METHODS: This observational study was conducted between December 2018 and October 2019 at 25 PHCs in three regions in Malaysia. Each PHC was linked to one or more hospitals, for referral of seropositive participants for confirmatory testing and pretreatment evaluation. Treatment was provided in PHCs for non-cirrhotic patients and at hospitals for cirrhotic patients.

RESULTS: During the study period, a total of 15 366 adults were screened at the 25 PHCs, using RDTs for HCV antibodies. Of the 2020 (13.2%) HCV antibody-positive participants, 1481/2020 (73.3%) had a confirmatory viral load test, 1241/1481 (83.8%) were HCV RNA-positive, 991/1241 (79.9%) completed pretreatment assessment, 632/991 (63.8%) initiated treatment, 518/632 (82.0%) completed treatment, 352/518 (68.0%) were eligible for a sustained virological response (SVR) cure assessment, 209/352 (59.4%) had an SVR cure assessment, and SVR was achieved in 202/209 (96.7%) patients. A significantly higher proportion of patients referred to PHCs initiated treatment compared with those who had treatment initiated at hospitals (71.0% vs 48.8%, p<0.001).

METHODS: STORM-C-1 is a two-stage, open-label, phase 2/3 single-arm clinical trial in six public academic and non-academic centres in Malaysia and four public academic and non-academic centres in Thailand. Patients with HCV with compensated cirrhosis (Metavir F4 and Child-Turcotte-Pugh class A) or without cirrhosis (Metavir F0-3) aged 18-69 years were eligible to participate, regardless of HCV genotype, HIV infection status, previous interferon-based HCV treatment, or source of HCV infection. Once daily ravidasvir (200 mg) and sofosbuvir (400 mg) were prescribed for 12 weeks for patients without cirrhosis and for 24 weeks for those with cirrhosis. The primary endpoint was sustained virological response at 12 weeks after treatment (SVR12; defined as HCV RNA <12 IU/mL in Thailand and HCV RNA <15 IU/mL in Malaysia at 12 weeks after the end of treatment). This trial is registered with ClinicalTrials.gov, number NCT02961426, and the National Medical Research Register of Malaysia, NMRR-16-747-29183.

FINDINGS: Between Sept 14, 2016, and June 5, 2017, 301 patients were enrolled in stage one of STORM-C-1. 98 (33%) patients had genotype 1a infection, 27 (9%) had genotype 1b infection, two (1%) had genotype 2 infection, 158 (52%) had genotype 3 infection, and 16 (5%) had genotype 6 infection. 81 (27%) patients had compensated cirrhosis, 90 (30%) had HIV co-infection, and 99 (33%) had received previous interferon-based treatment. The most common treatment-emergent adverse events were pyrexia (35 [12%]), cough (26 [9%]), upper respiratory tract infection (23 [8%]), and headache (20 [7%]). There were no deaths or treatment discontinuations due to serious adverse events related to study drugs. Of the 300 patients included in the full analysis set, 291 (97%; 95% CI 94-99) had SVR12. Of note, SVR12 was reported in 78 (96%) of 81 patients with cirrhosis and 153 (97%) of 158 patients with genotype 3 infection, including 51 (96%) of 53 patients with cirrhosis. There was no difference in SVR12 rates by HIV co-infection or previous interferon treatment.

INTERPRETATION: In this first stage, ravidasvir plus sofosbuvir was effective and well tolerated in this diverse adult population of patients with chronic HCV infection. Ravidasvir plus sofosbuvir has the potential to provide an additional affordable, simple, and efficacious public health tool for large-scale implementation to eliminate HCV as a cause of morbidity and mortality.

METHOD: This study was conducted using an exploratory qualitative approach on purposely selected healthcare providers at primary healthcare clinics. Twenty focus group discussions and three in-depth interviews were conducted using a semi-structured interview guide. Consent was obtained prior to interviews and for audio-recordings. Interviews were transcribed verbatim and thematically analysed, guided by the Consolidated Framework for Implementation Research (CFIR), a framework comprised of five major domains promoting implementation theory development and verification across multiple contexts.

RESULTS: The study revealed via CFIR that most primary healthcare providers were receptive towards any proposed changes or intervention for the betterment of NCD care management. However, many challenges were outlined across four CFIR domains-intervention characteristics, outer setting, inner setting, and individual characteristics-that included perceived barriers to implementation. Perception of issues that triggered proposed changes reflected the current situation, including existing facilitating aspects that can support the implementation of any future intervention. The importance of strengthening the primary healthcare delivery system was also expressed.

METHODS: Research impact of universal access and quality healthcare projects funded by the National Institutes of Health Malaysia were assessed based on the modified Payback Framework, addressing categories of informing policy, knowledge production, and benefits to health and health sector. For the HRPS process, the Child Health and Nutrition Research Initiative methodology was adapted and adopted, with the incorporation of stakeholder values using weights and monetary allocation survey. Workshop discussions and interviews with stakeholders and research groups were conducted to identify research gaps, with the use of conceptual frameworks to guide the search.

RESULTS: Seventeen ongoing and 50 completed projects were identified for research funding impact analysis. Overall, research fund allocation differed from stakeholders' expectation. For research impact, 48 out of 50 completed projects (96.0%) contributed to some form of policy-making efforts. Almost all completed projects resulted in outputs that contributed to knowledge production and were expected to lead to health and health sector benefits. The HRPS process led to the identification of research priority areas that stemmed from ongoing and new issues identified for universal access and quality healthcare.

METHODS: Free vaccination was offered to school girls in secondary school (year seven) in Malaysia, which is usually at the age of 13 in the index year. All recipients of the HPV vaccine were identified through school enrolments obtained from education departments from each district in Malaysia. A total of 242,638 girls aged between 12 to 13 years studying in year seven were approached during the launch of the program in 2010. Approximately 230,000 girls in secondary schools were offered HPV vaccine per year by 646 school health teams throughout the country from 2010 to 2016.

RESULTS: Parental consent for their daughters to receive HPV vaccination at school was very high at 96-98% per year of the programme. Of those who provided consent, over 99% received the first dose each year and 98-99% completed the course per year. Estimated population coverage for the full vaccine course, considering also those not in school, is estimated at 83 to 91% per year. Rates of adverse events reports following HPV vaccination were low at around 2 per 100,000 and the majority was injection site reactions.

METHODS: We performed a case-control association study by genotyping the HLA-B alleles of 55 patients with AIS [11 toxic epidermal necrolysis (TEN), 21 Steven Johnson syndrome (SJS) 22 drug reaction wit eosinophilia and systemic symptoms (DRESS) and one acute generalized exanthematous pustulosis (AGEP)] and 42 allopurinol-tolerant controls (ATC).

RESULTS: HLA-B*58:01 was positive in 89.1 and 14.3% of the AIS and ATC study groups [odds ratio (OR) = 49.0, 95% confidence interval (CI) = 14.6-164.4, P < 0.0001)], respectively. Our data showed that 93.8% of the AIS-SJS/TEN patients and 86.4% of the AIS-DRESS patients were HLA-B*58:01 positive (AIS-SJS/TEN, OR = 90, 95% CI = 16.9-470.1, P < 0.0001 and AIS-DRESS OR = 38, 95% CI = 8.5-169.2, P < 0.0001). Stratification by ethnicity and clinical phenotypes revealed a significant increased risk between HLA-B*58:01 and Chinese-AIS patients (OR = 137.5, 95% CI = 11.3-1680.2, P < 0.0001), in particular Chinese patients with AIS-SJS/TEN phenotype (100% HLA-B*58:01 positive). HLA-B*58:01 was positive in 90.9% Chinese AIS-DRESS (P < 0.0001). Highly significant associations of HLA-B*58:01 were observed in Malay AIS-SJS/TEN (OR = 78, 95% CI = 9.8-619.9, P < 0.0001) and Malay AIS-DRESS (OR = 54, 95% CI = 6.6-442.9, P < 0.0001). Although the number of Indian-AIS patients was relatively small (n = 2), both were HLA-B*58:01 positive.

METHODS: A multiplex analytic microarray system was used to analyze the occurrence of antibodies to 10 different citrullinated peptides (filaggrin [fil307-324], vimentin [Vim2-17, Vim60-75], fibrinogen [Fibα563-583, Fibα580-600, Fibβ36-52, Fibβ62-81a, Fibβ62-81b], enolase [Eno5-21], and type II collagen [CitCII355-378]) in serum samples from 4,089 RA patients (1,231 Malaysian and 2,858 Swedish) and 827 healthy control subjects (249 Malaysian and 578 Swedish). The positive reaction threshold for each peptide was set separately for each population based on a specificity of 98%.

RESULTS: Distinct differences in the frequencies of 5 ACPA fine specificities (Vim60-75, Vim2-17, Fibβ62-81b, Eno5-21, and CitCII355-378) were found between the Malaysian and Swedish RA populations, despite a nearly identical percentage of patients in each population who were positive for anti-cyclic citrullinated peptide 2 antibodies. In Malaysian RA patients compared with Swedish RA patients, the frequencies of antibodies to Vim60-75 (54% versus 44%, corrected P [Pcorr ] = 1.06 × 10-8 ) and CitCII355-378 (17% versus 13%, Pcorr  = 0.02) were significantly higher, while the frequencies of antibodies to Vim2-17 (25% versus 32%, Pcorr  = 1.91 × 10-4 ), Fibβ62-81b (15% versus 30%, Pcorr  = 2.47 × 10-22 ), and Eno5-21 (23% versus 50%, Pcorr  = 3.64 × 10-57 ) were significantly lower.