Background: Compared with chemotherapy, tarlatamab significantly prolonged overall survival in patients with extensive-stage small cell lung cancer (ES-SCLC) whose disease progressed during or after platinum-based chemotherapy. The aim of this study was to evaluate the cost-effectiveness of tarlatamab versus chemotherapy as a second-line treatment for ES-SCLC from the perspective of the US health care system. Methods: A partitioned survival model was constructed to simulate disease progression on the basis of the DeLLphi-304 trial results. A 28-day cycle length and a 10-year time horizon were adopted for the model. Direct medical costs and health utility estimates were extracted from previously published studies and publicly available databases. The model outputs included the total and incremental costs and quality-adjusted life years (QALYs). The primary outcome was the incremental cost-effectiveness ratio (ICER). The willingness-to-pay (WTP) thresholds were set at $150 000/QALY and $200 000/QALY for the United States. One-way sensitivity analysis and probabilistic sensitivity analyses were performed to evaluate the robustness of the model outcomes. Results: At an incremental cost of $203 332.28, tarlatamab yielded an additional 0.29 QALYs compared with chemotherapy. This resulted in an ICER of $701 145.79/QALY, which substantially exceeded the WTP thresholds. The cost of tarlatamab emerged as a major influential parameter in the sensitivity analyses, demonstrating its substantial impact on cost-effectiveness outcomes. Sensitivity and scenario analyses confirmed the robustness of the cost-effectiveness results. Conclusion: At WTP thresholds of $150 000/QALY and $200 000/QALY, tarlatamab was not considered a cost-effective option at the current price compared with chemotherapy for the treatment of recurrent ESCLC from the US payer perspective.

Competition law is ordinarily complex and multi-dimensional requiring detailed analysis and balancing of economic efficiencies, innovation, productivity, and consumer costs. However, competition law has an additional dimension of complexity in eras of strategic conflict as national security becomes a factor for regulators. The complexity in the era of China-US strategic rivalry is particularly acute for three reasons. One, the expanding conceptualization of national security means that security is no longer relegated solely to defence from armed attack but encompasses economic, technological, and ideological power. Two, large and strategic corporations are the leading economic actors globally, inextricably connected to economic, technological and ideological power, and therefore constitute paramount national security assets. Three, the two great powers have contrasting economic governance models. China’s distinct political-economic governance raises speculation that Chinese corporations are under the influence of a corporate parent, the Party-state, and utilized to advance Party-state objectives. This paper endeavours to outline and discuss competition law in the era of strategic conflict from a US and EU regulatory perspective and offers some pathways on analysing the issues.

Cost-Effectiveness Analysis of Guideline-Directed Medical Therapy Uptitration After Acute Decompensated Heart Failure From US and UK perspectives.

Overall, this is a useful book with some excellent insights, though written from a traditional US perspective and aimed at “clinicians” struggling to put SF techniques to helpful use.

Insights from Year 1 of Cardiothoracic Surgery Residency: A US Perspective.

ObjectiveIn the KEYNOTE-966 study, the clinical benefits of pembrolizumab plus chemotherapy were demonstrated for patients with advanced biliary tract cancer (BTC). At this point, it is unknown whether this expensive therapy is cost-effective. The purpose of this study was to evaluate the cost-effectiveness of pembrolizumab plus chemotherapy in treating BTC.MethodsWe constructed a partitioned survival model form the perspectives of US and Chinese payers. KEYNOTE-966 was used to obtain the baseline characteristics of the patients as well as their clinical data. Local databases and published literature were used to collect costs and utilities. Costs, life years, quality-adjusted life years (QALYs), incremental cost-effectiveness ratios (ICERs), incremental net health benefits (INHB), and incremental net monetary benefits (INMB) were measured and compared. We conducted sensitivity analyses in order to assess the robustness of the model. Subgroup analyses were also performed.ResultsPembrolizumab plus chemotherapy is not cost-effective in China at the willingness to pay (WTP) thresholds of $38,258 and $84,866. However, it yielded an additional 0.137 QALYs and an additional $63,864 (ICER $466,340) over chemotherapy alone. In the US, this treatment was not cost-effective, resulting in an improvement in effectiveness of 0.144 QALYs and an increase in overall cost of $141,000 (ICER of $976,925). There were INHBs of −0.616 QALYs and INMBs of -$52,237 for pembrolizumab plus chemotherapy in China if the WTP threshold for QALYs was set at $84,866, and INHBs of −0.796 QALYs and INMBs of -$119,400 when the WTP threshold was set at $150,000 for the US. Through sensitivity analyses, it was demonstrated that the results were stable. The results of the subgroup analysis indicate that better survival properties subgroups were more likely to be cost-effective, although pembrolizumab plus chemotherapy may not be cost-effective for all subgroups.ConclusionsIn the US and China, pembrolizumab plus chemotherapy may not be a cost-effective treatment option. This study provides evidence-based pricing strategies that may benefit decision makers and clinicians as they make clinical decisions. For a better understanding of the impact on budgets and the affordability of care for patients, more evidence is required.

This study focuses on the African policy of the Trump administration during his second term. The authors analyze why the formal framework for strategic planning in Africa proved too restrictive for the new US administration. Particular attention is paid to the consistent decline in international aid as a part of US African strategy. During Trump’s first term, there was a focus on streamlining goal-setting at the US Agency for International Development (USAID). In his second term, this agency was disbanded completely, creating new realities for international relations. The perception of the “trade instead of aid” concept is analyzed from both US and African perspectives in the context of implementation of the American AGOA initiative and trade wars affecting many of its participants. The authors also examine new mechanisms of American resource diplomacy that has expanded since 2025 to include conflict regions on the continent, paying particular attention to the agency of African states within the context of American strategy of situational pressure, as well as clear asymmetry in capabilities between the US and its African partners. The authors conclude that, as the African Continental Free Trade Area develops, collective agency of African countries increases, avoiding volatility in future trade wars, leading to greater stability in Africa’s economic development. The article also concludes with discussion about impact of current American strategy on Russia’s interests in Africa.

Today, Trump’s Greenland policy has brought the (potential) strategic importance of the Arctic in the East-West confrontation to the fore. However, this is not unprecedented, as there were already a number of strategic visions for the region during the Cold War. This paper examines the role of the Arctic in Cold War missile defence and nuclear plans and theories. The paper discusses how strategic changes have affected military presence in the Arctic during the Cold War, primarily from the US perspective, and what lessons can be identified from this today. It concludes that the US and NATO Arctic presence during the Cold War was strongly influenced by (nuclear) theoretical innovations, strategic changes, and military technological developments. As for NATO, the study also draws attention to how, at the conceptual level, the importance of the Arctic region has changed and evolved, as well as how it has become an operational arena in its own right.

Obesity has emerged as a significant public health concern in the US over the past five decades. This study analyses obesity mortality trends from 1968 to 2021, focusing on disparities across age, sex, race, and geographic regions. This population-based descriptive study used national mortality data from the CDC WONDER. Obesity deaths among individuals aged ≥25 years, recorded as the underlying cause, were identified using ICD codes from 1968 to 2021. Age-adjusted mortality rates (AAMRs) per 100 000 individuals were calculated. Temporal trends were analysed using Joinpoint regression. From 1968 to 2021, 174 625 obesity deaths were recorded. AAMRs increased from 1.15 (95% CI: 1.09-1.22) in 1968 to 3.39 (95% CI: 3.31-3.46) in 2019; AAMR rates increased from 3.39 (95% CI: 3.31-3.46) in 2019 to 4.54 (95% CI: 4.45-4.62) in 2021. The decline was noted from 1968 to 1985, followed by an increase until 2019; there was a substantial increase from 2019 to 2021 during the COVID-19 pandemic. Males had higher AAMRs than females during the latter part of the study period. Racial disparities persisted, with Black or African American individuals having higher AAMRs than White individuals during the study period. Between 1999 and 2019, obesity mortality rates ranged from 1.62 (95% CI: 1.44-1.80) in Hawaii to a high of 4.46 (95% CI: 4.21-4.72) in West Virginia. After a decline from 1968 to 1985, obesity AAMRs rose until 2019, and spiked during the pandemic, reaching their highest recorded level in 2021. Disparities persist across sex, race, and geography, warranting targeted public health strategies.

The Gulf of Mexico was recognized as the ‘Gulf of America’, via Presidential executive order in the United States, from February 2025. Renaming geographical or geological sites based on political or nationalist decisions risks places academics, editors, and publishers in complex situations where fact at one point in time may be labelled as false facts or misinformation at another point in time. Until 27 August 2025, 22 documents indexed in Scopus and 18 documents indexed in Web of Science had employed ‘Gulf of America’ in the title, abstract or keywords. Editors who allow authors to publish the term ‘Gulf of America’ are called upon to offer guidance. It is also important to publish the sentiment of those authors (from the US, Mexico, or elsewhere) who have employed ‘Gulf of Mexico’ in indexed academic papers from February 2025 onwards, since those papers might be interpreted as carrying – at least from a US perspective – an error of historical fact. To get a more granular appreciation of the extent of academic implications of this politically influenced toponym, the first 150 of 645 Google Scholar results (27 August 2025) were manually assessed. The analysis shows that the adoption of the politically imposed toponym ‘Gulf of America’ is confined almost entirely to U.S.-affiliated authors, while Gulf of Mexico remains the prevailing term internationally.

Arunadevi M, Karthikeyan B, Shrihari A, et al. (2024) Prediction of optimum operating parameters to enhance the performance of PEMFC using machine learning algorithms. Energy Exploration and Exploitation 43(2): 676-698. This commentary attempts to translate Santamarina and Ince's insights to the US context and draw out some implications for political organizing through the tumultuous present. Recognizing the importance of their emphasis on the local scale and bottom-up dimensions of contemporary far-right political organizing, we raise the question of whether national contexts might shape the extent to which such politics have a regional or city-level logic versus the neighbourhood scale they highlight in the UK and Spain. We also emphasize from our US perspective that the ‘local' and ‘neighbourhood’ serving as foundations of far-right politics is not a new development but is instead connected with a long and complicated political evolution that also sheds light on the strengths and limitations of past left responses. Finally, we build on Santamarina and Ince by exploring the cross-class character of white MAGA support in struggling US communities, in turn stressing the potential for local-scale labour organizing as a source of opposition to the far right.

Physiologically based pharmacokinetic (PBPK) modeling has emerged as a valuable tool in model-informed drug development (MIDD). This approach enables the integration of diverse experimental data to predict pharmacokinetics (PK) and dosing regimens and facilitates understanding of mechanism of action (MoA) and pharmacodynamics (PD). In this article we provide a landscape analysis of PBPK submissions at the U.S. Food and Drug Administration, Center for Biologics Evaluation and Research (CBER). We summarize CBER's experience on PBPK modeling and simulation (M&S) for therapeutic proteins, cell and gene therapy products. We discuss specific case studies that illustrate the use of PBPK for dose selection of therapeutic proteins, highlight recent progress and provide our perspectives on potential application of PBPK for adeno-associated virus (AAV)-based gene therapies and messenger RNA (mRNA) therapeutics. For cell and gene therapy products, PBPK M&S is emerging as MIDD approaches to support clinical trial design, dose selection, predicting PK/PD, and facilitate quantitative understanding of safety and efficacy. As the field continues to evolve, PBPK modeling is well positioned to provide supportive evidence to facilitate the development of safe and effective biological products.

Introduction: Obesity is increasingly recognized as a contributing factor in deaths from acute abdominal conditions such as obstruction, ischemia, and perforation. While these emergencies carry high mortality, national data on the role of obesity in such deaths remain limited. Prior studies focus on surgical cohorts, overlooking broader population trends. This study analyzes U.S. mortality records to assess temporal and demographic patterns in deaths where both obesity and acute abdominal emergencies were listed as contributing causes. Methods: Mortality data were extracted from the CDC WONDER database (1999-2020), identifying deaths using International Classification of Diseases, Tenth Revision (ICD-10) codes for obesity (E66) and acute abdominal emergencies, including perforations, obstruction, acute ischemia, complicated diverticular disease, and ruptured abdominal aortic aneurysm. Age-adjusted mortality rates (AAMRs) per 1,000,000 population were calculated using the 2000 U.S. standard population. Joinpoint regression evaluated annual percent changes (APCs), with statistical significance defined as a 95% confidence interval (CI) excluding zero (P < 0.05). Following STROBE guidelines, demographic and geographic factors were analyzed for patients aged ≥18 years, accounting for the growing burden of obesity among younger adults. Results: Between 1999 and 2020, 14,830 deaths were recorded (AAMR: 2.16), with a significant overall rise in mortality (APC = 3.42, CI: 2.66-4.19). Women had a higher AAMR (2.28) compared to men (1.99), both genders showing a significant gradual rise in mortality till 2018 (APC = 1.95 vs 3.49), followed by a significant sharp increase 2018 onwards (APC = 18.51, CI: 3.06-36.28 vs 20.90, CI: 6.16-37.70). Racial disparities were marked, American Indian/Alaska Natives had the highest AAMR (3.97), followed by non-Hispanic (NH) Blacks (2.75), NH Whites (2.19), and Hispanics (1.83); Asian/Pacific Islanders had the lowest (0.38) Regionally, the West reported the highest AAMR (2.58), while the Northeast had the lowest (1.76). At the state level, Vermont had the highest rate (5.94) and Virginia the lowest (1.03). Mortality was also higher in non-metro micropolitan areas (2.84) compared to large fringe metropolitan areas (1.67). Conclusion: The sharp recent rise in obesity-related mortality from acute abdominal emergencies, especially among rural and Indigenous populations, highlights the need for targeted health policy reforms addressing surgical access, perioperative care, and social determinants of health.

While Connecticut has successfully slowed overdose death (ODD) rates, additional progress is necessary. We examined policies that allocate resources with maximal efficiency to reduce ODDs. We developed a mechanistic simulation of overdose policies, including medications for opioid use disorder (OUD) among people involved in the criminal justice system both during incarceration (MOUD-INC) and post-release in the community (MOUD-COM), and naloxone in the community (NLX) to determine how maximally scaling all permutations compared to current MOUD and NLX levels (i.e., status quo) would impact five-year cohort ODDs, discounted life-years (LYs), discounted quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICER). A simulated cohort of 2748 people with OUD incarcerated in Connecticut moved between settings and OUD statuses. Costs were assessed in 2021 $US, employed health and public health sector perspective in base-case analyses and limited-societal perspective in sensitivity analyses, 3% discount rate, a cost-effectiveness criterion of < $100,000 per QALY gained. Analyses were performed over life-year and lifetime horizons. At status quo, the simulated cohort experienced 345 five-year ODDs, 16.1 per-person discounted LYs, and 12.5 per-person discounted QALYs. Individually, maximally scaling MOUD-INC reduced five-year ODDs 7%, added 0.3 LYs and 0.3 QALYs at an ICER $78,000/QALY gained; MOUD-COM reduced five-year ODDs 23%, added 1.2 LYs and 1.2 QALYs at $18,000/QALY gained; NLX reduced five-year ODDs 18%, added 0.4 LYs and 0.3 QALYs at $15,000/QALY gained. Considering all permutations, compared to status quo and each other, not all met the cost-effectiveness criterion. Maximally scaling MOUD-COM and NLX together was the most beneficial option meeting cost-effectiveness criterion, reducing five-year ODDs 39%, adding 1.5 LYs and 1.5 QALYs versus baseline at $18,000/QALY gained compared to the next-best option. Maximally scaling all had similar effects but an unfavorable ICER. In sensitivity analyses using a limited societal perspective, all options were cost-saving, and maximally scaling all three interventions was most beneficial and most cost-effective, adding 1.6 LYs, 1.5 QALYs, and averting 41% of ODD while saving society $363,000. Maximally scaling community MOUD and naloxone can reduce ODDs among people who are incarcerated by 39%. Considering societal costs, maximally scaling all three decreases ODDs while saving money.

Recently, the gene therapy eladocagene exuparvovec received accelerated approval from the US Food and Drug Administration (as eladocagene exuparvovec-tneq) for treatment of aromatic L-amino acid decarboxylase deficiency (AADCd), a rare, infantile-onset disorder characterized by developmental delays. To conduct a US, modified societal perspective cost-utility analysis comparing eladocagene exuparvovec versus best supportive care (BSC). Multistate survival modeling was implemented tracking disease progression from a "no motor function" health state to achievement of motor-function improvements, measured by: (1) multiples of the meaningful score difference (MSD) of the Peabody Developmental Motor Scales-Second Edition (PDMS-2) total score and (2) motor milestones. Eladocagene exuparvovec trials informed clinical inputs. Health-state utilities were from a US time-trade-off study that valued AADCd quality-of-life impacts. Outcomes were discounted (3%); costs were reported in 2024 US dollars. Scenario analyses, characterizing alternative approaches of the multistate survival model analyses and probabilistic sensitivity analysis to assess the impact of parameter uncertainty, were conducted. Discounted incremental quality-adjusted life-years (QALYs) for eladocagene exuparvovec were 20.83 (multiples of the MSD of total PDMS-2) and 18.44 (motor milestones). Incremental cost per QALY ranged from $199,007-$224,104. The scenario and sensitivity analyses results supported the validity of the base case analysis. Eladocagene exuparvovec is associated with considerable QALY gains compared with BSC. Within the context of other ultra-rare and/or one-time treatments, eladocagene exuparvovec provides substantial clinical improvements at lower cost than many other rare-disease treatments. Findings from this study highlight that eladocagene exuparvovec is an important treatment option for patients with AADCd.

Abstract This study investigates the evolution of protectionism metaphors in English-language media across China, the UK, and the US from 2001 to 2019. It reveals varying degrees of fundamental and incremental changes with cultural variations in the three corpora based on a refined metaphor evolution analytical model. Despite observed changes, the thematic contexts of the examined metaphors remain relatively stable within the UK, US and Chinese narratives with cultural variations and similarities. The Chinese corpus employs metaphors suggesting recurring themes that conceptualize protectionism in ‘dual roles’ and often frame China as a victim. In contrast, the UK and US corpora frame protectionism as a growing and contentious force. The consistent use of the ‘rising protectionism’ frame across three corpora suggests a shared bodily experience and global economic framework. This study contributes to metaphor theory by providing empirical insights into the diachronic metaphorical framing of protectionism from the UK, US and Chinese perspectives. It also contributes to proposing a refined analytical model for understanding metaphor evolution in global economic narratives.

ABSTRACT As the United States seeks to prioritise ‘competition with China’, debates have emerged about how this affects US engagements elsewhere. Europe occupies a contested role in this discussion. Traditionally, Washington has supported greater European unity to counter Soviet and Russian threats but resisted integration efforts that could challenge US influence. This article examines how Washington’s ambivalence about European unity is being recalibrated within the context of Sino-American competition. Drawing on alliance and coercion theory, it introduces two factors, cost tolerance and expected alignment, to explain this recalibration. It argues that US views on European unity depend not only on the perceived burdens of NATO commitments, but also on whether a more unified Europe is likely to align with US preferences on China. These factors produce a typology of US views ranging from support to opposition. The article also explores how Washington uses reward-based and coercive strategies to shape European behaviour.

Benmelstobart and anlotinib plus etoposide-carboplatin (EC) group has demonstrated substantial clinical efficacy in improving survival outcomes for patients with extensive-stage small-cell lung cancer (ES-SCLC). However, the high treatment cost raises concerns regarding its affordability and cost-effectiveness across healthcare systems with heterogeneous pricing and reimbursement mechanisms. This study aimed to evaluate the cost-effectiveness of benmelstobart and anlotinib plus EC group compared to EC alone group and anlotinib plus EC group from both US and Chinese payer perspectives. The findings are intended to inform value-based pricing strategies and evidence-based reimbursement decision-making. A partitioned survival model (PSM) with a lifetime horizon and 21-day cycles was constructed using clinical data from the ETER701 trial. Direct medical costs and health utility inputs were obtained from national databases, local hospitals, and published literature. The primary outcome was the incremental cost-effectiveness ratio (ICER), calculated by comparing costs and quality-adjusted life years (QALYs) between treatment strategies. Scenario analyses, including drug price simulations and deterministic and probabilistic sensitivity analyses, were conducted to evaluate model robustness. Willingness-to-pay (WTP) thresholds were set at $100,000/QALY and $150,000/QALY (US) and $40,011/QALY (China). In the US, the benmelstobart and anlotinib plus EC group yielded ICER of $121,560.40/QALY versus EC alone group and $127,579.09/QALY versus anlotinib plus EC group, both below the $150,000/QALY threshold. However, at the $100,000/QALY threshold, cost-effectiveness would require reducing benmelstobart's price to $1316.12/600mg. In China, the ICER of $117,667.17/QALY exceeded the local threshold. Price simulations suggested that cost-effectiveness could be achieved if prices were reduced below $2230.60/600mg (US) and $328.47/600mg (China). Sensitivity analyses identified progression-free survival (PFS) utility and benmelstobart pricing as major cost drivers. Probabilistic analysis indicated a 75.1% probability of cost-effectiveness at $150,000/QALY in the US. However, the probability of cost-effectiveness is 0% at WTP thresholds of $100,000/QALY in the US and $40,011/QALY in China. Benmelstobart plus anlotinib and EC group is likely to be cost-effective in the US at a WTP threshold of $150,000/QALY, but not in China at current prices. An 80% price reduction in China would be necessary to align with its WTP threshold, emphasizing the need for policy interventions in drug pricing and reimbursement to improve patient access.

Who should be responsible for setting standards for how automated vehicles are used? Insights of the US perspective from a 2021 nationwide survey

Metastatic urothelial carcinoma (mUC) is challenging to treat, with 37% of patients failing first-line therapy. Effective second-line treatments, like Erdafitinib, are crucial. This study evaluates the cost-effectiveness of Erdafitinib as a second-line treatment for mUC from US and Chinese payer perspectives. A Markov model was developed to project costs, life years, and quality-adjusted life years (QALYs) over lifetime. Data were collected from December 2023 to December 2024 for up-to-date estimates and were obtained from literature, health databases, and clinical trials.. The model was run to project long-term outcomes for both the United States and China. In the United States, Erdafitinib provides an additional 0.467 QALYs at a cost of $238,294.2 per QALY, which exceeds the $150,000 per QALY willingness-to-pay threshold. For China, when the cost of Erdafitinib is below $6.9 or $14 per milligram, there is a 90% probability that its incremental cost-effectiveness ratio will be below $38,223 or $84,966 per QALY, respectively. From the perspective of U.S. payers, Erdafitinib as a second-line treatment for mUC is not cost-effective. From the perspective of China, the cost-effectiveness of Erdafitinib is highly sensitive to its price, which could provide a reference for healthcare reimbursement negotiations.