Rivas-Ruiz Rodolfo, Villasis-Keever Miguel, Miranda-Novales Guadalupe, Castelán-Martínez Osvaldo D, Rivas-Contreras Silvia
Centro de adiestramiento en Investigación Clínica, Insitiuto Mexicano del Seguro Social, Centro Medico Nacional Siglo XXI, Hospital de Pediatria del CMN SXXI, Avenida Cuauhtemoc #330, Mexico City, Mexico.
Cochrane Database Syst Rev. 2019 Mar 19;3(3):CD009031. doi: 10.1002/14651858.CD009031.pub2.
People with febrile neutropaenia are usually treated in a hospital setting. Recently, treatment with oral antibiotics has been proven to be as effective as intravenous therapy. However, the efficacy and safety of outpatient treatment have not been fully evaluated.
To compare the efficacy (treatment failure and mortality) and safety (adverse events of antimicrobials) of outpatient treatment compared with inpatient treatment in people with cancer who have low-risk febrile neutropaenia.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 11) in the Cochrane Library, MEDLINE via Ovid (from 1948 to November week 4, 2018), Embase via Ovid (from 1980 to 2018, week 48) and trial registries (National Cancer Institute, MetaRegister of Controlled Trials, Medical Research Council Clinical Trial Directory). We handsearched all references of included studies and major reviews.
Randomised controlled trials (RCTs) comparing outpatient with inpatient treatment for people with cancer who develop febrile neutropaenia. The outpatient group included those who started treatment as an inpatient and completed the antibiotic course at home (sequential) as well as those who started treatment at home.
Two review authors independently assessed trial eligibility, methodological quality, and extracted data. Primary outcome measures were: treatment failure and mortality; secondary outcome measures considered were: duration of fever, adverse drug reactions to antimicrobial treatment, duration of neutropaenia, duration of hospitalisation, duration of antimicrobial treatment, and quality of life (QoL). We estimated risk ratios (RRs) with 95% confidence intervals (CIs) for dichotomous data; we calculated weighted mean differences for continuous data. Random-effects meta-analyses and sensitivity analyses were conducted.
We included ten RCTs, six in adults (628 participants) and four in children (366 participants). We found no clear evidence of a difference in treatment failure between the outpatient and inpatient groups, either in adults (RR 1.23, 95% CI 0.82 to 1.85, I 0%; six studies; moderate-certainty evidence) or children (RR 1.04, 95% CI 0.55 to 1.99, I 0%; four studies; moderate-certainty evidence). For mortality, we also found no clear evidence of a difference either in studies in adults (RR 1.04, 95% CI 0.29 to 3.71; six studies; 628 participants; moderate-certainty evidence) or in children (RR 0.63, 95% CI 0.15 to 2.70; three studies; 329 participants; moderate-certainty evidence).According to the type of intervention (early discharge or exclusively outpatient), meta-analysis of treatment failure in four RCTs in adults with early discharge (RR 1.48, 95% CI 0.74 to 2.95; P = 0.26, I 0%; 364 participants; moderate-certainty evidence) was similar to the results of the exclusively outpatient meta-analysis (RR 1.15, 95% CI 0.62 to 2.13; P = 0.65, I 19%; two studies; 264 participants; moderate-certainty evidence).Regarding the secondary outcome measures, we found no clear evidence of a difference between outpatient and inpatient groups in duration of fever (adults: mean difference (MD) 0.2, 95% CI -0.36 to 0.76, 1 study, 169 participants; low-certainty evidence) (children: MD -0.6, 95% CI -0.84 to 0.71, 3 studies, 305 participants; low-certainty evidence) and in duration of neutropaenia (adults: MD 0.1, 95% CI -0.59 to 0.79, 1 study, 169 participants; low-certainty evidence) (children: MD -0.65, 95% CI -0.1.86 to 0.55, 2 studies, 268 participants; moderate-certainty evidence). With regard to adverse drug reactions, although there was greater frequency in the outpatient group, we found no clear evidence of a difference when compared to the inpatient group, either in adult participants (RR 8.39, 95% CI 0.38 to 187.15; three studies; 375 participants; low-certainty evidence) or children (RR 1.90, 95% CI 0.61 to 5.98; two studies; 156 participants; low-certainty evidence).Four studies compared the hospitalisation time and found that the mean number of days of hospital stay was lower in the outpatient treated group by 1.64 days in adults (MD -1.64, 95% CI -2.22 to -1.06; 3 studies, 251 participants; low-certainty evidence) and by 3.9 days in children (MD -3.90, 95% CI -5.37 to -2.43; 1 study, 119 participants; low-certainty evidence). In the 3 RCTs of children in which days of antimicrobial treatment were analysed, we found no difference between outpatient and inpatient groups (MD -0.07, 95% CI -1.26 to 1.12; 305 participants; low-certainty evidence).We identified two studies that measured QoL: one in adults and one in children. QoL was slightly better in the outpatient group than in the inpatient group in both studies, but there was no consistency in the domains included.
AUTHORS' CONCLUSIONS: Outpatient treatment for low-risk febrile neutropaenia in people with cancer probably makes little or no difference to treatment failure and mortality compared with the standard hospital (inpatient) treatment and may reduce time that patients need to be treated in hospital.
发热性中性粒细胞减少症患者通常在医院环境中接受治疗。最近,已证明口服抗生素治疗与静脉治疗同样有效。然而,门诊治疗的疗效和安全性尚未得到充分评估。
比较门诊治疗与住院治疗对低风险发热性中性粒细胞减少症癌症患者的疗效(治疗失败和死亡率)和安全性(抗菌药物不良事件)。
我们检索了Cochrane图书馆中的Cochrane对照试验中心注册库(CENTRAL;2018年第11期)、通过Ovid检索的MEDLINE(从1948年至2018年11月第4周)、通过Ovid检索的Embase(从1980年至2018年第48周)以及试验注册库(美国国立癌症研究所、对照试验Meta注册库、医学研究理事会临床试验目录)。我们对纳入研究和主要综述的所有参考文献进行了手工检索。
比较门诊治疗与住院治疗对发生发热性中性粒细胞减少症癌症患者的随机对照试验(RCT)。门诊组包括那些开始作为住院患者治疗并在家中完成抗生素疗程(序贯治疗)的患者以及那些在家中开始治疗的患者。
两位综述作者独立评估试验的合格性、方法学质量并提取数据。主要结局指标为:治疗失败和死亡率;次要结局指标包括:发热持续时间、对抗菌治疗的药物不良反应、中性粒细胞减少持续时间、住院时间、抗菌治疗持续时间和生活质量(QoL)。我们对二分类数据估计风险比(RRs)及其95%置信区间(CIs);对连续数据计算加权均数差。进行了随机效应荟萃分析和敏感性分析。
我们纳入了10项RCT,其中6项针对成人(628名参与者),4项针对儿童(366名参与者)。我们未发现明确证据表明门诊组与住院组在治疗失败方面存在差异,无论是在成人中(RR 1.23,95%CI 0.82至1.85,I² 0%;6项研究;中等确定性证据)还是儿童中(RR 1.04,95%CI 0.55至1.99,I² 0%;4项研究;中等确定性证据)。对于死亡率,我们也未发现明确证据表明成人研究(RR 1.04,95%CI 0.29至3.71;6项研究;628名参与者;中等确定性证据)或儿童研究(RR 0.63,95%CI 0.15至2.70;3项研究;329名参与者;中等确定性证据)之间存在差异。根据干预类型(早期出院或完全门诊治疗),对4项针对早期出院成人的RCT中治疗失败的荟萃分析(RR 1.48,95%CI 0.74至2.95;P = 0.26,I² 0%;364名参与者;中等确定性证据)与完全门诊治疗荟萃分析的结果相似(RR 1.15,95%CI 0.62至2.13;P = 0.65,I² 19%;2项研究;264名参与者;中等确定性证据)。关于次要结局指标,我们未发现明确证据表明门诊组与住院组在发热持续时间方面存在差异(成人:均数差(MD)0.2,95%CI -0.36至0.76,1项研究,169名参与者;低确定性证据)(儿童:MD -0.6,95%CI -0.84至0.71,3项研究,305名参与者;低确定性证据)以及中性粒细胞减少持续时间方面存在差异(成人:MD 0.1,95%CI -0.59至0.79,1项研究,169名参与者;低确定性证据)(儿童:MD -0.65,95%CI -1.86至0.55,2项研究,268名参与者;中等确定性证据)。关于药物不良反应,尽管门诊组的发生率更高,但我们未发现明确证据表明与住院组相比存在差异,无论是在成人参与者中(RR 8.39,95%CI 0.38至187.15;3项研究;375名参与者;低确定性证据)还是儿童中(RR 1.90,95%CI 0.61至5.98;2项研究;156名参与者;低确定性证据)。4项研究比较了住院时间,发现门诊治疗组的成人平均住院天数减少了1.64天(MD -1.64,95%CI -2.22至-1.06;3项研究,251名参与者;低确定性证据),儿童减少了3.9天(MD -3.90,95%CI -5.37至-2.43;1项研究,119名参与者;低确定性证据)。在分析了抗菌治疗天数的3项儿童RCT中,我们未发现门诊组与住院组之间存在差异(MD -0.07,95%CI -1.26至1.12;305名参与者;低确定性证据)。我们确定了两项测量QoL的研究:一项针对成人,一项针对儿童。在两项研究中,门诊组的QoL均略优于住院组,但所纳入的领域并不一致。
与标准的医院(住院)治疗相比,癌症患者低风险发热性中性粒细胞减少症的门诊治疗可能对治疗失败和死亡率影响很小或没有影响,并且可能减少患者需要住院治疗的时间。