Marker-dependent observation and carry-forward of internal covariates in Cox regression.

Studies of chronic disease often involve modeling the relationship between marker processes and disease onset or progression. The Cox regression model is perhaps the most common and convenient approach to analysis in this setting. In most cohort studies, however, biospecimens and biomarker values are only measured intermittently (e.g. at clinic visits) so Cox models often treat biomarker values as fixed at their most recently observed values, until they are updated at the next visit. We consider the implications of this convention on the limiting values of regression coefficient estimators when the marker values themselves impact the intensity for clinic visits. A joint multistate model is described for the marker-failure-visit process which can be fitted to mitigate this bias and an expectation-maximization algorithm is developed. An application to data from a registry of patients with psoriatic arthritis is given for illustration.

The efficacy of inhaled hypertonic saline for bronchiectasis: a meta-analysis of randomized controlled studies.

INTRODUCTION: The efficacy of inhaled hypertonic saline for bronchiectasis remains controversial. We conduct a systematic review and meta-analysis to explore the influence of inhaled hypertonic saline versus 0.9% isotonic saline for the treatment of bronchiectasis. METHODS: We have searched PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through April 2020 for randomized controlled trials (RCTs) assessing the efficacy of inhaled hypertonic saline versus 0.9% isotonic saline for the treatment of bronchiectasis. This meta-analysis was performed using the random-effect model. RESULTS: Four RCTs were included in the meta-analysis. Overall, compared with control group for bronchiectasis, inhaled hypertonic saline had no obvious influence on forced expiratory volume in 1 s (FEV1, SMD = 0.12; 95% CI = -0.06 to 0.30; P = .18), forced vital capacity (FVC, SMD = 0.10; 95% CI = -0.09 to 0.28; P = .30), sputum expectorated (SMD = -0.03; 95% CI = -2.73 to 2.68; P = .99) or Leicester Cough Questionnaire (LCQ) score (SMD = -0.15; 95% CI = -0.89 to 0.58; P = .68). CONCLUSIONS: Inhaled hypertonic saline and 0.9% isotonic saline show similar efficacy for bronchiectasis.

[The effect of aluminum adjuvant and immunization schedule on immunogenicity of Sabin inactivated poliovirus vaccine].

OBJECTIVE: To study the effect of aluminume adjuvant and immunization schedule on immunogenicity of Sabin inactivated poliovirus vaccine. METHODS: Four batches of Sabin IPV were produced by different concentrations of type 1, 2, and 3 poliovirus and administrated on three-dose schedule at 0, 1, 2 months and 0, 2, 4 months on rats. Serum samples were collected one month after each dose and neutralizing antibody titers against three types poliovirus were determined by micro-neutralization assay. RESULTS: The GMTs of neutralizing antibodies against three types poliovirus increased significantly and the seropositivity rates were 100% in all groups after 3 doses. There was no significant difference between two immunization schedules, and the 0, 2, 4 month schedule could induce higher level neutralizing antibody compared to the 0, 1, 2 month schedule. The groups with aluminum adjuvant could induce higher level neutralizing antibody compared to the groups without adjuvant. CONCLUSION: Aluminum djuvant and immunization schedule could improve the immunogenicity of Sabin IPV.

[Immunogenicity of sabin inactivated poliovirus vaccine induced by diphtheria-tetanus-acellular pertussis and Sabin inactivated poliovirus combined vaccine].

OBJECTIVE: In order to search the preparation process and optimazing dosage ratio of adsorbed diphtheria-tetanus-acellular pertussis and sabin inactivated poliovirus combined vaccine (DTaP-sIPV), the neutralizing antibody titers of IPV induced by different concentration of DTaP-sIPV were investigated on rats. METHODS: Two batches of DTaP-sLPV were produced using different concentration of sIPV and the quality control was carried. Together with sabin-IPV and DTaP-wIPV ( boostrix-polio, GSK, Belgium) as control group, the DTaP-sIPV were administrated on three-dose schedule at 0, 1, 2 month on rats. Serum sample were collected 30 days after each dose and neutralizing antibody titers against three types poliovirus were determined using micro-neutralization test. RESULTS: Two batches of prepared DTaP-sIPV and control sLPV were according to the requirement of Chinese Pharmacopoeia (Volume III, 2005 edition) and showed good stability. The seropositivity rates were 100% for sabin inactivated poliovirus antigen in all groups. The GMTs (Geometric mean titers) of neutralizing antibodies against three types poliovirus increased. CONCLUSION: The prepared DTaP-sIPV was safe, stable and effective and could induced high level neutralizing antibody against poliovirus on rats.