Projected environmental and public health benefits of extended-interval dosing: an analysis of pembrolizumab use in a US national health system.

BACKGROUND: Health care is a major source of greenhouse gas emissions, leading to climate change and public health harms. Changes are needed to improve the environmental sustainability of health-care practices, but such changes should not sacrifice patient outcomes or financial sustainability. Alternative dosing strategies that reduce the frequency with which specialty drugs are administered, without sacrificing patient outcomes, are an attractive possibility for improving environmental sustainability. We sought to inform environmentally sustainable cancer care by estimating and comparing the environmental and financial effects of alternative, clinically equivalent strategies for pembrolizumab administration. METHODS: We conducted a retrospective analysis using a cohort of patients from the Veterans Health Administration (VHA) in the USA who received one or more pembrolizumab doses between May 1, 2020, and Sept 30, 2022. Using baseline, real-world administration of pembrolizumab, we generated simulated pembrolizumab use data under three near-equivalent counterfactual pembrolizumab administration strategies defined by combinations of weight-based dosing, pharmacy-level vial sharing and dose rounding, and extended-interval dosing (ie, every 6 weeks). For each counterfactual dosing strategy, we estimated greenhouse gas emissions related to pembrolizumab use across the VHA cohort using a deterministic environmental impact model that estimated greenhouse gas emissions due to patient travel, drug manufacture, and medical waste as the primary outcome measure. FINDINGS: We identified 7813 veterans who received at least one dose of pembrolizumab-containing therapy in the VHA during the study period. 59 140 pembrolizumab administrations occurred in the study period, of which 46 255 (78·2%) were dosed at 200 mg every 3 weeks, 12 885 (21·8%) at 400 mg every 6 weeks, and 14 955 (25·3%) were coadministered with infusional chemotherapies. Adoption of weight-based, extended-interval pembrolizumab dosing (4 mg/kg every 6 weeks) and pharmacy-level stewardship strategies (ie, dose rounding and vial sharing) for all pembrolizumab infusions would have resulted in 24·7% fewer administration events than baseline dosing (44 533 events vs 59 140 events) and an estimated 200 metric tons less CO2 emitted per year as a result of pembrolizumab use within the VHA (650 tons vs 850 tons of CO2, a relative reduction of 24%), largely due to reductions in distance travelled by patients to receive treatment. Similar results were observed when weight-based and extended-interval dosing were applied only to pembrolizumab monotherapy and pembrolizumab in combination with oral therapies. INTERPRETATION: Alternative pembrolizumab administration strategies might have environmental advantages over the current dosing and compounding paradigms. Specialty medication dosing can be optimised for health-care spending and environmental sustainability without sacrificing clinical outcomes. FUNDING: None.

Stigma towards mental illness in Asian nations and low-and-middle-income countries, and comparison with high-income countries: A literature review and practice implications.

Background: Stigma related to mental illness (and its treatment) is prevalent worldwide. This stigma could be at the structural or organizational level, societal level (interpersonal stigma), and the individual level (internalized stigma). Vulnerable populations, for example, gender minorities, children, adolescents, and geriatric populations, are more prone to stigma. The magnitude of stigma and its negative influence is determined by socio-cultural factors and macro (mental health policies, programs) or micro-level factors (societal views, health sectors, or individuals' attitudes towards mentally ill persons). Mental health stigma is associated with more serious psychological problems among the victims, reduced access to mental health care, poor adherence to treatment, and unfavorable outcomes. Although various nationwide and well-established anti-stigma interventions/campaigns exist in high-income countries (HICs) with favorable outcomes, a comprehensive synthesis of literature from the Low- and Middle-Income Countries (LMICs), more so from the Asian continent is lacking. The lack of such literature impedes growth in stigma-related research, including developing anti-stigma interventions. Aim: To synthesize the available mental health stigma literature from Asia and LMICs and compare them on the mental health stigma, anti-stigma interventions, and the effectiveness of such interventions from HICs. Materials and Methods: PubMed and Google Scholar databases were screened using the following search terms: stigma, prejudice, discrimination, stereotype, perceived stigma, associate stigma (for Stigma), mental health, mental illness, mental disorder psychiatric* (for mental health), and low-and-middle-income countries, LMICs, High-income countries, and Asia, South Asian Association for Regional Cooperation/SAARC (for countries of interest). Bibliographic and grey literature were also performed to obtain the relevant records. Results: The anti-stigma interventions in Asia nations and LMICs are generalized (vs. disorder specific), population-based (vs. specific groups, such as patients, caregivers, and health professionals), mostly educative (vs. contact-based or attitude and behavioral-based programs), and lacking in long-term effectiveness data. Government, international/national bodies, professional organizations, and mental health professionals can play a crucial in addressing mental health stigma. Conclusion: There is a need for a multi-modal intervention and multi-sectoral coordination to mitigate the mental health stigma. Greater research (nationwide surveys, cultural determinants of stigma, culture-specific anti-stigma interventions) in this area is required.

Decarbonization potential of electrifying 50% of U.S. light-duty vehicle sales by 2030.

The U.S. federal government has established goals of electrifying 50% of new light-duty vehicle sales by 2030 and reducing economy-wide greenhouse gas emissions 50-52% by 2030, from 2005 levels. Here we evaluate the vehicle electrification goal in the context of the economy-wide emissions goal. We use a vehicle fleet model and a life cycle emissions model to project vehicle sales, stock, and emissions. To account for state-level variability in electric vehicle adoption and electric grid emissions factors, we apply the models to each state. By 2030, greenhouse gas emissions are reduced by approximately 25% (from 2005) for the light-duty vehicle fleet, primarily due to fleet turnover of conventional vehicles. By 2035, emissions reductions approach 45% if both vehicle electrification and grid decarbonization goals (100% by 2035) are met. To meet climate goals, the transition to electric vehicles must be accompanied by an accelerated decarbonization of the electric grid and other actions.

Life Cycle Air Pollution, Greenhouse Gas, and Traffic Externality Benefits and Costs of Electrifying Uber and Lyft.

Transportation network companies (TNCs), such as Uber and Lyft, have pledged to fully electrify their ridesourcing vehicle fleets by 2030 in the United States. In this paper, we introduce AgentX, a novel agent-based model built in Julia for simulating ridesourcing services with high geospatial and temporal resolution. We then instantiate this model to estimate the life cycle air pollution, greenhouse gas, and traffic externality benefits and costs of serving rides based on Chicago TNC trip data from 2019 to 2022 with fully electric vehicles. We estimate that electrification reduces life cycle greenhouse gas emissions by 40-45% (9-10¢ per trip) but increases life cycle externalities from criteria air pollutants by 6-11% (1-2¢ per trip) on average across our simulations, which represent demand patterns on weekdays and weekends across seasons during prepandemic, pandemic, and post-vaccination periods. A novel finding of our work, enabled by our high resolution simulation, is that electrification may increase deadheading for TNCs due to additional travel to and from charging stations. This extra vehicle travel increases estimated congestion, crash risk, and noise externalities by 2-3% (2-3¢ per trip). Overall, electrification reduces net external costs to society by 3-11% (5-24¢ per trip), depending on the assumed social cost of carbon.

Psychiatric and neuropsychiatric issues in persons with COVID-19 infection: A case-control online study from India-Neorealist study.

Background: Many studies across the globe have evaluated the adverse mental health consequences of COVID-19 in patients who suffered from COVID-19 infection. However, a comparative study of persons who suffered from COVID-19 infection and those who witnessed the COVID-19 infection in their close relatives is lacking. Aims and Objectives: This study aims to compare the psychiatric morbidity in persons who suffered from COVID-19 infections, and those who witnessed the illness in one of their close relatives. Methods: In this cross-sectional online survey, 2,964 adult participants completed the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7) Scale, Fear of COVID-19 Scale (FCS-19), Brief Resilient Coping Scale (BRCS), The Brief Resilience Scale (BRS) and a self-designed questionnaire to evaluate other neuropsychiatric complications. Results: Compared to the close relatives who had witnessed COVID-19 infection, participants who developed COVID-19 infection had a significantly higher prevalence of depression (34.6%), anxiety disorder (32.3%), and fear of COVID-19 infection (18.8%), which was significantly higher than that noted in close relatives. However, BRS coping score was not significantly different between the two groups. Overall, about one-third of the participants who developed COVID-19 infection had depression and one-third had anxiety disorders. One-fifth of the participants reported high fear, post-traumatic symptoms, and obsessive-compulsive symptoms, whereas one-sixth reported other neuropsychiatric manifestations. Conclusion: Patients who suffered from COVID-19 have a higher prevalence of depression, anxiety, and fear as compared to those to witnessed COVID-19 in relatives.

Life Cycle Greenhouse Gas Emissions of the USPS Next-Generation Delivery Vehicle Fleet.

The United States Postal Service (USPS) plans to purchase 165,000 next-generation delivery vehicles (NGDVs) between 2023 and 2032. The USPS submitted an environmental impact statement (EIS) for two NGDV procurement scenarios: (1) 90% internal combustion engine vehicles (ICEVs) and 10% battery electric vehicles (BEVs) ("ICEV scenario") and (2) 100% BEVs ("BEV scenario"). To correct several significant deficiencies in the EIS, we conduct a cradle-to-grave life cycle greenhouse gas (GHG) assessment of these two scenarios. Our analysis improves upon the USPS's EIS by including vehicle production and end-of-life emissions, future grid decarbonization, and more accurate vehicle operating emissions. In our base case, we find that the ICEV and BEV scenarios would result in 15% greater and 8% fewer GHG emissions, respectively, than the USPS estimate. Favorable vehicle and grid development would result in 63% lower BEV scenario emissions than the USPS estimate. Consequently, we calculate a cumulative lifetime emission reduction of 57-82% (14.7-21.4 Mt CO2e) from procuring 100% BEVs instead of 10% BEVs, compared to the USPS's estimate of 10.3 Mt. Given the long NGDV lifetimes, committing to the ICEV scenario squanders an ideal use case for BEVs, jeopardizes meeting our climate goals, and forgoes potential climate and environmental justice co-benefits.

Charging Strategies to Minimize Greenhouse Gas Emissions of Electrified Delivery Vehicles.

Electrification of delivery fleets has emerged as an important opportunity to reduce the transportation sector's environmental impact, including reducing greenhouse gas (GHG) emissions. When, where, and how vehicles are charged, however, impact the reduction potential. Not only does the carbon intensity of the grid vary across time and space, but charging decisions also influence battery degradation rates, resulting in more or less frequent battery replacement. Here, we propose a model that accounts for the spatial and temporal differences in charging emissions using marginal emission factors and degradation-induced differences in production emissions using a semi-empirical degradation model. We analyze four different charging strategies and demonstrate that a baseline charging scenario, in which a vehicle is fully charged immediately upon returning to a central depot, results in the highest emissions and employing alternative charging methods can reduce emissions by 8-37%. We show that when, where, and how batteries are charged also impact the total cost of ownership. Although the lowest cost and the lowest emitting charging strategies often align, the lowest cost deployment location for electric delivery vehicles may not be in the same location that maximizes environmental benefits.

The Environmental Consequences of Electrifying Space Heating.

Decarbonization may require the efficient electrification of applications, like natural gas furnaces for space heating, that currently involve burning fossil fuels. The environmental consequences of such a fuel switch depend on location and time. Here we show that, in most parts of the U.S., a switch from natural gas to electric heat pumps would raise household heating bills and increase damages from carbon dioxide (CO2) and other pollutants. For single-family homes in 658 of the 883 locations we analyze, a shift to heat pumps would increase annual hourly peak demand for electricity. For 265 of these 658 locations peak demand already occurred in winter; for the remaining 393 heat pumps would shift peak demand from summer to winter. An economy-wide tax on CO2 emissions designed to substantially decarbonize electricity generation would make a switch to heat pumps beneficial for the environment and make electrified heating cheaper than burning natural gas. However, a sufficiently large tax would increase heating bills in cold parts of the country much more than in places with more moderate climates, even while making electric heat pumps cheaper to operate than natural gas furnaces. This differential impact raises questions about the feasibility of a carbon tax that is returned to each citizen as a uniform dividend.

Converting existing transmission corridors to HVDC is an overlooked option for increasing transmission capacity.

A changing generation mix and growing demand for carbon-free electricity will almost certainly require dramatic changes in the infrastructure and topology of the electricity system. Rather than build new lines, one way to minimize social opposition and regulatory obstacles is to increase the capacity of existing transmission corridors. In addition to upgrading the capacity of high-voltage alternating current (HVAC) lines, we identify a number of situations in which conversion from HVAC to high-voltage direct current (HVDC) is the least-cost strategy to increase the capacity of the corridor. If restricted to the existing right-of-way (ROW), we find DC conversion to be the least-cost, and in some cases the only, option for distances of >200 km or for increases of >50% capacity. Across all configurations analyzed, we assess HVDC conversion to be the lower-cost option at >350 km and >50% capacity increases. While we recognize that capacity expansion through HVDC conversion may be the optimal solution in only some situations, with future improvements in the cost and performance of solid-state power electronics, conversion to HVDC could be attractive in a growing set of circumstances.

Shore Power for Vessels Calling at U.S. Ports: Benefits and Costs.

When in port, ships burn marine diesel in on-board generators to produce electricity and are significant contributors to poor local and regional air quality. Supplying ships with grid electricity can reduce these emissions. We use two integrated assessment models to quantify the benefits of reducing the emissions of NOX, SO2, PM2.5, and CO2 that would occur if shore power were used. Using historical vessel call data, we identify combinations of vessels and berths at U.S. ports that could be switched to shore power to yield the largest gains for society. Our results indicate that, depending on the social costs of pollution assumed, an air quality benefit of $70-150 million per year could be achieved by retrofitting a quarter to two-thirds of all vessels that call at U.S. ports. Such a benefit could be produced at no net cost to society (health and environmental benefits would be balanced by the cost of ship and port retrofit) but would require many ships to be equipped to receive shore power, even if doing so would result in a private loss for the operator. Policy makers could produce a net societal gain by implementing incentives and mandates to encourage a shift toward shore power.

Electro Convulsive Therapy in Psychiatric Manifestations in Wilson's Disease.

Wilson's disease occurs due to an inborn error of metabolism. Psychiatric symptoms are often the first manifestation of the disease and can obscure the diagnosis. There are five neuropsychiatric symptoms clusters established for Wilson's disease patients: Behavior and/or personality disorders, mood disorders, cognitive deficits, psychotic manifestations, and others. The frequency with which psychiatric manifestations appears in Wilson's disease remains vague. However, whenever they occur, they need to be correctly identified and treated. Though encouraging results have been obtained in controlling psychiatric manifestations of Wilson's with psychotropic medications, some sub-group of patients fail to respond to any therapy. We aim at finding options for controlling psychosis in these patients with electro convulsive therapy (ECT). A patient exhibiting rare neuropsychiatric manifestations of Wilson's and who is not responding to psychotropic medication was considered for ECT. Considerable control over psychiatric manifestations with ECT was observed and later treated with maintenance ECTs for relapse control.