The Development and Performance of Alternative Criteria for Lung Cancer Screening.

BACKGROUND: The recommendation for lung cancer screening (LCS) developed by the U.S. Preventive Services Task Force (USPSTF) may exclude some high-benefit people. OBJECTIVE: To determine whether alternative criteria can identify these high-benefit people. DESIGN: Model-based projections. SETTING: United States. PARTICIPANTS: People from the 1997-2014 National Health Interview Survey (NHIS) to develop alternative criteria using fast-and-frugal tree algorithms and from the 2014-2018 NHIS and the 2022 Behavioral Risk Factor Surveillance System for comparisons of USPSTF criteria versus alternative criteria. MEASUREMENTS: Life-years gained from LCS were estimated using the life-years gained from screening computed tomography (LYFS-CT) model. "High-benefit" was defined as gaining an average of at least 16.2 days of life from 3 annual screenings, which reflects high lung cancer risk and substantial life gains if lung cancer is detected by screening. RESULTS: The final alternative criteria were 1) people who smoked any amount each year for at least 40 years, or 2) people aged 60 to 80 years with at least 40 pack-years of smoking. The USPSTF and alternative criteria selected similar numbers of people for LCS. Compared with the USPSTF criteria, the alternative criteria had higher sensitivity (91% vs. 78%; P < 0.001) and specificity (86% vs. 84%; P < 0.001) for identifying high-benefit people. For racial and ethnic minorities, the alternative criteria provided greater gains in sensitivity than the USPSTF criteria (Black: 83% vs. 56% [P < 0.001]; Hispanic: 95% vs. 73% [P = 0.086]; Asian: 94% vs. 68% [P = 0.171]) at similar specificity. The alternative criteria identify high-risk, high-benefit groups excluded by the USPSTF criteria (those with a smoking duration of ≥40 years but <20 pack-years and a quit history of >15 years), many of whom are members of racial and ethnic minorities. LIMITATION: The results were based on model projections. CONCLUSION: These results suggest that simple alternative LCS criteria can identify substantially more high-benefit people, especially in some racial and ethnic groups. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs Lung Precision Oncology Program.

Superonasal vs Inferonasal Subconjunctival Gel Stent Placement in Patients with Glaucoma.

Aim and background: To compare the safety and efficacy of subconjunctival gel stent implantation in the superonasal (SN) vs inferonasal (IN) quadrants in the treatment of glaucoma. Materials and methods: Patients with a history of IN (n = 29) or SN, (n = 96) gel stent placement with ≥3 months of follow-up were included. Intraocular pressure (IOP) and the number of glaucoma medications were collected preoperatively and postoperatively at months 1, 3, 6, and 12. Safety measures included the number of bleb needlings, complication rate, and additional surgeries. Results: Mean baseline IOP was 32.4 ± 11.7 mm Hg in the IN group and 21.6 ± 9.2 mm Hg in the SN group (p < 0.01). IOP was similar between groups at 3 months (IN = 15.8, SN = 15.6, p = 0.45), 6 months (IN = 17.4, SN = 15, p = 0.13), and 12 months (IN = 17.9, SN = 14.7, p = 0.15) follow-up. The number of glaucoma medications was also similar at 3 months (p = 0.31), 6 months (p = 0.24), and 12 months (p = 0.39) follow-up. Bleb needling rates were similar with 51.7% (15/29) in the IN group vs 42.7% (41/96) in the SN group (p = 0.39) and subjects requiring further surgery were 17.2% (5/29) in the IN group vs 24.0% (23/96) in the SN group (p = 0.45). Conclusion: Both IN and SN subconjunctival gel stent placements provide favorable safety and efficacy when treating open-angle glaucoma, with a meaningful decrease in medication use and IOP. Clinical significance: Implantation of the subconjunctival gel stent in the IN quadrant is an effective and safe alternative to superior implantation in refractory glaucoma. How to cite this article: Vander Zee BL, Wilson C, Berdahl JP, et al. Superonasal vs Inferonasal Subconjunctival Gel Stent Placement in Patients with Glaucoma. J Curr Glaucoma Pract 2024;18(2):63-67.

Methionine Restriction Reduces Lung Cancer Progression and Increases Chemotherapy Response.

Targeting tumor metabolism through dietary interventions is an area of growing interest, and may help to improve the significant mortality of aggressive cancers, including non-small cell lung cancer (NSCLC). Here we show that the restriction of methionine in the aggressive KRAS/Lkb1-mutant NSCLC autochthonous mouse model drives decreased tumor progression and increased carboplatin treatment efficacy. Importantly, methionine restriction during early stages of tumorigenesis prevents the lineage switching known to occur in the model, and alters the tumor immune microenvironment (TIME) to have fewer tumor-infiltrating neutrophils. Mechanistically, mutations in LKB1 are linked to anti-oxidant production through changes to cystathionine-ß-synthase (CBS) expression. Human cell lines with rescued LKB1 show increased CBS levels and resistance to carboplatin, which can be partially rescued by methionine restriction. Furthermore, LKB1 rescued cells, but not mutant cells, show less G2-M arrest and apoptosis in high methionine conditions. Knock-down of CBS sensitized both LKB1 mutant and non-mutated lines to carboplatin, again rescuing the carboplatin resistance of the LKB1 rescued lines. Given that immunotherapy is commonly combined with chemotherapy for NSCLC, we next wanted to understand if T cells are impaired by MR. Therefore, we examined the ability of T cells from MR and control tumor bearing mice to proliferate in culture and found that T cells from MR treated mice had no defects in proliferation, even though we continued the MR conditions ex vivo. We also identified that CBS is most highly correlated with smoking, adenocarcinomas with alveolar and bronchiolar features, and adenosquamous cell carcinomas, implicating its roles in oxidative stress response and lineage fate in human tumors. Taken together, we have shown the importance of MR as a dietary intervention to slow tumor growth and improve treatment outcomes for NSCLC.

Prediction-Augmented Shared Decision-Making and Lung Cancer Screening Uptake.

Importance: Addressing poor uptake of low-dose computed tomography lung cancer screening (LCS) is critical, especially for those having the most to gain-high-benefit persons with high lung cancer risk and life expectancy more than 10 years. Objective: To assess the association between LCS uptake and implementing a prediction-augmented shared decision-making (SDM) tool, which enables clinicians to identify persons predicted to be at high benefit and encourage LCS more strongly for these persons. Design, Setting, and Participants: Quality improvement interrupted time series study at 6 Veterans Affairs sites that used a standard set of clinical reminders to prompt primary care clinicians and screening coordinators to engage in SDM for LCS-eligible persons. Participants were persons without a history of LCS who met LCS eligibility criteria at the time (aged 55-80 years, smoked ≥30 pack-years, and current smoking or quit <15 years ago) and were not documented to be an inappropriate candidate for LCS by a clinician during October 2017 through September 2019. Data were analyzed from September to November 2023. Exposure: Decision support tool augmented by a prediction model that helps clinicians personalize SDM for LCS, tailoring the strength of screening encouragement according to predicted benefit. Main outcome and measure: LCS uptake. Results: In a cohort of 9904 individuals, the median (IQR) age was 64 (57-69) years; 9277 (94%) were male, 1537 (16%) were Black, 8159 (82%) were White, 5153 (52%) were predicted to be at intermediate (preference-sensitive) benefit and 4751 (48%) at high benefit, and 1084 (11%) received screening during the study period. Following implementation of the tool, higher rates of LCS uptake were observed overall along with an increase in benefit-based LCS uptake (higher screening uptake among persons anticipated to be at high benefit compared with those at intermediate benefit; primary analysis). Mean (SD) predicted probability of getting screened for a high-benefit person was 24.8% (15.5%) vs 15.8% (11.8%) for a person at intermediate benefit (mean absolute difference 9.0 percentage points; 95% CI, 1.6%-16.5%). Conclusions and Relevance: Implementing a robust approach to personalized LCS, which integrates SDM, and a decision support tool augmented by a prediction model, are associated with improved uptake of LCS and may be particularly important for those most likely to benefit. These findings are timely given the ongoing poor rates of LCS uptake.

National Trends in Emergency Department Visits for Suicide Attempts and Intentional Self-Harm.

OBJECTIVE: This study estimated national annual trends and characteristics of emergency department visits for suicide attempts and intentional self-harm in the United States from 2011 to 2020. METHODS: Data were from the National Hospital Ambulatory Medical Care Survey, an annual cross-sectional national sample survey of emergency departments. Visits for suicide attempts and intentional self-harm were identified using discharge diagnosis codes (ICD-9-CM for 2011-2015; ICD-10-CM for 2016-2020) or reason-for-visit codes. The annual proportion of emergency department visits for suicide attempts and intentional self-harm was estimated. RESULTS: The weighted number of emergency department visits for suicide attempts and intentional self-harm increased from 1.43 million, or 0.6% of total emergency department visits, in 2011-2012 to 5.37 million, or 2.1% of total emergency department visits in 2019-2020 (average annual percent change, 19.5%, 95% CI=16.9, 22.2). Visits per capita increased from 261 to 871 visits per 100,000 persons (average annual percent change, 18.8%, 95% CI=17.6, 20.0). The increase in visits was widely distributed across sociodemographic groups. While suicide attempt and intentional self-harm visits were most common among adolescents, adults age 65 or older demonstrated the largest increase (average annual percent change, 30.2%, 95% CI=28.5, 32.0). Drug-related diagnoses were the most common co-occurring diagnosis among suicide attempt and intentional self-harm visits. Despite the rise in emergency department visits for suicide attempts and intentional self-harm, less than 16% included an evaluation by a mental health professional. CONCLUSIONS: A significant national increase in emergency department visits for suicide attempts and intentional self-harm occurred from 2011 to 2020, as a proportion of total emergency department visits and as visits per capita. These trends underscore an urgent need to improve the continuum of mental health care for individuals with suicidal symptoms.

Lung Cancer Screening Before and After a Multifaceted Electronic Health Record Intervention: A Nonrandomized Controlled Trial.

Importance: Lung cancer is the deadliest cancer in the US. Early-stage lung cancer detection with lung cancer screening (LCS) through low-dose computed tomography (LDCT) improves outcomes. Objective: To assess the association of a multifaceted clinical decision support intervention with rates of identification and completion of recommended LCS-related services. Design, Setting, and Participants: This nonrandomized controlled trial used an interrupted time series design, including 3 study periods from August 24, 2019, to April 27, 2022: baseline (12 months), period 1 (11 months), and period 2 (9 months). Outcome changes were reported as shifts in the outcome level at the beginning of each period and changes in monthly trend (ie, slope). The study was conducted at primary care and pulmonary clinics at a health care system headquartered in Salt Lake City, Utah, among patients aged 55 to 80 years who had smoked 30 pack-years or more and were current smokers or had quit smoking in the past 15 years. Data were analyzed from September 2023 through February 2024. Interventions: Interventions in period 1 included clinician-facing preventive care reminders, an electronic health record-integrated shared decision-making tool, and narrative LCS guidance provided in the LDCT ordering screen. Interventions in period 2 included the same clinician-facing interventions and patient-facing reminders for LCS discussion and LCS. Main Outcome and Measure: The primary outcome was LCS care gap closure, defined as the identification and completion of recommended care services. LCS care gap closure could be achieved through LDCT completion, other chest CT completion, or LCS shared decision-making. Results: The study included 1865 patients (median [IQR] age, 64 [60-70] years; 759 female [40.7%]). The clinician-facing intervention (period 1) was not associated with changes in level but was associated with an increase in slope of 2.6 percentage points (95% CI, 2.4-2.7 percentage points) per month in care gap closure through any means and 1.6 percentage points (95% CI, 1.4-1.8 percentage points) per month in closure through LDCT. In period 2, introduction of patient-facing reminders was associated with an immediate increase in care gap closure (2.3 percentage points; 95% CI, 1.0-3.6 percentage points) and closure through LDCT (2.4 percentage points; 95% CI, 0.9-3.9 percentage points) but was not associated with an increase in slope. The overall care gap closure rate was 175 of 1104 patients (15.9%) at the end of the baseline period vs 588 of 1255 patients (46.9%) at the end of period 2. Conclusions and Relevance: In this study, a multifaceted intervention was associated with an improvement in LCS care gap closure. Trial Registration: ClinicalTrials.gov Identifier: NCT04498052.

A comprehensive qualitative investigation of the factors that affect surgical site infection prevention in cardiac surgery in England using observations and interviews.

BACKGROUND: Interview and questionnaire studies have identified barriers and challenges to preventing surgical site infections (SSIs) by focusing on compliance with recommendations and care bundles using interviews, questionnaires and expert panels. This study proposes a more comprehensive investigation by using observations of clinical practice plus interviews which will enable a wider focus. AIM: To comprehensively identify the factors which affect SSI prevention using cardiac surgery as an exemplar. METHODS: The study consisted of 130 h of observed clinical practice followed by individual semi-structured interviews with 16 surgeons, anaesthetists, theatre staff, and nurses at four cardiac centres in England. Data were analysed thematically. FINDINGS: The factors were complex and existed at the level of the intervention, the individual, the team, the organization, and even the wider society. Factors included: the attributes of the intervention; the relationship between evidence, personal beliefs, and perceived risk; power and hierarchy; leadership and culture; resources; infrastructure; supplies; organization and planning; patient engagement and power; hospital administration; workforce shortages; COVID-19 pandemic; 'Brexit'; and the war in Ukraine. CONCLUSION: This is one of the first studies to provide a comprehensive overview of the factors affecting SSI prevention. The factors are complex and need to be fully understood when trying to reduce SSIs. A strong evidence base was insufficient to ensure implementation of an intervention.

Clinical outcomes of the light adjustable lens in eyes with a history of prior corneal refractive surgery.

PURPOSE: This study aimed to evaluate the visual and refractive outcomes in eyes with a history of laser corneal refractive surgery implanted with the second-generation light-adjustable lens (LAL). SETTING: Private Practice, Sioux Falls, South Dakota, US. DESIGN: Retrospective, consecutive case series. METHODS: Eyes with a history of prior corneal refractive surgery that underwent cataract surgery with implantation of the LAL and were targeted for plano were included. Data on the type and number of prior refractive surgeries were collected, in addition to the timing and number of postoperative adjustments. The primary outcome measures were uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and the percentage (%) of eyes within ±0.25 diopter (D), ±0.50D, and ±1.00 D of their refractive target. RESULTS: 76 eyes from 70 patients were included. A total of 45 eyes with a history of one prior refractive surgery and 31 eyes with a history of ≥2 refractive surgeries were included. 74% (n=56) of all eyes achieved UDVA of 20/20 or better, 88% (n=67) achieved 20/25 UDVA or better and 93% (n=71) were correctable to 20/20 or better postoperatively. For refractive outcomes, 66% of eyes (n=50) were within ±0.25 D and 86% (n=65) were within ±0.50 D of refractive target. CONCLUSIONS: Patients with a history of laser corneal refractive surgery achieved favorable visual and refractive outcomes with the LAL. This intraocular lens (IOL), which affords postoperative adjustability, is a promising option for patients with a history of corneal refractive surgery who maintain high expectations for functional uncorrected acuity following cataract surgery.

Outcomes of Primary Anterior Cruciate Ligament (ACL) Repair for Proximal Tears: A Systematic Review and Meta-Analysis.

The purpose of this study is to compare failure rates among different techniques of primary anterior cruciate ligament (ACL) repair for the treatment of proximal ACL ruptures. Meta-analysis and systematic review were completed, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Studies from Embase, Cochrane, and PubMed published between June 2011 and June 2022 reporting outcomes of primary ACL repair on proximal tears with a minimum two-year follow-up were included. Primary ACL repair was divided into dynamic, static, and non-augmented repair. The primary outcome was failure rates, and the secondary outcomes included patient-reported outcomes (PROs) and anterior tibial stability (ATT). Eighteen studies on primary ACL repair were included, with a total of 614 patients (ages ranging from 6 to 65, 60% male). Only two studies were level 1 randomized controlled clinical trials. The static repair had a failure rate of 33 out of 261 (12.6%), non-augmented was 17 out of 179 (9.4%), and dynamic repair was 31 out of 174 (17.8%); no statistically significant difference was found comparing the failure rates (p = 0.090). PROs using the International Knee Documentation Committee (IKDC) and Lysholm scores had weighted averages of 91.7 (95% confidence interval (CI): 89.6-93.8) and 94.7 (95% CI: 92.7-96.7), respectively. ATT had a weighted average of 1.668 mm (95% CI: 1.002-2.334). The primary findings of this paper include a 12.6% combined failure rate for primary proximal ACL repair with no significant difference in failure rate or PROs when accounting for the methodology of repair at a minimum two-year follow-up. It is important to note the lack of high-quality randomized controlled trials, the heterogeneity of included studies, and the lack of long-term data. Despite these limitations, the findings of the current analysis suggest that primary repair may be a useful treatment option for indicated candidates with proximal ACL ruptures. Further long-term and higher-quality comparative studies on ACL reconstruction are warranted.

Clinician Perceptions on Using Decision Tools to Support Prediction-Based Shared Decision Making for Lung Cancer Screening.

Background: Considering a patient's full risk factor profile can promote personalized shared decision making (SDM). One way to accomplish this is through encounter tools that incorporate prediction models, but little is known about clinicians' perceptions of the feasibility of using these tools in practice. We examined how clinicians react to using one such encounter tool for personalizing SDM about lung cancer screening (LCS). Design: We conducted a qualitative study based on field notes from academic detailing visits during a multisite quality improvement program. The detailer engaged one-on-one with 96 primary care clinicians across multiple Veterans Affairs sites (7 medical centers and 6 outlying clinics) to get feedback on 1) the rationale for prediction-based LCS and 2) how to use the DecisionPrecision (DP) encounter tool with eligible patients to personalize LCS discussions. Results: Thematic content analysis from detailing visit data identified 6 categories of clinician willingness to use the DP tool to personalize SDM for LCS (adoption potential), varying from "Enthusiastic Potential Adopter" (n = 18) to "Definite Non-Adopter" (n = 16). Many clinicians (n = 52) articulated how they found the concept of prediction-based SDM highly appealing. However, to varying degrees, nearly all clinicians identified challenges to incorporating such an approach in routine practice. Limitations: The results are based on the clinician's initial reactions rather than longitudinal experience. Conclusions: While many primary care clinicians saw real value in using prediction to personalize LCS decisions, more support is needed to overcome barriers to using encounter tools in practice. Based on these findings, we propose several strategies that may facilitate the adoption of prediction-based SDM in contexts such as LCS. Highlights: Encounter tools that incorporate prediction models promote personalized shared decision making (SDM), but little is known about clinicians' perceptions of the feasibility of using these tools in practice.We examined how clinicians react to using one such encounter tool for personalizing SDM about lung cancer screening (LCS).While many clinicians found the concept of prediction-based SDM highly appealing, nearly all clinicians identified challenges to incorporating such an approach in routine practice.We propose several strategies to overcome adoption barriers and facilitate the use of prediction-based SDM in contexts such as LCS.

Vaccine effectiveness against emerging COVID-19 variants using digital health data.

BACKGROUND: Participatory surveillance of self-reported symptoms and vaccination status can be used to supplement traditional public health surveillance and provide insights into vaccine effectiveness and changes in the symptoms produced by an infectious disease. The University of Maryland COVID Trends and Impact Survey provides an example of participatory surveillance that leveraged Facebook's active user base to provide self-reported symptom and vaccination data in near real-time. METHODS: Here, we develop a methodology for identifying changes in vaccine effectiveness and COVID-19 symptomatology using the University of Maryland COVID Trends and Impact Survey data from three middle-income countries (Guatemala, Mexico, and South Africa). We implement conditional logistic regression to develop estimates of vaccine effectiveness conditioned on the prevalence of various definitions of self-reported COVID-like illness in lieu of confirmed diagnostic test results. RESULTS: We highlight a reduction in vaccine effectiveness during Omicron-dominated waves of infections when compared to periods dominated by the Delta variant (median change across COVID-like illness definitions: -0.40, IQR[-0.45, -0.35]. Further, we identify a shift in COVID-19 symptomatology towards upper respiratory type symptoms (i.e., cough and sore throat) during Omicron periods of infections. Stratifying COVID-like illness by the National Institutes of Health's (NIH) description of mild and severe COVID-19 symptoms reveals a similar level of vaccine protection across different levels of COVID-19 severity during the Omicron period. CONCLUSIONS: Participatory surveillance data alongside methodologies described in this study are particularly useful for resource-constrained settings where diagnostic testing results may be delayed or limited.

Surveys that are sent out to users of social media can be used to supplement traditional methods to monitor the spread of infectious diseases. This has the potential to be particularly useful in areas where other data is unavailable, such as areas with less surveillance of infectious disease prevalence and access to infectious disease diagnostics. We used data from a survey available to users of the social media platform Facebook to collect information about any potential symptoms of COVID-19 infection and vaccines received during the COVID-19 pandemic. We found a potential reduction in vaccine effectiveness and change in symptoms when the Omicron variant was known to be circulating compared to the earlier Delta variant. This method could be adapted to monitor the spread of COVID-19 and other infectious diseases in the future, which might enable the impact of infectious diseases to be recognized more quickly.

National trends and correlates of treatment resistance in major depressive episode and associated suicidal ideation and behaviors among adults in the United States.

OBJECTIVE: To examine recent 12-year trends in prevalence of suicidal ideation and behaviors (SIBs) among US adults experiencing a past-year treatment-resistant depression (TRD). METHODS: Using data from the National Survey of Drug Use and Health, we estimated the annual percentage of individuals aged ≥18 with TRD who reported past-year SIBs, and estimated linear trends adjusting for potentially confounding factors from 2009 to 2020. RESULTS: Of estimated 237.5 million US adults, 7.1 % met diagnostic criteria for a past-year major depressive episode (MDE) between 2009 and 2020. Of these, 9.7 % met criteria for TRD. The proportion reporting past-year suicidal ideation in TRD ranged from 39.5 % (95 % confidence interval [CI], 32.1-47.3 %) in 2009-2010 to 43.4 % (95 % CI, 36.7-503 %) in 2019-2020, with an average annual percent change (AAPC) of 1.3 % (95 % CI, -0.7 % to 3.3 %). The prevalence of past-year suicide attempts in TRD was 7.3 % across the study period (AAPC, 0.1 %; 95 % CI, -4.3 % to 4.7 %). Past-year SIBs were significantly associated with an increased likelihood of meeting criteria for TRD among adults with MDE (adjusted odds ratio [AOR], 1.53; 95 % CI, 1.35-1.75 for suicidal ideation; AOR, 2.17; 95 % CI, 1.79-2.62 for suicide attempts). No significant differences were observed between 2019 and 2020, reflecting the COVID-19 pandemic. CONCLUSION: Among individuals with TRD, proportions of SIBs are high. These findings underscore an urgent need for suicide prevention efforts in this high-risk population, including preventive services across diverse settings and accessibility to evidence-based pharmacological and non-pharmacological interventions.

Varenicline Solution Nasal Spray for the Treatment of Dry Eye Disease Following LASIK.

INTRODUCTION: The purpose of this study is to evaluate the use of a varenicline solution nasal spray (VNS) for reducing the signs and symptoms of dry eye following laser in situ keratomileusis (LASIK). METHODS: Subjects electing to undergo LASIK were randomized to VNS (study group) or placebo/vehicle (control group) and initiated treatment with the nasal spray twice daily 28 days prior to surgery with continued treatment for 84 days following LASIK. After initiation of treatment, subjects were seen on the day of surgery and postoperatively on Days 1, 7, 28, 84 (3 months) and 168 (6 months). The primary outcome measure was the mean change in NEI-VFQ-25, a 25-item dry eye questionnaire, from baseline to 3 months. The second primary outcome measure was the mean change in corneal fluorescein staining. Secondary outcome measures included evaluation of tear break-up time, Schirmer testing, tear osmolarity and eye dryness score (EDS). RESULTS: Twenty subjects were enrolled in each group and successfully underwent LASIK. Both groups demonstrated an improvement in the National Eye Institute Visual Function Questionnaire (NEI-VFQ) at 3 months. The study group demonstrated improved corneal staining scores at months 1 and 3. Similarly, the study group demonstrated improvement in tear osmolarity scores versus the placebo group at the same time points. Although the study group was numerically greater than placebo for each time point for both corneal staining and tear osmolarity, the differences were not statistically significant for any primary or secondary outcome measures. CONCLUSION: VNS is a dry eye treatment option for patients following LASIK and may have potential benefit for patients hoping to avoid additional topical medications. The results were not statistically significant compared to placebo in this trial, and further investigation of the use of VNS following LASIK in a larger trial would be beneficial.

Laser in situ keratomileusis (LASIK) is a very successful refractive surgery option for patients hoping to reduce or eliminate their need for spectacles. Signs and symptoms of dry eye disease are very common after LASIK owing to the transection of corneal nerves that occurs during the procedure, and many patients are advised to manage it with frequent instillation of artificial tears. This study evaluated the use of a varenicline solution nasal spray, a recently introduced pharmacologic option that stimulates natural tear production through activation of the trigeminal nerve pathway. This is the first study to evaluate the use of the varenicline solution nasal spray in patients after refractive surgery and demonstrates that it could represent a favorable, ocular surface-sparing option for patients to minimize the signs and symptoms of dry eye following LASIK, a procedure known to trigger symptoms of dry eye disease.

Molecular regulation of myocyte fusion.

Myocyte fusion is a pivotal process in the development and regeneration of skeletal muscle. Failure during fusion can lead to a range of developmental as well as pathological consequences. This review aims to comprehensively explore the intricate processes underlying myocyte fusion, from the molecular to tissue scale. We shed light on key players, such as the muscle-specific fusogens - Myomaker and Myomixer, in addition to some lesser studied molecules contributing to myocyte fusion. Conserved across vertebrates, Myomaker and Myomixer play a crucial role in driving the merger of plasma membranes of fusing myocytes, ensuring the formation of functional muscle syncytia. Our multiscale approach also delves into broader cell and tissue dynamics that orchestrate the timing and positioning of fusion events. In addition, we explore the relevance of muscle fusogens to human health and disease. Mutations in fusogen genes have been linked to congenital myopathies, providing unique insights into the molecular basis of muscle diseases. We conclude with a discussion on potential therapeutic avenues that may emerge from manipulating the myocyte fusion process to remediate skeletal muscle disorders.

Modeling Complex Ligands for High Oxidation State Catalysis: Titanium Hydroamination with Unsymmetrical Ligands.

A method for modeling high oxidation state catalysts is used on precatalysts with unsymmetrical and symmetrical bidentate ligands to get a more detailed understanding of how changes to ancillary ligands affect the hydroamination of alkynes catalyzed by titanium. To model the electronic donor ability, the ligand donor parameter (LDP) was used, and to model the steric effects, percent buried volume (% Vbur) was employed. For the modeling study, 7 previously unpublished unsymmetrical Ti(XX')(NMe2)2 precatalysts were prepared, where XX' is a chelating ligand with pyrrolyl/indolyl linkages. The rates of these unsymmetrical and 10 previously reported symmetrical precatalysts were used with the model kobs = a + b(LDP)1 + c(LDP)2 + d(% Vbur)1 + e(% Vbur)2, where a-e were found through least-squares refinement. The model suggests that (1) the two attachment points of the bidentate ligand XX' are in different environments on the metal (e.g., axial and equatorial in a trigonal bipyramidal or square pyramidal structure), (2) the position of the unsymmetrical ligand on the metal is determined by the electronics of the ligand rather than the sterics, and (3) that one side of the chelating ligand's electronics strongly influences the rate, while the other side's sterics more strongly influences the rate. From these studies, we were able to generate catalysts fitting to this model with rate constants larger than the fastest symmetrical catalyst tested.

"It Can't Hurt!": Why Many Patients With Limited Life Expectancy Decide to Accept Lung Cancer Screening.

PURPOSE: Lung cancer screening (LCS) has less benefit and greater potential for iatrogenic harm among people with multiple comorbidities and limited life expectancy. Yet, such individuals are more likely to undergo screening than healthier LCS-eligible people. We sought to understand how patients with marginal LCS benefit conceptualize their health and make decisions regarding LCS. METHODS: We interviewed 40 people with multimorbidity and limited life expectancy, as determined by high Care Assessment Need scores, which predict 1-year risk of hospitalization or death. Patients were recruited from 6 Veterans Health Administration facilities after discussing LCS with their clinician. We conducted a thematic analysis using constant comparison to explore factors that influence LCS decision making. RESULTS: Patients commonly held positive beliefs about screening and perceived LCS to be noninvasive. When posed with hypothetical scenarios of limited benefit, patients emphasized the nonlongevity benefits of LCS (eg, peace of mind, planning for the future) and generally did not consider their health status or life expectancy when making decisions regarding LCS. Most patients were unaware of possible additional evaluations or treatment of screen-detected findings, but when probed further, many expressed concerns about the potential need for multiple evaluations, referrals, or invasive procedures. CONCLUSIONS: Patients in this study with multimorbidity and limited life expectancy were unaware of their greater risk of potential harm when accepting LCS. Given patient trust in clinician recommendations, it is important that clinicians engage patients with marginal LCS benefit in shared decision making, ensuring that their values of desiring more information about their health are weighed against potential harms from further evaluations.

Tackling Guideline Non-concordance: Primary Care Barriers to Incorporating Life Expectancy into Lung Cancer Screening Decision-Making-A Qualitative Study.

BACKGROUND: Primary care providers (PCPs) are often the first point of contact for discussing lung cancer screening (LCS) with patients. While guidelines recommend against screening people with limited life expectancy (LLE) who are less likely to benefit, these patients are regularly referred for LCS. OBJECTIVE: We sought to understand barriers PCPs face to incorporating life expectancy into LCS decision-making for patients who otherwise meet eligibility criteria, and how a hypothetical point-of-care tool could support patient selection. DESIGN: Qualitative study based on semi-structured telephone interviews. PARTICIPANTS: Thirty-one PCPs who refer patients for LCS, from six Veterans Health Administration facilities. APPROACH: We thematically analyzed interviews to understand how PCPs incorporated life expectancy into LCS decision-making and PCPs' receptivity to a point-of-care tool to support patient selection. Final themes were organized according to the Cabana et al. framework Why Don't Physicians Follow Clinical Practice Guidelines, capturing the influence of clinician knowledge, attitudes, and behavior on LCS appropriateness determinations. KEY RESULTS: PCP referrals to LCS for patients with LLE were influenced by limited knowledge of the life expectancy threshold at which patients are less likely to benefit from LCS, discomfort estimating life expectancy, fear of missing cancer at the point of early detection, and prioritization of factors such as quality of life, patient values, clinician-patient relationship, and family support. PCPs were receptive to a decision support tool to inform and communicate LCS appropriateness decisions if easy to use and integrated into clinical workflows. CONCLUSIONS: Our study suggests knowledge gaps and attitudes may drive decisions to offer screening despite LLE, a behavior counter to guideline recommendations. Integrating a LCS decision support tool that incorporates life expectancy within the electronic medical record and existing clinical workflows may be one acceptable solution to improve guideline concordance and increase confidence in selecting high benefit patients for LCS.

Investigating the role of tumour-to-skin proximity in predicting nodal metastasis in breast cancer.

BACKGROUND: Understanding the factors influencing nodal status in breast cancer is vital for axillary staging, therapy, and patient survival. The nodal stage remains a crucial factor in prognostication indices. This study investigates the relationship between tumour-to-skin distance (in T1-T3 tumours where the skin is not clinically involved) and the risk of nodal metastasis. METHODS: We retrospectively reviewed data from 100 patients who underwent neoadjuvant chemotherapy (NACT). Besides patient demographics and tumour variables, a radiologist retrospectively reviewed pre-operative MRI to measure tumour-to-skin distance. R core packages were used for univariate (χ2 and T-Wilcoxon tests) and bivariate logistic regression statistical analysis. RESULTS: Of 95 analysable datasets, patients' median age was 51 years (IQR: 42-61), 97% were symptomatic (rest screen detected), and the median tumour size was 43 mm (IQR, 26-52). On multivariate analysis, increasing invasive tumour size (p = 0.02), ER positivity (p = 0.007) and shorter tumour-to-skin distance (p = 0.05) correlated with nodal metastasis.  HER2 was not included in multivariate analysis as there was no association with nodal status on univariate analysis. In node-positive tumours, as tumour size increased, the tumour-to-skin distance decreased (r = - 0.34, p = 0.026). In node-negative tumours, there was no correlation (r = + 0.18, p = 0.23). CONCLUSION: This study shows that non-locally advanced cancers closer to the skin (and consequent proximity to subdermal lymphatics) are associated with a greater risk of nodal metastasis. Pre-operative identification of those more likely to be node positive may suggest the need for a second-look USS since a higher nodal stage may lead to a change in therapeutic strategies, such as upfront systemic therapy, node marking, and axillary clearance without the need to return to theatre following sentinel node biopsy.