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: We examined e-cigarette market data from the Euromonitor Global Market Information Database (GMID) Passport database, searched in the academic literature, grey literature and news archives for any reports or studies of e-cigarette related diseases or injuries, e-cigarette marketing, and e-cigarette policy responses in Southeast Asian countries, and browsed the websites of online e-cigarette retailers catering to the region's active e-cigarette markets.
RESULTS: In 2019, e-cigarettes were sold in six Southeast Asian markets with a total market value of $595 million, projected to grow to $766 million by 2023. E-commerce is a significant and growing sales channel in the region, with most of the popular or featured brands in online shops originating from China. Southeast Asian youth are targeted with a wide variety of flavours, trendy designs and point of sale promotions, and several e-cigarette related injuries and diseases have been reported in the region. Policy responses vary considerably between countries, ranging from strict bans to no or partial regulations.
CONCLUSION: Although Southeast Asia's e-cigarette market is relatively nascent, this is likely to change if transnationals invest more heavily in the region. Populous countries with weak e-cigarette regulations, notably Indonesia, Malaysia, Vietnam and the Philippines, are desirable targets for the transnationals. Regulatory action is needed to prevent e-cigarette use from becoming entrenched into these societies, especially among young people.
METHODS/DESIGN: This study is a two-arm parallel group randomized controlled trial (RCT) in which adolescents are randomly assigned (after baseline assessment) to one of two group interventions (PEERS® vs. active control condition). In total, 150 adolescents are to be included, with multi-informant involvement of their parents and teachers. The ACCEPT study uses an active control condition (puberty psychoeducation group training, focussing on social-emotional development) and explores possible moderators and mediators in improving social skills. The primary outcome measure is the Contextual Assessment of Social Skills (CASS). The CASS assesses social skills performance in a face to face social interaction with an unfamiliar, typically developing peer, making this a valuable instrument to assess the social conversational skills targeted in PEERS®. In addition, to obtain a complete picture of social skills, self-, parent- and teacher-reported social skills are assessed using the Social Skills improvement System (SSiS-RS) and Social Responsiveness Scale (SRS-2). Secondary outcome measures (i.e. explorative mediators) include social knowledge, social cognition, social anxiety, social contacts and feelings of parenting competency of caregivers. Moreover, demographic and diagnostic measures are assessed as potential moderators of treatment effectiveness. Assessments of adolescents, parents, and teachers take place at baseline (week 0), intermediate (week 7), post intervention (week 14), and at follow-up (week 28).
CONCLUSION: This is the first RCT on the effectiveness of the PEERS® parent-assisted curriculum which includes an active control condition. The outcome of social skills is assessed using observational assessments and multi-informant questionnaires. Additionally, factors related to social learning are assessed at several time points, which will enable us to explore potential mediators and moderators of treatment effect.
TRAIL REGISTRATION: Dutch trail register NTR6255 (NL6117). Registered February 8th, 2017 - retrospectively registered.
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
OBJECTIVES: (1) Evaluate the four published equations' performance in estimating ionised calcium; (2) Determine the accuracy of calculated ionised and adjusted total calcium in classifying patients according to calcium states; and (3) Identify factors associated with hypocalcaemia in the critically ill population.
MATERIALS AND METHODS: This is a cross-sectional study involving 281 critically ill patients aged 18-80 years of both genders in a Malaysian tertiary intensive care unit. Performance of the four equations was analysed using Bland-Altman difference plot and Passing Bablok regression analysis. Crosstabulation was conducted to assess classification accuracy. Mann-Whitney U or Pearson Chi-Square tests were performed to identify variables associated with hypocalcaemia.
RESULTS: Calculated ionised calcium using all four equations significantly overestimated ionised calcium. Calculated ionised and adjusted total calcium had poor accuracies in classifying hypocalcaemic patients. pH was significantly higher in hypocalcaemics.
CONCLUSION: Calculated ionised and adjusted total calcium significantly overestimate ionised calcium in the critically ill. In this specific population, calcium status should only be confirmed with ionised calcium measured by direct ion-selective electrode (ISE).
MATERIALS AND METHODS: This review has two parts. The first part is a scoping review of the factors associated with suicidal ideation and attempt among young people. The search was conducted in Pubmed, Scopus, and PsycInfo. The second part is the development of preventive strategies according to the identified factors. Both parts will be guided by the SEM model.
RESULTS: A total of ten studies with 45,278 participants that matched the criteria are included in this review. The review found that the risk factors for suicidal ideation among young people in LMIC are being female, psychiatric illness, psychology problem, smoking, alcohol intake, victim of abuse, bullied, and food insecurity. The preventive strategies include policy, mental healthcare services, awareness programme, and coping strategies.
CONCLUSION: More epidemiological studies are needed to evaluate the risk factors of suicide that are unique in LMIC, such as help-seeking behaviour and available mental healthcare services. Suicide prevention requires concerted effort of policymakers, healthcare services, community and individual; thus, SEM framework is suitable as a guidance for suicide prevention.