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

项目摘要 据估计，每年有150万人死于结核病。其中许多人寻求照顾， 资源不足的诊所（例如，在农村地区或非正规住区）， 不可用.这些患者通常无法及时返回以获得结果并开始治疗， 导致疾病的持续传播和死亡。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，可以避免大量死亡和传播。我们的团队已被 开发并验证了成人肺结核的临床风险评分（“PredictTB”）， 决策的该风险评分范围为1-10，可以在一分钟内使用 可用的临床数据（例如，年龄，性别，自我报告的艾滋病毒状态），并具有足够高的准确性， 在确认性检测结果待定时，决定当天开始经验性治疗。当日 治疗的开始改善了其他传染病（例如，性传播疾病）的患者结局 包括艾滋病毒在内的疾病），而这种新的临床风险评分对结核病也有类似的希望，结核病是导致艾滋病的主要原因。 全世界的传染病死亡率。然而，在进行大规模的随机分组试验以评估 无论该评分是否可以改善患者重要的结局，关键是要首先生成证据， 在资源最有限的情况下，评分系统可以有效地实施。 我们提出了一种2型混合有效性-实施评估的PredictTB临床风险评分在四个 在乌干达的城市周边诊所，另外四个诊所作为对照组。我们的具体目标 评估PredictTB对临床结果的有效性，包括快速治疗启动，结核病 死亡率和失去护理（目标1）;从覆盖面、采用率 实施和维护（目标2）;以及项目的长期影响和成本效益 PredictTB实施（目标3）。我们的主要结果是， 微生物学确诊的结核病患者在首次出现后7天内开始治疗。完成我们 为了达到这一目标，我们将采用一种高度实用的研究设计，培训临床医生使用PredictTB 每季度进行一次研究中心访视，但尽量减少研究人员与治疗人员之间的接触 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 在实际现场设置下的决策和患者结果。如果成功，该评估将提供 关键数据来证明（或停止）大规模务实的临床试验的进行-它不仅会产生 有效性的初步证据，但它也将为适当的实施提供信息。患者高度 资源有限的环境遭受结核病不良影响的风险最大，包括长期 发病率和死亡率。这项研究代表了改善临床管理的重要的第一步， 这些被边缘化的病人，从而实现全球目标，结束结核病流行。

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.