Nevin Manimala

Soc Sci Med. 2022 Jan 5;294:114694. doi: 10.1016/j.socscimed.2021.114694. Online ahead of print.

ABSTRACT

Some evidence indicates under-perception of overweight is associated with lower levels of weight loss. This might be due to ‘visual normalisation’ of overweight through comparisons made in communities where average body mass index (BMI) is high, resulting in under-perception of overweight, which in turn, may protect against negative weight-related self-perceptions and/or reduce motivation to lose weight. Evidence in support of this hypothesis was found initially in a precision-weighted multilevel logistic regression analysis of 3729 overweight Australians aged >18 y, after adjusting for age, sex and area-level disadvantage. Participants whose BMI was -1 kg/m² or less than the community mean BMI had lower odds of weight-related dissatisfaction (OR = 0.64, 95%CI = 0.51-0.80) and perceived overweight (OR = 0.56, 95%CI = 0.45-0.70), compared with peers whose BMI was within ± 1 kg/m² of the community mean. Moreover, participants whose BMI was 1 kg/m² or greater than the community mean BMI had higher odds of weight-related dissatisfaction (OR = 1.97, 95%CI = 1.69-2.30) and perceived overweight (OR = 2.81, 95%CI = 2.41-3.28) when compared to the same reference group. These findings were consistent for men and women; however, they were attenuated towards the null and rendered statistically insignificant after adjustment for personal BMI. Overall, these results indicate that among adults who are overweight, personal BMI, rather than the relative difference between personal and community BMI, is the stronger determinant of weight-related perception and satisfaction.

PMID:35038633 | DOI:10.1016/j.socscimed.2021.114694

Public Health. 2021 Dec 18;203:110-115. doi: 10.1016/j.puhe.2021.12.010. Online ahead of print.

ABSTRACT

OBJECTIVES: At the end of 2020, many countries commenced a vaccination programme against SARS-CoV-2. Public health authorities aim to prevent and interrupt outbreaks of infectious disease in social care settings. We aimed to investigate the association between the introduction of the vaccination programme and the frequency and duration of COVID-19 outbreaks in Northern Ireland (NI).

STUDY DESIGN: We undertook an ecological study using routinely available national data.

METHODS: We used Poisson regression to measure the relationship between the number of RT-PCR confirmed COVID-19 outbreaks in care homes, and as a measure of community COVID-19 prevalence, the Office for National Statistics COVID-19 Infection Survey estimated the number of people testing positive for COVID-19 in NI. We estimated the change in this relationship and estimated the expected number of care home outbreaks in the absence of the vaccination programme. A Cox proportional hazards model estimated the hazard ratio of a confirmed COVID-19 care home outbreak closure.

RESULTS: Care home outbreaks reduced by two-thirds compared to expected following the introduction of the vaccination programme, from a projected 1625 COVID-19 outbreaks (95% prediction interval 1553-1694) between 7 December 2020 and 28 October 2021 to an observed 501. We estimated an adjusted hazard ratio of 2.53 of the outbreak closure assuming a 21-day lag for immunity.

CONCLUSIONS: These findings describe the association of the vaccination with a reduction in outbreak frequency and duration across NI care homes. This indicates probable reduced harm and disruption from COVID-19 in social care settings following vaccination. Future research using individual level data from care home residents will be needed to investigate the effectiveness of the vaccines and the duration of their effects.

PMID:35038629 | DOI:10.1016/j.puhe.2021.12.010

Public Health. 2021 Dec 9;203:100-109. doi: 10.1016/j.puhe.2021.12.003. Online ahead of print.

ABSTRACT

OBJECTIVES: Countries throughout the world are experiencing COVID-19 viral load in their populations, leading to potential transmission and infectivity of asymptomatic COVID-19 cases. The current systematic review and meta-analysis aims to investigate the role of asymptomatic infection and transmission reported in family clusters, adults, children and health care workers, globally.

STUDY DESIGN: Systematic review and meta-analysis.

METHODS: An online literature search of PubMed, Google Scholar, medRixv and BioRixv was performed using standard Boolean operators and included studies published up to 17 August 2021. For the systematic review, case reports, short communications and retrospective studies were included to ensure sufficient asymptomatic COVID-19 transmission data were reported. For the quantitative synthesis (meta-analysis), participant data from a collection of cohort studies focusing on groups of familial clusters, adults, children and health care workers were included. Inconsistency among studies was assessed using I² statistics. The data synthesis was computed using the STATA 16.0 software.

RESULTS: This study showed asymptomatic transmission among familial clusters, adults, children and health care workers of 15.72%, 29.48%, 24.09% and 0%, respectively. Overall, asymptomatic transmission was 24.51% (95% confidence interval [CI]: 14.38, 36.02) among all studied population groups, with a heterogeneity of I² = 95.30% (P < 0.001). No heterogeneity was seen in the population subgroups of children and health care workers. The risk of bias in all included studies was assessed using the Newcastle Ottawa Scale.

CONCLUSIONS: For minimising the spread of COVID-19 within the community, this study found that following the screening of asymptomatic cases and their close contacts for chest CT scan (for symptomatic patients), even after negative nucleic acid testing, it is essential to perform a rigorous epidemiological history, early isolation, social distancing and an increased quarantine period (a minimum of 14-28 days). This systematic review and meta-analysis supports the notion of asymptomatic COVID-19 infection and person-to-person transmission and suggests that this is dependent on the varying viral incubation period among individuals. Children, especially those of school age (i.e. <18 years), need to be monitored carefully and follow mitigation strategies (e.g. social distancing, hand hygiene, wearing face masks) to prevent asymptomatic community transmission of COVID-19.

PMID:35038628 | DOI:10.1016/j.puhe.2021.12.003

Early Hum Dev. 2022 Jan 14;165:105535. doi: 10.1016/j.earlhumdev.2021.105535. Online ahead of print.

ABSTRACT

BACKGROUND: Breast milk feeding (BMF) improved neurodevelopment in children born very preterm (VPT, <32 weeks of gestation), but knowledge about its effect on other mental health outcomes remains limited.

OBJECTIVE: To estimate the association of BMF practices with behavioral and emotional problems at preschool age in children born VPT.

METHODS: We studied 263 children born VPT during 2011-12 and enrolled in the Portuguese EPICE cohort. At the age of 3, information on BMF initiation and duration was collected and behavioral and emotional problems were assessed using the parents’ completed Child Behavior Checklist 1.5-5 years (CBCL/1½-5). Children were categorized for all CBCL/1½-5 sub-scales and for Diagnostic and Statistical Manual of Mental Disorders (DSM5)-oriented scales. Risk ratios were estimated to assess the association of BMF with subclinical/clinical problems, fitting a Poisson regression.

RESULTS: Behavioral or emotional subclinical/clinical problems were found in almost 20% of children (11.8% in the clinical range). BMF was consistently associated with lower adverse behavioral and emotional outcomes, particularly risks of externalizing problems, somatic complaints, aggressive behavior, as well as autism spectrum and attention deficit/hyperactivity symptoms, although the magnitude of the unadjusted risks was attenuated by adjustment for relevant confounders and wider confidence intervals included the null.

CONCLUSION: Lower exposure to BMF seemed to increase the risk of adverse behavioral and emotional outcomes at preschool age in children born VPT. These results raise questions about explanatory pathways and strengthen evidence underpinning BMF promotion for VPT children.

PMID:35038626 | DOI:10.1016/j.earlhumdev.2021.105535

Spine J. 2022 Jan 14:S1529-9430(22)00009-2. doi: 10.1016/j.spinee.2022.01.008. Online ahead of print.

ABSTRACT

BACKGROUND CONTEXT: The ethics of industry payments to physicians and the potential impact on healthcare costs and research outcomes have long been topics of debate. Industry payments to spine surgeons are frequently scrutinized. Transparency of industry relationships with physicians provides insight into their possible impact on clinical decision-making and utilization of care.

PURPOSE: To analyze trends in medical industry payments to spine surgeons and all physicians from 2014 to 2019, and further evaluate whether specific payments to spine surgeons vary based on company size.

STUDY DESIGN/SETTING: Cross-sectional investigation of publicly reported Center for Medicare and Medicaid Services (CMS) Open Payments Database (OPD) Population Sample: All US providers listed as receiving industry payments with further evaluation of payments to neurosurgeons and orthopaedic spine surgeons.

OUTCOME MEASURES: Main measures were the magnitude and trends of industry general and research payments and subcategories of general payments, such as royalty/license and consulting fees, to spine surgeons and comparison to all physicians over the six-year period. Variations in payment patterns among spine device manufacturers with the highest reported level of spine surgeon payments in 2019.

METHODS: 2014 to 2019 publicly reported general and research industry payments in the CMS OPD were analyzed. Trends in payments to all physicians were compared to trends in payments to neurosurgeons and orthopaedic spine surgeons. Trends in payment patterns among spine device manufacturers with the highest payments in 2019 were determined. Linear regression analysis was completed to find statistically significant outcomes.

RESULTS: Our investigation found an aggregate of $42,710,365,196 general and research payments reported to all physicians over the six-year period, 2.6% ($1,112,936,203) of which went to spine surgeons. Industry general and research payments to spine surgeons decreased by 17.5% ($195,571,109, 2014; $161,283,683, 2019), while increasing by 8.7% ($6,706,208,391, 2014; $7,288,003,832, 2019) to all physicians. Industry research payments to spine surgeons were notably low each year and decreased to only 0.5% of research payments made to all physicians in 2019. Median payment received by spine surgeons as well as the overall distribution of payments to the 75^th and 95^th percentile significantly increased over the six-year period in comparison to the stable distribution of payments to all physicians. Top eight spine device manufactures with the highest level of spine surgeon payments accounted for 72.9% payments in 2014 but decreased payments by 17.6% to 2019 ($120,409,083.75, 2014; $99,283,264.49, 2019).

CONCLUSIONS: Industry general and research payments to all physicians increased from 2014 to 2019 but decreased to spine surgeons, largely due to decreasing payments from eight device manufacturers with the highest level of surgeon payments. A small subset of spine surgeons continues to receive increasing payments. The implications of decreasing investments in research by industry and of large payments made to a small group of spine surgeons bears cautious oversight, both for the future of the specialty and any impact on patient care outcomes.

PMID:35038572 | DOI:10.1016/j.spinee.2022.01.008

J Ethnopharmacol. 2022 Jan 14:114991. doi: 10.1016/j.jep.2022.114991. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Platycodon grandiflorus (Jacq.) A.DC. (PG) is a common natural medicine with a history of thousands of years. The processing products were mainly recorded as raw, honey-processed, wine-fried, yellow-fried, and bran-fried PG, which were respectively used for different clinical purposes. Therefore, it is necessary to study the chemical composition and pharmacological activity of PG after processing.

AIM OF THE STUDY: To explore the effects of different processing methods on the composition and biological activity of PG using metabonomics and pharmacologic design.

MATERIALS AND METHODS: UPLC-QTOF-MS combined with multivariate statistical analysis was used to identify different metabolites before and after the processing of PG. Network pharmacology was used to construct the metabolite-target-disease network. CCK-8 assay, flow cytometry, and western blotting were used to detect cell viability, apoptosis, and the expression of related proteins, respectively.

RESULT: A total of 43 differentially expressed metabolites (VIP >10) were detected and identified in the analyzed groups. Based on their chemical nature, these metabolites were divided into five categories, namely, saccharolipids, flavonoid glycosides, alkynes, saponins, and lipids (including fatty acids, phospholipids, fatty aldehydes, and sterols). The content of lipids in the five processed groups (CH, FC, JZ, MZI, and MZG) was found to be higher than that in raw PG. In particular, the processing approaches explored herein increased the contents of many phospholipids, namely, glycerophosphoinositols, phosphatidic acids, and lysophosphatidyle·thanolamines. In total 8 metabolites were found by venn diagram to distinguish different processed products (metabolites 2, 6, 19, 20, 21, 26, 28, and 38). The results of network pharmacology analysis showed that the primary anti-cancer targets of 43 metabolites of PG processing products are PIK3CA, Akt, and STAT3, and based on CCK-8 assay, MZI-processed PG has a significant killing effect on A549 cells, compared to other processing techniques. Moreover, flow cytometry analysis showed that the cells treated with MZI-processed PG exhibit significantly increased cell apoptosis, and that the effect is dose-dependent. Finally, the western blots performed herein demonstrated that the MZI-processed PG effectively inhibits the expression of p-Akt and p-STAT3, which is consistent with the network pharmacology results.

CONCLUSION: Depending on the processing technique, the contents of 43 different metabolites in PG vary significantly. Specifically, the contents of phospholipids and fatty acids increase, whereas the contents of large Mw saponins decrease. Compared to the other investigated processing methods, MZI increases the potential of PG in inducing cell apoptosis and inhibiting cell proliferation by affecting the Akt and STAT3 signaling pathways. The increased levels of 3-O-β-glucopyranosyl polygalacic acid and platycoside F after honey-frying confirm these results.

PMID:35038566 | DOI:10.1016/j.jep.2022.114991

Contraception. 2022 Jan 14:S0010-7824(22)00004-X. doi: 10.1016/j.contraception.2022.01.003. Online ahead of print.

ABSTRACT

OBJECTIVE(S): The Medicaid consent policy has been identified as a major barrier to desired permanent contraception, particularly for low-income communities and communities of color. As each state may modify their state Medicaid sterilization consent form, variation in the form has been reported. This study aims to characterize state-level variation in Medicaid Title XIX consent form interpretation and application.

STUDY DESIGN: We aimed to collect primary data from Medicaid officials in all 50 United States from January to May 2020 via a 25-question electronic survey regarding state-level consent form implementation. Questions targeted consent form details and definitions, insurance and billing, clinician correspondence, and administrative processes. We used Qualtrics XM® to collect survey responses. We performed descriptive statistics on the survey responses. There were no exclusion criteria.

RESULTS: We had 41 responses from 36/50 states (72% participation rate). Heterogeneity existed in the key definitions of “Premature Delivery” and “Emergency Abdominal Surgery.” One in five respondents reported the consent form was only available in English. Variation among Current Procedural Terminology codes covered in each state’s sterilization policy were noted. Nearly a quarter of respondents did not know how Medicaid informed healthcare providers of consent form denials. Most participants (90%) were unaware of differences between state sterilization policies.

CONCLUSION: This study demonstrates variation in terms of consent form definitions, procedures covered, correspondence with clinicians, and administrative review processes among state Medicaid offices regarding the sterilization consent form. Greater transparency is necessary in order to reduce administrative barriers to desired permanent contraception.

PMID:35038447 | DOI:10.1016/j.contraception.2022.01.003

Microvasc Res. 2022 Jan 14:104316. doi: 10.1016/j.mvr.2022.104316. Online ahead of print.

ABSTRACT

INTRODUCTION: Frailty is highly prevalent in heart failure (HF) patients. HF is associated with oxidative stress and chronic inflammation, which impair oxygen use by skeletal muscles. Little is known about the influence of frailty on vascular responsiveness and tissue oxygenation.

OBJECTIVE: Analyze the influence of frailty on vascular responsiveness and muscle oxygenation in elderly individuals with and without HF.

METHODS: Individuals aged ≥60 years, with or without HF, were evaluated for frailty (phenotype). Near-infrared spectroscopy (NIRS) was used to assess muscle oxygenation at rest (oxygen saturation – StO₂ and deoxyhemoglobin) and during handgrip exercise (minimum StO₂ and maximum deoxyhemoglobin), and oxygenation variables.

STATISTICAL ANALYSIS: Results were grouped according to the frailty phenotype: non-frail, pre-frail, and frail. Shapiro-Wilk test was used to assess normality. Data were compared using a two-way analysis of variance (ANOVA). Bonferroni post hoc test was applied to determine the influence of frailty or HF on NIRS variables. SPSS software was used in the analyses; p < 0.05 was considered significant.

RESULTS: 55 elderly participants (61.8% female; 70.4 ± 7.2 years old; 28 HF patients) participated in the study. 32.7% (n = 18) were classified as non-frail, 43.3% (n = 24) as pre-frail, and 23.6% (n = 13) as frail. The analysis of vascular responsiveness (n = 52) identified an influence (p < 0.05) of frailty on the reperfusion rate (slope 2 and ∆StO₂ of nadir-peak) and desaturation during occlusion (area under the curve of StO₂) in HF patients. There was no influence of frailty or HF on muscle oxygenation at rest and during exercise (n = 54; p > 0.05).

CONCLUSION: The coexistence of frailty and HF seems to impair vascular responsiveness, as frail elderly participants with HF presented lower reperfusion rates and higher desaturation levels during the arterial occlusion test. However, the presence of frailty or HF alone had no influence on muscle oxygenation at rest or during exercise.

PMID:35038445 | DOI:10.1016/j.mvr.2022.104316

Lancet Oncol. 2022 Jan 14:S1470-2045(21)00718-X. doi: 10.1016/S1470-2045(21)00718-X. Online ahead of print.

ABSTRACT

BACKGROUND: Trastuzumab is a monoclonal antibody against HER2 (also known as ERBB2). The primary objective of the NRG Oncology/RTOG-1010 trial was to establish whether trastuzumab improves disease-free survival when combined with trimodality treatment (paclitaxel plus carboplatin and radiotherapy, followed by surgery) for patients with untreated HER2-overexpressing oesophageal adenocarcinoma.

METHODS: NRG Oncology/RTOG-1010 was an open label, randomised, phase 3 trial for which patients were accrued from 111 NRG-affiliated institutions in the USA. Eligible patients were adults (aged ≥18 years) with newly diagnosed pathologically confirmed oesophageal adenocarcinoma, American Joint Committee on Cancer 7th edition T1N1-2 or T2-3N0-2 stage disease, and a Zubrod performance status of 0-2. Patients were stratified by adenopathy (no vs yes [coeliac absent] vs yes [coeliac present ≤2 cm]) and randomly assigned (1:1) to receive weekly intravenous paclitaxel (50 mg/m² intravenously over 1 h) and carboplatin (area under the curve 2, intravenously over 30-60 min) for 6 weeks with radiotherapy 50·4 Gy in 28 fractions (chemoradiotherapy) followed by surgery, with or without intravenous trastuzumab (4 mg/kg in week one, 2 mg/kg per week for 5 weeks during chemoradiotherapy, 6 mg/kg once presurgery, and 6 mg/kg every 3 weeks for 13 treatments starting 21-56 days after surgery). The primary endpoint, disease-free survival, was defined as the time from randomisation to death or first of locoregional disease persistence or recurrence, distant metastases, or second primary malignancy. Analyses were done by modified intention to treat. This study is registered with Clinicaltrials.gov, NCT01196390; it is now closed and in follow-up.

FINDINGS: 606 patients were entered for HER2 assessment from Dec 30, 2010 to Nov 10, 2015, and 203 eligible patients who were HER2-positive were enrolled and randomly assigned to chemoradiotherapy plus trastuzumab (n=102) or chemoradiotherapy alone (n=101). Median duration of follow-up was 2·8 years (IQR 1·4-5·7). Median disease-free survival was 19·6 months (95% CI 13·5-26·2) with chemoradiotherapy plus trastuzumab compared with 14·2 months (10·5-23·0) for chemoradiotherapy alone (hazard ratio 0·99 [95% CI 0·71-1·39], log-rank p=0·97). Grade 3 treatment-related adverse events occurred in 41 (43%) of 95 patients in the chemoradiotherapy plus trastuzumab group versus 52 (54%) of 96 in the chemoradiotherapy group and grade 4 events occurred in 20 (21%) versus 21 (22%). The most common grade 3 or worse treatment-related adverse events for both groups were haematological (53 [56%] of 95 patients in the chemoradiotherapy plus trastuzumab group vs 55 [57%] of 96 patients in the chemotherapy group) or gastrointestinal disorders (28 [29%] vs 20 [21 %]). 34 (36%) of 95 patients in the chemoradiotherapy plus trastuzumab group and 27 (28%) of 96 patients in the chemoradiotherapy only group had treatment-related serious adverse events. There were eight treatment-related deaths: five (5%) of 95 patients in the chemoradiotherapy plus trastuzumab group (bronchopleural fistula, oesophageal anastomotic leak, lung infection, sudden death, and death not otherwise specified), and three (3%) of 96 in the chemoradiotherapy group (two multiorgan failure and one sepsis).

INTERPRETATION: The addition of trastuzumab to neoadjuvant chemoradiotherapy for HER2-overexpressing oesophageal cancer was not effective. Trastuzumab did not lead to increased toxicities, suggesting that future studies combining it with or using other agents targeting HER2 in oesophageal cancer are warranted.

FUNDING: National Cancer Institute and Genentech.

PMID:35038433 | DOI:10.1016/S1470-2045(21)00718-X

Lancet Oncol. 2022 Jan 14:S1470-2045(21)00650-1. doi: 10.1016/S1470-2045(21)00650-1. Online ahead of print.

ABSTRACT

BACKGROUND: PD-1 inhibitor plus chemotherapy had been shown to be an effective first-line treatment for patients with metastatic non-small-cell lung cancer (NSCLC). However, there was no robust evidence showing a PD-L1 inhibitor combined with chemotherapy benefited patients with squamous and non-squamous NSCLC. GEMSTONE-302 aimed to evaluate the efficacy and safety of a PD-L1 inhibitor, sugemalimab, plus chemotherapy for patients with metastatic squamous or non-squamous NSCLC.

METHODS: This randomised, double-blind, phase 3 trial was done in 35 hospitals and academic research centres in China. Eligible patients were aged 18-75 years, had histologically or cytologically confirmed stage IV squamous or non-squamous NSCLC without known EGFR sensitising mutations, ALK, ROS1, or RET fusions, no previous systemic treatment for metastatic disease, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients were randomly assigned (2:1) to receive sugemalimab (1200 mg, intravenously, every 3 weeks) plus platinum-based chemotherapy (carboplatin [area under the curve (AUC) 5 mg/mL per min, intravenously] and paclitaxel [175 mg/m², intravenously] for squamous NSCLC, or carboplatin [AUC 5 mg/mL per min, intravenously] and pemetrexed [500 mg/m², intravenously] for non-squamous NSCLC; sugemalimab group) or placebo plus the same platinum-based chemotherapy regimens for squamous or non-squamous NSCLC as in the sugemalimab group; placebo group) for up to four cycles, followed by maintenance therapy with sugemalimab or placebo for squamous NSCLC, and intravenous sugemalimab 500 mg/m² or matching placebo plus pemetrexed for non-squamous NSCLC. Randomisation was done by an interactive voice-web-response system via permuted blocks (block size was a mixture of three and six with a random order within each stratum) and stratified by ECOG performance status, PD-L1 expression, and tumour pathology. The investigators, patients, and the sponsor were masked to treatment assignment. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population. Safety was analysed in all patients who received at least one treatment dose. Results reported are from a prespecified interim analysis (ie, when the study met the primary endpoint) and an updated analysis (prespecified final analysis for progression-free survival) with a longer follow-up. This study is registered with ClinicalTrials.gov (NCT03789604), is closed to new participants, and follow-up is ongoing.

FINDINGS: Between Dec 13, 2018, and May 15, 2020, 846 patients were assessed for eligibility; 367 were ineligible, and the remaining 479 patients were randomly assigned to the sugemalimab group (n=320) or placebo group (n=159). At the preplanned interim analysis (data cutoff June 8, 2020; median follow-up 8·6 months [IQR 6·1-11·4]), GEMSTONE-302 met its primary endpoint, with significantly longer progression-free survival in the sugemalimab group compared with the placebo group (median 7·8 months [95% CI 6·9-9·0] vs 4·9 months [4·7-5·0]; stratified hazard ratio [HR] 0·50 [95% CI 0·39-0·64], p<0·0001]). At the final analysis (March 15, 2021) with a median follow-up of 17·8 months (IQR 15·1-20·9), the improvement in progression-free survival was maintained (median 9·0 months [95% CI 7·4-10·8] vs 4·9 months [4·8-5·1]; stratified HR 0·48 [95% CI 0·39-0·60], p<0·0001). The most common grade 3 or 4 any treatment-related adverse events were neutrophil count decreased (104 [33%] of 320 with sugemalimab vs 52 [33%] of 159 with placebo), white blood cell count decreased (45 [14%] vs 27 [17%]), anaemia (43 [13%] vs 18 [11%]), platelet count decreased (33 [10%] vs 15 [9%]), and neutropenia (12 [4%] vs seven [4%]). Any treatment-related serious adverse events occurred in 73 (23%) patients in the sugemalimab group and 31 (20%) patients in the placebo group. Any treatment-related deaths were reported in ten (3%) patients in the sugemalimab group (pneumonia with respiratory failure in one patient; myelosuppression with septic shock in one patient; pneumonia in two patients; respiratory failure, abdominal pain, cardiac failure, and immune-mediated pneumonitis in one patient each; the other two deaths had an unspecified cause) and in two (1%) patients in the placebo group (pneumonia and multiple organ dysfunction syndrome).

INTERPRETATION: Sugemalimab plus chemotherapy showed a statistically significant and clinically meaningful progression-free survival improvement compared with placebo plus chemotherapy, in patients with previously untreated squamous and non-squamous metastatic NSCLC, regardless of PD-L1 expression, and could be a newfirst-line treatment option for both squamous and non-squamous metastatic NSCLC.

FUNDING: CStone Pharmaceuticals.

TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

PMID:35038432 | DOI:10.1016/S1470-2045(21)00650-1