Service utilization among adolescents seeking trauma-related care: Differences by risk for suicide and ethnoracial background.

Adolescents from ethnoracially minoritized backgrounds increasingly report high rates of attempted suicide, trauma exposure, and limited access to mental healthcare services. However, less is known regarding their use of services across different youth-serving systems. This study examines the associations and interactions between self-injurious thoughts and behaviors (SITBs), race/ethnicity, and service sector utilization (mental healthcare, general healthcare, school, and social services) among a sample of trauma-exposed and treatment-seeking adolescents. Participants were treatment-seeking adolescents (N = 4406) ages 12-17 from the National Child Traumatic Stress Network Core Data Set who had available data for SITBs, race/ethnicity, services utilized, and other key variables. Mixed effects logistic regression was used to examine main and interactive effects for whether adolescents' race/ethnicity and SITBs were associated with service utilization in each of the identified service sectors. SITBs were associated with adolescents' utilization of mental healthcare (OR = 1.38 p < 0.001), general healthcare (OR = 2.30; p < 0.001), and school services (OR = 1.38 p < 0.001). NH Black adolescents reporting SITBs were less likely to use mental health services than other NH Black youths (OR = 0.53; p = 0.004). Hispanic adolescents reporting SITBs were more likely to utilize healthcare services than other Hispanic youths (OR = 1.51; p = 0.039). Trauma-exposed adolescents reporting SITBs are more likely to utilize mental healthcare, general healthcare, and school-based services than other trauma-exposed adolescents. However, NH Black adolescents experiencing SITBs may face additional barriers to utilizing mental healthcare services. Findings can be used to develop nursing practices and policies to address barriers faced by adolescents reporting SITBs.

New insights on a recurring theme: A secondary analysis of nurse turnover using the National Sample Survey of Registered Nurses.

BACKGROUND: Registered nurse (RN) turnover is a recurring phenomenon that accelerated during COVID-19 and heightened concerns about contributing factors. PURPOSE: Provide baseline RN turnover data to which pandemic and future RN workforce turnover behaviors can be compared. METHODS: A cross-sectional, secondary analysis of RN turnover using U.S. National Sample Survey of Registered Nurses 2018 data. Responses from 41,428 RNs (weighted N = 3,092,991) across the United States were analyzed. Sociodemographic, professional, employment, and economic data and weighting techniques were used to model prepandemic RN turnover behaviors. DISCUSSION: About 17% of the sample reported a job turnover, with 6.2% reporting internal and 10.8% reporting external turnover. The factors common across both internal and external turnover experiences included education, employment settings, and years of nursing experience. CONCLUSIONS: Baseline RN turnover data can help employers and policymakers understand new and recurring nursing workforce trends and develop targeted actions to reduce nurse turnover.

Chronic alcohol use primes bronchial cells for altered inflammatory response and barrier dysfunction during SARS-CoV-2 infection.

Alcohol use disorder (AUD) is a significant public health concern and people with AUD are more likely to develop severe acute respiratory distress syndrome (ARDS) in response to respiratory infections. To examine whether AUD was a risk factor for more severe outcome in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we examined early responses to infection using cultured differentiated bronchial epithelial cells derived from brushings obtained from people with AUD or without AUD. RNA-seq analysis of uninfected cells determined that AUD cells were enriched for expression of epidermal genes as compared with non-AUD cells. Bronchial epithelial cells from patients with AUD showed a significant decrease in barrier function 72 h postinfection, as determined by transepithelial electrical resistance. In contrast, barrier function of non-AUD cells was enhanced 72 h after SARS-CoV-2 infection. AUD cells showed claudin-7 that did not colocalize with zonula occludens-1 (ZO-1), indicative of disorganized tight junctions. However, both AUD and non-AUD cells showed decreased ß-catenin expression following SARS-CoV-2 infection. To determine the impact of AUD on the inflammatory response to SARS-CoV-2 infection, cytokine secretion was measured by multiplex analysis. SARS-CoV-2-infected AUD bronchial cells had enhanced secretion of multiple proinflammatory cytokines including TNFα, IL-1ß, and IFNγ as opposed to non-AUD cells. In contrast, secretion of the barrier-protective cytokines epidermal growth factor (EGF) and granulocyte macrophage-colony stimulating factor (GM-CSF) was enhanced for non-AUD bronchial cells. Taken together, these data support the hypothesis that AUD is a risk factor for COVID-19, where alcohol primes airway epithelial cells for increased inflammation and increased barrier dysfunction and increased inflammation in response to infection by SARS-CoV-2.NEW & NOTEWORTHY Alcohol use disorder (AUD) is a significant risk factor for severe acute respiratory distress syndrome. We found that AUD causes a phenotypic shift in gene expression in human bronchial epithelial cells, enhancing expression of epidermal genes. AUD cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had higher levels of proinflammatory cytokine secretion and barrier dysfunction not present in infected non-AUD cells, consistent with increased early COVID-19 severity due to AUD.

A study of error reporting by nurses: the significant impact of nursing team dynamics.

Background: Error reporting is crucial for organisational learning and improving patient safety in hospitals, yet errors are significantly underreported. Aims: The aim of this study was to understand how the nursing team dynamics of leader inclusiveness, safety climate and psychological safety affected the willingness of hospital nurses to report errors. Methods: The study was a cross-sectional design. Self-administered surveys were used to collect data from nurses and nurse managers. Data were analysed using linear mixed models. Bootstrap confidence intervals with bias correction were used for mediation analysis. Results: Leader inclusiveness, safety climate and psychological safety significantly affected willingness to report errors. Psychological safety mediated the relationship between safety climate and error reporting as well as the relationship between leader inclusiveness and error reporting. Conclusion: The findings of the study emphasise the importance of nursing team dynamics to error reporting and suggest that psychological safety is especially important to error reporting.

Post-acute (long) COVID-19 quality of life: validation of the German version of (PAC19QoL) instrument.

Purpose: The aim of our study was to validate a German translation of the post-acute (long) COVID-19 quality of life (PAC-19QoL) instrument among German patients with long COVID-19 syndrome. Patients and methods: The PAC-19QoL instrument was translated into the German language and administrated to patients with long COVID-19 syndrome. Cronbach's alpha coefficient was used to analyze the internal consistency of the instrument. Construction validity was evaluated by using Pearson's correlation coefficient and Spearman's rank correlation. Scores of patients and controls were compared using the Mann-Whitney U-test. Results: A total of 45 asymptomatic and 41 symptomatic participants were included. In total, 41 patients with long COVID-19 syndrome completed the PAC-19QoL and EQ-5D-5L questionnaires. PAC-19QoL domain scores were significantly different between symptomatic and asymptomatic participants. All items achieved a Cronbach's alpha >0.7. There was a significant correlation between all domains on the test (p < 0.001), with the highest correlation between total (r = 0.994) and domain 1 (r = 0.991). Spearman's rank correlation analysis confirmed that the instrument items correlated with the objective PAC-19QoL examination findings. Conclusion: The German version of the instrument is valid and reliable and can be a suitable tool for research and daily clinical practice among patients with long COVID-19 syndrome.

Outcomes in Patients With von Willebrand Disease Receiving Recombinant von Willebrand Factor on Demand and in Surgical Settings: Chart Review.

This European observational chart review assessed the efficacy/safety of recombinant von Willebrand factor (rVWF) for on-demand treatment of spontaneous/traumatic bleeds and prevention and/or treatment of surgery-related bleeding in adults with von Willebrand disease (VWD). Patients (n = 91) were enrolled at first rVWF administration (index). Data were collected for the 12 months before index and until death, loss to follow-up, or end of study (3-12 months after index). Fifteen patients reported an rVWF-treated spontaneous/traumatic bleed at index. Bleed resolution was obtained for 14 patients (unknown status, n = 1), and investigators assessed treatment satisfaction for 13 rVWF prescriptions (2 moderate, 5 good, and 6 excellent). rVWF was used to prevent/treat surgery-related bleeds at index in 76 patients. Bleed resolution was achieved in 25/58 rVWF-treated surgeries; bleed resolution was not applicable for 33 surgeries. In both groups, there were no reports of treatment-emergent adverse events after initiating rVWF, including hypersensitivity reactions, thrombotic events, and VWF inhibitor development. rVWF was shown to be effective for the on-demand treatment of spontaneous/traumatic bleeds, and for the prevention and treatment of surgical bleeds in this real-world VWD population.

Characteristics of neonatal herpes simplex central nervous system disease in Australia (1997-2020).

BACKGROUND: Neonatal herpes simplex virus (HSV) central nervous system (CNS) disease can occur in isolation or as part of disseminated infection. We sought to describe neonatal HSV CNS disease in Australia over 24 years. METHODS: Neonates (≤28 days) with confirmed HSV infection, reported prospectively to the Australian Paediatric Surveillance Unit (1997-2020), were evaluated for HSV CNS disease (laboratory confirmation with clinical evidence of encephalitis, e.g., lethargy, seizures, focal signs; and/or abnormalities on neuroimaging or electroencephalogram), and compared with neonates without CNS disease. CNS-restricted disease was compared with CNS-disseminated disease. FINDINGS: Of 195 neonates with HSV disease; 87 (45%) had CNS disease (1.29 cases/100,000 live births per year, 95% CI: 1·04-1·59). Neonates with CNS disease were significantly more likely to be male than neonates without CNS disease (60% versus 39%, OR=2·32, 95% CI 1·29-4·18). Of the neonates with CNS disease, those with CNS-restricted disease (52/87, 60%) presented later than neonates with CNS-disseminated disease (35/87, 40%), (mean 12 versus 6 days). Twenty (23%) neonates with CNS disease died, the majority with CNS-disseminated disease (n = 19). Most neonates received aciclovir therapy (94·3%), however five neonates with unrecognised CNS disseminated disease (diagnosed at autopsy) had not been treated. Survivors of CNS disease were significantly more likely to have adverse neurological sequelae, compared with those without CNS disease (30% versus 4%, OR: 9·60, 95% CI: 2·6-35·0). INTERPRETATION: Male neonates have a higher burden of HSV CNS disease. Despite the use of antiviral agents, morbidity following neonatal HSV CNS disease remains high. Evaluation of adjunctive therapies to improve outcomes is needed.

4'-Fluorouridine mitigates lethal infection with pandemic human and highly pathogenic avian influenza viruses.

Influenza outbreaks are associated with substantial morbidity, mortality and economic burden. Next generation antivirals are needed to treat seasonal infections and prepare against zoonotic spillover of avian influenza viruses with pandemic potential. Having previously identified oral efficacy of the nucleoside analog 4'-Fluorouridine (4'-FlU, EIDD-2749) against SARS-CoV-2 and respiratory syncytial virus (RSV), we explored activity of the compound against seasonal and highly pathogenic influenza (HPAI) viruses in cell culture, human airway epithelium (HAE) models, and/or two animal models, ferrets and mice, that assess IAV transmission and lethal viral pneumonia, respectively. 4'-FlU inhibited a panel of relevant influenza A and B viruses with nanomolar to sub-micromolar potency in HAE cells. In vitro polymerase assays revealed immediate chain termination of IAV polymerase after 4'-FlU incorporation, in contrast to delayed chain termination of SARS-CoV-2 and RSV polymerase. Once-daily oral treatment of ferrets with 2 mg/kg 4'-FlU initiated 12 hours after infection rapidly stopped virus shedding and prevented transmission to untreated sentinels. Treatment of mice infected with a lethal inoculum of pandemic A/CA/07/2009 (H1N1)pdm09 (pdmCa09) with 4'-FlU alleviated pneumonia. Three doses mediated complete survival when treatment was initiated up to 60 hours after infection, indicating a broad time window for effective intervention. Therapeutic oral 4'-FlU ensured survival of animals infected with HPAI A/VN/12/2003 (H5N1) and of immunocompromised mice infected with pdmCa09. Recoverees were protected against homologous reinfection. This study defines the mechanistic foundation for high sensitivity of influenza viruses to 4'-FlU and supports 4'-FlU as developmental candidate for the treatment of seasonal and pandemic influenza.

Where are the critical care nurses? A statewide analysis of actively practicing nurses' transitions out of the clinical area.

BACKGROUND: Critical care nurse shortages and burnout have spurred interest in the adequacy of nursing supply in the United States. Nurses can move between clinical areas without  additional education or licensure. PURPOSE: To identify transitions that critical care nurses make into non-critical care areas, and examine the prevalence and characteristics associated with those transitions. METHODS: Secondary analysis of state licensure data from 2001-2013. DISCUSSION: More than 75% of nurses (n = 8,408) left critical care in the state, with 44% making clinical area transitions within 5 years. Critical care nurses transitioned into emergency, peri-operative, and cardiology areas. Those observed in recession years were less likely to make transitions; female and nurses with masters/doctorate degrees were more likely. CONCLUSION: This study used state workforce data to examine transitions out of critical care nursing. Findings can inform policies to retain and recruit nurses back into critical care, especially during public health crises.

Quality and safety education for nurses: A bibliometric analysis.

PURPOSE: Since its origin in the United States in 2005, Quality and Safety Education for Nurses (QSEN) has guided nurses' preparation for alleviating preventable harm and improving quality safe care. QSEN's value is illustrated through specific inclusion in the competency-based 2021 American Association for Colleges of Nursing (AACN) Essentials. The purpose of this bibliometric analysis is to explore publication patterns of the extant QSEN literature to assess QSEN's spread and global penetration and to map the available knowledge and data regarding quality and safety education for nurses. DESIGN: Bibliometric analysis. METHOD: Two QSEN investigators and two health science librarians completed database searches to identify articles with keywords QSEN or Quality and safety education for nursing. Inclusion criteria were (1) QSEN-specific and (2) published in a peer-reviewed journal. Using PRISMA screening, the final sample included 221 articles between 2007 and 2021. RESULTS: Average annual QSEN publications was 14.5 articles; the highest was 26 publications in 2017. Article types were 84 research, 77 descriptive/reviews, 28 quality improvement projects or case studies, 20 statements, and 12 editorials. Focus analysis revealed 165 education articles, 35 clinical practice, 17 professional development, and 4 leadership/administration. Fourteen journals published three or more; eight were education journals. Nine topic clusters indicated areas of publication focus, including clinical teaching, simulations, performance, context, and criteria of analysis, factors of efficacy, innovation and advanced practice, patient care and outcomes, academic concepts, and research frameworks. CONCLUSIONS: Results reveal far less QSEN penetration for guiding professional practice, research measuring outcomes and impact, and global collaboration to examine cultural implications for diversity and inclusion. Results present future recommendations to assure all nurses worldwide have access to competency development to alleviate preventable healthcare harm. CLINICAL RELEVANCE: Originating in the United States (US), the QSEN project provided the seminal framework for transforming education and practice through defining the six quality and safety competencies (patient-centered care, teamwork and collaboration, evidence-based practice, quality improvement, safety, and informatics) essential to alleviate preventable healthcare harm. Results reveal opportunities to advance QSEN penetration in developing professional practice, guiding research measuring outcomes and impact, and extending global collaboration to examine cultural implications for diversity and inclusion.

How Does Workplace Violence-Reporting Culture Affect Workplace Violence, Nurse Burnout, and Patient Safety?

BACKGROUND: Workplace violence (WPV) against nurses has a negative impact on the nurses and the care they provide. Formal reporting of WPV is necessary to understand the nature of violent incidents, develop proactive coping strategies, and provide support for nurses affected by WPV. PURPOSE: This study explored the relationships among nurses' WPV experiences, burnout, patient safety, and the moderating effect of WPV-reporting culture on these relationships. METHODS: This descriptive cross-sectional study used secondary data collected from 1781 nurses at a large academic medical center. RESULTS: Workplace violence increased nurse burnout, which in turn negatively affected patient safety. A strong WPV-reporting culture increased the negative effect of WPV on burnout but mitigated the negative effect of burnout on patient safety. CONCLUSIONS: The findings indicate that nurses may perceive WPV-reporting behavior as a stressor. Violence-reporting systems and procedures need to be improved to reduce the burden of reporting.

Targeted screening for congenital cytomegalovirus: A micro-costing analysis.

AIM: We aimed to determine the cost and potential cost-savings of delivering a targeted congenital cytomegalovirus (cCMV) screening programme through a universal newborn hearing screening (UNHS) programme to detect cCMV-related hearing loss in infants from Victoria, Australia. METHODS: We completed a micro-costing analysis from a health-care perspective using data from a targeted cCMV screening programme piloted between June 2019 and March 2020. The programme involved collection of saliva samples to test for cCMV in infants who: received a 'refer' result on their second newborn hearing screen; were aged 21 days or less; and born at one of four maternity hospitals in Victoria, Australia. All costs to complete targeted cCMV screening were recorded in Australian 2020 dollars. Potential costs and benefits of adding targeted cCMV screening to the pre-existing UNHS programme were compared to when no screening was available up to 18 years to determine the likely cost or cost savings. RESULTS: The cost of adding targeted cCMV screening to Victoria's UNHS is $202 per infant screened. The total cost per positive case identified is $21 456. The overall cost of adding targeted salivary cCMV screening at the point of a second 'refer' result on the UNHS programme in Victoria's four largest hospitals is estimated to be $28 966 for the first year. CONCLUSION: Targeted screening for cCMV provides families the opportunity to detect and, if appropriate, treat cCMV in the first month of life in line with current recommendations. It falls within the range between cost neutral and cost saving.

Patient Safety Culture: The Impact on Workplace Violence and Health Worker Burnout.

BACKGROUND: Patient and health care worker safety is an interconnected phenomenon. To date, few studies have examined the relationship between patient and worker safety, specifically with respect to work safety culture. Therefore, we examined patient safety culture, workplace violence (WPV), and burnout in health care workers to identify whether patient safety culture factors influence worker burnout and WPV. METHODS: This cross-sectional study used secondary survey data sent to approximately 7,100 health care workers at a large academic medical center in the United States. Instruments included the Hospital Survey on Patient Safety Culture, a WPV scale measuring physical and verbal violence perpetrated by patients or visitors, and the Emotional Exhaustion scale from the Maslach Burnout Inventory. FINDINGS: These analyses included 3,312 (47%) hospital staff who directly interacted with patients. Over half of nurse (62%), physician (53%), and allied health professional respondents (52%) reported experiencing verbal violence from a patient, and 39% of nurses and 14% of physicians reported experiencing physical violence from a patient. Burnout levels for nurses (2.67 ± 1.02) and physicians (2.65 ± 0.93) were higher than the overall average for all staff (2.61 ± 1.0). Higher levels of worker-reported patient safety culture were associated with lower odds of WPV (0.47) and lower burnout scores among workers (B = -1.02). Teamwork across units, handoffs, and transitions were dimensions of patient safety culture that also influenced WPV and burnout. CONCLUSIONS/APPLICATION TO PRACTICE: Our findings suggest that improvements in hospital strategies aimed at patient safety culture, including team cohesion with handoffs and transitions, could positively influence a reduction in WPV and burnout among health care workers.

Relational Coordination as a Predictor of Job Satisfaction and Intent to Stay Among Nurses and Physicians in the Military Health System.

INTRODUCTION: Job satisfaction and retention of military and civilian nurses and physicians who work in military treatment facilities (MTFs) are critical to maintaining quality of care and operational readiness. Civilian nurses and physicians working in MTFs supplement staffing for active duty military nurses and physicians and support operational readiness when military nurses and physicians deploy in wartime crises or humanitarian efforts. Decreased retention of military and civilian nurses and physicians can negatively impact operational readiness and patient care outcomes. Although several factors (e.g., burnout, pay, and leadership) influence job satisfaction and retention among nurses and physicians in both military and civilian healthcare settings, high-quality communication and relationships between nurses and physicians are associated with better job satisfaction and retention. However, little is known about how high-quality communication and relationships affect job satisfaction and retention among nurses and physicians in MTFs. Relational coordination (RC) is a process of high-quality communication supported by relationships of shared knowledge, shared goals, and mutual respect among members of the healthcare team. By strengthening RC, hospital leaders can more effectively achieve desired outcomes. The purpose of this study was to explore how RC influences job satisfaction and intent to stay among nurses, residents, and physicians in an Army hospital, and whether job satisfaction mediated the relationship between RC and intent to stay. MATERIALS AND METHODS: We conducted an exploratory, cross-sectional study in a 138-bed MTF in the southeastern USA and invited a convenience sample of military and civilian nurses, residents, and physicians to complete a 47-item survey on RC, job satisfaction, and intent to stay. We used Pearson's correlation to explore relationships between RC, job satisfaction, and intent to stay and then employed multiple regression to explore whether RC predicts job satisfaction and intent to stay, after controlling for professional role, demographic characteristics, and other covariates. Furthermore, we explored whether job satisfaction mediates the relationship between RC and intent to stay. RESULTS: Two hundred and eighty-nine participants completed the survey. Seventy percentage of respondents were civilian, were Caucasian (61%), and had a mean age of 40 years old. The RCs within roles (ß = 0.76, P < .001) and between roles (ß = 0.46, P < .001) were both positively associated with job satisfaction. RCs within roles was associated with higher intent to stay (ß = 0.38, P = .005). Civilian nurses and physicians reported higher intent to stay, followed by officers and enlisted service members. Job satisfaction mediated the relationship between RC within roles and intent to stay. CONCLUSION: Our findings suggest that RC is a powerful workplace dynamic that influences job satisfaction and intent to stay, for nurses, residents, and physicians in MTFs. Specifically, we found that RC was positively associated with job satisfaction and intent to stay and that job satisfaction mediates the relationship between RC and intent to stay. We recommend that hospital leaders in MTFs explore interventions to strengthen RC among health professionals by including relational, work process and structural interventions as part of their strategy for retaining military healthcare professionals.

Australian Paediatric Surveillance Unit (APSU) Annual Surveillance Report 2021.

Abstract: The Australian Paediatric Surveillance Unit (APSU) has been conducting surveillance of rare communicable and non-communicable conditions in children since its inception in 1993. In this report, the results are described of surveillance of ten communicable diseases (and complications) for 2021, including the numbers of cases and incidence estimates; demographics; clinical features; and management and short-term outcomes. The included diseases are: acute flaccid paralysis (AFP); congenital cytomegalovirus (CMV); neonatal herpes simplex virus (HSV) infection; paediatric human immunodeficiency virus (HIV) infection; perinatal exposure to HIV; severe complications from influenza; juvenile-onset respiratory papillomatosis (JoRRP); congenital rubella syndrome; congenital varicella syndrome; and neonatal varicella infection. In 2021, cases of JoRRP were reported to the APSU for the first time since 2017, indicating potential gaps in HPV vaccination. AFP surveillance by APSU again contributed to Australia achieving a minimum target incidence of one AFP case per 100,000 children aged < 15 years. There were no cases of children with severe complications of influenza. No cases of varicella or congenital rubella were reported; however, at-risk populations, especially young migrant and refugee women from countries without universal vaccination programs, need to be screened and prioritised for vaccination prior to pregnancy. Cases of perinatal exposure to HIV continue to increase; however, the rate of mother-to-child-transmission remains at low levels due to the use of effective intervention strategies. Case numbers of congenital CMV and neonatal HSV remain steady in the absence of vaccines, prompting the need for greater awareness and education, with recent calls for target screening of at-risk infants for congenital CMV.

Embodied Interaffectivity in the Emergence and Maintenance of Group Cohesion.

Group cohesion is an affect-laden construct, with a large body of research indicating its importance for success of teams. Surprisingly, it has received scant attention in collaborative learning contexts, and little is known about its development as dynamically emergent in the spontaneous, interdependent actions of actors during groupwork. This paper details an illustrative case analysis which took an embodied perspective to explore the role of interaffectivity in the emergence and maintenance of cohesion in one small group of university students who reported a highly positive and productive experience of collaborative science activities over a semester. The case analysis made visible group cohesion as unfolding and enactive in the myriad ephemeral and seemingly inconsequential microlevel behaviors that evolved into macro-temporal patterns of positive embodied interaffectivity, magnifying their visibility and collective impact. A fine-grained embodiment lens unveiled how participants cocreated collaborative affordances in actions that involved corporeal orientation as well as use of space, task, and other material artifacts. Task-related humor within routine task interaction offered the potential for establishing group cohesion in early group life, but also posed a potential threat to task-focused cohesiveness, requiring careful modulation at critical task points. Attentiveness not only to the task but importantly, to one another as interpersonal attentiveness, appeared to be a key factor in developing and maintaining group cohesion, also demonstrating collaborative learning as a process of orienting to and understanding tasks through one another. An embodiment lens highlighted mutual attentiveness in the ongoing orienter-orientee microprocesses that facilitated group orientation early in group life, and in reorienting to positive embodied interaffectivity when the group reconvened for their joint science activities in subsequent weeks.

Cost-effectiveness analysis of nivolumab plus ipilimumab plus two cycles of platinum-doublet chemotherapy versus platinum-doublet chemotherapy alone for first-line treatment of stage IV or recurrent non-small cell lung cancer in the United States.

AIM: This economic analysis evaluated the cost-effectiveness of nivolumab (NIVO) plus ipilimumab (IPI) plus two cycles of platinum-doublet chemotherapy (PDC) compared with four cycles of PDC as first-line treatment for patients with advanced NSCLC in the United States (US). METHODS: A partitioned survival model was constructed with three mutually exclusive health states: progression free, progressed disease, and death. The analysis was conducted from a US healthcare payer perspective, using a time horizon of 25 years. Costs and outcomes were discounted at 3% annually. Survival outcomes from CheckMate 9LA were extrapolated with longer follow-up data from CheckMate 227 Part 1 (NIVO + IPI) and validated against data from other relevant clinical trials and real-world registries. Health-related quality of life utility values were derived from EQ-5D-3L data collected in CheckMate 9LA. US-specific costs (2020 dollars) were used for disease management; drug acquisition, administration, and monitoring; end-of-life care; adverse events; and subsequent treatments. Model outcomes included life years (LYs) gained, quality-adjusted LYs (QALYs) gained, and incremental cost-effectiveness ratio (ICER) for NIVO + IPI + PDC versus PDC. Sensitivity and scenario analyses were conducted. RESULTS: NIVO + IPI + PDC was associated with higher projected health benefits than PDC, including gains in LYs (3.71 vs 1.89) and QALYs (2.86 vs 1.37), and higher costs ($317,581 vs $119,909). The ICER was $132,960/QALY gained. NIVO + IPI + PDC had a 78-100% probability of being cost-effective at a willingness-to-pay threshold of $150,000-$250,000/QALY. Sensitivity and scenario analyses indicated that the results were robust to changes in key parameters. LIMITATIONS: The inherent limitation in extrapolating clinical trial data was mitigated using data from the more mature CheckMate 227 Part 1 trial and validating the outcomes against data from other relevant trials and real-world registries. CONCLUSION: NIVO + IPI + PDC (two cycles) provides a new first-line treatment option for patients with advanced NSCLC that is cost-effective within a range considered acceptable in the US.