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.
AIM: To investigate the (dis)agreement between, and compare the determinants of, parent and clinician severity scores.
DESIGN AND SETTING: Secondary analysis of data from a prospective cohort study of 8394 children presenting to primary care with acute (≤28 days) cough and RTI.
METHOD: Data on sociodemographic factors, parent-reported symptoms, clinician-reported findings, and severity assessments were used. Kappa (κ)-statistics were used to investigate (dis) agreement, whereas multivariable logistic regression was used to identify the factors associated with illness severity.
RESULTS: Parents reported higher illness severity (mean 5.2 [standard deviation (SD) 1.8], median 5 [interquartile range (IQR) 4-7]), than clinicians (mean 3.1 [SD 1.7], median 3 [IQR 2-4], P<0.0001). There was low positive correlation between these scores (+0.43) and poor inter-rater agreement between parents and clinicians (κ 0.049). The number of clinical signs was highly correlated with clinician scores (+0.71). Parent-reported symptoms (in the previous 24 hours) that were independently associated with higher illness severity scores, in order of importance, were: severe fever, severe cough, rapid breathing, severe reduced eating, moderate-to-severe reduced fluid intake, severe disturbed sleep, and change in cry. Three of these symptoms (severe fever, rapid breathing, and change in cry) along with inter/subcostal recession, crackles/crepitations, nasal flaring, wheeze, and drowsiness/irritability were associated with higher clinician scores.
CONCLUSION: Clinicians and parents use different factors and make different judgements about the severity of children's RTI. Improved understanding of the factors that concern parents could improve parent-clinician communication and consultation outcomes.
SUBJECTS/METHODS: A taste database including 467 foods' sweet, sour, bitter, salt, umami and fat sensation values was combined with food intake data to assess dietary taste patterns: the contribution to energy intake of 6 taste clusters. The FFQ's reliability was assessed against 3-d 24hR and urinary biomarkers for sodium (Na) and protein intake (N) in Dutch men (n = 449) and women (n = 397) from the NQplus validation study (mean age 53 ± 11 y, BMI 26 ± 4 kg/m2).
RESULTS: Correlations of dietary taste patterns ranged from 0.39-0.68 between FFQ and 24hR (p
METHODS: Item selection for the FFQ was based on explained variation and contribution to intake of energy and 24 nutrients. For validation, the FFQ was completed by 135 participants (25-70 y of age) of the Nutrition Questionnaires plus study. Per person, on average 2.8 (range 1-5) telephone-based 24-h dietary recalls (24HRs), two 24-h urinary samples, and one blood sample were available. Validity of 54 nutrients and 22 food groups was assessed by ranking agreement, correlation coefficients, attenuation factors, and ultimately deattenuated correlation coefficients (validity coefficients).
RESULTS: Median correlation coefficients for energy and macronutrients, micronutrients, and food groups were 0.45, 0.36, and 0.38, respectively. Median deattenuated correlation coefficients were 0.53 for energy and macronutrients, 0.45 for micronutrients, and 0.64 for food groups, being >0.50 for 18 of 22 macronutrients, 16 of 30 micronutrients and >0.50 for 17 of 22 food groups. The FFQ underestimated protein and potassium intake compared with 24-h urinary nitrogen and potassium excretion by -18% and -2%, respectively. Correlation coefficients ranged from 0.50 and 0.55 for (fatty) fish intake and plasma eicosapentaenoic acid and docosahexaenoic acid, and from 0.26 to 0.42 between fruit and vegetable intake and plasma carotenoids.
CONCLUSION: Overall, the validity of the 253-item Maastricht FFQ was satisfactory. The comprehensiveness of this FFQ make it well suited for use in The Maastricht Study and similar populations.
METHODS: A cross sectional study by adopting European Quality of Life scale (EQ-5D) for the assessment of HRQoL was conducted. All registered HB patients attending two public hospitals in Quetta, Pakistan were approached for study. Descriptive statistics were used to describe demographic and disease related characteristics of the patients. HRQoL was scored using values adapted from the United Kingdom general population survey. EQ-5D scale scores were compared with Mann-Whitney and Kruskal-Wallis test. Standard multiple regression analysis was performed to identify predictors of HRQoL. All analyses were performed using SPSS v 16.0.
RESULTS: Three hundred and ninety HB patients were enrolled in the study. Majority of the participants (n = 126, 32.3%) were categorized in the age group of 18-27 years (36.07 ± 9.23). HRQoL was measured as poor in the current study patients (0.3498 ± 0.31785). The multivariate analysis revealed a significant model (F(10, 380) = 40.04, P