Superior Orbital Fissure Syndrome in the Setting of Relapsing Polychondritis with Concurrent Sjogren's Syndrome: A Case Report.

PURPOSE: Ophthalmic manifestations of varying severity are often associated with systemic autoimmune conditions. Superior orbital fissure syndrome (SOFS) is a rare cranial neuropathy affecting nerves passing through the superior orbital fissure that causes a distinctive pattern of extraocular and pupillary findings. We report the coexistence of SOFS, relapsing polychondritis (RP) and Sjögren's syndrome (SS) in a 52-year-old female who presented with a past medical history of hypothyroidism, Raynaud's syndrome, and intermittent dry mouth and a 1-week history of worsening chemosis, proptosis, diplopia, and painful ophthalmoplegia. METHODS: Following a comprehensive eye examination, the patient underwent a CT head with contrast, MRI of the orbit, lumbar puncture, and laboratory investigations. RESULTS: CT and MRI examination revealed inflammatory standing in periorbital subcutaneous soft tissues and bilateral exophthalmos with right intraconal fat stranding surrounding the intraorbital and intracanalicular segments of the nerve, respectively. Lumbar puncture and laboratory investigations revealed an elevation in inflammatory biomarkers, a negative infectious workup, and ruled in SS when considering her history alongside a positive Schirmer test. She was started on high-dose steroids, which led to significant improvement; however, treatment revealed type 2 diabetes, necessitating a faster steroid taper, during which there was a reoccurrence of scleritis and ophthalmoplegia, leading to the initiation of rituximab infusions. After completing rituximab course, she was transitioned back to steroid therapy and was successfully tapered without event. CONCLUSION: This case is notable for the rare coexistence of SOFS with RP/SS overlap syndrome and highlights the management of concurrent orbital inflammatory syndrome and autoimmune diseases.

Clinical and economic impacts of a modified-observational screening approach to well-appearing infants born to mothers with chorioamnionitis.

OBJECTIVE: Term infants born to mothers with chorioamnionitis are at risk for early-onset sepsis (EOS). We aimed to measure the impact of changing from a categorical to a modified-observational EOS screening approach on NICU admission, antibiotic utilization, and hospitalization costs. STUDY DESIGN: Single-center retrospective pre-post cohort study of full-term infants born to mothers with chorioamnionitis. Primary outcomes included NICU admission, antibiotic utilization, and hospitalization costs. Outcomes were adjusted for demographic variables. Budget-impact analysis was performed using bootstrapping with replication. RESULTS: 380 term infants were included (197 categorical; 183 modified-observational). There was a significant decrease in NICU admission and antibiotic utilization (p < 0.05) in the modified-observational cohort but no significant difference in per-patient total hospitalization costs. Budget-impact analysis suggested a high probability of cost savings. CONCLUSION: A modified-observational approach to evaluating term infants of mothers with chorioamnionitis can reduce NICU admission and unnecessary antibiotic therapy, and may lead to cost-savings.

The Concise Guide to PHARMACOLOGY 2023/24: Ion channels.

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and over 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org/), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.16178. Ion channels are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.

Towards two decades of Atlantic Ocean mass and heat transports at 26.5° N.

Continuous measurements of the Atlantic meridional overturning circulation (AMOC) and meridional ocean heat transport at 26.5° N began in April 2004 and are currently available through December 2020. Approximately 90% of the total meridional heat transport (MHT) at 26.5° N is carried by the zonally averaged overturning circulation, and an even larger fraction of the heat transport variability (approx. 95%) is explained by the variability of the zonally averaged overturning. A physically based separation of the heat transport into large-scale AMOC, gyre and shallow wind-driven overturning components remains challenging and requires new investigations and approaches. We review the major interannual changes in the AMOC and MHT that have occurred over the nearly two decades of available observations and their documented impacts on North Atlantic heat content. Changes in the flow-weighted temperature of the Florida Current (Gulf Stream) over the past two decades are now taken into account in the estimates of MHT, and have led to an increased heat transport relative to the AMOC strength in recent years. Estimates of the MHT at 26.5° N from coupled models and various surface flux datasets still tend to show low biases relative to the observations, but indirect estimates based on residual methods (top of atmosphere net radiative flux minus atmospheric energy divergence) have shown recent promise in reproducing the heat transport and its interannual variability. This article is part of a discussion meeting issue 'Atlantic overturning: new observations and challenges'.

Current Trends in Invasive Closure of Patent Ductus Arteriosus in Very Low Birth Weight Infants in United States Children's Hospitals, 2016-2021.

OBJECTIVE: To describe the current practices in invasive patent ductus arteriosus (PDA) closure (surgical ligation or transcatheter occlusion) in very low birth weight (VLBW) infants and changes in patient characteristics and outcomes from 2016 to 2021 among US children's hospitals. STUDY DESIGN: We evaluated a retrospective cohort of VLBW infants (birth weight 400-1499 g and gestational age 22-31 weeks) who had invasive PDA closure within 6 months of age from 2016 to 2021 in children's hospitals in the Pediatric Health Information System. Changes in patient characteristics and outcomes over time were evaluated using generalized linear models and generalized linear mixed models. RESULTS: 2418 VLBW infants (1182 surgical ligation; 1236 transcatheter occlusion) from 42 hospitals were included. The proportion of infants receiving transcatheter occlusion increased from 17.2% in 2016 to 84.4% in 2021 (P < .001). In 2021, 28/42 (67%) hospitals had performed transcatheter occlusion in > 80% of their VLBW infants needing invasive PDA closure, compared with only 2/42 (5%) in 2016. Although median postmenstrual age (PMA) at PDA closure did not change for the overall cohort, PMA at transcatheter occlusion decreased from 38 weeks in 2016 to 31 weeks by 2020, P < .001. Among those infants not intubated prior to PDA closure, extubation within 3 days postprocedure increased over time (yearly adjusted odds ratios of 1.26 [1.08-1.48]). Length of stay and mortality did not change over time. CONCLUSION: We report rapid adoption of transcatheter occlusion for PDA among VLBW infants in US children's hospitals over time. Transcatheter occlusions were performed at younger PMA over time.

Tracing the impacts of recent rapid sea ice changes and the A68 megaberg on the surface freshwater balance of the Weddell and Scotia Seas.

The Southern Ocean upper-layer freshwater balance exerts a global climatic influence by modulating density stratification and biological productivity, and hence the exchange of heat and carbon between the atmosphere and the ocean interior. It is thus important to understand and quantify the time-varying freshwater inputs, which is challenging from measurements of salinity alone. Here we use seawater oxygen isotopes from samples collected between 2016 and 2021 along a transect spanning the Scotia and northern Weddell Seas to separate the freshwater contributions from sea ice and meteoric sources. The unprecedented retreat of sea ice in 2016 is evidenced as a strong increase in sea ice melt across the northern Weddell Sea, with surface values increasing approximately two percentage points between 2016 and 2018 and column inventories increasing approximately 1 to 2 m. Surface meteoric water concentrations exceeded 4% in early 2021 close to South Georgia due to meltwater from the A68 megaberg; smaller icebergs may influence meteoric water at other times also. Both these inputs highlight the importance of a changing cryosphere for upper-ocean freshening; potential future sea ice retreats and increases in iceberg calving would enhance the impacts of these freshwater sources on the ocean and climate. This article is part of a discussion meeting issue 'Heat and carbon uptake in the Southern Ocean: the state of the art and future priorities'.

Finale: impact of the ORCHESTRA/ENCORE programmes on Southern Ocean heat and carbon understanding.

The 5-year Ocean Regulation of Climate by Heat and Carbon Sequestration and Transports (ORCHESTRA) programme and its 1-year extension ENCORE (ENCORE is the National Capability ORCHESTRA Extension) was an approximately 11-million-pound programme involving seven UK research centres that finished in March 2022. The project sought to radically improve our ability to measure, understand and predict the exchange, storage and export of heat and carbon by the Southern Ocean. It achieved this through a series of milestone observational campaigns in combination with model development and analysis. Twelve cruises in the Weddell Sea and South Atlantic were undertaken, along with mooring, glider and profiler deployments and aircraft missions, all contributing to measurements of internal ocean and air-sea heat and carbon fluxes. Numerous forward and adjoint numerical experiments were developed and supported by the analysis of coupled climate models. The programme has resulted in over 100 peer-reviewed publications to date as well as significant impacts on climate assessments and policy and science coordination groups. Here, we summarize the research highlights of the programme and assess the progress achieved by ORCHESTRA/ENCORE and the questions it raises for the future. This article is part of a discussion meeting issue 'Heat and carbon uptake in the Southern Ocean: the state of the art and future priorities'.

Using Quality Improvement to Improve Value and Reduce Waste.

Value is defined as health outcomes achieved per dollar spent. Addressing value in quality improvement (QI) efforts can help optimize patient outcomes while reducing unnecessary spending. In this article, we discuss how QI focused on reducing morbidities frequently reduces costs, and how proper cost accounting can help demonstrate improvements in value. We provide examples of high-yield opportunities for value improvement in neonatology and review the literature associated with these topics. Opportunities include reducing neonatal intensive care admissions for low-acuity infants, sepsis evaluations in low-risk infants, unnecessary total parental nutrition use, and utilization of laboratory and imaging.

Evaluation of statewide restrictions on e-cigarette nicotine strength-United States, 2017-2022.

AIMS: To evaluate statewide policies restricting e-cigarette nicotine strength. DESIGN: A difference-in-difference regression analysis was used to compare e-cigarette sales in states that restrict nicotine strength with states with no restrictions. Because flavor restrictions might affect sales and nicotine strength, states with flavor restrictions were also assessed. SETTING AND CASES: United States e-cigarette retail sales data during January 2017 to March 2022 were licensed from Information Resources Incorporated. States with restrictions included Massachusetts (restricted maximum nicotine strength to 3.5% and nontobacco flavored e-cigarette sales in December 2019); Utah (restricted nicotine strength to 3.6% in September 2021); and Rhode Island, New York and Washington (restricted nontobacco flavor sales in October 2019, May 2020 and October 2019 to January 2020, respectively). These were compared with data from 34 states with no e-cigarette nicotine strength or flavor restrictions. MEASUREMENTS: Weighted mean nicotine strength and total unit sales. Total unit sales per 1000 state population were summed into 4-week periods by state. Models controlled for emergency responses, state demographics, tobacco control policies, time and state fixed effects. FINDINGS: Restricting both nicotine strength and flavors in Massachusetts was associated with a 2.04 percentage point (pp) reduction in mean nicotine strength and 86.76-unit reduction in monthly unit sales per 1000 persons compared with states with no restrictions (all P < 0.01). Restricting nicotine strength only in Utah was associated with a 1.77 pp (P < 0.01) reduction in mean nicotine strength; however, there was no impact on unit sales. Restricting nontobacco flavor sales only in Rhode Island, New York and Washington slightly reduced mean nicotine strength (0.21, 0.62 and 0.19 pp, respectively) and sales (36.66, 34.51 and 16.37 units, respectively) (all P < 0.01). CONCLUSIONS: United States statewide policies restricting e-cigarette nicotine strength appear to be associated with reductions in average nicotine strength in sales within that state; however, there appears to be no impact on unit sales. When these policies are implemented along with flavor restrictions; reductions in average nicotine strength occur in addition to reduced unit sales.

Use of a multi-method approach to rapidly assess the impact of public health policies at the state and local level: a case study of flavored e-cigarette policies.

BACKGROUND: E-cigarettes are the most-commonly used tobacco product by youth since 2014. To prevent youth access and use of e-cigarettes, many U.S. states and localities have enacted policies over a relatively short period of time. The adoption of these policies has necessitated timely data collection to evaluate impacts. METHODS: To assess the impact of flavored e-cigarette policies in select states and local jurisdictions across the United States, a multi-method, complementary approach was implemented from July 2019 to present, which includes analyses of cross-sectional online surveys of young people ages 13-24 years with retail sales data. RESULTS: From February 2020 through February 2023, cross-sectional surveys have been conducted in three cities, one county, and eight states where policy changes have been enacted or are likely to be enacted. Data collection occurred every six months to provide near real-time data and examine trends over time. Additionally, weekly retail sales data were aggregated to showcase monthly sales trends at the national level and for the selected states. DISCUSSION: This rapid and efficient method of coupling online survey data with retail sales data provides a timely and effective approach for monitoring a quickly changing tobacco product landscape, particularly for states and localities where rapidly-available data is often not available. This approach can also be used to monitor other health behaviors and relevant policy impacts.

Rehabilitation of the P2X5 receptor: a re-evaluation of structure and function.

Of the extended family of ATP-gated P2X ion-channels, the P2X5 receptor has received comparatively little attention since first cloned over 25 years ago. Disinterest in studying this P2X subtype stems from two commonly held beliefs: (i) canonical human P2X5 is non-functional because the P2X5 subunit is truncated (hP2X5A, 422 aa) and missing the critical peptide sequence (22 aa) encoded by exon 10; (ii) rat and mouse P2X5 subunits are fully formed (455 aa) but the receptor is only weakly functional, and successive ATP responses rapidly run down in amplitude. However, newer studies have re-evaluated these notions. First, a low proportion (around 10%) of humans possess full-length P2X5 subunits (444 aa) and can form competent P2X5 receptors. Full-length P2X5 has been identified only in black Americans, but may occur in a wider population as more ethnicities are screened. Second, replacement of one of three amino acids in rat P2X5 subunits with corresponding residues in human P2X5 subunits (V67I, S191F, or F195H) significantly improves the responsiveness of rat P2X5 to ATP. Replaced residues exert an allosteric action on the left flipper, allowing the docking jaw for ATP to flex the lower body of the subunit and fully open the ion pore. This proposed action may drive the search for naturally occurring modulators which act allosterically on wildtype rat P2X5. This review collates the available information on the structure and function of human and rat P2X5 receptors, with the view to rehabilitating the reputation of these ATP-gated ion channels and stimulating future lines of research.

Hospital variation in neonatal echocardiography among very preterm infants at US children's hospitals.

OBJECTIVE: Estimate hospital variation in echocardiography (echo) among very preterm infants. STUDY DESIGN: Retrospective cohort study of very preterm (<32 weeks) infants discharged between 2012 and 2019 from US children's hospitals. Echo exposure was identified using daily billing, and hospital variation was estimated after adjustment for illness severity. Variation in very early echo use (<3 days of life) was compared to exposure to treatment of a patent ductus arteriosus (PDA), and other practice patterns. RESULTS: 27,498 subjects across 39 children's hospitals were included. Very early echo use had the greatest hospital variation (3-34%). Increasing very early echo use was not associated with PDA treatment (p = 0.93), but was associated with nitric oxide (p < 0.01) and vasoactive medications (p < 0.01). CONCLUSIONS: Hospital variation in echo use among preterm infants was greatest in the first few days of life and was associated with increasing nitric oxide and vasoactive medication use. The impact of this variation on clinical outcomes is uncertain and warrants further investigation.

Guidance for the use and reporting of anaesthetic agents in BJP manuscripts involving work with animals.

Scientists who plan to publish in the British Journal of Pharmacology (BJP) should read this article before undertaking studies utilising anaesthetics in mammalian animals. This editorial identifies certain gaps in the reporting of details on the use of anaesthetics in animal research studies published in the BJP. The editorial also provides guidance, based upon current best practices, for performing in vivo experiments that require anaesthesia. In addition, mechanisms of action and physiological impact of specific anaesthetic agents are discussed. Our goal is to identify best practices and to provide guidance on the information required for manuscripts submitted to the BJP that involve the use of anaesthetic agents in studies with experimental animals.

The Need for a Smoking Cessation "Care Package".

This Viewpoint from leadership at the US Food and Drug Administration (FDA) proposes the creation of a comprehensive "care package" framework of resources to help maximize cessation of tobacco use, including components focused on strategies at the individual, health system, and population levels.

Trends in US E-cigarette Sales and Prices by Nicotine Strength, Overall and by Product and Flavor Type, 2017-2022.

INTRODUCTION: The e-cigarette market has expanded considerably in recent years, resulting in changes in availability and use of e-cigarettes with varying characteristics. AIMS AND METHODS: This study assessed trends in sales and prices of e-cigarettes by nicotine strength level, including by product type and flavor, during January 2017-March 2022. US e-cigarette retail sales data were licensed from IRI company. Nicotine strength was categorized as: <1%; 1% to <2%; 2% to <3%; 3% to <4%; 4% to <5%; ≥5%. E-cigarette flavors were categorized as tobacco, menthol, mint, or other flavors. Product type was categorized as prefilled cartridge devices, disposable devices, or e-liquid bottles. Trend analyses were performed using Joinpoint Regression. RESULTS: During January 2017-March 2022, the unit share of products containing ≥5% nicotine strength increased by 1486.3%, while the dollar share increased by 1345.5%. By March 2022, 80.9% of total unit sales were composed of products containing ≥5% nicotine strength. By flavor, the percentage of units sold with ≥5% nicotine strength was 61.3% of tobacco-flavor sales, 79.3% of menthol sales, 87.4% of mint sales, and 96.1% of other flavor sales. By product type, the percentage of units sold with ≥5% nicotine strength was 90.6% of disposable e-cigarette sales and 74.2% of prefilled cartridge sales. During January 2017-March 2022, the price of low-nicotine strength e-cigarettes increased, while the price of high-nicotine products either decreased or did not change. CONCLUSIONS: Sales of high nicotine-strength e-cigarettes have dominated the US e-cigarette market. Limiting the nicotine strength of e-cigarettes could be considered as part of a comprehensive tobacco control strategy to reduce youth access to and use of these products. IMPLICATIONS: The findings from this study indicate that previously reported increases in e-cigarette nicotine strength during 2013-2018 have continued through 2022. The US e-cigarette market sales continue to be dominated by relatively high-nicotine products. Strategies to address factors that make these products, particularly appealing to youth, including flavors and product innovations, are critical. Such strategies are important-as part of a comprehensive approach alongside other evidence-based population-level actions-to address youth e-cigarette use. Importantly, actions to reduce e-cigarette use among youth are not mutually exclusive from actions to maximize the potential benefits of e-cigarettes for increasing smoking cessation among adults.

COVID-19 Scientific Publications From the Centers for Disease Control and Prevention, January 2020-January 2022.

OBJECTIVE: High-quality scientific evidence underpins public health decision making. The Centers for Disease Control and Prevention (CDC) agency provides scientific data, including during public health emergencies. To understand CDC's contributions to COVID-19 science, we conducted a bibliometric evaluation of publications authored by CDC scientists from January 20, 2020, through January 20, 2022, by using a quality improvement approach (SQUIRE 2.0). METHODS: We catalogued COVID-19 articles with ≥1 CDC-affiliated author published in a scientific journal and indexed in the World Health Organization's COVID-19 database. We identified priority topic areas from the agency's COVID-19 Public Health Science Agenda by using keyword scripts in EndNote and then assessed the impact of the published articles by using Scopus and Altmetric. RESULTS: During the first 2 years of the agency's pandemic response, CDC authors contributed to 1044 unique COVID-19 scientific publications in 208 journals. Publication topics included testing (n = 853, 82%); prevention strategies (n = 658, 63%); natural history, transmission, breakthrough infections, and reinfections (n = 587, 56%); vaccines (n = 567, 54%); health equity (n = 308, 30%); variants (n = 232, 22%); and post-COVID-19 conditions (n = 44, 4%). Publications were cited 40 427 times and received 81 921 news reports and 1 058 893 social media impressions. As the pandemic evolved, CDC adapted to address new scientific questions, including vaccine effectiveness, safety, and access; viral variants, including Delta and Omicron; and health equity. CONCLUSION: The agency's COVID-19 Public Health Science Agenda helped guide impactful scientific activities. CDC continues to evaluate COVID-19 priority topic areas and contribute to development of new scientific work. CDC is committed to monitoring emerging issues and addressing gaps in evidence needed to improve health.

Geographic variations in opioid overdose patterns in Pennsylvania during the COVID-19 pandemic.

The convergence of the opioid epidemic and the COVID-19 pandemic has created new health challenges throughout the United States. Since the onset of the pandemic, media attention and scholarly research have drawn attention to the intersections of addiction and COVID-19. However, there remain few empirical studies that examine the direct impacts of the COVID-19 pandemic for opioid overdose patterns. Even fewer have integrated quantitative and qualitative methods to detail the place-specific dynamics shaping opioid overdose and addiction treatment during the COVID-19 pandemic. This article measures and maps change in the age-adjusted rate of opioid-related overdose incidents at the county level from 2018 to 2020. These analyses are combined with interviews conducted since December 2020 with public health providers in the state of Pennsylvania to identify the key factors influencing opioid misuse and transformations in addiction treatment practices.