School of Medicine, University of Central Lancashire, Preston, UK.
Pediatric Gastroenterology, Sidra Medicine, Doha, Qatar.
Cochrane Database Syst Rev. 2021 Nov 29;11(11):CD013531. doi: 10.1002/14651858.CD013531.pub2.
BACKGROUND: Crohn's disease is a remitting and relapsing disorder that can affect the whole gastrointestinal tract. Active disease symptoms include abdominal pain, fatigue, weight loss, and diarrhoea. There is no known cure; however, the disease can be managed, and therefore places a huge financial burden on healthcare systems. Abdominal pain is a common and debilitating symptom of Crohn's and other inflammatory bowel diseases (IBDs), and is multifaceted. Abdominal pain in Crohn's disease could be a symptom of disease relapse or related to medication adverse effects, surgical complications and strictures or adhesions secondary to IBD. In the absence of these factors, around 20 to 50% of people with Crohn's in remission still experience pain. OBJECTIVES: To assess the efficacy and safety of interventions for managing abdominal pain in people with Crohn's disease and IBD (where data on ulcerative colitis and Crohn's disease could not be separated). SEARCH METHODS: We searched CENTRAL, MEDLINE, three other databases, and clinical trials registries on 29 April 2021. We also searched the references of trials and systematic reviews for any additional trials. SELECTION CRITERIA: All published, unpublished, and ongoing randomised trials that compared interventions for the management of abdominal pain in the setting of Crohn's disease and IBD, with other active interventions or standard therapy, placebo, or no therapy were included. We excluded studies that did not report on any abdominal pain outcomes. DATA COLLECTION AND ANALYSIS: Five review authors independently conducted data extraction and 'Risk of bias' assessment of the included studies. We analysed data using Review Manager 5. We expressed dichotomous and continuous outcomes as risk ratios and mean differences with 95% confidence intervals. We assessed the certainty of the evidence using GRADE methodology. MAIN RESULTS: We included 14 studies (743 randomised participants). Five studies evaluated participants with Crohn's disease; seven studies evaluated participants with IBD where the data on ulcerative colitis and Crohn's disease could not be separated; and two studies provided separate results for Crohn's disease participants. Studies considered a range of disease activity states. Two studies provided intervention success definitions, whilst the remaining studies measured pain as a continuous outcome on a rating scale. All studies except one measured pain intensity, whilst three studies measured pain frequency. Withdrawals due to adverse events were directly or indirectly reported in 10 studies. No conclusions could be drawn about the efficacy of the majority of the interventions on pain intensity, pain frequency, and treatment success, except for the comparison of transcranial direct current stimulation to sham stimulation. The certainty of the evidence was very low in all but one comparison because of imprecision due to sparse data and risk of bias assessed as unclear or high risk. Two studies compared a low FODMAP diet (n=37) to a sham diet (n=45) in IBD patients. The evidence on pain intensity was of very low certainty (MD -12.00, 95% CI -114.55 to 90.55). One study reported pain intensity separately for CD participants in the low FODMAP group [n=14, mean(SD)=24 (82.3)] and the sham group [n=12, mean(SD)=32 (69.3)]. The same study also reported pain frequency for IBD participants in the low FODMAP group [n=27, mean(SD)=36 (26)] and sham group [n=25, mean(SD)=38(25)] and CD participants in the low FODMAP group [n=14, mean(SD)=36 (138.4)] and sham group [n=12, mean(SD)=48 (128.2)]. Treatment success was not reported. One study compared a low FODMAP diet (n=25) to high FODMAP/normal diet (n=25) in IBD patients. The data reported on pain intensity was unclear. Treatment success and pain frequency were not reported. One study compared medicine-separated moxibustion combined with acupuncture (n=51) versus wheat bran-separated moxibustion combined with shallow acupuncture (n=51) in CD patients. The data reported on pain intensity and frequency were unclear. Treatment success was not reported. One study compared mindfulness with CBT (n=33) versus no treatment (n=33) in IBD patients. The evidence is very uncertain about the effect of this treatment on pain intensity and frequency (MD -37.00, 95% CI -87.29 to 13.29). Treatment success was not reported. One study compared soft non-manipulative osteopathic treatment (n=16) with no treatment besides doctor advice (n=14) in CD patients. The evidence is very uncertain about the effect of this treatment on pain intensity (MD 0.01, 95% CI -1.81 to 1.83). Treatment success and pain frequency were not reported. One study compared stress management (n=15) to self-directed stress management(n=15) and to standard treatment (n=15) in CD patients. The evidence is very uncertain about the effect of these treatments on pain intensity (MD -30.50, 95% CI -58.45 to -2.55 and MD -34.30, 95% CI -61.99 to -6.61). Treatment success and pain frequency were not reported. One study compared enteric-release glyceryl trinitrate (n=34) with placebo (n=36) in CD patients. The data reported on pain intensity was unclear. Treatment success and pain frequency were not reported. One study compared 100 mg olorinab three times per day (n=8) with 25 mg olorinab three times per day (n=6) in CD patients. Pain intensity was measured as a 30% reduction in weekly average abdominal pain intensity score for the 100mg group (n=5) and the 25mg group (n=6). The evidence is very uncertain about the effect of this treatment on pain intensity (RR 0.66, 95% CI 0.38 to 1.15). Treatment success and pain frequency were not reported. One study compared relaxation training (n=28) to a waitlist (n=28) in IBD patients. The evidence is very uncertain about the effect of this treatment on pain intensity (MD -0.72, 95% CI -1.85 to 0.41). Treatment success and pain frequency were not reported. One study compared web-based education (n=30) with a book-based education (n=30) in IBD patients. The evidence is very uncertain about the effect of this treatment on pain intensity (MD -0.13, 95% CI -1.25 to 0.99). Treatment success and pain frequency were not reported. One study compared yoga (n=50) with no treatment (n=50) in IBD patients. The data reported on treatment success were unclear. Pain frequency and intensity were not reported. One study compared transcranial direct current stimulation (n = 10) to sham stimulation (n = 10) in IBD patients. There may be an improvement in pain intensity when transcranial direct current is compared to sham stimulation (MD -1.65, 95% CI -3.29 to -0.01, low-certainty evidence). Treatment success and pain frequency were not reported. One study compared a kefir diet (Lactobacillus bacteria) to no intervention in IBD patients and provided separate data for their CD participants. The evidence is very uncertain about the effect of this treatment on pain intensity in IBD (MD 0.62, 95% CI 0.17 to 1.07) and CD (MD -1.10, 95% CI -1.67 to -0.53). Treatment success and pain frequency were not reported. Reporting of our secondary outcomes was inconsistent. The most adverse events were reported in the enteric-release glyceryl trinitrate and olorinab studies. In the enteric-release glyceryl trinitrate study, the adverse events were higher in the intervention arm. In the olorinab study, more adverse events were observed in the higher dose arm of the intervention. In the studies on non-drug interventions, adverse events tended to be very low or zero. However, no clear judgements regarding adverse events can be drawn for any interventions due to the low number of events. Anxiety and depression were measured and reported at the end of intervention in only one study; therefore, no meaningful conclusions can be drawn for this outcome. AUTHORS' CONCLUSIONS: We found low certainty evidence that transcranial direct current stimulation may improve pain intensity compared to sham stimulation. We could not reach any conclusions on the efficacy of any other interventions on pain intensity, pain frequency, and treatment success. The certainty of the evidence was very low due to the low numbers of studies and participants in each comparison and clinical heterogeneity amongst the studies. While no serious or total adverse events were elicited explicitly with any of the treatments studied, the reported events were very low. The certainty of the evidence for all comparisons was very low, so no conclusions can be drawn.
背景:克罗恩病是一种缓解和复发的疾病,可影响整个胃肠道。活跃疾病的症状包括腹痛、疲劳、体重减轻和腹泻。目前尚无已知的治愈方法;然而,可以对该病进行治疗,因此给医疗保健系统带来了巨大的经济负担。腹痛是克罗恩病和其他炎症性肠病(IBD)的常见且使人虚弱的症状,且具有多面性。克罗恩病的腹痛可能是疾病复发的症状,也可能与药物的不良反应、手术并发症以及 IBD 引起的狭窄或粘连有关。在不存在这些因素的情况下,大约 20%至 50%的缓解期克罗恩病患者仍会出现疼痛。 目的:评估用于管理克罗恩病和 IBD(其中溃疡性结肠炎和克罗恩病的数据无法分开)患者腹痛的干预措施的疗效和安全性。 检索方法:我们于 2021 年 4 月 29 日检索了 CENTRAL、MEDLINE、其他三个数据库以及临床试验注册库。我们还检索了试验的参考文献和系统评价,以获取任何额外的试验。 选择标准:我们纳入了所有已发表、未发表和正在进行的随机试验,这些试验比较了管理克罗恩病和 IBD 患者腹痛的干预措施,与其他主动干预或标准治疗、安慰剂或无治疗的干预措施,排除了未报告任何腹痛结局的研究。 数据收集和分析:五名综述作者独立进行了数据提取和纳入研究的“偏倚风险”评估。我们使用 Review Manager 5 分析了数据。我们将二分类和连续结局表示为风险比和均数差及其 95%置信区间。我们使用 GRADE 方法评估证据的确定性。 主要结果:我们纳入了 14 项研究(743 名随机参与者)。其中 5 项研究评估了克罗恩病患者;7 项研究评估了 IBD 患者,其中溃疡性结肠炎和克罗恩病的数据无法分开;2 项研究提供了克罗恩病患者的单独结果。研究考虑了多种疾病活动状态。两项研究定义了干预成功的定义,而其余研究则将疼痛作为评分量表上的连续结局进行测量。所有研究均测量疼痛强度,除了一项研究外,其余研究均测量疼痛频率。10 项研究均直接或间接报告了因不良事件而退出的情况。由于数据稀疏和偏倚评估为不确定或高风险,除了经颅直流电刺激与假刺激的比较外,除了经颅直流电刺激与假刺激的比较外,我们无法对大多数干预措施对疼痛强度、疼痛频率和治疗成功的疗效得出任何结论。两项研究比较了低 FODMAP 饮食(n=37)与假饮食(n=45)在 IBD 患者中的作用。疼痛强度的证据确定性非常低(MD-12.00,95%CI-114.55 至 90.55)。一项研究报告了低 FODMAP 组中 CD 参与者的疼痛强度(n=14,均值[标准差]=24[82.3])和假组中 CD 参与者的疼痛强度(n=12,均值[标准差]=32[69.3])。同一项研究还报告了 IBD 参与者的低 FODMAP 组的疼痛频率(n=27,均值[标准差]=36[26])和假组的疼痛频率(n=25,均值[标准差]=38[25])以及 CD 参与者的低 FODMAP 组的疼痛频率(n=14,均值[标准差]=36[138.4])和假组的疼痛频率(n=12,均值[标准差]=48[128.2])。未报告治疗成功。一项研究比较了低 FODMAP 饮食(n=25)与高 FODMAP/正常饮食(n=25)在 IBD 患者中的作用。报告的疼痛强度数据不清楚。治疗成功和疼痛频率未报告。一项研究比较了药灸结合针刺(n=51)与麦粒灸结合浅针刺(n=51)在 CD 患者中的作用。报告的疼痛强度和频率数据不清楚。治疗成功未报告。一项研究比较了正念与 CBT(n=33)与无治疗(n=33)在 IBD 患者中的作用。关于这种治疗对疼痛强度和频率的影响的证据非常不确定(MD-37.00,95%CI-87.29 至 13.29)。治疗成功未报告。一项研究比较了软非手术整骨治疗(n=16)与除医生建议外的无治疗(n=14)在 CD 患者中的作用。关于这种治疗对疼痛强度的影响的证据非常不确定(MD 0.01,95%CI-1.81 至 1.83)。治疗成功和疼痛频率未报告。一项研究比较了应激管理(n=15)与自我指导的应激管理(n=15)和标准治疗(n=15)在 CD 患者中的作用。关于这些治疗对疼痛强度的影响的证据非常不确定(MD-30.50,95%CI-58.45 至-2.55 和 MD-34.30,95%CI-61.99 至-6.61)。治疗成功和疼痛频率未报告。一项研究比较了肠道释放硝酸甘油(n=34)与安慰剂(n=36)在 CD 患者中的作用。报告的疼痛强度数据不清楚。治疗成功和疼痛频率未报告。一项研究比较了 100mg 奥洛里纳布每日三次(n=8)与 25mg 奥洛里纳布每日三次(n=6)在 CD 患者中的作用。奥洛里纳布 100mg 组(n=5)和奥洛里纳布 25mg 组(n=6)的每周平均腹痛强度评分减少 30%,作为疼痛强度的测量指标。关于这种治疗对疼痛强度的影响的证据非常不确定(RR 0.66,95%CI 0.38 至 1.15)。治疗成功和疼痛频率未报告。一项研究比较了放松训练(n=28)与等待名单(n=28)在 IBD 患者中的作用。关于这种治疗对疼痛强度的影响的证据非常不确定(MD-0.72,95%CI-1.85 至 0.41)。治疗成功和疼痛频率未报告。一项研究比较了基于网络的教育(n=30)与基于书籍的教育(n=30)在 IBD 患者中的作用。关于这种治疗对疼痛强度的影响的证据非常不确定(MD-0.13,95%CI-1.25 至 0.99)。治疗成功和疼痛频率未报告。一项研究比较了瑜伽(n=50)与无治疗(n=50)在 IBD 患者中的作用。报告的治疗成功数据不清楚。疼痛频率和强度未报告。一项研究比较了经颅直流电刺激(n=10)与假刺激(n=10)在 IBD 患者中的作用。与假刺激相比,经颅直流电刺激可能会改善疼痛强度(MD-1.65,95%CI-3.29 至-0.01,低确定性证据)。治疗成功和疼痛频率未报告。一项研究比较了 kefir 饮食(乳杆菌细菌)与 IBD 患者的无干预,并提供了他们的 CD 参与者的单独数据。关于这种治疗对 IBD 患者疼痛强度的影响的证据非常不确定(MD 0.62,95%CI 0.17 至 1.07)和 CD(MD-1.10,95%CI-1.67 至-0.53)。治疗成功和疼痛频率未报告。我们对次要结局的报告不一致。在 enteric-release glyceryl trinitrate 和 olorinab 研究中,最常见的不良事件报告。在 enteric-release glyceryl trinitrate 研究中,干预组的不良事件更高。在 olorinab 研究中,更高剂量干预组观察到更多的不良事件。在非药物干预研究中,不良事件往往非常低或为零。然而,由于每个干预措施的不良事件数量较少,因此无法对任何干预措施的不良事件做出明确的判断。焦虑和抑郁仅在一项研究中在干预结束时进行了测量和报告;因此,对于这一结局无法得出有意义的结论。 作者结论:我们发现经颅直流电刺激可能比假刺激更能改善疼痛强度。我们无法得出任何关于其他干预措施
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