METHODS: EMPOWER-Lung 1 was a multicentre, open-label, randomised, phase 3 trial. We enrolled patients (aged ≥18 years) with histologically confirmed squamous or non-squamous advanced non-small-cell lung cancer with PD-L1 tumour expression of 50% or more. We randomly assigned (1:1) patients to intravenous cemiplimab 350 mg every 3 weeks for up to 108 weeks, or until disease progression, or investigator's choice of chemotherapy. Central randomisation scheme generated by an interactive web response system governed the randomisation process that was stratified by histology and geographical region. Primary endpoints were overall survival and progression free survival, as assessed by a blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumours version 1.1. Patients with disease progression on cemiplimab could continue cemiplimab with the addition of up to four cycles of chemotherapy. We assessed response in these patients by BICR against a new baseline, defined as the last scan before chemotherapy initiation. The primary endpoints were assessed in all randomly assigned participants (ie, intention-to-treat population) and in those with a PD-L1 expression of at least 50%. We assessed adverse events in all patients who received at least one dose of their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT03088540.
FINDINGS: Between May 29, 2017, and March 4, 2020, we recruited 712 patients (607 [85%] were male and 105 [15%] were female). We randomly assigned 357 (50%) to cemiplimab and 355 (50%) to chemotherapy. 284 (50%) patients assigned to cemiplimab and 281 (50%) assigned to chemotherapy had verified PD-L1 expression of at least 50%. At 35 months' follow-up, among those with a verified PD-L1 expression of at least 50% median overall survival in the cemiplimab group was 26·1 months (95% CI 22·1-31·8; 149 [52%] of 284 died) versus 13·3 months (10·5-16·2; 188 [67%] of 281 died) in the chemotherapy group (hazard ratio [HR] 0·57, 95% CI 0·46-0·71; p<0·0001), median progression-free survival was 8·1 months (95% CI 6·2-8·8; 214 events occurred) in the cemiplimab group versus 5·3 months (4·3-6·1; 236 events occurred) in the chemotherapy group (HR 0·51, 95% CI 0·42-0·62; p<0·0001). Continued cemiplimab plus chemotherapy as second-line therapy (n=64) resulted in a median progression-free survival of 6·6 months (6·1-9·3) and overall survival of 15·1 months (11·3-18·7). The most common grade 3-4 treatment-emergent adverse events were anaemia (15 [4%] of 356 patients in the cemiplimab group vs 60 [17%] of 343 in the control group), neutropenia (three [1%] vs 35 [10%]), and pneumonia (18 [5%] vs 13 [4%]). Treatment-related deaths occurred in ten (3%) of 356 patients treated with cemiplimab (due to autoimmune myocarditis, cardiac failure, cardio-respiratory arrest, cardiopulmonary failure, septic shock, tumour hyperprogression, nephritis, respiratory failure, [n=1 each] and general disorders or unknown [n=2]) and in seven (2%) of 343 patients treated with chemotherapy (due to pneumonia and pulmonary embolism [n=2 each], and cardiac arrest, lung abscess, and myocardial infarction [n=1 each]). The safety profile of cemiplimab at 35 months, and of continued cemiplimab plus chemotherapy, was generally consistent with that previously observed for these treatments, with no new safety signals INTERPRETATION: At 35 months' follow-up, the survival benefit of cemiplimab for patients with advanced non-small-cell lung cancer was at least as pronounced as at 1 year, affirming its use as first-line monotherapy for this population. Adding chemotherapy to cemiplimab at progression might provide a new second-line treatment for patients with advanced non-small-cell lung cancer.
FUNDING: Regeneron Pharmaceuticals and Sanofi.
METHODS: A total of 207 elderly patients aged 60 years and above with chronic diseases attending a university-based primary care clinic were recruited via a systematic randomised sampling method from the clinic patient attendance registry. Respondents were assessed using self-administered online questionnaires distributed via mobile devices. The questionnaire assessed awareness, i.e. ability to correctly answer a self-reported questionnaire on basic dementia knowledge; (adapted from Northern Ireland Life and Times Survey 2010), risk of MCI; (using Towards Useful Aging (TUA)-WELLNESS screening questionnaire) and help-seeking behaviour. Bivariate analysis was used to determine factors associated with dementia awareness.
RESULTS: The response rate was 77.1%, with the majority of participants were females, Chinese and had secondary school education. 39.1% of participants were categorised as high risk of developing MCI. The majority (92.8%) had low dementia awareness and had never shared their concerns regarding dementia (93.2%) nor had any discussion (87.0%) on cognitive impairment with their physicians. Three factors had an association with total dementia awareness score, i.e., younger age group, higher risk of MCI and presence of cardiovascular diseases have significantly lower awareness score (p
METHOD: Clinical records from the Selangkah system of all patients with COVID-19 aged above 18 years seen at COVID-19 assessment centres located in 10 government health clinics in Gombak district, Selangor, from 1 October to 31 December 2021 with complete documentation and outcomes were retrieved. Demographics, comorbidities, clinical features and vaccination statuses and types were retrospectively evaluated. The variables were compared between mild and severe diseases. Univariate and multivariable logistic regressions were used to identify the factors affecting disease severity.
RESULTS: A total of 4406 patients (median age=37 years, men=51.2%) were analysed. Approximately 97.1% of the cases were mild, while 2.9% were severe. Fever, difficulty breathing, lethargy, throat irritation/runny nose, oxygen saturation of <95%, respiratory rate of >20 breaths per minute, CoronaVac vaccination and hypertension were the determinants of severity (P<0.05).
CONCLUSION: The high proportion (97.1%) of mild cases in this study compared with an earlier report (81.8%) during the pre-vaccination period may suggest the impact of vaccine, as 84.9% of this cohort was fully vaccinated. Our study also demonstrated a significant difference in COVID-19 severity between the vaccine types. The identified clinical features and comorbidities could assist primary care doctors in stratifying patients with COVID-19 judiciously in terms of hospital referral or home quarantine.
METHODS: The involved approaches build molecules from fragments that are either isosteric to GSH sub-moieties (ligand-based) or successfully docked to GSH binding sub-pockets (structure-based). Compared to reference GST inhibitor of S-hexyl GSH, ligands with improved rigidity, synthetic accessibility, and affinity to receptor were successfully designed. The method involves joining fragments to create ligands. The ligands were then explored using molecular docking, Cartesian coordinate's optimization, and simplified free energy determination as well as MD simulation and MMPBSA calculations. Several tools were used which include OPENEYE toolkit, Open Babel, Autodock Vina, Gromacs, and SwissParam server, and molecular mechanics force field of MMFF94 for optimization and CHARMM27 for MD simulation. In addition, in-house scripts written in Matlab were used to control fragments connection and automation of the tools.