Periodontology, Faculty of Dentistry, The University of Hong Kong, 3F, The Prince Philip Dental Hospital, 34 Hospital Road, Sai Yin Pun, Hong Kong.
Dr D Y Patil Dental College and Hospital, Pimpri, Pune, India.
BMC Oral Health. 2019 Apr 27;19(1):65. doi: 10.1186/s12903-019-0754-0.
Past meta-analyses have shown adjunctive systemic Azithromycin (AZI) to provide minor clinical benefits in scaling and root surface debridement (S/RSD). However, these have not considered the covariance of key outcome parameters; probing pocket depth (PPD) and Clinical Attachment Level (CAL) or systematically examined some potential sources of heterogeneity.
To jointly synthesize 6-month outcomes of systemic AZI as adjunctive to S/RSD in chronic periodontitis and investigate 3 potential sources of heterogeneity.
Four databases were searched for suitable randomized controlled clinical trials (RCTs). Standardized mean differences (SMD) in PPD and CAL between AZI + S/RSD and S/RSD alone, at 6-month follow-up were computed. Within-study covariances of PPD and CAL were derived from reported multiple time-point data. A multivariate meta-analysis with random effects jointly modelled PPD and CAL, factoring in their covariance. This model included 3 moderators with interaction effects; timing of AZI initiation (pre-therapy/post-therapy), type of S/RSD [full-mouth debridement (FMD)/partial-mouth debridement (PMD)], and baseline study-level mean values of PPD/CAL.
Among 276 abstracts, 11 observations from 9 RCTs qualified for meta-analysis. Within-study correlation-coefficients of PPD with CAL significantly increased with increasing study-level baseline mean values (Spearman's r = 0.79, p < 0.01). The full multivariate meta-analysis model showed significant effects for the 3 moderators (Q statistic = 150.03, p < 0.01), retained significant residual heterogeneity (Q statistic = 88.50, p < 0.01) but outperformed (Likelihood- ratio statistic = 102.95, p < 0.01,) a null-model with no moderators (Q statistic = 201.5, p < 0.01). A significant effect was seen only on the SMD for PPD (estimate = 1.16 mm, 95% CI: 0.27 mm-2.07 mm mm, p = 0.01) but not CAL (estimate = 0.17 mm, 95% CI: -0.92 mm-1.26 mm, p = 0.76). SMD in PPD positively interacted with study baseline value (estimate = 0.11, 95% CI: 0.08-0.15, p < 0.01). Significant negative interactions of SMD in PPD with PMD (estimate = - 1.25 mm, 95% CI: -1.73 mm- -0.78 mm, p < 0.01) and pre-therapy drug initiation (estimate = - 1.18 mm, 95% CI: -1.48 mm--0.87 mm, p < 0.01) were evident.
Joint synthesis of PPD and CAL showed, at 6-months, AZI + S/RSD provided a benefit over S/RSD alone for PPD alone when correlation with CAL was accounted for. Deeper study-level baseline PPD, FMD type of S/RSD, and post-therapy drug initiation associated with greater PPD reduction.
过去的荟萃分析表明，辅助使用全身性阿奇霉素（AZI）在刮治和根面清创术（S/RSD）中可提供轻微的临床益处。然而，这些分析并未考虑关键结局参数的协方差；探测袋深度（PPD）和临床附着水平（CAL），或系统地检查一些潜在的异质性来源。
联合综合评估慢性牙周炎中全身性 AZI 辅助 S/RSD 的 6 个月结局，并调查 3 个潜在的异质性来源。
在四个数据库中搜索合适的随机对照临床试验（RCT）。计算 6 个月随访时 AZI+S/RSD 与 S/RSD 单独治疗时 PPD 和 CAL 的标准化均数差值（SMD）。从报告的多个时间点数据中得出 PPD 和 CAL 的内研究协方差。使用具有随机效应的多变量荟萃分析联合建模 PPD 和 CAL，同时考虑它们的协方差。该模型包括 3 个具有交互作用的调节因素；AZI 起始时间（治疗前/治疗后）、S/RSD 类型[全口清创术（FMD）/部分口清创术（PMD）]和研究水平基线 PPD/CAL 的平均数值。
在 276 篇摘要中，9 项 RCT 的 11 个观察结果符合荟萃分析的要求。PPD 与 CAL 的内研究相关系数随着研究水平基线均值的增加而显著增加（Spearman 相关系数 r=0.79，p<0.01）。全多元荟萃分析模型显示 3 个调节因素有显著效果（Q 统计量=150.03，p<0.01），保留了显著的剩余异质性（Q 统计量=88.50，p<0.01），但优于没有调节因素的零模型（似然比统计量=102.95，p<0.01）（Q 统计量=201.5，p<0.01）。仅对 PPD 的 SMD 有显著影响（估计值=1.16mm，95%CI：0.27mm-2.07mm，p=0.01），但对 CAL 的 SMD 没有影响（估计值=0.17mm，95%CI：-0.92mm-1.26mm，p=0.76）。PPD 的 SMD 与研究基线值呈正交互作用（估计值=0.11，95%CI：0.08-0.15，p<0.01）。PPD 的 SMD 与 PMD（估计值=-1.25mm，95%CI：-1.73mm- -0.78mm，p<0.01）和治疗前药物起始（估计值=-1.18mm，95%CI：-1.48mm- -0.87mm，p<0.01）的显著负交互作用也很明显。
联合综合分析 PPD 和 CAL 显示，在 6 个月时，当考虑到与 CAL 的相关性时，AZI+S/RSD 对 PPD 提供了优于 S/RSD 单独治疗的益处。更深的研究水平基线 PPD、FMD 类型的 S/RSD 和治疗后药物起始与 PPD 减少量更大有关。
