Background In meta-analyses of a binary outcome, double zero events in some studies cause a critical methodology problem. The generalized linear mixed model (GLMM) has been proposed as a valid statistical tool for pooling such data. Three parameter estimation methods, including the Laplace approximation (LA), penalized quasi-likelihood (PQL) and adaptive Gauss–Hermite quadrature (AGHQ) were frequently used in the GLMM. However, the performance of GLMM via these estimation methods is unclear in meta-analysis with zero events. Methods A simulation study was conducted to compare the performance. We fitted five random-effects GLMMs and estimated the results through the LA, PQL and AGHQ methods, respectively. Each scenario conducted 20,000 simulation iterations. The data from Cochrane Database of Systematic Reviews were collected to form the simulation settings. The estimation methods were compared in terms of the convergence rate, bias, mean square error, and coverage probability. Results Our results suggested that when the total events were insufficient in either of the arms, the GLMMs did not show good point estimation to pool studies of rare events. The AGHQ method did not show better properties than the LA estimation in terms of convergence rate, bias, coverage, and possibility to produce very large odds ratios. In addition, although the PQL had some advantages, it was not the preferred option due to its low convergence rate in some situations, and the suboptimal point and variance estimation compared to the LA. Conclusion The GLMM is an alternative for meta-analysis of rare events and is especially useful in the presence of zero-events studies, while at least 10 total events in both arms is recommended when employing GLMM for meta-analysis. The penalized quasi-likelihood and adaptive Gauss–Hermite quadrature are not superior to the Laplace approximation for rare events and thus they are not recommended.

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Background: Internal migration places individuals at high risk of contracting tuberculosis (TB). However, there is a scarcity of national-level spatial analyses regarding the association between TB and internal migration in China. In our research, we aimed to explore the spatial variation in cases of sputum smear-positive pulmonary TB (SS + PTB) in China; and the associations between SS + PTB, internal migration, socioeconomic factors, and demographic factors in the country between 2005 and 2015. Methods: Reported cases of SS + PTB were obtained from the national PTB surveillance system database; cases were obtained at the provincial level. Internal migration data were extracted from the national population sampling survey and the census. Spatial autocorrelations were explored using the global Moran's statistic and local indicators of spatial association. The spatial temporal analysis was performed using Kulldorff's scan statistic. Fixed effects regression was used to explore the association between SS + PTB and internal migration. Results: A total of 4 708 563 SS + PTB cases were reported in China between 2005 and 2015, of which 3 376 011 (71.7%) were male and 1 332 552 (28.3%) were female. There was a trend towards decreasing rates of SS + PTB notifications between 2005 and 2015. The result of global spatial autocorrelation indicated that there were significant spatial correlations between SS + PTB rate and internal migration each year (2005-2015). Spatial clustering of SS + PTB cases was mainly located in central and southern China and overlapped with the clusters of emigration. The proportions of emigrants and immigrants were significantly associated with SS + PTB. Per capita GDP and education level were negatively associated with SS + PTB. The internal migration flow maps indicated that migrants preferred neighboring provinces, with most migrating for work or business. Conclusions: This study found a significant spatial autocorrelation between SS + PTB and internal migration. Both emigration and immigration were statistically associated with SS + PTB, and the association with emigration was stronger than that for immigration. Further, we found that SS + PTB clusters overlapped with emigration clusters, and the internal migration flow maps suggested that migrants from SS + PTB clusters may influence the TB epidemic characteristics of neighboring provinces. These findings can help stakeholders to implement effective PTB control strategies for areas at high risk of PTB and those with high rates of internal migrants.

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Background We aimed to prospectively evaluate the associations between the baseline and changes in high-density C-reactive protein (hs-CRP) and incident metabolic syndrome (MetS) in China and update the evidence based on a meta-analysis of cohort studies in different populations. Methods Data from the China Health and Retirement Longitudinal Study among adults aged 45 years or older were analyzed. Participants who were recruited in the study in 2011–2012 without MetS and successfully followed up to 2015–2016 were included in our final analysis. Logistic regressions were applied to examine the prospective associations of baseline and changes in hs-CRP with incident MetS and estimate corresponding odds ratios (ORs) and 95% confidence intervals (95% CIs). A meta-analysis was conducted to synthesize effect estimates from our findings and other cohort studies on this topic. Results Among 4,116 participants, 535 developed MetS after a 4-year follow-up. Compared with the participants with hs-CRP in the lowest quartile, those with hs-CRP in the second, third, and highest quartiles had higher odds of MetS, with multivariable-adjusted ORs (95% CIs) of 1.51 (1.12, 2.06), 1.50 (1.11, 2.04), and 1.83 (1.37, 2.47). For the hs-CRP changes, ORs (95% CIs) were 3.24 (2.51, 4.02), 3.34 (2.56, 4.38), and 3.34 (2.54, 4.40) respectively. One unit (log of 1 mg/L) increase in hs-CRP was associated with 23% higher risk of MetS (OR 1.23; 95% CI 1.10, 1.38). In a meta-analysis of 6 cohort studies, the pooled relative risk for MetS was 1.63 (1.38, 1.93) for the highest versus lowest level of hs-CRP. In addition, the pooled relative risk for MetS was 1.29 (1.05, 1.59) for each unit increase of hs-CRP after log-transformation. Conclusions Both higher baseline hs-CRP and longitudinal hs-CRP increases were associated with higher risks of incident MetS. Individuals with high hs-CRP levels may need to be closely monitored for future risk of MetS.

Backgrounds Zero-events studies frequently occur in systematic reviews of adverse events, which consist of an important source of evidence. We aimed to examine how evidence of zero-events studies was utilized in the meta-analyses of systematic reviews of adverse events. Methods We conducted a survey of systematic reviews published in two periods: January 1, 2015, to January 1, 2020, and January 1, 2008, to April 25, 2011. Databases were searched for systematic reviews that conducted at least one meta-analysis of any healthcare intervention and used adverse events as the exclusive outcome. An adverse event was defined as any untoward medical occurrence in a patient or subject in healthcare practice. We summarized the frequency of occurrence of zero-events studies in eligible systematic reviews and how these studies were dealt with in the meta-analyses of these systematic reviews. Results We included 640 eligible systematic reviews. There were 406 (63.45%) systematic reviews involving zero-events studies in their meta-analyses, among which 389 (95.11%) involved single-arm-zero-events studies and 223 (54.93%) involved double-arm-zero-events studies. The majority (98.71%) of these systematic reviews incorporated single-arm-zero-events studies into the meta-analyses. On the other hand, the majority (76.23%) of them excluded double-arm-zero-events studies from the meta-analyses, of which the majority (87.06%) did not discuss the potential impact of excluding such studies. Systematic reviews published at present (2015-2020) tended to incorporate zero-events studies in meta-analyses than those published in the past (2008-2011), but the difference was not significant (proportion difference=−0.09, 95% CI −0.21 to 0.03, p = 0.12). Conclusion Systematic review authors routinely treated studies with zero-events in both arms as “non-informative” carriers and excluded them from their reviews. Whether studies with no events are “informative” or not largely depends on the methods and assumptions applied, thus sensitivity analyses using different methods should be considered in future meta-analyses.

Background Human migration facilitate the spread of tuberculosis (TB). Migrants face an increased risk of TB infection. In this study, we aim to explore the spatial inequity of sputum smear-positive pulmonary TB (SS + PTB) in China; and the spatial heterogeneity between SS + PTB and internal migration. Methods Notified SS + PTB cases in 31 provinces in mainland China were obtained from the national web-based PTB surveillance system database. Internal migrant data were extracted from the report on China’s migrant population development. Spatial autocorrelations were explored using the global Moran’s statistic and local indicators of spatial association. The spatial variation in temporal trends was performed using Kulldorff’s scan statistic. Fixed effect and spatial autoregressive models were used to explore the spatial inequity between SS + PTB and internal migration. Results A total of 2 380 233 SS + PTB cases were reported in China between 2011 and 2017, of which, 1 716 382 (72.11%) were male and 663 851 (27.89%) were female. Over 70% of internal migrants were from rural households and had lower income and less education. The spatial variation in temporal trend results showed that there was an 9.9% average annual decrease in the notification rate of SS + PTB from 2011 to 2017; and spatial clustering of SS + PTB cases was mainly located in western and southern China. The spatial autocorrelation results revealed spatial clustering of internal migration each year (2011–2017), and the clusters were stable within most provinces. Internal emigration, urban-to-rural migration and GDP per capita were significantly associated with SS + PTB, further, internal emigration could explain more variation in SS + PTB in the eastern region in mainland. However, internal immigration and rural-to-urban migration were not significantly associated with SS + PTB across China. Conclusions Our study found the spatial inequity between SS + PTB and internal migration. Internal emigration, urban-to-rural migration and GDP per capita were statistically associated with SS + PTB; the negative association was identified between internal emigration, urban-to-rural migration and SS + PTB. Further, we found those migrants with lower income and less education, and most of them were from rural households. These findings can help stakeholders to implement effective PTB control strategies for areas at high risk of PTB and those with high rates of internal migration.

We analyzed COVID-19 influences on the design, implementation, and validity of assessing the quality of primary health care using unannounced standardized patients (USPs) in China. Because of the pandemic, we crowdsourced our funding, removed tuberculosis from the USP case roster, adjusted common cold and asthma cases, used hybrid online–offline training for USPs, shared USPs across provinces, and strengthened ethical considerations. With those changes, we were able to conduct fieldwork despite frequent COVID-19 interruptions. Furthermore, the USP assessment tool maintained high validity in the quality checklist (criteria), USP role fidelity, checklist completion, and physician detection of USPs. Our experiences suggest that the pandemic created not only barriers but also opportunities to innovate ways to build a resilient data collection system. To build data system reliance, we recommend harnessing the power of technology for a hybrid model of remote and in-person work, learning from the sharing economy to pool strengths and optimize resources, and dedicating individual and group leadership to problem-solving and results. (Am J Public Health. 2022;112(6):913–922. https://doi.org/10.2105/AJPH.2022.306779 )