In Vitro Evaluation oF Aerosol Drug Delivery With And Without High Flow Nasal Cannula Using Pressurized Metered Dose Inhaler And Jet Nebulizer in Pediatrics

Background: HFNC system is a novel device used with aerosol therapy and seems to be rapidly accepted. Although there are some studies conducted on HFNC and vibrating mesh nebulizer, the effect of HFNC on aerosol delivery using jet nebulizer or pressurized metered-dose inhaler (pMDI) has not been reported. In an effort to examine the effect of HFNC on aerosol deposition, this study was conducted to quantify aerosol drug delivery with or without a HFNC using either pMDI or jet nebulizer. Methodology: The SAINT model, attached to an absolute filter (Respirgard II, Vital Signs Colorado Inc., Englewood, CO, USA) for aerosol collection, was connected to a pediatric breathing simulator (Harvard Apparatus, Model 613, South Natick, MA, USA). To keep the filter and the SAINT model in upright position to collect aerosolized drug, an elbow adapter was connected between the absolute filter and the breathing simulator. An infant HFNC (Optiflow, Fisher & Paykel Healthcare LTD., Auckland, New Zealand) ran at 3 l/min O2 was attached to the nares of the SAINT model. Breathing parameters used in this study were Vt of 100 mL, RR of 30 breaths/min, and I:E ratio of 1: 1.4. Aerosol drug was administered using: 1) Misty-neb jet nebulizer (Allegiance Healthcare, McGaw Park, Illinois, USA) powered by air at 8 l/min using pediatric aerosol facemask (B&F Medical, Allied Healthcare Products, Saint Louis, MO, USA) to deliver albuterol sulfate (2.5 mg/3 mL NS), and 2) Four actuations of Ventolin HFA pMDI (90 μg/puff) (GlaxoSmithKline, Research Triangle Park, NC, USA) combined with VHC (AeroChamber plus with Flow-Vu, Monaghan Medical, Plattsburgh, NY, USA). Aerosol was administered to the model with and without the HFNC and another without (n=3). Drug was collected on an absolute filter, eluted and measured using spectrophotometry. Independent t tests were performed for data analysis. Statistical significance was determined with a p value of \u3c0.05. Results: The mean inhaled mass percent was greatest for pMDI with (p = 0.0001) or without HFNC (p = 0.003). Removing HFNC from the nares before aerosol treatment trended to increase drug delivery with the jet nebulizer (p = 0.024), and increased drug delivery by 6 fold with pMDI (p = 0.003). Conclusions: Aerosol drug may be administered in pediatrics receiving HFNC therapy using either jet nebulizer or pMDI. However, using pMDI, either with or without HFNC, is the best option. When delivering medical aerosol by mask, whether by jet nebulizer or pMDI, removing HFNC led to an increase in inhaled mass percent. However, the benefit of increased aerosol delivery must be weighed against the risk of lung derecruitment when nasal prongs are removed

Factors Associated with Quit Interest and Quit Attempts among Young Adult JUUL Users

Despite reports suggesting young people are interested in quitting e-cigarettes, little work has examined predictors of quit outcomes. This study aimed to identify factors associated with quit outcomes among JUUL e-cigarette users in a longitudinal sample of young adults. We assessed undergraduate past-30-day JUUL users during autumn 2018 (N = 225); Our outcomes included short-term quit attempts and interest (spring 2019), and long-term quit attempts (spring 2020). We used logistic regression to examine the associations between our outcomes and JUUL use characteristics, other tobacco use, and sociodemographic factors. Findings indicated 76% of users were interested in quitting JUUL, and more than 40% reported a quit attempt. Quit outcomes were not related to sociodemographics. Short-term quit outcomes were more likely among freshmen and less likely among recent cigarillo users. Heavy JUUL users were more likely to report short- and long-term quit attempts, but JUUL device owners were less likely to report short- and long-term quit attempts. Higher nicotine dependence reduced the likelihood of a long-term quit attempt. There is a need for policy level actions that address tobacco control among this population. Findings suggest a range of unique factors that can inform such policies and programs to curb young adult e-cigarette use

The Effects of Oral Nicotine Pouch Packaging Features on Adult Tobacco Users’ and Non-Users’ Product Perceptions

Background: Oral nicotine pouches (ONPs) are novel products that are marketed as “tobacco-free” alternatives to cigarettes and smokeless tobacco (ST). This study examined the effects of ONP packaging features on adult tobacco users’ and non-users’ product perceptions. Materials and Methods: Adult tobacco users (cigarettes, ST, and dual cigarette/ST) and non-users (total N = 301) viewed ONP pack images in a 4 × 3 × 2 between-subject experiment testing the effects of the displayed flavor (cool mint, coffee, dark frost, and smooth), nicotine concentration (none displayed on the package, 3 mg, and 6 mg), and addiction warning label (yes or no). The outcomes were perceived substitutability of ONPs for cigarettes and ST and perceived risks. We modeled the effects of tobacco user status and the experimental factors on these outcomes. Results: All tobacco user groups perceived ONPs to be significantly less harmful and less addictive than non-users. There were significant effects of nicotine concentration on perceived risks. Compared to packages that did not display nicotine concentration, packages displaying 6 mg nicotine concentration produced significantly lower perceived harm (β = −0.23, 95% CI −0.44, −0.02), perceived addictiveness (β = −0.28, 95% CI −0.51, −0.05), risk appraisals of harm (β = −0.50, 95% CI −0.88, −0.12) and risk appraisals of addictiveness (β = −0.53, 95% CI −0.95, −0.11). Conclusions: The study findings demonstrate that the nicotine concentration displayed on ONP packaging can affect adults’ perceptions of ONPs. Further research on the effects of ONP packaging features emphasizing nicotine (e.g., “tobacco free” nicotine claims) on tobacco users and non-users is needed to assess their potential public health impact

Perceptions of oral nicotine pouches & their marketing among Ohio Appalachia smokers and smokeless tobacco users.

BackgroundOral nicotine pouches (ONPs) are novel products, gaining popularity and marketed as "tobacco-free" alternatives to cigarettes and smokeless tobacco (SLT), but their public health impact is unknown. This study qualitatively examined ONP appeal and perceptions among cigarette smokers and SLT users from Ohio Appalachia.MethodsIn 2022, we conducted 10 virtual focus groups with smokers (n = 19) and smokeless tobacco users (n = 18) from Appalachia Ohio aged ≥21 to examine perceptions of risks and benefits, substitutability for cigarettes and SLT, and ONP marketing. We transcribed focus groups verbatim, thematically coded transcripts, and analyzed coded data for prominent themes.ResultsParticipants perceived ONPs to have similar or less risk than cigarettes/SLT but prominently discussed gastrointestinal and cardiovascular risks. Addiction risk was thought to be comparable to cigarettes/SLT, citing "nicotine is nicotine." Participants viewed ONPs to be situational rather than complete substitutes for cigarettes/SLT, viewing them as "cleaner," more socially acceptable, and discrete. Despite appealing features of ONP marketing, participants surmised ads would appeal to youth, new users, tobacco users seeking to cut down/quit, or to "high class," "white-collar" demographics.ConclusionsParticipants' perceptions of ONPs and their marketing suggest ONPs are more likely to be used as situational versus complete substitutes for cigarettes and SLT. While situational substitution could exacerbate disparities in Appalachia by facilitating more frequent tobacco/nicotine use, complete substitution could reduce disparities. Research is needed to understand how perceptions, the appeal of ONP marketing, and novel product features translate to patterns of use to understand ONPs' potential impact

Racial, Lifestyle, and Healthcare Contributors to Perceived Cancer Risk among Physically Active Adolescent and Young Adult Women Aged 18–39 Years

The cancer incidence among adolescents and young adults (AYAs) has significantly increased in recent years, but there is limited information about the factors that influence the perceived cancer risk among AYAs. A cross-sectional, web-based survey of 281 physically active Black and White AYA women was administered to assess the influences of demographic characteristics, family history of cancer, cancer risk factor knowledge, and lifestyle-related risk and protective behaviors on perceived cancer risk. Linear regression analyses were performed in SAS version 9.4. Self-reported Black race (β = −0.62, 95% CI: −1.07, −0.17) and routine doctor visits (β = −0.62, 95% CI: −1.18, −0.07) were related to a lower perceived cancer risk. Family history of cancer (β = 0.56, 95% CI: 0.13, 0.99), cancer risk factor knowledge (β = 0.11, 95% CI: 0.03, 0.19), and current smoking status (β = 0.80, 95% CI: 0.20, 1.40) were related to a higher perceived cancer risk. Perceptions of cancer risk varied among this sample of physically active, AYA women. Lower perceptions of cancer risk among Black AYA women demonstrate a need for culturally tailored cancer educational information that presents objective data on lifetime cancer risk. Reportedly higher perceptions of cancer risk among AYA smokers presents an ideal opportunity to promote smoking cessation interventions. Future interventions to address cancer risk perception profiles among physically active, AYA women should tailor approaches that are inclusive of these unique characteristics

Global fertility in 204 countries and territories, 1950–2021, with forecasts to 2100: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

BackgroundAccurate assessments of current and future fertility—including overall trends and changing population age structures across countries and regions—are essential to help plan for the profound social, economic, environmental, and geopolitical challenges that these changes will bring. Estimates and projections of fertility are necessary to inform policies involving resource and health-care needs, labour supply, education, gender equality, and family planning and support. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 produced up-to-date and comprehensive demographic assessments of key fertility indicators at global, regional, and national levels from 1950 to 2021 and forecast fertility metrics to 2100 based on a reference scenario and key policy-dependent alternative scenarios. MethodsTo estimate fertility indicators from 1950 to 2021, mixed-effects regression models and spatiotemporal Gaussian process regression were used to synthesise data from 8709 country-years of vital and sample registrations, 1455 surveys and censuses, and 150 other sources, and to generate age-specific fertility rates (ASFRs) for 5-year age groups from age 10 years to 54 years. ASFRs were summed across age groups to produce estimates of total fertility rate (TFR). Livebirths were calculated by multiplying ASFR and age-specific female population, then summing across ages 10–54 years. To forecast future fertility up to 2100, our Institute for Health Metrics and Evaluation (IHME) forecasting model was based on projections of completed cohort fertility at age 50 years (CCF50; the average number of children born over time to females from a specified birth cohort), which yields more stable and accurate measures of fertility than directly modelling TFR. CCF50 was modelled using an ensemble approach in which three sub-models (with two, three, and four covariates variously consisting of female educational attainment, contraceptive met need, population density in habitable areas, and under-5 mortality) were given equal weights, and analyses were conducted utilising the MR-BRT (meta-regression—Bayesian, regularised, trimmed) tool. To capture time-series trends in CCF50 not explained by these covariates, we used a first-order autoregressive model on the residual term. CCF50 as a proportion of each 5-year ASFR was predicted using a linear mixed-effects model with fixed-effects covariates (female educational attainment and contraceptive met need) and random intercepts for geographical regions. Projected TFRs were then computed for each calendar year as the sum of single-year ASFRs across age groups. The reference forecast is our estimate of the most likely fertility future given the model, past fertility, forecasts of covariates, and historical relationships between covariates and fertility. We additionally produced forecasts for multiple alternative scenarios in each location: the UN Sustainable Development Goal (SDG) for education is achieved by 2030; the contraceptive met need SDG is achieved by 2030; pro-natal policies are enacted to create supportive environments for those who give birth; and the previous three scenarios combined. Uncertainty from past data inputs and model estimation was propagated throughout analyses by taking 1000 draws for past and present fertility estimates and 500 draws for future forecasts from the estimated distribution for each metric, with 95% uncertainty intervals (UIs) given as the 2·5 and 97·5 percentiles of the draws. To evaluate the forecasting performance of our model and others, we computed skill values—a metric assessing gain in forecasting accuracy—by comparing predicted versus observed ASFRs from the past 15 years (2007–21). A positive skill metric indicates that the model being evaluated performs better than the baseline model (here, a simplified model holding 2007 values constant in the future), and a negative metric indicates that the evaluated model performs worse than baseline. FindingsDuring the period from 1950 to 2021, global TFR more than halved, from 4·84 (95% UI 4·63–5·06) to 2·23 (2·09–2·38). Global annual livebirths peaked in 2016 at 142 million (95% UI 137–147), declining to 129 million (121–138) in 2021. Fertility rates declined in all countries and territories since 1950, with TFR remaining above 2·1—canonically considered replacement-level fertility—in 94 (46·1%) countries and territories in 2021. This included 44 of 46 countries in sub-Saharan Africa, which was the super-region with the largest share of livebirths in 2021 (29·2% [28·7–29·6]). 47 countries and territories in which lowest estimated fertility between 1950 and 2021 was below replacement experienced one or more subsequent years with higher fertility; only three of these locations rebounded above replacement levels. Future fertility rates were projected to continue to decline worldwide, reaching a global TFR of 1·83 (1·59–2·08) in 2050 and 1·59 (1·25–1·96) in 2100 under the reference scenario. The number of countries and territories with fertility rates remaining above replacement was forecast to be 49 (24·0%) in 2050 and only six (2·9%) in 2100, with three of these six countries included in the 2021 World Bank-defined low-income group, all located in the GBD super-region of sub-Saharan Africa. The proportion of livebirths occurring in sub-Saharan Africa was forecast to increase to more than half of the world's livebirths in 2100, to 41·3% (39·6–43·1) in 2050 and 54·3% (47·1–59·5) in 2100. The share of livebirths was projected to decline between 2021 and 2100 in most of the six other super-regions—decreasing, for example, in south Asia from 24·8% (23·7–25·8) in 2021 to 16·7% (14·3–19·1) in 2050 and 7·1% (4·4–10·1) in 2100—but was forecast to increase modestly in the north Africa and Middle East and high-income super-regions. Forecast estimates for the alternative combined scenario suggest that meeting SDG targets for education and contraceptive met need, as well as implementing pro-natal policies, would result in global TFRs of 1·65 (1·40–1·92) in 2050 and 1·62 (1·35–1·95) in 2100. The forecasting skill metric values for the IHME model were positive across all age groups, indicating that the model is better than the constant prediction. InterpretationFertility is declining globally, with rates in more than half of all countries and territories in 2021 below replacement level. Trends since 2000 show considerable heterogeneity in the steepness of declines, and only a small number of countries experienced even a slight fertility rebound after their lowest observed rate, with none reaching replacement level. Additionally, the distribution of livebirths across the globe is shifting, with a greater proportion occurring in the lowest-income countries. Future fertility rates will continue to decline worldwide and will remain low even under successful implementation of pro-natal policies. These changes will have far-reaching economic and societal consequences due to ageing populations and declining workforces in higher-income countries, combined with an increasing share of livebirths among the already poorest regions of the world. FundingBill & Melinda Gates Foundation

Global fertility in 204 countries and territories, 1950–2021, with forecasts to 2100: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

BackgroundAccurate assessments of current and future fertility—including overall trends and changing population age structures across countries and regions—are essential to help plan for the profound social, economic, environmental, and geopolitical challenges that these changes will bring. Estimates and projections of fertility are necessary to inform policies involving resource and health-care needs, labour supply, education, gender equality, and family planning and support. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 produced up-to-date and comprehensive demographic assessments of key fertility indicators at global, regional, and national levels from 1950 to 2021 and forecast fertility metrics to 2100 based on a reference scenario and key policy-dependent alternative scenarios.MethodsTo estimate fertility indicators from 1950 to 2021, mixed-effects regression models and spatiotemporal Gaussian process regression were used to synthesise data from 8709 country-years of vital and sample registrations, 1455 surveys and censuses, and 150 other sources, and to generate age-specific fertility rates (ASFRs) for 5-year age groups from age 10 years to 54 years. ASFRs were summed across age groups to produce estimates of total fertility rate (TFR). Livebirths were calculated by multiplying ASFR and age-specific female population, then summing across ages 10–54 years. To forecast future fertility up to 2100, our Institute for Health Metrics and Evaluation (IHME) forecasting model was based on projections of completed cohort fertility at age 50 years (CCF50; the average number of children born over time to females from a specified birth cohort), which yields more stable and accurate measures of fertility than directly modelling TFR. CCF50 was modelled using an ensemble approach in which three sub-models (with two, three, and four covariates variously consisting of female educational attainment, contraceptive met need, population density in habitable areas, and under-5 mortality) were given equal weights, and analyses were conducted utilising the MR-BRT (meta-regression—Bayesian, regularised, trimmed) tool. To capture time-series trends in CCF50 not explained by these covariates, we used a first-order autoregressive model on the residual term. CCF50 as a proportion of each 5-year ASFR was predicted using a linear mixed-effects model with fixed-effects covariates (female educational attainment and contraceptive met need) and random intercepts for geographical regions. Projected TFRs were then computed for each calendar year as the sum of single-year ASFRs across age groups. The reference forecast is our estimate of the most likely fertility future given the model, past fertility, forecasts of covariates, and historical relationships between covariates and fertility. We additionally produced forecasts for multiple alternative scenarios in each location: the UN Sustainable Development Goal (SDG) for education is achieved by 2030; the contraceptive met need SDG is achieved by 2030; pro-natal policies are enacted to create supportive environments for those who give birth; and the previous three scenarios combined. Uncertainty from past data inputs and model estimation was propagated throughout analyses by taking 1000 draws for past and present fertility estimates and 500 draws for future forecasts from the estimated distribution for each metric, with 95% uncertainty intervals (UIs) given as the 2·5 and 97·5 percentiles of the draws. To evaluate the forecasting performance of our model and others, we computed skill values—a metric assessing gain in forecasting accuracy—by comparing predicted versus observed ASFRs from the past 15 years (2007–21). A positive skill metric indicates that the model being evaluated performs better than the baseline model (here, a simplified model holding 2007 values constant in the future), and a negative metric indicates that the evaluated model performs worse than baseline.FindingsDuring the period from 1950 to 2021, global TFR more than halved, from 4·84 (95% UI 4·63–5·06) to 2·23 (2·09–2·38). Global annual livebirths peaked in 2016 at 142 million (95% UI 137–147), declining to 129 million (121–138) in 2021. Fertility rates declined in all countries and territories since 1950, with TFR remaining above 2·1—canonically considered replacement-level fertility—in 94 (46·1%) countries and territories in 2021. This included 44 of 46 countries in sub-Saharan Africa, which was the super-region with the largest share of livebirths in 2021 (29·2% [28·7–29·6]). 47 countries and territories in which lowest estimated fertility between 1950 and 2021 was below replacement experienced one or more subsequent years with higher fertility; only three of these locations rebounded above replacement levels. Future fertility rates were projected to continue to decline worldwide, reaching a global TFR of 1·83 (1·59–2·08) in 2050 and 1·59 (1·25–1·96) in 2100 under the reference scenario. The number of countries and territories with fertility rates remaining above replacement was forecast to be 49 (24·0%) in 2050 and only six (2·9%) in 2100, with three of these six countries included in the 2021 World Bank-defined low-income group, all located in the GBD super-region of sub-Saharan Africa. The proportion of livebirths occurring in sub-Saharan Africa was forecast to increase to more than half of the world's livebirths in 2100, to 41·3% (39·6–43·1) in 2050 and 54·3% (47·1–59·5) in 2100. The share of livebirths was projected to decline between 2021 and 2100 in most of the six other super-regions—decreasing, for example, in south Asia from 24·8% (23·7–25·8) in 2021 to 16·7% (14·3–19·1) in 2050 and 7·1% (4·4–10·1) in 2100—but was forecast to increase modestly in the north Africa and Middle East and high-income super-regions. Forecast estimates for the alternative combined scenario suggest that meeting SDG targets for education and contraceptive met need, as well as implementing pro-natal policies, would result in global TFRs of 1·65 (1·40–1·92) in 2050 and 1·62 (1·35–1·95) in 2100. The forecasting skill metric values for the IHME model were positive across all age groups, indicating that the model is better than the constant prediction.InterpretationFertility is declining globally, with rates in more than half of all countries and territories in 2021 below replacement level. Trends since 2000 show considerable heterogeneity in the steepness of declines, and only a small number of countries experienced even a slight fertility rebound after their lowest observed rate, with none reaching replacement level. Additionally, the distribution of livebirths across the globe is shifting, with a greater proportion occurring in the lowest-income countries. Future fertility rates will continue to decline worldwide and will remain low even under successful implementation of pro-natal policies. These changes will have far-reaching economic and societal consequences due to ageing populations and declining workforces in higher-income countries, combined with an increasing share of livebirths among the already poorest regions of the world.</p