. The current version of the device needs a moderate number of modifications and customization to ready it for use by clinicians. This Phase I SBIR will demonstrate that diagnosis of gout/pseudogout by POCR as executed by the non-specialist staff at point of service will agree with the diagnosis by PLM conducted by certified operators. During first aim the prototype developed in CWRU will be transferred to Spectral Energies LLC who will refine it to make a clinically executable prototype. The clinical prototype will be used and evaluated by clinical staff in the second aim. The diagnostic outcome of synovial fluid analysis on freshly collected samples by POCR in the hands of non-expert clinical staff will be compared to PLM analysis performed as standard of care. The Phase I study will provide us with a clinically applicable POCR and pave the way for a multi-site clinical assessment of the device in a follow up Phase II study that aims to demonstrate that POCR enables the diagnosis of gout in settings which are not equipped with PLM and CLIA certified laboratories and accredited operators.

痛风影响着美国数百万人，该疾病造成的经济负担与其他疾病相当帕金森病或偏头痛等慢性疾病。准确鉴定晶体身份寻求适当的治疗方式至关重要。痛风发作的患者到医院寻求治疗，门诊中心、紧急护理或关节热、肿胀和疼痛的急诊室；因此，痛风症状可能是与其他形式的关节炎混淆。结论性诊断需要通过以下方式观察滑膜抽吸物偏光显微镜（PLM）可确认负双折射晶体或正双折射晶体的存在。在在实践中，PLM 分析作为一项计费服务需要配备补偿偏振的显微镜光学和实验室临床实验室改进修正案 (CLIA)。认证机构病理学家或风湿病学家由专业组织完成，然后进行资格认证和执行分析并遵守有关谁可以报告 PLM 结果的医院政策的医院或实验室。因此，对于所有密集型目的，PLM 仅适用于大型医疗中心和中心实验室在选定的风湿病实践中。因此，前线的临床医生可能无法诊断痛风在他们的临床遭遇中，或者他们依赖于基于临床症状的推定诊断，但缺乏敏感性和特异性。新的美国风湿病学会痛风分类标准是尝试解决这个问题，但实际上，针对痛风和假性痛风的简便且自动化的护理测试初级保健机构需要为这些疾病的诊断和治疗提供信息。护理点拉曼设备（POCR）是凯斯西储大学（CWRU）过去开发的现有原型 NIH R21 和 R01 用于识别滑液中的 MSU 和 CPPD 晶体。该方法涉及一个简单且容易的样品制备以在一次性盒中分离晶体，然后将其插入紧凑、经济高效的容器中以及基于指纹分子光谱识别晶体种类的自动化装置。经过设计时，该方法应该能够由非专业人员通过最少的培训来执行。 POCR 是使用有症状患者 (N=174) 的滑液样本进行评估，超过 90% 由经过认证的技术人员/病理学家进行的 POCR 和 PLM 诊断之间的一致性。期间在 R01（Akkus/Singer）之前，研究人员进行了临床滑膜样本分析。目前的该设备的版本需要进行一定数量的修改和定制才能准备好供使用临床医生。该 I 期 SBIR 将证明 POCR 对痛风/假性痛风的诊断是由 POCR 执行的服务点的非专业工作人员将同意由经过认证的操作员进行的 PLM 诊断。在第一个目标期间，CWRU 开发的原型将转移给 Spectral Energies LLC，后者将对其进行改进它可以制作临床上可执行的原型。临床原型将由临床工作人员使用和评估第二个目标。通过 POCR 对新鲜采集的滑液样本进行分析的诊断结果非专业临床工作人员的双手将与作为护理标准进行的 PLM 分析进行比较。第一阶段研究将为我们提供临床适用的 POCR，并为多中心临床评估铺平道路该设备在后续 II 期研究中，旨在证明 POCR 能够诊断痛风未配备 PLM 和 CLIA 认证实验室和认可操作员的设置。