PredicTB: Validating a clinical risk score for early management of tuberculosis in Ugandan primary health clinics

项目总结 据估计，每年有150万人死于结核病。他们中的许多人都是在 资源不足的诊所(例如，在农村地区或非正式住区)当天确诊为结核病的诊所 不可用。这些患者往往无法及时返回接受结果并开始治疗， 导致疾病持续传播，并经常导致死亡。如果结核病治疗可以在同一天开始 这些患者最初寻求治疗，大量死亡和传播是可以避免的。我们队有 开发并验证了成人肺结核的临床风险评分(“PredicTB”)，这可能有助于临床 决策。此风险分数范围为1-10，可在一分钟以下手工计算，使用方便 可用的临床数据(例如，年龄、性别、自我报告的艾滋病毒状况)，并具有足够高的准确性，以告知 关于当天经验性治疗开始的决定，同时验证性测试结果仍在等待。同一天 开始治疗改善了患者对其他传染病(例如，性传播疾病)的预后 包括艾滋病毒在内的疾病)，而这一新的临床风险评分对结核病也有类似的前景，结核病是 世界范围内的传染病死亡率。然而，在进行大规模的整群随机试验之前， 这一评分是否可以改善患者的重要预后，关键是首先要产生证据证明这一点 SCORE可能是有效的，并且可以在资源最有限的情况下实施。 我们提出了一种预测结核病临床风险评分的类型2混合有效性-实施评估 乌干达的城市周边诊所，另有四家诊所作为对照组。我们的具体目标 评估PredicTB对临床结果的有效性，包括快速治疗开始，TB 死亡率和失去护理(目标1)；从覆盖面、收养、 实施和维护(目标2)；项目的长期影响和成本效益 预测结核病的实施(目标3)。我们的主要结果是患者的比例增加 微生物确诊的结核病患者在首次发病后7天内开始治疗。为了实现我们的目标 目的，我们将采用高度务实的研究设计，培训临床医生使用PredictTB 对每季度进行一次实地考察，但尽量减少研究人员与治疗人员的接触 临床医生。这将使我们能够评估PredictTB的实施是否可能影响临床 在实际现场环境下的决策和患者结果。如果成功，这项评估将提供 证明(或停止)进行大规模实用临床试验的关键数据-它不仅将产生 这是有效的初步证据，但也将有助于适当的执行。高度危重的患者 资源有限的环境最有可能遭受结核病的不良影响，包括长期的 发病率和死亡率。这项研究是朝着改善临床管理迈出的重要的第一步 这些被边缘化的患者，从而朝着实现结束结核病流行的全球目标的方向迈进。

PROJECT SUMMARY An estimated 1.5 million people die of tuberculosis (TB) every year. Many of these are people who seek care in under-resourced clinics (for example, in rural areas or informal settlements) where same-day TB diagnosis is not available. These patients are often unable to return promptly to receive their results and start treatment, resulting in ongoing disease transmission and often death. If TB treatment could be started on the same day as these patients initially seek care, substantial mortality and transmission could be averted. Our team has developed and validated a clinical risk score (“PredicTB”) for adult pulmonary TB that could aid in clinical decision-making. This risk score ranges from 1-10, can be calculated by hand in under a minute using readily available clinical data (e.g., age, sex, self-reported HIV status), and has sufficiently high accuracy to inform decisions about same-day empiric treatment initiation while confirmatory test results are pending. Same-day treatment initiation improves patient outcomes for other infectious diseases (for example, sexually transmitted diseases including HIV), and this novel clinical risk score holds similar promise for TB, the leading cause of infectious mortality worldwide. However, before conducting a large-scale cluster randomized trial to evaluate whether this score could improve patient-important outcomes, it is critical to first generate evidence that this score could be effective and be implemented in the most-resource-limited settings for which it is intended. We propose a type 2 hybrid effectiveness-implementation evaluation of the PredicTB clinical risk score in four peri-urban clinics in Uganda, with an additional four clinics serving as a comparison group. Our Specific Aims are to evaluate the effectiveness of PredicTB on clinical outcomes including rapid treatment initiation, TB mortality, and loss to care (Aim 1); to evaluate the implementation of PredicTB in terms of reach, adoption, implementation, and maintenance (Aim 2); and the project the long-term impact and cost-effectiveness of PredicTB implementation (Aim 3). Our primary outcome is the increase in the proportion of patients with microbiologically confirmed TB who start treatment within seven days of initial presentation. To accomplish our aims, we will adopt a highly pragmatic study design in which we train clinicians in the use of the PredicTB score and perform quarterly site visits but otherwise minimize contact between study staff and treating clinicians. This will enable us to evaluate whether implementation of PredicTB is likely to impact clinical decision-making and patient outcomes under actual field settings. If successful, this evaluation will provide critical data to justify (or halt) the conduct of a large-scale pragmatic clinical trial – not only will it generate preliminary evidence of effectiveness, but it will also inform appropriate implementation. Patients in highly resource-constrained settings are at greatest risk of suffering the ill effects of TB disease, including long-term morbidity and death. This study represents an important first step toward improving clinical management for these marginalized patients and thus toward reaching global targets for ending the TB epidemic.