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Benjamin A King1,2 Elizabeth U Rosenberger,1 Vanessa M Morales-Tirado,1,3 Matthew W Wilson1,2 1Department of Ophthalmology, Hamilton Eye Institute, University of Tennessee Health Science Center, College of Medicine, Memphis, TN, USA; 2Department of Surgery, St Jude Children’s Research Hospital, Memphis, TN, USA; 3Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Science Center, College of Medicine, Memphis, TN, USA Purpose: To report the clinical features of uveal metastases in a geographic region associated with high tobacco use. Methods: Medical records from all patients diagnosed with uveal metastasis at a single tertiary referral center between 2000 and 2017 were retrospectively reviewed. The clinical features and the primary tumor site associated with each metastatic lesion were recorded. Results: Ninety-nine uveal metastatic tumors were identified in 85 eyes of 74 patients (34 males). Median age at diagnosis was 62 years. Median tumor diameter was 11.6 mm and median height was 3.1 mm. Carcinoma of the lung was the most common primary tumor occurring in 37 patients (50%) followed by breast in 16 patients (21%). Among females, metastatic lesions originated from the lung in 18 patients and from the breast in 16 patients. Median survival following intraocular metastasis was 9 months for patients with a primary lung malignancy and 36 months for patients with breast cancer (log-rank test, P=0.002).Conclusion: Intraocular metastasis is more frequently observed in patients with carcinomas of the lung rather than breast at our treatment center. Both regional and global changes in cancer epidemiology most likely account for the findings in this study.Keywords: iris, choroid, cancer, metastases, lung, breast, eye

BackgroundValid patient-reported outcome (PRO) measures are required to evaluate alopecia areata (AA) treatments.ObjectivesTo develop a content-valid and clinically meaningful PRO measure to assess AA scalp hair loss with scores comparable with the five-response-level Alopecia Areata Investigator Global Assessment (AA-IGA™).MethodsA draft PRO measure was developed based on input from 10 clinical experts in AA. The PRO measure was cognitively debriefed, modified and finalized through two rounds of qualitative semistructured interviews with patients with AA who had experienced ≥ 50% scalp hair loss. Data were thematically analysed.ResultsAdults (round 1: n = 25; round 2: n = 15) and adolescents aged 15-17 years (round 1: n = 5) in North America participated. All patients named scalp hair loss as a key AA sign or symptom. Patients demonstrated the ability to self-report their current amount of scalp hair using percentages. In round 1 not all patients interpreted the measurement concept consistently; therefore, the PRO was modified to clarify the measurement concept to improve usability. Following modifications, patients in round 2 responded without difficulty to the PRO measure. Patients confirmed that they could use the five-level response scale to rate their scalp hair loss: no missing hair, 0%; limited, 1-20%; moderate, 21-49%; large, 50-94%; nearly all or all, 95-100%. Almost all patients deemed hair regrowth resulting in ≤ 20% scalp hair loss a treatment success.ConclusionsThe Scalp Hair Assessment PRO™ is a content-valid, clinically meaningful assessment of distinct gradations of scalp hair loss for evaluating AA treatment for patients with ≥ 50% hair loss at baseline.

BackgroundContent-valid and clinically meaningful instruments are required to evaluate outcomes of therapeutic interventions in alopecia areata (AA).ObjectivesTo develop an Investigator's Global Assessment (IGA) to interpret treatment response in AA treatment studies.MethodsQualitative interviews were conducted in the USA with expert dermatologists and with patients with AA who had experienced ≥ 50% scalp-hair loss. Thematic data analysis identified critical outcomes and evaluated the content validity of the new IGA.ResultsExpert clinicians (n = 10) judged AA treatment success by the amount of scalp-hair growth (median 80% scalp hair). Adult (n = 25) and adolescent (n = 5) patients participated. Scalp-hair loss was the most bothersome AA sign/symptom for most patients. Perceived treatment success - short of 100% scalp hair - was the presence of ~ 70-90% scalp hair (median 80%). Using additional clinician and patient insights, the Alopecia Areata Investigator Global Assessment (AA-IGA™) was developed. This clinician-reported outcome assessment is an ordinal, static measure comprising five severity categories of scalp-hair loss. Nearly all clinicians and patients in this study agreed that, for patients with ≥ 50% scalp-hair loss, successful treatment would be hair regrowth resulting in ≤ 20% scalp-hair loss.ConclusionsWe recommend using the Severity of Alopecia Tool to assess the extent (0-100%) of scalp-hair loss. The AA-IGA is a robust ordinal measure providing distinct and clinically meaningful gradations of scalp-hair loss that reflects patients' and expert clinicians' perspectives and treatment expectations. What is already known about this topic? The Severity of Alopecia Tool is widely used to assess the extent of scalp-hair loss in patients with alopecia areata. Guidelines define treatment success as a 50% improvement in scalp hair, and clinical trials have used dynamic thresholds of 50% and 90%. However, there is no clinical consensus on these endpoints, and patient perspectives on treatment success are unknown. What does this study add? Through qualitative interviews with 10 expert dermatologists and 30 patients with alopecia areata who had experienced ≥ 50% scalp-hair loss, we developed the Alopecia Areata Investigator Global Assessment (AA-IGA™) to measure five clinically meaningful gradations of alopecia areata scalp-hair loss that reflects patients' and clinicians' perspectives and expectations of treatment success in alopecia areata treatment studies. What are the clinical implications of this work? The AA-IGA is a robust ordinal measure that can inform clinical evaluation of alopecia areata treatment outcomes. The AA-IGA can be used to determine clinically meaningful treatment success for alopecia areata, with success defined by patients and clinicians as reaching ≤ 20% scalp-hair loss. Linked Comment: Blome. Br J Dermatol 2020; 183:609.

Introduction: Secondhand smoke (SHS) causes significant disease and death. A person's home represents a prominent source of SHS, and the potential for exposure is elevated among those who live in close proximity to smokers in multiunit housing (MUH). This study assessed the prevalence and predictors of SHS exposure and smoke-free policy support among MUH residents.Methods: Data were obtained from 5,936 MUH residents who participated in the New York State Adult Tobacco Survey between May 2007 and May 2009. Bivariate analyses were used to assess the prevalence of smoke-free home policies, SHS incursions, and support for smoke-free policies. Logistic regression was used to identify predictors of these measures while adjusting for gender, age, ethnicity, education, region, children in household, and housing type.Results: A total of 73.1% of respondents reported a personal smoke-free home policy in their home. Among these individuals, 46.2% indicated that SHS has ever entered their home in the past year, while 9.2% reported daily incursions. Overall, a majority of respondents (55.6%) support a policy that bans smoking in all areas of their building, including residential units; support was significantly higher among ethnic minorities and individuals who reside with children.Discussion: Nearly half of New York MUH residents with a smoke-free home policy have experienced a SHS incursion in their home. Since a majority of MUH residents support smoke-free policies and nearly three quarters already prohibit smoking in their home, opportunities exist for initiatives to promote smoke-free building policies. [ABSTRACT FROM AUTHOR]

You need sharp assessment skills to anticipate and avert acute renal failure. But even if you can recognize early-stage failure, you'll increase the chances of a positive patient outcome. [ABSTRACT FROM AUTHOR]

Abstract Background Non-alcoholic fatty liver disease (NAFLD) has a prevalence of over 20% in Western societies. Affected individuals are at risk of developing both cirrhosis and hepatocellular cancer (HCC). Presently there is no cost effective population based means of identifying cirrhotic individuals and even if there were, our ability to perform HCC surveillance in the at risk group is inadequate. We have performed a pilot proteomic study to assess this as a strategy for serum biomarker detection. Methods 2D Gel electrophoresis was performed on immune depleted sera from 3 groups of patients, namely those with (1) pre-cirrhotic NAFLD (2) cirrhotic NAFLD and (3) cirrhotic NAFLD with co-existing HCC. Five spots differentiating at least one of these three groups were characterised by mass spectroscopy. An ELISA assay was optimised and a cross sectional study assessing one of these serum spots was performed on serum from 45 patients with steatohepatitis related cirrhosis and HCC and compared to 77 patients with histologically staged steatohepatitis. Results Four of the spots identified were apolipoprotein isoforms, the pattern of which was able to differentiate the three groups. The 5th spot, seen in the serum of cirrhotic individuals and more markedly in those with HCC, was identified as CD5 antigen like (CD5L). By ELISA assay, although CD5L was markedly elevated in a number of cirrhotic individuals with HCC, its overall ability to distinguish non-cancer from cancer individuals as determined by AUC ROC analysis was poor. However, serum CD5L was dramatically increased, independently of age, sex, and the presence of necroinflammation, in the serum of individuals with NAFLD cirrhosis relative to those with pre-cirrhotic disease. Conclusion This novel proteomic strategy has identified a number of candidate biomarkers which may have benefit in the surveillance and diagnosis of individuals with chronic liver disease and/or HCC.

Importance: The results of small studies suggest that off-label use of low-dose oral minoxidil (LDOM) may be safe and effective for patients with hair loss, but larger trials and standardized guidelines are lacking., Objective: To create an expert consensus statement for LDOM prescribing for patients with hair loss., Evidence Review: The current literature on the pharmacological properties, adverse effect profile, and use of LDOM for patients with hair loss was reviewed. Topics of interest were identified, and a modified Delphi consensus process was created. A total of 43 hair loss specialist dermatologists from 12 countries participated in a modified Delphi process. Consensus was reached if at least 70% agreed or strongly agreed on a 5-point Likert scale., Findings: Over 4 survey rounds, 180 items in the first round, 121 items in the second round, 16 items in the third round, and 11 items in the fourth round were considered and revised. A total of 76 items achieved consensus including diagnoses for which LDOM may provide direct or supportive benefit, indications for LDOM compared to topical minoxidil, dosing for adults (18 years and older) and adolescents (aged 12 to 17 years), contraindications, precautions, baseline evaluation, monitoring, adjunctive therapy, and specialty consultation. Pediatric use and dosing items for children younger than 12 years, and LDOM titration protocols fell short of consensus., Conclusions and Relevance: This international expert consensus statement regarding the off-label prescribing of LDOM for patients with hair loss can help guide clinical practice until more data emerge. Hair loss experts with experience treating pediatric patients were underrepresented on this expert panel. Future research should investigate best practices for LDOM use in pediatric patients. Other critical topics for further investigation include the comparative efficacy of topical minoxidil vs oral minoxidil, the safety of oral minoxidil for patients with a history of allergic contact dermatitis to topical minoxidil, the long-term safety of LDOM, and the use of other off-label forms of minoxidil, such as compounded formulations of oral minoxidil and sublingual minoxidil. As additional evidence-based data emerge, these recommendations should be updated.

Background: Prior research suggests that physicians' personal experience with breastfeeding may influence their attitudes toward breastfeeding. This phenomenon has not been explored in well-newborn care physician leaders, whose administrative responsibilities often include drafting and approval of hospital breastfeeding and formula supplementation policies., Methods: We conducted a mixed-methods study, surveying physicians in the Better Outcomes through Research for Newborns (BORN) network. We examined physician attitudes toward recommending breastfeeding and their breastfeeding experience. Qualitative analysis was conducted on responses to the question: "How do you think your breastfeeding experience influences your clinical practice?", Results: Of 71 participants, most (92%) had a very positive attitude toward breastfeeding with 75% of respondents reporting personal experience with breastfeeding. Of these, 68% had a very positive experience, 25% had a somewhat positive experience, and 6% had a neutral experience. Four themes emerged with respect to the effect of breastfeeding experience on practice: (1) empathy with breastfeeding struggles, (2) increased knowledge and skills, (3) passion for breastfeeding benefits, and (4) application of personal experience in lieu of evidence-based medicine, particularly among those who struggled with breastfeeding., Conclusions: Well-newborn care physician leaders reported positive attitudes about breastfeeding, increased support toward breastfeeding persons, and a perception of improved clinical lactation skills. Those who struggled with breastfeeding reported increased comfort with recommending formula supplementation to their own patients. Medical education about evidence-based breastfeeding support practices and provision of lactation support to physicians has the potential to affect public health through improved care for the patients they serve., (© 2023 Wiley Periodicals LLC.)

Objective: Flavours that produce a cooling sensation, such as menthol, enhance the appeal of e-cigarettes among youth; but not all e-cigarettes that produce cooling sensations are labelled as menthol. This study assessed trends in unit sales of cooling flavoured e-cigarettes in the USA., Design: E-cigarette retail sales during 26 January 2017 to 28 November 2021 were licensed from Information Resources, Inc, which records brick-and-mortar retail scanner sales but not online or vape shop sales. Cooling flavours were identified using six descriptors: menthol, ice, cool, chill, freeze or frost; ambiguous flavours were verified using online searches. Cooling flavours were categorised by characterising flavour (menthol, mint, other) and product type (prefilled cartridges, disposables, e-liquids). Joinpoint regression was used to assess sales and price trends., Results: During January 2017 to November 2021, unit sales of cooling flavoured e-cigarettes increased by 693.0% (1.5 to 12.0 million units); the percentage of these sales from total sales increased from 26.4% to 54.9%. Among cooling flavours, percentage of menthol sales decreased from 94.5% to 73.0% (p<0.001). Among menthol cooling flavours, percentage of prefilled cartridges increased from 67.2% to 96.6% (p<0.001); among non-menthol cooling flavours, percentage of disposable e-cigarettes increased from 5.2% to 99.2% (p<0.001). There were no significant price differences between cooling and non-cooling flavoured disposable e-cigarettes., Conclusion: The percentage of cooling flavoured e-cigarette sales from total sales doubled during 2017-2021, and sales of non-menthol cooling disposable e-cigarettes experienced the highest percentage increase. Cooling flavoured e-cigarettes are important to consider when developing strategies to address flavoured e-cigarette use among youth., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2023 National Foundation for the Centers For Disease Control and Prevention “CDC Foundation”. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Janus kinase (JAK) inhibitors have ushered in a new era in alopecia areata (AA). Historically, moderate-to-severe AA was refractory to treatment. JAK inhibitors have changed that; now, treatment of moderate-to-severe AA is possible. Here, we briefly review the history of and rationale for JAK inhibitor treatment of AA, phase 3 clinical trial data, and considerations regarding differences among JAK inhibitors, safety, and patient selection., (Copyright © 2023. Published by Elsevier Inc.)

Purpose: (1) To describe the technique of postoperative echography to confirm the intended treatment dose to the tumor apex in patients with uveal melanoma treated with plaque brachytherapy. (2) To describe the local tumor control rate and visual outcomes with the brachytherapy strategies used at our institution., Design: Retrospective review., Subjects: Three hundred seventy-two consecutive patients with uveal melanoma (small, medium, and large) treated with plaque brachytherapy at the University of Iowa from August 2008 to February 2019., Methods: Patient demographics and tumor characteristics were recorded for each patient. Patients with posterior tumors treated with plaque brachytherapy (n = 355) underwent intraoperative ultrasound to confirm plaque placement, and additional postoperative ultrasound on day 1 to 3 postplaque insertion. In cases where intratumor/episcleral plaque edema or hemorrhage shifted the dose to the prescription point to < 85 Gray (Gy), the duration of plaque brachytherapy was increased to compensate. Statistical analysis was performed to compare variables associated with the need for plaque adjustment., Main Outcomes Measures: Variables associated with plaque dose needing to be recalculated, local tumor control, and visual acuity outcomes., Results: In 31 (8.3%) cases, postoperative echography showed that the tumor apex had shifted outside the 85 Gy isodose curve, requiring adjustment of the duration of brachytherapy (28 cases) or repositioning of the plaque (3 cases). Collaborative Ocular Melanoma Study tumor size was significantly associated with need to adjust the plaque prescription dose (P = 0.03), with large tumors having the highest rate of adjustment. Tumor thickness was larger in cases requiring plaque adjustment compared with those that were not adjusted (median 4.9 mm vs. 3.0 mm, P < 0.01). Local tumor control was 99% (95% confidence interval, 97%-100%) at 5 years and 99% (95% confidence interval, 97%-100%) at 10 years. The percentage of patients who had experienced a visual acuity decline of ≥ 3 lines of vision or had < 20/200 acuity was 14.9% at 1 year after brachytherapy, 35.3% at 3 years, and 51.6% at 5 years., Conclusions: Postoperative ultrasound performed on postoperative day 1 to 3 after plaque insertion for patients undergoing brachytherapy for uveal melanoma may result in improved local tumor control, particularly in the setting of thicker or larger tumors., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Morbidly obese patients undergoing cemented primary total knee arthroplasty (TKA) can pose a challenging problem with implant survivorship due to greater stress at the cement-bone interface. With the advent of additive manufacturing (three-dimensional printing), highly porous implants are now readily available. The purpose of this study was to review the results of primary TKA in the morbidly obese (body mass index [BMI] ≥ 40) patient using a highly porous cementless tibial baseplate. This is a retrospective study of 167 TKAs in patients with morbid obesity undergoing primary cementless TKA with a minimum 5-year follow-up. A total of 6 patients died and 14 were lost to follow-up, leaving 147 TKAs in 136 patients with a mean follow-up of 66 months (range 60-79 months). The average age was 59 years (range 36-84 years) and average BMI was 45 kg/m 2 (range 39.5-63.9). Clinical results, patient-reported outcome measures, radiographs, and complications were reviewed. There were 9 failures requiring revision, including 3 for aseptic tibial loosening (2.0%), 2 for deep infection (1.4%), 2 for patellar resurfacing (1.4%), 1 for patella instability (0.7%), and 1 for extensor mechanism rupture (0.7%). Knee Society Score (KSS) improved from 48 to 90 at 2- and 5-year follow-up. KSS function score improved from 49 to 68 and 79 at 2- and 5-year follow-up, respectively. Survivorship with aseptic loosening as the endpoint was 98.0% at 5 years. Cementless TKA using a highly porous tibial baseplate in morbidly obese patients demonstrated excellent clinical results with 98% survivorship at 5 years and appears to offer durable long-term biologic fixation as an alternative to mechanical cement fixation in this challenging group of patients., Competing Interests: A.M. declares the following conflicts of interest: Journal of Arthroplasty: Editorial or governing board; Stryker: IP royalties; paid consultant; paid presenter or speaker; research support S.H. declares the following conflicts of interest: Orthopedics: Editorial or governing board SLACK Incorporated: Editorial or governing board; Stryker: IP royalties; Paid consultant; Paid presenter or speaker; Stock or stock Options; Thieme, Inc., Journal of Hip Surgery, Journal of Knee Surgery: Editorial or governing board; Thieme, Inc., Journal of Knee Surgery, Journal of Hip Surgery: Publishing royalties, financial or material support. The rest authors declare no conflict of interest., (Thieme. All rights reserved.)

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'.

Purpose: Traditionally, appropriate anchors are used to investigate the amount of change on a clinician-reported outcome assessment that is meaningful to individual patients. However, novel qualitative methods involving input from disease state experts together with patients may better inform the individual improvement threshold for demonstrating the clinical benefit of new treatments. This study aimed to establish a clinically meaningful threshold for treatment success for the clinician-reported Severity of Alopecia Tool (SALT) score for patients with alopecia areata (AA)., Methods: A purposive sample of 10 dermatologists expert in AA and 30 adult and adolescent patients with AA and a history of ≥ 50% scalp hair loss were recruited. Semi-structured interview questions explored the outcome that represented treatment success to clinicians and patients. Findings were analyzed using thematic methods to identify treatment success thresholds., Results: Both informant groups confirmed scalp hair amount as the outcome of priority. Most expert clinicians considered a static threshold of 80% (n = 5) or 75% (n = 3) of the scalp hair as a treatment success. Most patient responses ranged from 70 to 90% (median: 80% of the scalp hair). Subsequently, queried patients confirmed that achieving SALT score ≤ 20 with treatment would be a success, as reflected in the Alopecia Areata Investigator Global Assessment (AA-IGA™). The novel qualitative processes used to inform this meaningful threshold reflects a clinician-then-patient process for: (a) confirmation of the patient outcome of priority; and (b) clinician input on a preliminary treatment success level for independent understanding among patients., Conclusion: This qualitative investigation of expert clinicians-then-patients with AA confirmed that achieving an amount of 80% or more scalp hair (SALT score ≤ 20) was an appropriate individual treatment success threshold indicating clinically meaningful improvement for patients with ≥ 50% scalp hair loss. A qualitative investigation of a quantifiable treatment success threshold is possible through a well-designed interview process with expert clinicians and the appropriate patient population., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.)

Purpose: To determine the safety and toxicity profile of intravitreal carboplatin as salvage treatment for retinoblastoma with vitreous disease., Design: Single-institution, interventional prospective clinical trial., Participants: Patients with progressive or recurrent vitreous seeds after completion of primary treatment for intraocular retinoblastoma., Methods: Eligible eyes received an intravitreal injection of carboplatin every 14 to 21 days with simultaneous focal therapy (laser, thermotherapy, and brachytherapy) provided at the discretion of the ocular oncologist. The evaluation with examination under anesthesia, ultrasound biomicroscopy, and electroretinography (ERG) were performed before each injection to assess for tumor response and drug-related toxicity. A serious adverse event resulted in dose recalculation and ultimately early closure of the study., Main Outcome Measures: Regression pattern of vitreous disease and incidence of dose-limiting toxicities., Results: Four patients were enrolled at an initial dose of 0.3 mg. Complete regression of vitreous seeds was noted in all patients after 5, 2, 2, and 1 injections (respectively). Two patients developed recurrent vitreous disease at 3 and 25 months after complete regression and ultimately required enucleation. A serious adverse event occurred in 1 patient who developed acute vision loss with extinguished ERG response 72 hours after the second injection; ultimately, this eye developed a cataract and required enucleation. After temporary suspension and dose modification, 3 patients were enrolled at an injection dose of 3 μg and treated with a total of 5, 2, and 1 injections, respectively. Complete regression of vitreous disease was not achieved in any patient though ERG amplitudes remained stable. After removal from protocol, all 3 patients had a complete response to intravitreal melphalan. Concern for dose escalation and further toxicity in the setting of an effective and safe alternative (melphalan) led to the termination of the study., Conclusions: Intravitreal carboplatin may be effective in treating progressive vitreous seeding at higher doses, but permanent retinal toxicity was observed. Other alternative agents should be considered., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: Surfactant protein D (SP-D) is an innate host defense protein that clears infectious pathogens from the lung and regulates pulmonary host defense cells. SP-D is also detected in lower concentrations in plasma and many other non-pulmonary tissues. Plasma levels of SP-D increase during infection and other proinflammatory states; however, the source and functions of SP-D in the systemic circulation are largely unknown. We hypothesized that systemic SP-D may clear infectious pathogens and regulate host defense cells in extrapulmonary systems., Methods: To determine if SP-D inhibited inflammation induced by systemic lipopolysaccharide (LPS), E.coli LPS was administered to mice via tail vein injection with and without SP-D and the inflammatory response was measured., Results: Systemic SP-D has a circulating half-life of 6 h. Systemic IL-6 levels in mice lacking the SP-D gene were similar to wild type mice at baseline but were significantly higher than wild type mice following LPS treatment (38,000 vs 29,900 ng/ml for 20 mg/kg LPS and 100,700 vs 73,700 ng/ml for 40 mg/kg LPS). In addition, treating wild type mice with purified intravenous SP-D inhibited LPS induced secretion of IL-6 and TNFα in a concentration dependent manner. Inhibition of LPS induced inflammation by SP-D correlated with SP-D LPS binding suggesting SP-D mediated inhibition of systemic LPS requires direct SP-D LPS interactions., Conclusions: Taken together, the above results suggest that circulating SP-D decreases systemic inflammation and raise the possibility that a physiological purpose of increasing systemic SP-D levels during infection is to scavenge systemic infectious pathogens and limit inflammation-induced tissue injury., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr Kingma was previously a consultant and employee for Airway Therapeutics Inc which is currently developing surfactant protein D as a therapeutic agent. However, this relationship ended in 2021 and Dr. Kingma has no further financial or other interest in Airway Therapeutics Inc., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

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.

Background: E-cigarettes are the most commonly used tobacco product among US youth and are regularly used on school grounds. We assessed school staff's awareness of students' e-cigarette use, response by schools, and resources needed to address use, and examined e-cigarettes confiscated by school staff in North Carolina to guide prevention and identify needed resources., Methods: In May 2019, staff from a random sample of 25 of 451 North Carolina public and charter high schools were invited to complete an online survey and semistructured interview; 12 schools consented to ≥ 1 component (survey, N = 514; interviews, N = 35). Staff knowledge and perceptions of students' e-cigarette use and school tobacco policies were assessed, including school efforts to address e-cigarette use. E-cigarette products confiscated by nine schools from students during the 2018-2019 school year were collected., Limitations: Only 12 public high schools participated, and these schools might not be representative of all North Carolina high schools. Quantitative surveys were not collected from all staff at participating schools; however, the response rate was 62% and included different staff positions and both urban and rural schools. Finally, e-cigarette products collected by schools might not be representative of all devices used by students., Results: Among surveyed staff, 33% observed students using e-cigarettes on school grounds; 86% believed e-cigarette use somewhat or largely contributes to learning disruptions. Overall, 94% of respondents knew their school's policy prohibits student e-cigarette use on school grounds, and 57% were not confident their school has resources to help students quit. From 35 interviews, themes included concern that schools' tobacco-free policies do not deter use and additional resources are needed to address e-cigarette use in schools. Of 336 collected devices, there were different e-cigarette types and most (65%) e-liquid bottles were flavored., Conclusion: Efforts are warranted to incorporate evidence-based curricula; educate staff, parents, and youth regarding health risks of e-cigarette use; and help youth quit e-cigarettes., Competing Interests: Acknowledgments Disclosure of interests. No interests were disclosed.

Background: In June 2020, Massachusetts implemented a law prohibiting the sale of all flavored tobacco products, including menthol cigarettes. This law was associated with significant declines in overall cigarette and menthol cigarette sales in Massachusetts, however it is unknown whether the law has increased cross-border sales in neighboring states where menthol cigarettes are still sold., Methods: U.S. cigarette retail scanner data were licensed from the IRi Company. Cigarette pack sales were summed in 4-week periods during January 2020-December 2021 (n = 832). Outcomes were state-level pack sales per 1000 population, overall and by flavor status (menthol and non-flavored). A difference-in-differences analysis was used to examine adjusted sales for Massachusetts border states (New Hampshire, Connecticut, Vermont, and Rhode Island) before (January 2020-May 2020) and after (June 2020-December 2021) the Massachusetts's law, compared to 28 non-border states. Control variables included state and time fixed effects; real price per pack; tobacco control policies; COVID-19 cases and deaths, and related statewide closure; and state sociodemographic characteristics., Results: Following the law, unadjusted sales of menthol, non-flavored, and overall cigarettes trended upward in border states; however, these increases were not statistically significant or different from sales patterns in non-border states. This finding persisted after accounting for product prices, tobacco control policies, the COVID-19 pandemic, sociodemographic factors, and fixed effects., Conclusion: Laws prohibiting the sale of flavored tobacco products, including menthol products, reduce access to these products, while having no significant impact on cross-border sales in neighboring states where menthol cigarettes are sold., Competing Interests: The authors have declared that no competing interests exist.