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

项目概要 据估计，每年有 150 万人死于结核病 (TB)。其中许多人是在以下地方寻求护理的人： 资源不足的诊所（例如，在农村地区或非正规住区），需要当天进行结核病诊断 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常常导致死亡。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。我们的团队有 开发并验证了成人肺结核的临床风险评分（“PredicTB”），可以帮助临床 决策。该风险评分范围为 1-10，可以轻松地在一分钟内手动计算出来 可用的临床数据（例如年龄、性别、自我报告的艾滋病毒状况），并且具有足够高的准确性来告知 在确认测试结果尚未确定的情况下，决定当天开始经验性治疗。当日 开始治疗可以改善其他传染病（例如性传播疾病）的患者预后 疾病，包括艾滋病毒），这种新的临床风险评分对结核病也有类似的前景，结核病是导致结核病的主要原因 全球传染性死亡率。然而，在进行大规模整群随机试验来评估之前 该评分是否可以改善患者重要的结果，首先生成证据表明这一点至关重要 分数可能是有效的，并且可以在资源最有限的环境中实施。 我们建议对 PredicTB 临床风险评分进行 2 类混合有效性实施评估，分为四个阶段： 乌干达的城郊诊所，还有另外四家诊所作为对照组。我们的具体目标 旨在评估 PredicTB 对临床结果的有效性，包括快速开始治疗、结核病 死亡率和护理损失（目标 1）；从覆盖范围、采用率、 实施和维护（目标 2）；以及该项目的长期影响和成本效益 PredictTB 实施（目标 3）。我们的主要结果是患有以下疾病的患者比例增加 微生物学确诊的结核病患者，在初次就诊后 7 天内开始治疗。为了完成我们的 为了实现这一目标，我们将采用高度务实的研究设计，培训临床医生使用 PredicTB 评分并进行季度现场访问，但尽量减少研究人员和治疗人员之间的接触 临床医生。这将使我们能够评估 PredicTB 的实施是否可能影响临床 实际现场环境下的决策和患者结果。如果成功，该评估将提供 证明（或停止）进行大规模实用临床试验的关键数据——它不仅会产生 有效性的初步证据，但也将为适当的实施提供信息。患者处于高度 资源有限的环境遭受结核病不良影响的风险最大，包括长期影响 发病率和死亡。这项研究代表着改善临床管理的重要第一步 这些边缘化患者，从而实现结束结核病流行的全球目标。

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.