The Impact of Postoperative COVID-19 Infection on 30-day Outcomes of Laparoscopic Cholecystectomy.

Introduction: Preoperative Coronavirus Disease 2019 (COVID-19) infections are associated with postoperative adverse outcomes. However, there is limited data on the impact of postoperative COVID-19 infection on postoperative outcomes of common general surgery procedures.Objective: To evaluate the impact of postoperative COVID-19 diagnosis on laparoscopic cholecystectomy outcomes.Methods: Patients with symptomatic cholelithiasis, acute cholecystitis, or gallstone pancreatitis who underwent laparoscopic cholecystectomy with or without intraoperative cholangiogram were identified using the 2021 National Surgical Quality Improvement Program (NSQIP) database. Patients were categorized into two groups: patients with and without a postoperative COVID-19 diagnosis. Coarsened Exact Matching was used to match the groups based on preoperative risk factors, and outcomes were compared.Results: A total of 47,948 patients were included. In the aggregate cohort, 31% were male, and mean age was 50 years. Age, BMI, smoking, COPD, CHF, preoperative sepsis, and ASA class were significantly different between the two groups. After matching, there were no differences in characteristics. 30-day morbidity (OR = 2.7, 95% CI 1.4-5.1), pneumonia (OR = 5.0, 95% CI 1.7-15.0), DVT (OR = 8.22, 95% CI 1.0-66), reoperation (OR = 9.3, 95% CI 1.2-73.8), and readmission (OR = 4.8, 95% CI 2.3-10.1) continued to be significantly worse in the matched cohort.Conclusion: Postoperative COVID-19 infection was associated with worse outcomes after laparoscopic cholecystectomy. These findings suggest that even postoperative COVID-19 diagnosis increases the risk for adverse outcomes in patients recovering from laparoscopic cholecystectomy and may indicate that precautions should be taken and new COVID-19 infections even after surgery should be closely monitored.

Magnesium sulfate and risk of hypoxic-ischemic encephalopathy in a high-risk cohort.

BACKGROUND: Hypoxic-ischemic encephalopathy contributes to morbidity and mortality among neonates ≥36 weeks of gestation. Evidence of preventative antenatal treatment is limited. Magnesium sulfate has neuroprotective properties among preterm fetuses. Hypertensive disorders of pregnancy are a risk factor for hypoxic-ischemic encephalopathy, and magnesium sulfate is recommended for maternal seizure prophylaxis among patients with preeclampsia with severe features. OBJECTIVE: (1) Determine trends in the incidence of hypertensive disorders of pregnancy, antenatal magnesium sulfate, and hypoxic-ischemic encephalopathy; (2) evaluate the association between hypertensive disorders of pregnancy and hypoxic-ischemic encephalopathy; and (3) evaluate if, among patients with hypertensive disorders of pregnancy, the odds of hypoxic-ischemic encephalopathy is mitigated by receipt of antenatal magnesium sulfate. STUDY DESIGN: We analyzed a prospective cohort of live births ≥36 weeks of gestation between 2012 and 2018 within the California Perinatal Quality Care Collaborative registry, linked with the California Department of Health Care Access and Information files. We used Cochran-Armitage tests to assess trends in hypertensive disorders, encephalopathy diagnoses, and magnesium sulfate utilization and compared demographic factors between patients with or without hypertensive disorders of pregnancy or treatment with magnesium sulfate. Hierarchical logistic regression models were built to explore if hypertensive disorders of pregnancy were associated with any severity and moderate/severe hypoxic-ischemic encephalopathy. Separate hierarchical logistic regression models were built among those with hypertensive disorders of pregnancy to evaluate the association of magnesium sulfate with hypoxic-ischemic encephalopathy. RESULTS: Among 44,314 unique infants, the diagnosis of hypoxic-ischemic encephalopathy, maternal hypertensive disorders of pregnancy, and the use of magnesium sulfate increased over time. Compared with patients with hypertensive disorders of pregnancy alone, patients with hypertensive disorders treated with magnesium sulfate represented a high-risk population. They were more likely to be publicly insured, born between 36 and 38 weeks of gestation, be small for gestational age, have lower Apgar scores, require a higher level of resuscitation at delivery, have prolonged rupture of membranes, experience preterm labor and fetal distress, and undergo operative delivery (all P<.002). Hypertensive disorders of pregnancy were associated with hypoxic-ischemic encephalopathy (adjusted odds ratio, 1.26 [95% confidence interval, 1.13-1.40]; P<.001) and specifically moderate/severe hypoxic-ischemic encephalopathy (adjusted odds ratio, 1.26 [95% confidence interval, 1.11-1.42]; P<.001). Among patients with hypertensive disorders of pregnancy, treatment with magnesium sulfate was associated with 29% reduction in the odds of neonatal hypoxic-ischemic encephalopathy (adjusted odds ratio, 0.71 [95% confidence interval, 0.52-0.97]; P=.03) and a 37% reduction in the odds of moderate/severe neonatal hypoxic-ischemic encephalopathy (adjusted odds ratio, 0.63 [95% confidence interval, 0.42-0.94]; P=.03). CONCLUSION: Hypertensive disorders of pregnancy are associated with hypoxic-ischemic encephalopathy and, specifically, moderate/severe disease. Among people with hypertensive disorders, receipt of antenatal magnesium sulfate is associated with a significant reduction in the odds of hypoxic-ischemic encephalopathy and moderate/severe disease in a neonatal cohort admitted to neonatal intensive care unit at ≥36 weeks of gestation. The findings of this observational study cannot prove causality and are intended to generate hypotheses for future clinical trials on magnesium sulfate in term infants.

Predicting Primary Care Physician Burnout From Electronic Health Record Use Measures.

OBJECTIVE: To evaluate the ability of routinely collected electronic health record (EHR) use measures to predict clinical work units at increased risk of burnout and potentially most in need of targeted interventions. METHODS: In this observational study of primary care physicians, we compiled clinical workload and EHR efficiency measures, then linked these measures to 2 years of well-being surveys (using the Stanford Professional Fulfillment Index) conducted from April 1, 2019, through October 16, 2020. Physicians were grouped into training and confirmation data sets to develop predictive models for burnout. We used gradient boosting classifier and other prediction modeling algorithms to quantify the predictive performance by the area under the receiver operating characteristics curve (AUC). RESULTS: Of 278 invited physicians from across 60 clinics, 233 (84%) completed 396 surveys. Physicians were 67% women with a median age category of 45 to 49 years. Aggregate burnout score was in the high range (≥3.325/10) on 111 of 396 (28%) surveys. Gradient boosting classifier of EHR use measures to predict burnout achieved an AUC of 0.59 (95% CI, 0.48 to 0.77) and an area under the precision-recall curve of 0.29 (95% CI, 0.20 to 0.66). Other models' confirmation set AUCs ranged from 0.56 (random forest) to 0.66 (penalized linear regression followed by dichotomization). Among the most predictive features were physician age, team member contributions to notes, and orders placed with user-defined preferences. Clinic-level aggregate measures identified the top quartile of clinics with 56% sensitivity and 85% specificity. CONCLUSION: In a sample of primary care physicians, routinely collected EHR use measures demonstrated limited ability to predict individual burnout and moderate ability to identify high-risk clinics.

Does source matter? Examining the effects of health experts, friends, and social media influencers on young adult perceptions of Instagram e-cigarette education messages.

PURPOSE: Young adults' e-cigarette use is a leading public health concern. Using messages from credible sources can help improve message acceptance, yet little research has examined the role of source credibility on young adults' responses to e-cigarette education messages. METHODS: We examined the impact of source on young adults' perceptions of e-cigarette education messages and e-cigarettes. In July 2022, we conducted an experimental study using an online sample of young adults (N=459, Mage=24.6) who were randomized to one of three source conditions: expert, friend, or influencer, and viewed e-cigarette education messages. We used one-way ANOVA to estimate the association between the conditions and outcomes (perceived source credibility, message trust, curiosity, use interests, perceived message effectiveness, beliefs, harm perceptions, and intentions to refrain). RESULTS: The expert condition was associated with significantly higher perceived source credibility (vs. friend, influencer; p<0.001), message trust (vs. friend, influencer; p<0.001), and curiosity (vs. influencer; p's<0.05). CONCLUSIONS: Public health campaigns may leverage health experts to deliver e-cigarette education messages targeting young adults to improve effectiveness of the messages.

High-Frequency Spinal Stimulation Suppresses Microglial Kaiso-P2X7 Receptor Axis-Induced Inflammation to Alleviate Neuropathic Pain in Rats.

OBJECTIVE: Neuropathic pain poses a persistent challenge in clinical management. Neuromodulation has emerged as a last-resort therapy. Conventional spinal cord stimulation (Con SCS) often causes abnormal sensations and provides short analgesia, whereas high-frequency spinal cord stimulation (HF SCS) is a newer therapy that effectively alleviates pain without paresthesia. However, the modes of action of 10kHz HF SCS (HF10 SCS) in pain relief remain unclear. To bridge this knowledge gap, we employed preclinical models that mimic certain features of clinical SCS to explore the underlying mechanisms of HF10 SCS. Addressing these issues would provide the scientific basis for improving and evaluating the effectiveness, reliability, and practicality of different frequency SCS in clinical settings. METHODS: We established a preclinical SCS model to examine its effects in a neuropathic pain rat model. We conducted bulk and single-cell RNA sequencing in the spinal dorsal horn (SDH) to examine cellular and molecular changes under different treatments. We employed genetic manipulations through intrathecal injection of a lentiviral system to explore the SCS-mediated signaling axis in pain. Various behavioral tests were performed to evaluate pain conditions under different treatments. RESULTS: We found that HF10 SCS significantly reduces immune responses in the SDH by inactivating the Kaiso-P2X7R pathological axis in microglia, promoting long-lasting pain relief. Targeting Kaiso-P2X7R in microglia dramatically improved efficacy of Con SCS treatment, leading to reduced neuroinflammation and long-lasting pain relief. INTERPRETATION: HF10 SCS could improve the immunopathologic state in the SDH, extending its benefits beyond symptom relief. Targeting the Kaiso-P2X7R axis may enhance Con SCS therapy and offer a new strategy for pain management. ANN NEUROL 2024;95:966-983.

Intrinsic and extrinsic actions of human neural progenitors with SUFU inhibition promote tissue repair and functional recovery from severe spinal cord injury.

Neural progenitor cells (NPCs) derived from human pluripotent stem cells(hPSCs) provide major cell sources for repairing damaged neural circuitry and enabling axonal regeneration after spinal cord injury (SCI). However, the injury niche and inadequate intrinsic factors in the adult spinal cord restrict the therapeutic potential of transplanted NPCs. The Sonic Hedgehog protein (Shh) has crucial roles in neurodevelopment by promoting the formation of motorneurons and oligodendrocytes as well as its recently described neuroprotective features in response to the injury, indicating its essential role in neural homeostasis and tissue repair. In this study, we demonstrate that elevated SHH signaling in hNPCs by inhibiting its negative regulator, SUFU, enhanced cell survival and promoted robust neuronal differentiation with extensive axonal outgrowth, counteracting the harmful effects of the injured niche. Importantly, SUFU inhibition in NPCs exert non-cell autonomous effects on promoting survival and neurogenesis of endogenous cells and modulating the microenvironment by reducing suppressive barriers around lesion sites. The combined beneficial effects of SUFU inhibition in hNPCs resulted in the effective reconstruction of neuronal connectivity with the host and corticospinal regeneration, significantly improving neurobehavioral recovery in recipient animals. These results demonstrate that SUFU inhibition confers hNPCs with potent therapeutic potential to overcome extrinsic and intrinsic barriers in transplantation treatments for SCI.

Dual-Vaping of Nicotine and Cannabis among Adults who Currently Use Tobacco Products in Five New England States.

INTRODUCTION: Current measures of vaping behaviors do not distinguish what substances participants are vaping and to what extent they are dual-vaping nicotine and cannabis. This study describes the use of new survey questions that more specifically ask whether participants who vape are vaping nicotine, cannabis, CBD, or another substance. METHODS: Adults, who reported any past-30-day tobacco use, from five New England states participated in an online survey from April 2021 to July 2022. Participants who vaped were asked, "Have you used any of the following vape substances in the past 30 days?" with the possible responses of nicotine, cannabis, CBD, other, and "don't know." Dual-use of both nicotine and cannabis was defined as the vaping of both nicotine and cannabis and/or CBD in the past-30-days, operationalized as a dichotomous outcome. Data were collected in monthly, repeated cross-sectional waves. Multinomial logistic regression was used to examine correlates of dual-vaping. RESULTS: The analytic sample included 1547 adults who reported past-30-day tobacco use (mean age 42.9 years, 62.8% female, 85.4% White, 48.5% income of less than $50,000). Over one-quarter (26.1%) reported dual-vaping in the past-30-days. Identifying as male (p=0.002) and self-rated anxiety (p=0.043) were associated with a higher odds of dual-vaping. CONCLUSIONS: Our findings show that a sizable proportion of a sample of New England adults who have used tobacco in the past-30-days are dual-vaping nicotine and cannabis. Adequate survey measures for assessing the vaping of multiple substances can help in better screening and characterization of health behaviors around dual-use. IMPLICATIONS: This study addresses a key gap in adequate survey measures for assessing vaping of multiple substances. We found that among adults with past 30-day tobacco use, dual-vaping was prevalent and associated with different correlates, such as self-reported anxiety and education level, compared to sole-vaping of nicotine or cannabis. Our findings may help in characterizing and targeting future population-level surveillance and intervention efforts for multiple substance use behaviors.

Association Between Social Media Use and Substance Use Among Middle and High School-Aged Youth.

Purpose: The purpose of our study was to identify whether different aspects of social media use were associated with substance use among middle- and high school-aged youth. Methods: Participants were recruited from four Northeast U.S. middle schools and invited to complete an online survey in Fall 2019 and Fall 2020. We conducted separate adjusted logistic mixed effects models the substance use outcomes: ever use of alcohol, cannabis, e-cigarettes, tobacco cigarettes, prescription drugs, and multiple substances. Our sample included N = 586 participants (52.7% female, 58% White). Results: Seeing a social media post about drugs/alcohol in the past-12-months was significantly associated with higher odds of ever using alcohol, cannabis, e-cigarettes, and multiple substance use. Total number of social media sites ever used was significantly associated with higher odds of ever using cannabis, cigarettes, e-cigarettes, and multiple substances. Checking social media every hour or more was significantly associated with higher odds of ever using alcohol. Higher problematic internet use score was significantly associated with higher odds of ever using cannabis, e-cigarettes, and multiple substances. Online social support seeking score was not associated substance use. Conclusions: Our findings support the need for substance use prevention and social media literacy education and screening to begin early, ideally in elementary school before youth are using social media and substances.

Racial and Ethnic Composition of Populations Served by Freestanding Children's Hospitals and Disparities in Outcomes of Pediatric Lupus.

OBJECTIVE: Health disparities may be driven by hospital-level factors. We assessed whether racial and ethnic composition of populations hospitals serve explain or modify disparities in hospital outcomes of children with systemic lupus erythematosus (SLE). METHODS: In this retrospective cohort study of patients 5 to 26 years old with SLE at 47 children's hospitals in the Pediatric Health Information System (2006-2021), race and ethnicity were assessed at the patient level and hospital level (proportion of total admissions composed of Black or Hispanic patients, respectively). Outcomes included intensive care unit (ICU) admission or adverse renal outcome (end-stage renal disease, dialysis, or transplant) during follow-up. We estimated racial and ethnic disparities, adjusted or stratified by hospital racial or ethnic composition. RESULTS: Of 8,125 patients with SLE, 2,293 (28%) required ICU admission, and 698 (9%) had an adverse renal outcome. Black and non-Hispanic White disparities in ICU admission were observed only at hospitals serving higher proportions of Black patients (odds ratio [OR] 1.29, 95% confidence interval [95% CI] 1.04-1.59 vs OR 1.07, 95% CI 0.83-1.38). Larger Black and non-Hispanic White disparities in adverse renal outcomes were observed at hospitals with higher Black racial composition (OR 2.0, 95% CI 1.4-2.8 vs OR 1.7, 95% CI 1.1-2.4). Conversely, Hispanic versus non-Hispanic disparities in renal outcomes persisted after adjustment for hospital-reported Hispanic ethnic composition but were observed only at hospitals with lower proportions of Hispanic patients. CONCLUSION: Worse Black and White disparities in SLE outcomes are observed at children's hospitals serving more Black children, whereas distinct patterns are observed for Hispanic and non-Hispanic disparities. Reporting of hospital characteristics related to populations served is needed to identify modifiable drivers of hospital-level variation.

Persistently high HBsAg levels during HBeAg-seropositive stage predict lower risk of hepatocellular carcinoma in chronic hepatitis B patients.

BACKGROUND: High hepatitis B surface antigen (HBsAg) level predicts hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients with low viral load. The role of longitudinal HBsAg levels in predicting HCC in HBeAg-positive CHB patients remains unknown. METHOD: HBeAg-positive CHB participants from the REVEAL-HBV cohort with ≥2 HBsAg measurements before HBeAg seroclearance were enrolled. Group-based trajectory modelling identified distinct HBsAg trajectory groups during a median of 11 years of HBeAg-positive status. Cox regression models were applied for investigating independent predictors of HCC and estimating adjusted hazard ratio (HRadj) with a 95% confidence interval (CI). A p-value less than 0.05 was considered statistically significant. RESULTS: A total of 319 patients were enrolled and classified by HBsAg trajectory patterns as (A) persistently high group (n = 72): HBsAg persistently ≥104 IU/mL, and (B) non-stationary group (n = 233): low HBsAg at baseline or declining to <104 IU/mL during the follow-up. Group B had higher proportions of abnormal ALT levels, HBV genotype C and basal core mutation than group A (p < 0.05); age at entry and gender were comparable. The annual incidence of HCC in group A and group B were 0.37% and 1.16%, respectively (p = 0.03). In multivariate analysis, age >40 years (HRadj [95% CI] = 4.11 [2.26-7.48]), genotype C (HRadj [95% CI] = 4.39 [1.96-9.81]) and the non-stationary group (HRadj [95% CI] = 3.50 [1.49-8.21]) were independent predictors of HCC. Basal core promoter mutation was the only risk factor of HCC in the persistently high HBsAg group (HRadj [95% CI] = 32.75 [5.41-198.42]). CONCLUSION: Patients with persistently high HBsAg levels during HBeAg-seropositive stage represent a unique population with low risk of HCC development.

Protocol for the air purification for eosinophilic COPD study (APECS): a randomised controlled trial of home air filtration by HEPA.

INTRODUCTION: Exposure to particulate matter (PM) pollution has been associated with lower lung function in adults with chronic obstructive pulmonary disease (COPD). Patients with eosinophilic COPD have been found to have higher levels of airway inflammation, greater responsiveness to anti-inflammatory steroid inhalers and a greater lung function response to PM pollution exposure compared with those with lower eosinophil levels. This study will evaluate if reducing home PM exposure by high-efficiency particulate air (HEPA) air filtration improves respiratory health in eosinophilic COPD. METHODS AND ANALYSIS: The Air Purification for Eosinophilic COPD Study (APECS) is a double-blinded randomised placebo-controlled trial that will enrol 160 participants with eosinophilic COPD living in the area of Boston, Massachusetts. Real and sham air purifiers will be placed in the bedroom and living rooms of the participants in the intervention and control group, respectively, for 12 months. The primary trial outcome will be the change in forced expiratory volume in 1 s (FEV1). Lung function will be assessed twice preintervention and three times during the intervention phase (at 7 days, 6 months and 12 months postrandomisation). Secondary trial outcomes include changes in (1) health status by St. George's Respiratory Questionnaire; (2) respiratory symptoms by Breathlessness, Cough and Sputum Scale (BCSS); and (3) 6-Minute Walk Test (6MWT). Inflammatory mediators were measured in the nasal epithelial lining fluid (NELF). Indoor PM will be measured in the home for the week preceding each study visit. The data will be analysed to contrast changes in outcomes in the intervention and control groups using a repeated measures framework. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Institutional Review Board of Beth Israel Deaconess Medical Centre (protocol #2019P0001129). The results of the APECS trial will be presented at scientific conferences and published in peer-reviewed journals. TRIAL REGISTRATION: NCT04252235. Version: October 2023.

Prevalence and correlates of past 30-day dual-vaping of nicotine and cannabis among adolescents in five New England states.

SIGNIFICANCE: Adolescent vaping behavior includes vaping of multiple substances, including both nicotine and cannabis (dual-vaping). This study describes the prevalence and the sociodemographic correlates of past 30-day dual-vaping. METHODS: We recruited adolescents ages 13-17 from five New England states (Massachusetts, Connecticut, Rhode Island, Vermont, New Hampshire) through the Prodege online survey panel from April 2021 to August 2022. Dual-vaping was defined as vaping both nicotine and cannabis (THC and/or CBD) in the past 30-days. We analyzed the prevalence of sole-nicotine, sole-cannabis, and dual-vaping of nicotine and cannabis and used multinomial logistic regression to examine associations between sociodemographic factors and sole- and dual-vaping of nicotine and cannabis. RESULTS: The analytic sample included 2013 observations from 1858 participants (mean age 15.1 years, 46.2% female, 74.1% White, 82.2% heterosexual). Among these observations, 5.6% reported past 30-day sole-nicotine vaping, 5.5% reported sole-cannabis vaping, and 7.3% had dual-vaped. Correlates for higher odds of past 30-day dual-vaping included total social media sites used and household tobacco use, in contrast with sole-cannabis vaping, which included older age and self-reported depression (all p's <0.05). DISCUSSION: Adolescent past 30-day dual-vaping of nicotine and cannabis was more prevalent than past 30-day sole-vaping of either nicotine or cannabis alone. Future studies should continue to collect detailed data on the type of substances, besides nicotine, that adolescents are vaping.

Quercetin, Main Active Ingredient of Moutan Cortex, Alleviates Chronic Orofacial Pain via Block of Voltage-Gated Sodium Channel.

BACKGROUND: Chronic orofacial pain (COP) therapy is challenging, as current medical treatments are extremely lacking. Moutan Cortex (MC) is a traditional Chinese medicine herb widely used for chronic inflammatory diseases. However, the mechanism behind MC in COP therapy has not been well-established. The purpose of this study was to identify the active ingredients of MC and their specific underlying mechanisms in COP treatment. METHODS: In this study, the main active ingredients and compound-target network of MC in COP therapy were identified through network pharmacology and bioinformatics analysis. Adult male Sprague-Dawley rats received oral mucosa lipopolysaccharide (LPS) injection to induce COP. Pain behaviors were evaluated by orofacial mechanical nociceptive assessment after intraganglionar injection. In vitro inflammatory cytokines in LPS-pretreated human periodontal ligament stem cells (hPDLSCs) and rat primary cultural trigeminal ganglion (TG) neurons were quantified by real-time quantitative polymerase chain reaction (RT-qPCR). Schrödinger software was used to verify the molecular docking of quercetin and critical targets. Whole-cell recording electrophysiology was used to evaluate the effect of quercetin on voltage-gated sodium (Na v ) channel in rat TG neurons. RESULTS: The assembled compound-target network consisted of 4 compounds and 46 targets. As 1 of the active components of MC correlated with most related targets, quercetin alleviated mechanical allodynia in LPS-induced rat model of COP (mechanical allodynia threshold median [interquartile range (IQR) 0.5 hours after drug administration: vehicle 1.3 [0.6-2.0] g vs quercetin 7.0 [6.0-8.5] g, P = .002). Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that immune response and membrane functions play essential roles in MC-COP therapy. Five of the related targets were identified as core targets by protein-protein interaction analysis. Quercetin exerted an analgesic effect, possibly through blocking Na v channel in TG sensory neurons (peak current density median [IQR]: LPS -850.2 [-983.6 to -660.7] mV vs LPS + quercetin -589.6 [-711.0 to -147.8] mV, P = .006) while downregulating the expression level of proinflammatory cytokines-FOS (normalized messenger RNA [mRNA] level mean ± standard error of mean [SEM]: LPS [2. 22 ± 0.33] vs LPS + quercetin [1. 33 ± 0.14], P = .034) and TNF-α (normalized mRNA level mean ± SEM: LPS [8. 93 ± 0.78] vs LPS + quercetin [3. 77 ± 0.49], P < .0001). CONCLUSIONS: Identifying Na v as the molecular target of quercetin clarifies the analgesic mechanism of MC, and provides ideas for the development of novel selective and efficient chronic pain relievers.

Evaluating Epidemiologic Trends and Variations in NICU Admissions in California, 2008 to 2018.

OBJECTIVE: Previous research suggests increasing numbers of and variation in NICU admissions. We explored whether these trends were reflected in California by examining NICU admissions and birth data in aggregate and among patient and hospital subpopulations more susceptible to variations in care. METHODS: In this retrospective cohort study, we evaluated NICU utilization between 2008 and 2018 for all live births at hospitals that provide data to the California Perinatal Quality Care Collaborative. We compared hospital- and admission-level data across birth weight (BW), gestational age (GA), and illness acuity categories. Trends were analyzed by using linear regression models. RESULTS: We identified 472 402 inborn NICU admissions and 3 960 441 live births across 144 hospitals. Yearly trends in NICU admissions remained stable among all births and higher acuity births (mean admission rates 11.9% and 4.1%, respectively). However, analysis of the higher acuity births revealed significant increases in NICU admission rates for neonates with higher BW and GA (BW ≥ 2500g: 1.8% in 2008, 2.1% in 2018; GA ≥ 37 weeks: 1.5% in 2010, 1.8% in 2018). Kaiser hospitals had a decreasing trend of NICU admissions compared to non-Kaiser hospitals (Kaiser: 13.9% in 2008, 10.1% in 2018; non-Kaiser: 11.3% in 2008, 12.3% in 2018). CONCLUSIONS: Overall NICU admission rates in California were stable from 2008-2018. However, trends similar to national patterns emerged when stratified by infant GA, BW, and illness acuity as well as Kaiser or non-Kaiser hospitals, with increasing admission rates for infants born at higher BW and GA and within non-Kaiser hospitals.

Sexual orientation and gender identity differences in perceptions and product appeal in response to e-cigarette advertising.

INTRODUCTION: E-cigarette use is disparately high among sexual minoritized populations. As e-cigarette advertising may influence product appeal, this study tested sexual orientation- and gender-based differences in response to e-cigarette advertisement exposure on advertisement perceptions and product appeal. METHODS: We recruited 497 adults (mean age=31.9 years, 45.1% women, 54.3% heterosexual, 71.2% Non-Hispanic White) living in the United States via the crowdsourcing platform Prolific. Participants viewed two randomly selected e-cigarette advertisements (from n=173 advertisements). Post-exposure, participants rated the perceived advertisement effectiveness, relevance, and product use intention. Associations between sexual orientation and outcomes were estimated using multivariable linear mixed-effects models. We tested interaction effects between sexual orientation, gender, and advertisement feature (e.g. presence of humans, flavors, and product packaging), and ran Tukey post hoc tests for pairwise comparisons. RESULTS: Post-exposure, heterosexual women, sexual minoritized men, and sexual minoritized women (reference group: heterosexual men) rated perceived advertisement effectiveness and relevance lower after viewing advertisements featuring flavors (vs no flavors; all p<0.001). Sexual minoritized men and sexual minoritized women rated perceived advertisement relevance lower after viewing advertisements featuring humans (all p<0.001) or fruit (all p<0.001). Heterosexual women, sexual minoritized men, and sexual minoritized women reported lower product use intention after viewing advertisements featuring an e-liquid bottle (vs no e-liquid bottle; all p<0.05). CONCLUSIONS: Sexual minoritized women and men reported lower e-cigarette advertisement appeal and product use intentions than heterosexual men. More evidence is needed to understand advertisement perceptions and product appeal in this group to inform e-cigarette advertising regulations and anti-tobacco messaging campaigns that aim to reduce tobacco-related health inequities.

Identifying clusters of coexisting conditions and outcomes among adults admitted to hospital with community-acquired pneumonia: a multicentre cohort study.

BACKGROUND: Little is known about patterns of coexisting conditions and their influence on clinical care or outcomes in adults admitted to hospital for community-acquired pneumonia (CAP). We sought to evaluate how coexisting conditions cluster in this population to advance understanding of how multimorbidity affects CAP. METHODS: We studied 11 085 adults admitted to hospital with CAP at 7 hospitals in Ontario, Canada. Using cluster analysis, we identified patient subgroups based on clustering of comorbidities in the Charlson Comorbidity Index. We derived and replicated cluster analyses in independent cohorts (derivation sample 2010-2015, replication sample 2015-2017), then combined these into a total cohort for final cluster analyses. We described differences in medications, imaging and outcomes. RESULTS: Patients clustered into 7 subgroups. The low comorbidity subgroup (n = 3052, 27.5%) had no comorbidities. The DM-HF-Pulm subgroup had prevalent diabetes, heart failure and chronic lung disease (n = 1710, 15.4%). One disease category defined each remaining subgroup, as follows: pulmonary (n = 1621, 14.6%), diabetes (n = 1281, 11.6%), heart failure (n = 1370, 12.4%), dementia (n = 1038, 9.4%) and cancer (n = 1013, 9.1%). Corticosteroid use ranged from 11.5% to 64.9% in the dementia and pulmonary subgroups, respectively. Piperacillin-tazobactam use ranged from 9.1% to 28.0% in the pulmonary and cancer subgroups, respectively. The use of thoracic computed tomography ranged from 5.7% to 36.3% in the dementia and cancer subgroups, respectively. Adjusting for patient factors, the risk of in-hospital death was greater in the cancer (adjusted odds ratio [OR] 3.12, 95% confidence interval [CI] 2.44-3.99), dementia (adjusted OR 1.57, 95% CI 1.05-2.35), heart failure (adjusted OR 1.66, 95% CI 1.35-2.03) and DM-HF-Pulm subgroups (adjusted OR 1.35, 95% CI 1.12-1.61), and lower in the diabetes subgroup (adjusted OR 0.67, 95% CI 0.50-0.89), compared with the low comorbidity group. INTERPRETATION: Patients admitted to hospital with CAP cluster into clinically recognizable subgroups based on coexisting conditions. Clinical care and outcomes vary among these subgroups with little evidence to guide decision-making, highlighting opportunities for research to personalize care.

Predictors of response to a lapse in anti-VEGF treatment in patients with macular edema secondary to retinal vein occlusion.

BACKGROUND: Macular edema (ME) in the setting of retinal vein occlusions (RVO) is a common cause of vision loss worldwide. Anti-vascular endothelial growth factor (anti-VEGF) injections are the gold standard for ME secondary to RVO. Despite their efficacy, anti-VEGF injections carry significant burdens for patients, resulting in high rates of loss to follow-up and treatment lapses. METHODS: A sub-analysis examining the effects of a treatment lapse in RVO patients was conducted. Sixty patients were included and separated into vision-loss and stable-vision groups based on change in vision after a lapse. A logistic regression with age, body mass index (BMI), history of dyslipidemia, and time since diagnosis of RVO as predictors was used to predict whether patients would experience vision loss after a lapse. RESULTS: The average lapse was 5.6 months and similar in the vision-loss and stable-vision groups. At baseline, the vision-loss group was older and had a lower BMI (p < 0.05). Age and history of dyslipidemia increased the odds of vision loss by factors of 1.23 (range, 1.10-1.45) and 8.40 (range, 1.62-66.2), respectively. BMI and time since RVO diagnosis decreased the odds of vision loss by factors of 0.83 (range, 0.69-0.95) and 0.95 (range, 0.90-0.99), respectively. The final model had a specificity of 87.5% and a sensitivity of 70.0%. CONCLUSIONS: Patients' responses to treatment lapses for ME secondary to RVO can be predicted with reasonable accuracy using readily available clinical data, particularly age, BMI, time since diagnosis, and history of dyslipidemia. Providers should consider these factors when counselling patients and determining follow-up schedules.

Vaping of Cannabis, Cannabidiol, and Synthetic Cannabis Among US Sexual Minority Youths.

This cross-sectional study investigates rates of vaping of cannabis, cannabidiol, and synthetic cannabis among US sexual minority youths.