International journal of epidemiology最新文献

Background: Epithelial ovarian cancer (EOC) is the eighth most common cancer in women, with poor survival outcomes. Observational evidence suggests that nitrogen-based bisphosphonate (NBB) use may be associated with reduced risk of EOC, particularly the endometrioid and serous histotypes; however, confounding by indication is a concern. An alternative approach to investigate the chemo-preventive potential of NBBs is to emulate a target trial by identifying all women who initiate use of NBBs and investigate the risk of EOC for continued users compared with discontinued users.

Methods: Using population-based linked data, we identified all Australian women aged over 50 years who first used NBBs over 2004-12. We used the year after first use to define treatment for each woman as either continued or discontinued use. We emulated randomization using stabilized inverse probability weights to balance the treatment groups using covariates including age, comorbidities and socioeconomic status. We followed women from treatment assignment until EOC diagnosis, death or 31 December 2013. We assessed the risk of EOC (overall and by histotype) using flexible parametric time-to-event models allowing for time-varying effects, and produced time-varying coefficients.

Results: Of the 313 383 women in the study, 472 were diagnosed with EOC during follow-up (261 serous EOC), with an average age at diagnosis of 72 years. Continued use of NBBs was associated with reduced risk of EOC overall (HR = 0.87, 95% CI: 0.69, 1.10), and serous EOC (HR = 0.71, 95% CI: 0.53, 0.96), compared with discontinued treatment, with estimates remaining constant over the 9-year follow-up.

Conclusions: Results from our emulated trial suggest that in women who initiated NBB treatment, those who continued use had 13% and 29% lower hazards of being diagnosed with EOC overall and serous EOC, respectively, compared with women who discontinued use.

Background: Perceived discrimination in health care settings can have adverse consequences on mental health in minority groups. However, the association between perceived discrimination and mental health is prone to unmeasured confounding. The study aims to quantitatively evaluate the influence of unmeasured confounding in this association, using g-estimation.

Methods: In a predominantly African American cohort, we applied g-estimation to estimate the association between perceived discrimination and mental health, adjusted and unadjusted for measured confounders. Mental health was measured using clinical diagnoses of anxiety, depression and bipolar disorder. Perceived discrimination was measured as the number of patient-reported discrimination events in health care settings. Measured confounders included demographic, socioeconomic, residential and health characteristics. The influence of confounding was denoted as α1 from g-estimation. We compared α1 for measured and unmeasured confounding.

Results: Strong associations between perceived discrimination in health care settings and mental health outcomes were observed. For anxiety, the odds ratio (95% confidence interval) unadjusted and adjusted for measured confounders were 1.30 (1.21, 1.39) and 1.26 (1.17, 1.36), respectively. The α1 for measured confounding was -0.066. Unmeasured confounding with α1=0.200, which was over three times that of measured confounding, corresponds to an odds ratio of 1.12 (1.01, 1.24). Similar results were observed for other mental health outcomes.

Conclusion: Compared with measured confounding, unmeasured that was three times measured confounding was not enough to explain away the association between perceived discrimination and mental health, suggesting that this association is robust to unmeasured confounding. This study provides a novel framework to quantitatively evaluate unmeasured confounding.

Background: Epstein-Barr virus (EBV) is a major cause of nasopharyngeal carcinoma (NPC) and measurement of different EBV antibodies in blood may improve early detection of NPC. Prospective studies can help assess the roles of different EBV antibodies in predicting NPC risk over time.

Methods: A case-cohort study within the prospective China Kadoorie Biobank of 512 715 adults from 10 (including two NPC endemic) areas included 295 incident NPC cases and 745 subcohort participants. A multiplex serology assay was used to quantify IgA and IgG antibodies against 16 EBV antigens in stored baseline plasma samples. Cox regression was used to estimate adjusted hazard ratios (HRs) for NPC and C-statistics to assess the discriminatory ability of EBV-markers, including two previously identified EBV-marker combinations, for predicting NPC.

Results: Sero-positivity for 15 out of 16 EBV-markers was significantly associated with higher NPC risk. Both IgA and IgG antibodies against the same three EBV-markers showed the most extreme HRs, i.e. BGLF2 (IgA: 124.2 (95% CI: 63.3-243.9); IgG: 8.6 (5.5-13.5); LF2: [67.8 (30.0-153.1), 10.9 (7.2-16.4)]); and BFRF1: 26.1 (10.1-67.5), 6.1 (2.7-13.6). Use of a two-marker (i.e. LF2/BGLF2 IgG) and a four-marker (i.e. LF2/BGLF2 IgG and LF2/EA-D IgA) combinations yielded C-statistics of 0.85 and 0.84, respectively, which persisted for at least 5 years after sample collection in both endemic and non-endemic areas.

Conclusions: In Chinese adults, plasma EBV markers strongly predict NPC occurrence many years before clinical diagnosis. LF2 and BGLF2 IgG could identify NPC high-risk individuals to improve NPC early detection in community and clinical settings.