Equity implications of tobacco taxation: results from WHO FCTC investment cases.

BACKGROUND: Across time, geographies and country income levels, smoking prevalence is highest among people with lower incomes. Smoking causes further impoverishment of those on the lower end of the income spectrum through expenditure on tobacco and greater risk of ill health. METHODS: This paper summarises the results of investment case equity analyses for 19 countries, presenting the effects of increased taxation on smoking prevalence, health and expenditures. We disaggregate the number of people who smoke, smoking-attributable mortality and cigarette expenditures using smoking prevalence data by income quintile. A uniform 30% increase in price was applied across countries. We estimated the effects of the price increase on smoking prevalence, mortality and cigarette expenditures. RESULTS: In all but one country (Bhutan), a one-time 30% increase in price would reduce smoking prevalence by the largest percent among the poorest 20% of the population. All income groups in all countries would spend more on cigarettes with a 30% increase in price. However, the poorest 20% would pay an average of 12% of the additional money spent. CONCLUSIONS: Our results confirm that health benefits from increases in price through taxation are pro-poor. Even in countries where smoking prevalence is higher among wealthier groups, increasing prices can still be pro-poor due to variable responsiveness to higher prices. The costs associated with higher smoking prevalence among the poor, together with often limited access to healthcare services and displaced spending on basic needs, result in health inequality and perpetuate the cycle of poverty.

Advancing progress on tobacco control in low-income and middle-income countries through economic analysis.

BACKGROUND: More than 80% of the world's 1.3 billion tobacco users live in low-income and middle-income countries (LMICs), where progress to address tobacco and its harms has been slow. The perception that tobacco control detracts from economic priorities has impeded progress. The Secretariat of the WHO Framework Convention on Tobacco Control (FCTC) is leading the FCTC 2030 project, which includes technical assistance to LMICs to analyse the economic costs of tobacco use and the benefits of tobacco control. METHODS: The Secretariat of the WHO FCTC, United Nations Development Programme and WHO supported 21 LMICs between 2017 and 2022 to complete national investment cases to guide country implementation of the WHO FCTC, with analytical support provided by RTI International. These country-level cases combine customised estimates of tobacco's economic impact with qualitative analysis of socio-political factors influencing tobacco control. This paper overviews the approach, observed tobacco control advancements and learnings from 21 countries: Armenia, Cabo Verde, Cambodia, Chad, Colombia, Costa Rica, El Salvador, Eswatini, Georgia, Ghana, Jordan, Laos, Madagascar, Myanmar, Nepal, Samoa, Sierra Leone, Sri Lanka, Suriname, Tunisia and Zambia. RESULTS: Tobacco control advancements in line with investment case findings and recommendations have been observed in 17 of the 21 countries, and many have improved collaboration and policy coherence between health and economic stakeholders. CONCLUSIONS: Tobacco control must be seen as more than a health concern. Tobacco control leads to economic benefits and contributes to sustainable development. National investment cases can support country ownership and leadership to advance tobacco control.

Interpreting results, impacts and implications from WHO FCTC tobacco control investment cases in 21 low-income and middle-income countries.

BACKGROUND: Tobacco control investment cases analyse the health and socioeconomic costs of tobacco use and the benefits that can be achieved from implementing measures outlined in the WHO Framework Convention on Tobacco Control (WHO FCTC). They are intended to provide policy-makers and other stakeholders with country-level evidence that is relevant, useful and responsive to national priorities and policy context. METHODS: This paper synthesises findings from investment cases conducted in Armenia, Cabo Verde, Cambodia, Chad, Colombia, Costa Rica, El Salvador, Eswatini, Georgia, Ghana, Jordan, Laos, Madagascar, Myanmar, Nepal, Samoa, Sierra Leone, Sri Lanka, Suriname, Tunisia and Zambia. We examine annual socioeconomic costs associated with tobacco use, focusing on smoking-related healthcare expenditures, the value of lives lost due to tobacco-related mortality and workplace productivity losses due to smoking. We explore potential benefits associated with WHO FCTC tobacco demand-reduction measures. RESULTS: Tobacco use results in average annual socioeconomic losses of US$95 million, US$610 million and US$1.6 billion among the low-income (n=3), lower-middle-income (n=12) and upper-middle-income countries (n=6) included in this analysis, respectively. These losses are equal to 1.1%, 1.8% and 2.9% of average annual national gross domestic product, respectively. Implementation and enforcement of WHO FCTC tobacco demand-reduction measures would lead to reduced tobacco use, fewer tobacco-related deaths and reduced socioeconomic losses. CONCLUSIONS: WHO FCTC tobacco control measures would provide a positive return on investment in every country analysed.

Test-guided dietary management of eczema in children: A randomized controlled feasibility trial (TEST).

BACKGROUND: Parents commonly ask about food allergy tests, to find a cause for their child's eczema, yet the value of routine testing is uncertain. OBJECTIVE: To determine whether a clinical trial comparing test-guided dietary advice versus usual care, for the management of eczema, is feasible. METHODS: Children (>3 months and <5 years) with mild-to-severe eczema, recruited via primary care, were individually randomized (1:1) to intervention or usual care. Intervention participants underwent structured allergy history and skin prick tests (SPT) with dietary advice for cow's milk, hen's egg, wheat, peanut, cashew and codfish. All participants were followed up for 24 weeks. A sample of doctors and parents was interviewed. Registration ISRCTN15397185. RESULTS: From 1059 invitation letters sent to carers of potentially eligible children, 84 were randomized (42 per group) with mean age of 32.4 months (SD 13.9) and POEM of 8.7 (4.8). Of the 42, 6 (14%) intervention participants were advised to exclude one or more foods, most commonly egg, peanut or milk. By participant, 1/6 had an oral food challenge (negative); 3/6 were told to exclude until review in allergy clinic; and 6/6 advised a home dietary trial (exclusion and reintroduction of food over 4-6 weeks) - with 1/6 partially completing it. Participant retention (four withdrawals) and data completeness (74%-100%) were acceptable and contamination low (two usual care participants had allergy tests). There were three minor SPT-related adverse events. During follow-up, 12 intervention and 8 usual care participants had minor, unrelated adverse events plus one unrelated hospital admission. CONCLUSIONS: It is possible to recruit, randomize and retain children with eczema from primary care into a trial of food allergy screening and to collect the outcomes of interest. Changes to recruitment and inclusion criteria are needed in a definitive trial, to ensure inclusion of younger children from more diverse backgrounds.

Financing intersectoral action for health: a systematic review of co-financing models.

BACKGROUND: Addressing the social and other non-biological determinants of health largely depends on policies and programmes implemented outside the health sector. While there is growing evidence on the effectiveness of interventions that tackle these upstream determinants, the health sector does not typically prioritise them. From a health perspective, they may not be cost-effective because their non-health outcomes tend to be ignored. Non-health sectors may, in turn, undervalue interventions with important co-benefits for population health, given their focus on their own sectoral objectives. The societal value of win-win interventions with impacts on multiple development goals may, therefore, be under-valued and under-resourced, as a result of siloed resource allocation mechanisms. Pooling budgets across sectors could ensure the total multi-sectoral value of these interventions is captured, and sectors' shared goals are achieved more efficiently. Under such a co-financing approach, the cost of interventions with multi-sectoral outcomes would be shared by benefiting sectors, stimulating mutually beneficial cross-sectoral investments. Leveraging funding in other sectors could off-set flat-lining global development assistance for health and optimise public spending. Although there have been experiments with such cross-sectoral co-financing in several settings, there has been limited analysis to examine these models, their performance and their institutional feasibility. AIM: This study aimed to identify and characterise cross-sectoral co-financing models, their operational modalities, effectiveness, and institutional enablers and barriers. METHODS: We conducted a systematic review of peer-reviewed and grey literature, following PRISMA guidelines. Studies were included if data was provided on interventions funded across two or more sectors, or multiple budgets. Extracted data were categorised and qualitatively coded. RESULTS: Of 2751 publications screened, 81 cases of co-financing were identified. Most were from high-income countries (93%), but six innovative models were found in Uganda, Brazil, El Salvador, Mozambique, Zambia, and Kenya that also included non-public and international payers. The highest number of cases involved the health (93%), social care (64%) and education (22%) sectors. Co-financing models were most often implemented with the intention of integrating services across sectors for defined target populations, although models were also found aimed at health promotion activities outside the health sector and cross-sectoral financial rewards. Interventions were either implemented and governed by a single sector or delivered in an integrated manner with cross-sectoral accountability. Resource constraints and political relevance emerged as key enablers of co-financing, while lack of clarity around the roles of different sectoral players and the objectives of the pooling were found to be barriers to success. Although rigorous impact or economic evaluations were scarce, positive process measures were frequently reported with some evidence suggesting co-financing contributed to improved outcomes. CONCLUSION: Co-financing remains in an exploratory phase, with diverse models having been implemented across sectors and settings. By incentivising intersectoral action on structural inequities and barriers to health interventions, such a novel financing mechanism could contribute to more effective engagement of non-health sectors; to efficiency gains in the financing of universal health coverage; and to simultaneously achieving health and other well-being related sustainable development goals.

A double-reprocessing high-level disinfection protocol does not eliminate positive cultures from the elevators of duodenoscopes.

BACKGROUND AND STUDY AIM: Duodenoscopes have been the source of serious infection, despite correct performance of high-level disinfection (HLD). This study aimed to observe the impact of performing HLD twice on the rate of positive cultures from duodenoscope elevators. METHODS: We performed double HLD (DHLD; i. e. complete manual cleaning followed by automated reprocessing, with the entire process repeated) and then randomly cultured the elevators of our duodenoscopes on about 30 % of occasions. RESULTS: DHLD was associated with positive elevator cultures for any microorganism in 9.4 % of cases, with a 0.8 % rate of known pathogens (627 cultures) between May 2015 and February 2016. After February 2016, and in association with changing the precleaning fluid, as well as use of a new FDA-recommended cleaning brush, the rate of positive cultures for any microorganism after DHLD was 4.8 % and 0.2 % for known pathogens (420 cultures). In a third phase, characterized by a change in personnel performing DHLD and retirement of a duodenoscope with a high rate of positive cultures, the rate of positive cultures for any microorganism was 4.9 % (783 cultures) and the rate of positive culture for known pathogens was 0.3 %. To our knowledge, no duodenoscope transmission of infection occurred during the study interval. CONCLUSIONS: DHLD resulted in a low rate of positive cultures for known pathogens and for organisms of low pathogenic potential, but did not eliminate these, from duodenoscope elevators. Additional improvements in HLD protocols and/or duodenoscope design are needed.

Candida auris outbreak at a tertiary care hospital during the COVID-19 pandemic.

BACKGROUND: Candida auris (C auris) is a fungal pathogen that has the potential for environmental persistence leading to outbreaks in health care settings. There has been a worldwide surge in C auris outbreaks during the COVID-19 pandemic. In this report, we describe an outbreak of C auris, its control, patient outcomes, and lessons learned. METHODS: The outbreak occurred in a 600-bed adult academic tertiary care hospital. Contact tracing was initiated immediately after identification of the index case and surveillance testing for C auris was obtained from patients who were exposed to the index case. Infection prevention measures were closely followed. RESULTS: A total of 560 cultures were performed on 453 unique patients between August 2021 and December 2021. Of those, 31 cultures (5.5%) were positive for C auris; 27 (87.1%) were colonized with C auris, while 4 patients developed a clinical infection (12.9%). The secondary attack rate was 6.8% (31/453). The 30-day all-cause mortality rate for all patients who tested positive for C auris was 9.7%. DISCUSSION: C auris can cause protracted outbreaks that result in colonization and invasive infections. Multidisciplinary work to improve adherence to infection prevention measures as well as targeted admission screening are essential to limit outbreaks.

The reported impact of non-communicable disease investment cases in 13 countries.

Non-communicable diseases (NCDs) are a leading health and development challenge worldwide. Since 2015, WHO and the United Nations Development Programme have provided support to governments to develop national NCD investment cases to describe the socioeconomic dimensions of NCDs. To assess the impact of the investment cases, semistructured interviews and a structured process for gathering written feedback were conducted between July and October 2022 with key informants in 13 countries who had developed a national NCD investment case between 2015 and 2020. Investment cases describe: (1) the social and economic costs of NCDs, including their distribution and projections over time; (2) priority areas for scaled up action; (3) the cost and returns from investing in WHO-recommended measures to prevent and manage NCDs; and (4) the political dimensions of NCD responses. While no country had implemented all the recommendations set out in their investment case reports, actions and policy changes attributable to the investment cases were identified, across (1) governance; (2) financing; and (3) health service access and delivery. The pathways of these changes included: (1) stronger collaboration across government ministries and partners; (2) advocacy for NCD prevention and control; (3) grounding efforts in nationally owned data and evidence; (4) developing mutually embraced 'language' across health and finance; and (5) elevating the priority accorded to NCDs, by framing action as an investment rather than a cost. The assessment also identified barriers to progress on the investment case implementation, including the influence of some private sector entities on sectors other than health, the impact of the COVID-19 pandemic, and changes in senior political and technical government officials. The results suggest that national NCD investment cases can significantly contribute to catalysing the prevention and control of NCDs through strengthening governance, financing, and health service access and delivery.

Universal health coverage: necessary but not sufficient.

In this article, we highlight key considerations for better addressing sexual and reproductive health and rights issues within universal health coverage (UHC), particularly in the context of the post-2015 sustainable development agenda. We look at UHC as a health, development and health care financing issue, and its history. We discuss its limitations as currently understood from a human rights perspective, and show why structural barriers to health and the legal and policy environment, which are essential to health (particularly to sexual and reproductive health and rights), require critical consideration in current discussions about health in the post-2015 development framework and must be taken into account above and beyond UHC in any future health goal. As a result, we suggest that UHC alone will not result in universal access to sexual and reproductive health, and certainly not to sexual and reproductive rights. Instead, it should be considered as a means to achieving broader health and development goals. A goal such as seeking to reach the highest attainable standard of health or maximizing healthy lives that is informed by a rights-based approach should be the aspiration for the post-2015 development agenda.

Two-step algorithm-based Clostridioides difficile testing as a tool for antibiotic stewardship.

OBJECTIVES: Diagnosis of Clostridium difficile infection (CDI) can be challenging due to high colonization rates. Unlike PCR-only testing, two-step algorithm testing (that includes toxin and PCR) may help differentiate colonization from active infection, but it is unknown if this type of testing impacts treatment decisions. We examined the association between changing CDI diagnostic methods, the way the testing results were displayed, and the rates of CDI-specific treatment. METHODS: We performed a retrospective analysis of positive C. difficile cases over 2 years, a year preceding and following our institution's transition from PCR to two-step testing. During the PCR period, results were displayed in the electronic medical record as 'positive'. In the two-step period, positive results were either displayed as 'likely colonized' or 'toxin positive'. Rates of CDI-specific therapy and adverse patient outcomes (30-day mortality and intensive care unit admission) were compared among the three groups. RESULTS: A total of 610 patients had positive results over the study period. Of the 354 patients in the PCR group, 329 (93%) were treated with CDI-specific therapy. Of the 142 patients in the likely colonized group, 59 (42%) were treated. All 114 patients in the toxin-positive group were treated. Multivariate analysis of patients who were PCR positive or likely colonized showed that tests sent in the two-step era were less likely to be associated with treatment for CDI (odds ratio 0.05, 95% CI 0.03-0.09). DISCUSSION: We found a correlation between changing the type of test and the way the results were displayed and reduction in CDI-specific antibiotic use without restricting clinician diagnostic ordering.

Comparison of lotions, creams, gels and ointments for the treatment of childhood eczema: the BEE RCT.

Background: Emollients are recommended for children with eczema (atopic eczema/dermatitis). A lack of head-to-head comparisons of the effectiveness and acceptability of the different types of emollients has resulted in a 'trial and error' approach to prescribing. Objective: To compare the effectiveness and acceptability of four commonly used types of emollients for the treatment of childhood eczema. Design: Four group, parallel, individually randomised, superiority randomised clinical trials with a nested qualitative study, completed in 2021. A purposeful sample of parents/children was interviewed at ≈ 4 and ≈ 16 weeks. Setting: Primary care (78 general practitioner surgeries) in England. Participants: Children aged between 6 months and 12 years with eczema, of at least mild severity, and with no known sensitivity to the study emollients or their constituents. Interventions: Study emollients sharing the same characteristics in the four types of lotion, cream, gel or ointment, alongside usual care, and allocated using a web-based randomisation system. Participants were unmasked and the researcher assessing the Eczema Area Severity Index scores was masked. Main outcome measures: The primary outcome was Patient-Oriented Eczema Measure scores over 16 weeks. The secondary outcomes were Patient-Oriented Eczema Measure scores over 52 weeks, Eczema Area Severity Index score at 16 weeks, quality of life (Atopic Dermatitis Quality of Life, Child Health Utility-9 Dimensions and EuroQol-5 Dimensions, five-level version, scores), Dermatitis Family Impact and satisfaction levels at 16 weeks. Results: A total of 550 children were randomised to receive lotion (analysed for primary outcome 131/allocated 137), cream (137/140), gel (130/135) or ointment (126/138). At baseline, 86.0% of participants were white and 46.4% were female. The median (interquartile range) age was 4 (2-8) years and the median Patient-Oriented Eczema Measure score was 9.3 (SD 5.5). There was no evidence of a difference in mean Patient-Oriented Eczema Measure scores over the first 16 weeks between emollient types (global p = 0.765): adjusted Patient-Oriented Eczema Measure pairwise differences - cream-lotion 0.42 (95% confidence interval -0.48 to 1.32), gel-lotion 0.17 (95% confidence interval -0.75 to 1.09), ointment-lotion -0.01 (95% confidence interval -0.93 to 0.91), gel-cream -0.25 (95% confidence interval -1.15 to 0.65), ointment-cream -0.43 (95% confidence interval -1.34 to 0.48) and ointment-gel -0.18 (95% confidence interval -1.11 to 0.75). There was no effect modification by parent expectation, age, disease severity or the application of UK diagnostic criteria, and no differences between groups in any of the secondary outcomes. Median weekly use of allocated emollient, non-allocated emollient and topical corticosteroids was similar across groups. Overall satisfaction was highest for lotions and gels. There was no difference in the number of adverse reactions and there were no significant adverse events. In the nested qualitative study (n = 44 parents, n = 25 children), opinions about the acceptability of creams and ointments varied most, yet problems with all types were reported. Effectiveness may be favoured over acceptability. Parents preferred pumps and bottles over tubs and reported improved knowledge about, and use of, emollients as a result of taking part in the trial. Limitations: Parents and clinicians were unmasked to allocation. The findings may not apply to non-study emollients of the same type or to children from more ethnically diverse backgrounds. Conclusions: The four emollient types were equally effective. Satisfaction with the same emollient types varies, with different parents/children favouring different ones. Users need to be able to choose from a range of emollient types to find one that suits them. Future work: Future work could focus on how best to support shared decision-making of different emollient types and evaluations of other paraffin-based, non-paraffin and 'novel' emollients. Trial registration: This trial is registered as ISRCTN84540529 and EudraCT 2017-000688-34. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (HTA 15/130/07) and will be published in full in Health Technology Assessment; Vol. 27, No. 19. See the NIHR Journals Library website for further project information.

One in five children in the UK have eczema, a long-term, itchy, dry skin condition. It can significantly affect both the child and their family. Most children are diagnosed and looked after by their family doctor (general practitioner) and are prescribed moisturisers (also called emollients) to relieve skin dryness and other creams (topical corticosteroids) to control flare-ups. However, there are many different types of emollients and, to our knowledge, limited research to show which is better. In the Best Emollients for Eczema clinical trial, we compared the four main types of moisturisers ­ lotions, creams, gels and ointments. These types vary in their consistency, from thin to thick. We recruited 550 children (most of whom were white and had moderate eczema) and randomly assigned them to use one of the four different types as their main moisturiser for 16 weeks. We found no difference in effectiveness. Parent-reported eczema symptoms, eczema severity and quality of life were the same for all the four types of moisturisers. However, overall satisfaction was highest for lotions and gels. Ointments may need to be used less and cause less stinging. We interviewed 44 parents and 25 children who took part. Opinions of all four types of moisturisers varied. What one family liked about a moisturiser was not necessarily the same for another and preferences were individual to each user. Sometimes there was a tension between how well a moisturiser worked (effectiveness) and how easy it was to use (acceptability). In these cases, effectiveness tended to decide whether or not parents kept using it. People found moisturisers in pumps and bottles easier to use than those in tubs. A number of participants valued the information they were given about how to use moisturisers. Our results suggest that the type of moisturiser matters less than finding one that suits the child and family.

Competing Frames in Global Health Governance: An Analysis of Stakeholder Influence on the Political Declaration on Non-communicable Diseases.

BACKGROUND: Non-communicable diseases (NCDs) are increasingly recognized as a significant threat to health and development globally, and United Nations (UN) Member States adopted the Political Declaration of the Third High-level Meeting (HLM) on the prevention and control of NCDs in 2018. The negotiation process for the Declaration included consultations with Member States, intergovernmental organizations (IGOs), and non-state actors such as non-governmental organizations (NGOs) and the private sector. With NCD responses facing charges of inadequacy, it is important to scrutinize the governance process behind relevant high-level global decisions and commitments. METHODS: Through a review of 159 documents submitted by stakeholders during the negotiation process, we outline a typology of policy positions advocated by various stakeholders in the development of the Declaration. We document changes in text from the draft to the final version of the Declaration to analyse the extent to which various positions and their proponents were influential. RESULTS: NGOs and low- and middle-income countries (LMICs) generally pursued 'stricter' governance of NCD risk factors including stronger regulation of unhealthy products and improved management of conflicts of interest that arise when health-harming industries are involved in health policy-making. The private sector and high-income countries generally opposed greater restrictions on commercial factors. The pattern of changes between the draft and final Declaration indicate that advocated positions tended to be included in the Declaration if there was no clear opponent, whereas opposed positions were either not included or included with ambiguous language. CONCLUSION: Many cost-effective policy options to address NCDs, such as taxation of health-harming products, were opposed by high-income countries and the private sector and not well-represented in the Declaration. To ensure robust political commitments and action on NCDs, multi-stakeholder governance for NCDs must consider imbalances in power and influence amongst constituents as well as biases and conflicts in positioning.

Clinical comparison and agreement of PCR, antigen, and viral culture for the diagnosis of COVID-19: Clinical Agreement Between Diagnostics for COVID19.

The aim of this study is to compare the COVID-19 nasopharyngeal PCR (NP PCR) to antigen, nasal PCR, and viral culture. One-hundred-and-fourteen risk-stratified patients were tested by culture, nasal PCR, NP PCR, and Ag testing. Twenty (48%) of the high risk and 23 (32%) of the low risk were NP PCR positive. Compared with NP PCR, the sensitivity of nasal PCR, Sofia Ag, BinaxNOW Ag, and culture were 44%, 31%, 37%, and 15%. In the high risk group, the sensitivity of these tests improved to 71%, 37%, 50%, and 22%. Agreement between tests was highest between nasal PCR and both antigen tests. Patients who were NP PCR positive but antigen negative were more likely to have remote prior COVID-19 infection (p<0.01). Nasal PCR and antigen positive patients were more likely to have symptoms (p = 0.01).

Effectiveness and safety of lotion, cream, gel, and ointment emollients for childhood eczema: a pragmatic, randomised, phase 4, superiority trial.

BACKGROUND: To our knowledge, there are no trials comparing emollients commonly used for childhood eczema. We aimed to compare the clinical effectiveness and safety of the four main emollient types: lotions, creams, gels, and ointments. METHODS: We did a pragmatic, individually randomised, parallel group, phase 4 superiority trial in 77 general practice surgeries in England. Children aged between 6 months and 12 years with eczema (Patient Orientated Eczema Measure [POEM] score >2) were randomly assigned (1:1:1:1; stratified by centre and minimised by baseline POEM score and age, using a web-based system) to lotions, creams, gels, or ointments. Clinicians and parents were unmasked. The initial emollient prescription was for 500 g or 500 mL, to be applied twice daily and as required. Subsequent prescriptions were determined by the family. The primary outcome was parent-reported eczema severity over 16 weeks (weekly POEM), with analysis as randomly assigned regardless of adherence, adjusting for baseline and stratification variables. Safety was assessed in all randomly assigned participants. This trial was registered with the ISRCTN registry, ISRCTN84540529. FINDINGS: Between Jan 19, 2018, and Oct 31, 2019, 12 417 children were assessed for eligibility, 550 of whom were randomly assigned to a treatment group (137 to lotion, 140 to cream, 135 to gel, and 138 to ointment). The numbers of participants who contributed at least two POEM scores and were included in the primary analysis were 131 in the lotion group, 137 in the cream group, 130 in the gel group, and 126 in the ointment group. Baseline median age was 4 years (IQR 2-8); 255 (46%) participants were girls, 295 (54%) were boys; 473 (86%) participants were White; and the mean POEM score was 9·3 (SD 5·5). There was no difference in eczema severity between emollient types over 16 weeks (global p value=0·77), with adjusted POEM pairwise differences of: cream versus lotion 0·42 (95% CI -0·48 to 1·32), gel versus lotion 0·17 (-0·75 to 1·09), ointment versus lotion -0·01 (-0·93 to 0·91), gel versus cream -0·25 (-1·15 to 0·65), ointment versus cream -0·43 (-1·34 to 0·48), and ointment versus gel -0·18 (-1·11 to 0·75). This result remained unchanged following multiple imputation, sensitivity, and subgroup analyses. The total number of adverse events did not significantly differ between the treatment groups (lotions 49 [36%], creams 54 [39%], gels 54 [40%], and ointments 48 [35%]; p=0·79), although stinging was less common with ointments (12 [9%] of 138 participants) than lotions (28 [20%] of 137), creams (24 [17%] of 140), or gels (25 [19%] of 135). INTERPRETATION: We found no difference in effectiveness between the four main types of emollients for childhood eczema. Users need to be able to choose from a range of emollients to find one that they are more likely to use effectively. FUNDING: National Institute for Health and Care Research.

Cellular association and assembly of a multistage delivery system.

The realization that blood-borne delivery systems must overcome a multiplicity of biological barriers has led to the fabrication of a multistage delivery system (MDS) designed to temporally release successive stages of particles or agents to conquer sequential barriers, with the goal of enhancing delivery of therapeutic and diagnostic agents to the target site. In its simplest form, the MDS comprises stage-one porous silicon microparticles that function as carriers of second-stage nanoparticles. Cellular uptake of nontargeted discoidal silicon microparticles by macrophages is confirmed by electron and atomic force microscopy (AFM). Using superparamagnetic iron oxide nanoparticles (SPIONs) as a model of secondary nanoparticles, successful loading of the porous matrix of silicon microparticles is achieved, and retention of the nanoparticles is enhanced by aminosilylation of the loaded microparticles with 3-aminopropyltriethoxysilane. The impact of silane concentration and reaction time on the nature of the silane polymer on porous silicon is investigated by AFM and X-ray photoelectron microscopy. Tissue samples from mice intravenously administered the MDS support co-localization of silicon microparticles and SPIONs across various tissues with enhanced SPION release in spleen, compared to liver and lungs, and enhanced retention of SPIONs following silane capping of the MDS. Phantom models of the SPION-loaded MDS display negative contrast in magnetic resonance images. In addition to forming a cap over the silicon pores, the silane polymer provides free amines for antibody conjugation to the microparticles, with both VEGFR-2- and PECAM-specific antibodies leading to enhanced endothelial association. This study demonstrates the assembly and cellular association of a multiparticle delivery system that is biomolecularly targeted and has potential for applications in biological imaging.

Changing the culture of urine culturing: Utilizing Agile Implementation to improve diagnostic stewardship in the ICU.

Over diagnosis of catheter-associated urinary tract infection (CAUTI) contributes to unnecessary and excessive antibiotic use, selection for resistant organisms, increased risk for Clostridiodes difficile infections, as well as a false elevation in CAUTI rates. Utilizing agile implementation to implement a urine culture algorithm achieved statistically significant reduction in CAUTI rates in a critical care unit resulting in sustainment and spread throughout the system.

Correction: The investment case as a mechanism for addressing the NCD burden: Evaluating the NCD institutional context in Jamaica, and the return on investment of select interventions.

[This corrects the article DOI: 10.1371/journal.pone.0223412.].

Utilizing a real-time discussion approach to improve the appropriateness of Clostridioides difficile testing and the potential unintended consequences of this strategy.

We report electronic medical record interventions to reduce Clostridioides difficile testing risk 'alert fatigue.' We used a behavioral approach to diagnostic stewardship and observed a decrease in the number of tests ordered of ~4.5 per month (P < .0001). Although the number of inappropriate tests decreased during the study period, delayed testing increased.