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Multiple imputation with delta adjustment provides a flexible and transparent means to impute univariate missing data under general missing-not-at-random mechanisms. This facilitates the conduct of analyses assessing sensitivity to the missing-at-random (MAR) assumption. We review the delta-adjustment procedure and demonstrate how it can be used to assess sensitivity to departures from MAR, both when estimating the prevalence of a partially observed outcome and when performing parametric causal mediation analyses with a partially observed mediator. We illustrate the approach using data from 34,446 respondents to a tuberculosis and human immunodeficiency virus (HIV) prevalence survey that was conducted as part of the Zambia-South Africa TB and AIDS Reduction Study (2006-2010). In this study, information on partially observed HIV serological values was supplemented by additional information on self-reported HIV status. We present results from 2 types of sensitivity analysis: The first assumed that the degree of departure from MAR was the same for all individuals with missing HIV serological values; the second assumed that the degree of departure from MAR varied according to an individual’s self-reported HIV status. Our analyses demonstrate that multiple imputation offers a principled approach by which to incorporate auxiliary information on self-reported HIV status into analyses based on partially observed HIV serological values.
causal mediation analysis, incomplete data, nonignorable nonresponse, sensitivity analysis
Analyses of Sensitivity to the Missing-at-Random Assumption Using Multiple Imputation With Delta Adjustment: Application to a Tuberculosis/HIV Prevalence Survey With Incomplete HIV-Status Data
Finbarr P Leacy,1,2 Sian Floyd,3 Tom A Yates,4 and Ian R White2
Little is known about genetic basis and proteomics in valvular heart disease (VHD) including rheumatic (RVD) and degenerative (DVD) valvular disease. The present proteomic study examined the hypothesis that certain proteins may be associated with the pathological changes in the plasma of VHD patients.
Methods and Results
Differential protein analysis in the plasma identified 18 differentially expressed protein spots and 14 corresponding proteins or polypeptides by two-dimensional electrophoresis and mass spectrometry in 120 subjects. Two up-regulated (complement C4A and carbonic anhydrase 1) and three down-regulated proteins (serotransferrin, alpha-1-antichymotrypsin, and vitronectin) were validated by ELISA in enlarging samples. The plasma levels (n = 40 for each) of complement C4A in RVD (715.8±35.6 vs. 594.7±28.2 ng/ml, P = 0.009) and carbonic anhydrase 1 (237.70±15.7 vs. 184.7±10.8 U/L, P = 0.007) in DVD patients were significantly higher and that of serotransferrin (2.36±0.20 vs. 2.93±0.16 mg/ml, P = 0.025) and alpha-1-antichymotrypsin (370.0±13.7 vs. 413.0±11.6 µg/ml, P = 0.019) in RVD patients were significantly lower than those in controls. The plasma vitronectin level in both RVD (281.3±11.0 vs. 323.2±10.0 µg/ml, P = 0.006) and DVD (283.6±11.4 vs. 323.2±10.0 µg/ml, P = 0.011) was significantly lower than those in normal controls.
We have for the first time identified alterations of 14 differential proteins or polypeptides in the plasma of patients with various VHD. The elevation of plasma complement C4A in RVD and carbonic anhydrase 1 in DVD and the decrease of serotransferrin and alpha-1-antichymotrypsin in RVD patients may be useful biomarkers for these valvular diseases. The decreased plasma level of vitronectin – a protein related to the formation of valvular structure – in both RVD and DVD patients might indicate the possible genetic deficiency in these patients.
Identification of Altered Plasma Proteins by Proteomic Study in Valvular Heart Diseases and the Potential Clinical Significance
Ge Gao, 1 Chao Xuan, 2 Qin Yang, 1 , 3 Xiao-Cheng Liu, 2 Zhi-Gang Liu, 2 and Guo-Wei He 1 , 4 , * Yu Huang, Editor
Antenatal corticosteroids are commonly used to reduce neonatal mortality, but most research to date has been in high-resource settings and few studies have evaluated its impact on stillbirth. In the Antenatal Corticosteroids Trial (ACT), a multi-country trial to assess impact of a multi-faceted intervention including antenatal corticosteroids to reduce neonatal mortality associated with preterm birth, we found an overall increase in 28-day neonatal mortality and stillbirth associated with the intervention.
The ACT was a cluster-randomized trial conducted in 102 clusters across 7 research sites in 6 countries (India [2 sites], Pakistan, Zambia, Kenya, Guatemala and Argentina), comparing an intervention to train birth attendants at all levels of the health system to identify women at risk of preterm birth, administer corticosteroids and refer women at risk. Because of inadequate gestational age dating, the <5th percentile birth weight was used as a proxy for preterm birth. A pre-specified secondary outcome of the trial was stillbirth. Results After adjusting for the pre-trial imbalance in stillbirth rates, the ACT intervention was associated with a non-significant increased risk of stillbirth (aRR 1.08, 95 % CI, 0.99-1.17, p-0.073). Additionally, the stillbirth rate was higher in the term births (1.20 95 % CI 1.06-1.37, 0.004) and among those with signs of maceration (RR 1.18 (1.04-1.35), p = 0.013) in the intervention vs. control clusters. Differences in obstetric care favored the control clusters and maternal infection was likely more common in the intervention clusters. Conclusions In this pragmatic trial, limited data were available to identify the causes of the increase in stillbirths in the intervention clusters. A higher rate of stillbirth in the intervention clusters prior to the trial, differences in obstetric care and an increase in maternal infection are potential explanations for the observed increase in stillbirths in the intervention clusters during the trial. Trial registration clinicaltrials.gov (NCT01084096)
The global network antenatal corticosteroids trial: impact on stillbirth
Robert L. Goldenberg,corresponding author Vanessa R. Thorsten, Fernando Althabe, Sarah Saleem, Ana Garces, Waldemar A. Carlo, Omrana Pasha, Elwyn Chomba, Shivaprasad Goudar, Fabian Esamai, Nancy F. Krebs, Richard J. Derman, Edward A. Liechty, Archana Patel, Patricia L. Hibberd, Pierre M. Buekens, Marion Koso-Thomas, Menachem Miodovnik, Alan H. Jobe, Dennis D. Wallace, Jose M. Belizan, and Elizabeth M. McClure