Impact of PD1 and PDL1 immunotherapy on non-small cell lung cancer outcomes: a systematic review.

INTRODUCTION: Despite comprising many cancer diagnoses, few treatments are suitable for patients with advanced non-small cell lung cancer (aNSCLC). Trials suggest blockade of programmed death 1 (PD1) or its ligand (PDL1) may be effective for these patients. However, this therapy's impact on outcomes other than survival, and outcomes of patients not in trials, remains largely unknown. Therefore, we compared the effectiveness of PD1 and PDL1 immunotherapy to chemotherapy and placebo across multiple clinical outcomes. METHODS: Six databases were searched on 12-13 October 2019 for randomised controlled trials (RCTs) and observational studies investigating nivolumab, pembrolizumab, atezolizumab or durvalumab. Study selection was performed independently by two reviewers. Data for overall survival, progression-free survival, adverse effects (AEs) and quality of life (QoL) were descriptively and meta-analysed. Factors impacting treatment outcomes, including PDL1 expression, were explored. The similarity between RCT and observational data was assessed. RESULTS: From 5423 search results, 139 full texts and abstracts were included. Immunotherapy was associated with a lower risk of death than both comparators. In RCTs, the incidence of treatment-related AEs was approximately 20% lower among patients using immunotherapy compared with chemotherapy. However, no other consistent benefits were observed. Progression-free survival results were inconsistent. Improvements to QoL varied according to the instrument used; however, QoL was not recorded widely. Survival results were similar between study designs; however, AEs incidence was lower in observational studies. DISCUSSION: Among patients with aNSCLC, immunotherapy improved overall survival and incidence of treatment-related AEs compared with chemotherapy. Benefits to progression-free survival and QoL were less consistent. PROSPERO REGISTRATION NUMBER: CRD42019153345.

Levelling the learning ground for healthcare professionals across the world through SIMBA: a mixed-methods study.

OBJECTIVES: To compare the acceptance, strengths and limitations of Simulation via Instant Messaging-Birmingham Advance (SIMBA) in low/middle-income countries (LMICs) and high-income countries (HICs), on healthcare professionals' professional development and learning. DESIGN: Cross-sectional study. SETTING: Online (either mobile or computer/ laptop or both). PARTICIPANTS: 462 participants (LMICs: 29.7%, n=137 and HICs: 71.3%, n=325) were included. INTERVENTIONS: Sixteen SIMBA sessions were conducted between May 2020 and October 2021. Doctors-in-training solved anonymised real-life clinical scenarios over WhatsApp. Participants completed pre-SIMBA and post-SIMBA surveys. PRIMARY AND SECONDARY OUTCOME MEASURES: Outcomes were identified using Kirkpatrick's training evaluation model. LMIC and HIC participants' reactions (level 1) and self-reported performance, perceptions and improvements in core competencies (level 2a) were compared using the χ2 test. Content analysis of open-ended questions was performed. RESULTS: Postsession, there were no significant differences in application to practice (p=0.266), engagement (p=0.197) and overall session quality (p=0.101) between LMIC and HIC participants (level 1). Participants from HICs showed better knowledge of patient management (LMICs: 77.4% vs HICs: 86.5%; p=0.01), whereas participants from LMICs self-reported higher improvement in professionalism (LMICs: 41.6% vs HICs: 31.1%; p=0.02). There were no significant differences in improved clinical competency scores in patient care (p=0.28), systems-based practice (p=0.05), practice-based learning (p=0.15) and communication skills (p=0.22), between LMIC and HIC participants (level 2a). In content analysis, the major strengths of SIMBA over traditional methods were providing individualised, structured and engaging sessions. CONCLUSIONS: Healthcare professionals from both LMICs and HICs self-reported improvement in their clinical competencies, illustrating that SIMBA can produce equivalent teaching experiences. Furthermore, SIMBA's virtual nature enables international accessibility and presents potential for global scalability. This model could steer future standardised global health education policy development in LMICs.

Clinical disease characteristics of patients with Niemann-Pick Disease Type C: findings from the International Niemann-Pick Disease Registry (INPDR).

BACKGROUND: Niemann-Pick Disease Type C (NPC) is an autosomal recessive rare disease characterised by progressive neurovisceral manifestations. The collection of on-going large-scale NPC clinical data may generate better understandings of the natural history of the disease. Here we report NPC patient data from the International Niemann-Pick Disease Registry (INPDR). METHOD: The INPDR is a web-based, patient-led independent registry for the collection of prospective and retrospective clinical data from Niemann-Pick Disease patients. Baseline data from NPC patients enrolled into the INPDR from September 2014 to December 2019 was extracted to analyse the demographic, genetic and clinical features of the disease. RESULTS: A total of 203 NPC patients from six European countries were included in this study. The mean age (SD) at diagnosis was 11.2 years (14.2). Among enrolled patients, 168 had known neurological manifestations: 43 (24.2%) had early-infantile onset, 47 (26.4%) had late-infantile onset, 41 (23.0%) had juvenile onset, and 37 (20.8%) had adult onset. 10 (5.6%) patients had the neonatal rapidly fatal systemic form. Among the 97 patients with identified NPC1 variants, the most common variant was the c. 3182T > C variant responsible for the p.lle1061Thr protein change, reported in 35.1% (N = 34) of patients. The frequencies of hepatomegaly and neonatal jaundice were greatest in patients with early-infantile and late-infantile neurological onset. Splenomegaly was the most commonly reported observation, including 80% of adult-onset patients. The most commonly reported neurological manifestations were cognitive impairment (78.5%), dysarthria (75.9%), ataxia (75.9%), vertical supranuclear gaze palsy (70.9%) and dysphagia (69.6%). A 6-domain composite disability scale was used to calculate the overall disability score for each neurological form. Across all with neurological onset, the majority of patients showed moderate to severe impairments in all domains, except for 'swallowing' and 'seizure'. The age at diagnosis and death increased with increased age of neurological symptom onset. Miglustat use was recorded in 62.4% of patients and the most common symptomatic therapies used by patients were antiepileptics (32.9%), antidepressants (11.8%) and antacids (9.4%). CONCLUSION: The proportion of participants at each age of neurological onset was relatively equal across the cohort. Neurological manifestations, such as ataxia, dysphagia, and dysarthria, were frequently observed across all age categories.

Utility of Simulation via Instant Messaging - Birmingham Advance (SIMBA) in medical education during COVID-19 pandemic.

BACKGROUND: Simulation via Instant Messaging - Birmingham Advance (SIMBA) aimed to improve clinicians' confidence in managing various clinical scenarios during the COVID-19 pandemic. METHODS: Five SIMBA sessions were conducted between May and August 2020. Each session included simulation of scenarios and interactive discussion. Participants' self-reported confidence, acceptance, and relevance of the simulated cases were measured. RESULTS: Significant improvement was observed in participants' self-reported confidence (overall n = 204, p<0.001; adrenal n = 33, p<0.001; thyroid n = 37, p<0.001; pituitary n = 79, p<0.001; inflammatory bowel disease n = 17, p<0.001; acute medicine n = 38, p<0.001). Participants reported improvements in clinical competencies: patient care 52.0% (n = 106/204), professionalism 30.9% (n = 63/204), knowledge on patient management 84.8% (n = 173/204), systems-based practice 48.0% (n = 98/204), practice-based learning 69.6% (n = 142/204) and communication skills 25.5% (n = 52/204). CONCLUSION: SIMBA is a novel pedagogical virtual simulation-based learning model that improves clinicians' confidence in managing conditions across various specialties.