Analysis of Plasma Epstein-Barr Virus DNA to Screen for Nasopharyngeal Cancer.

BACKGROUND: Circulating cell-free Epstein-Barr virus (EBV) DNA is a biomarker for nasopharyngeal carcinoma. We conducted a prospective study to investigate whether EBV DNA in plasma samples would be useful to screen for early nasopharyngeal carcinoma in asymptomatic persons. METHODS: We analyzed EBV DNA in plasma specimens to screen participants who did not have symptoms of nasopharyngeal carcinoma. Participants with initially positive results were retested approximately 4 weeks later, and those with persistently positive EBV DNA in plasma underwent nasal endoscopic examination and magnetic resonance imaging (MRI). RESULTS: A total of 20,174 participants underwent screening. EBV DNA was detectable in plasma samples obtained from 1112 participants (5.5%), and 309 (1.5% of all participants and 27.8% of those who initially tested positive) had persistently positive results on the repeated sample. Among these 309 participants, 300 underwent endoscopic examination, and 275 underwent both endoscopic examination and MRI; of these participants, 34 had nasopharyngeal carcinoma. A significantly higher proportion of participants with nasopharyngeal carcinoma that was identified by screening had stage I or II disease than in a historical cohort (71% vs. 20%, P<0.001 by the chi-square test) and had superior 3-year progression-free survival (97% vs. 70%; hazard ratio, 0.10; 95% confidence interval, 0.05 to 0.18). Nine participants declined to undergo further testing, and 1 of them presented with advanced nasopharyngeal carcinoma 32 months after enrollment. Nasopharyngeal carcinoma developed in only 1 participant with negative EBV DNA in plasma samples within 1 year after testing. The sensitivity and specificity of EBV DNA in plasma samples in screening for nasopharyngeal carcinoma were 97.1% and 98.6%, respectively. CONCLUSIONS: Analysis of EBV DNA in plasma samples was useful in screening for early asymptomatic nasopharyngeal carcinoma. Nasopharyngeal carcinoma was detected significantly earlier and outcomes were better in participants who were identified by screening than in those in a historical cohort. (Funded by the Kadoorie Charitable Foundation and the Research Grants Council of the Hong Kong government; ClinicalTrials.gov number, NCT02063399 .).

Development and validation of the Chinese osteoporosis screening algorithm (COSA) in identification of people with high risk of osteoporosis.

Objectives: To enhance the public awareness and facilitate diagnosis of osteoporosis, we aim to develop a new Chinese Osteoporosis Screening Algorithm (COSA) to identify people at high risk of osteoporosis. Methods: A total of 4747 postmenopausal women and men aged ≥ 50 from the Hong Kong Osteoporosis Study were randomly split into a development (N = 2373) and an internal validation cohort (N = 2374). An external validation cohort comprising 1876 community-dwelling subjects was used to evaluate the positive predictive value (PPV). Results: Among 11 predictors included, age, sex, weight, and history of fracture were significantly associated with osteoporosis after correction for multiple testing. Age- and sex-stratified models were developed due to the presence of significant sex and age interactions. The area under the curve of the COSA in the internal validation cohort was 0.761 (95% CI, 0.711-0.811), 0.822 (95% CI, 0.792-0.851), and 0.946 (95% CI, 0.908-0.984) for women aged < 65, women aged ≥ 65, and men, respectively. The COSA demonstrated improved reclassification performance when compared to Osteoporosis Self-Assessment Tool for Asians. In the external validation cohort, the PPV of COSA was 40.6%, 59.4%, and 19.4% for women aged < 65, women aged ≥ 65, and men, respectively. In addition, COSA > 0 was associated with an increased 10-year risk of hip fracture in women ≥ 65 (OR, 4.65; 95% CI, 2.24-9.65) and men (OR, 11.51; 95% CI, 4.16-31.81). Conclusions: We have developed and validated a new osteoporosis screening algorithm, COSA, specific for Hong Kong Chinese.

Illicit drug use is associated with lower bone mineral density and bone strength.

Objectives: To evaluate the association of illicit drug use with bone mineral density (BMD) and hip geometric parameters at the narrow neck. Methods: This is a cross-sectional matched cohort study conducted in the Hong Kong Chinese population. Associations with illicit drug use were estimated using linear regression for BMD (lumbar spine and femoral neck) and hip geometrical parameters (cross-sectional area [CSA], cross-sectional moment of inertia [CSMI], section modulus [SM], average cortical thickness [ACT] and BMD at the narrow neck) after adjusting for age, body mass index (BMI), smoking status, drinking status, physical activity, and history of antipsychotic and antidepressant use. Mean difference and 95% confidence intervals (95% CI) were calculated between 108 illicit drug users and 108 controls using an adjusted linear model and cluster-robust standard errors after matching by age and sex. The false discovery rate was used to correct for multiple testing. Results: Illicit drug users had a significantly lower BMD (g/cm2) at the lumbar spine (mean difference: -0.062; 95% CI: -0.108 to -0.015), and femoral neck (mean difference: -0.058; 95% CI: -0.106 to -0.010) in the fully adjusted model. Illicit drug users also had a significantly lower CSA (mean difference: -0.238 cm2; 95% CI: -0.462 to -0.013), ACT (mean difference: -0.018 cm; 95% CI: -0.030 to -0.006) and BMD (mean difference: -0.070 g/cm2; 95% CI: -0.128 to -0.012) at the narrow neck. Conclusions: Illicit drug use is associated with lower BMD and bone strength. Future studies evaluating the risk of illicit drug use with fragility fracture are warranted.