METHODS: In this single-arm, open-label, phase 3 trial, we recruited patients from 38 sites across China, Thailand, Vietnam, Singapore, and Malaysia, who were chronically infected with HCV genotypes 1-6, and were HCV treatment-naive or treatment-experienced, either without cirrhosis or with compensated cirrhosis. Patients self-administered a combined sofosbuvir (400 mg) and velpatasvir (100 mg) tablet once daily for 12 weeks. The primary efficacy endpoint was sustained virological response, defined as HCV RNA less than 15 IU/mL at 12 weeks after completion of treatment (SVR12), assessed in all patients who received at least one dose of study drug. The primary safety endpoint was the proportion of adverse events leading to premature discontinuation of study drug. This trial is registered with ClinicalTrials.gov, number NCT02671500, and is completed.
FINDINGS: Between April 14, 2016, and June 30, 2017, 375 patients were enrolled in the study, of whom 374 completed the full treatment course and one discontinued treatment. Overall, 362 (97% [95% CI 94-98]) of 375 patients achieved SVR12. Among 42 patients with HCV genotype 3b, all of whom had baseline resistance-associated substitutions in NS5A, 25 (89% [95% CI 72-98]) of 28 patients without cirrhosis and seven (50% [23-77]) of 14 patients with cirrhosis achieved SVR12. The most common adverse events were upper respiratory tract infection (36 [10%] patients) and headache (18 [5%] patients). There were no discontinuations due to adverse events. Serious adverse events were reported in three (1%) patients, none of which was judged to be related to sofosbuvir-velpatasvir treatment.
INTERPRETATION: Consistent with data from other phase 3 studies, single-tablet sofosbuvir-velpatasvir for 12 weeks is an efficacious and safe treatment for Asian patients with chronic HCV infection, but might have lower efficacy in those infected with HCV genotype 3b and with cirrhosis.
FUNDING: Gilead Sciences.
DESIGN: Cross-sectional, cross national.
SETTING: Multi-centre, primary care clinics Malaysia and Singapore.
PARTICIPANTS: 1123 adults with hypertension enrolled and analysed.
PRIMARY AND SECONDARY OUTCOME MEASURES: Comparison between sociodemography, disease characteristics and the mean scores of HTN-SCP domains (behaviour, motivation and self-efficacy) and the factors influencing hypertension self-care.
RESULTS: 1123 adults with hypertension attending primary care clinics in Malaysia and Singapore were involved. The participants' mean age was 63.6 years (SD 9.7) in Singapore and 60.4 (SD 9.1) in Malaysia. Most of the participants in Singapore had tertiary education (22.3%) compared with Malaysia (13.0%), p<0.001. A higher proportion of participants from Singapore had controlled blood pressure (74.6%) compared with Malaysia (33.8%), p<0.001. The mean total score of HTN-SCP was significantly higher among Singapore participants compared with Malaysia participants 190 (SD 28) versus 184 (SD 23) (p<0.001). Similarly, the mean score for motivation domain 67 (SD 10) versus 65 (SD 9), followed by self-efficacy score 65 (SD 11) versus 62 (SD 9) and behaviour score (58 SD 9 vs 56 SD 9) were higher among Singapore participants. In both countries, the factors which influenced higher HTN-SCP mean scores across all domains were being Indian and had tertiary education.
CONCLUSIONS: The study population in Singapore had a higher HTN-SCP mean score compared with Malaysia. The common factors influencing higher HTN-SCP mean scores at both study sites were ethnicity and level of education. Future intervention to improve self-care among people with hypertension may need to be tailored to their behaviour, motivation and self-efficacy levels.
MATERIALS AND METHODS: The EQ- 5D was cross-culturally adapted and translated using an iterative process following standard guidelines. Consenting adult Malay- and Tamil-speaking subjects at a primary care facility in Singapore were interviewed using a questionnaire (including the EQ-5D, a single item assessing global health, the SF-8 and sociodemographic questions) in their respective language versions. Known-groups and convergent construct validity of the EQ-5D was investigated by testing 30 a priori hypotheses per language at attribute and overall levels.
RESULTS: Complete data were obtained for 94 Malay and 78 Indian patients (median age, 54 years and 51 years, respectively). At the attribute level, all 16 hypotheses were fulfilled with several reaching statistical significance (Malay: 4; Tamil: 5). At the overall level, 42 of 44 hypotheses related to the EQ-5D/ EQ-VAS were fulfilled (Malay: 22; Tamil: 20), with 21 reaching statistical significance (Malay: 9; Tamil: 12).
CONCLUSION: In this study among primary care patients, the Singapore Malay and Tamil EQ-5D demonstrated satisfactory known-groups and convergent validity.
RESULTS: We developed a stand-alone software that implements the FineMAV statistic. To graphically visualise the FineMAV scores, it outputs the statistics as bigWig files, which is a common file format supported by many genome browsers. It is available as a command-line and graphical user interface. The software was tested by replicating the FineMAV scores obtained using 1000 Genomes Project African, European, East and South Asian populations and subsequently applied to whole-genome sequencing datasets from Singapore and China to highlight population specific variants that can be subsequently modelled. The software tool is publicly available at https://github.com/fadilla-wahyudi/finemav .
CONCLUSIONS: The software tool described here determines genome-wide FineMAV scores, using low or high-coverage whole-genome sequencing datasets, that can be used to prioritize a list of population specific, highly differentiated candidate variants for in vitro or in vivo functional screens. The tool displays these scores on the human genome browsers for easy visualisation, annotation and comparison between different genomic regions in worldwide human populations.