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Sally Tran,1 Biyao Zou,1,2 Leslie Kam,1 KeeSeok Lee,1 Daniel Q Huang,3,4 Linda Henry,1 Ramsey Cheung,1,5 Mindie H Nguyen1,2 1Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA; 2Department of Epidemiology and Population Health, Stanford University School of Medicine, Palo Alto, CA, USA; 3Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; 4Division of Gastroenterology and Hepatology, National University Health System, Singapore, Singapore; 5Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USACorrespondence: Mindie H Nguyen, Department of Medicine and Department of Epidemiology and Population Health (by courtesy), Stanford University Medical Center, 780 Welch Road, CJ250K, Palo Alto, CA, 94304, USA, Tel +1 650-498-5691, Fax +1 650-498-5692, Email mindiehn@stanford.eduBackground & Aim: Causes of hepatocellular carcinoma (HCC) may change as treatments become available for some liver diseases. We examined the distribution of HCC cause and survival of a nationwide cohort of insured patients.Methods: Optum’s de-identified Clinformatics® Data Mart Database (CDM), 2003– 2021.Results: A total of 34707 patients with HCC were included: mean age: 68.3± 11.6 years, 61% male, 62% Caucasian, 74% cirrhosis. Non-alcoholic fatty liver disease (NAFLD) was the most common etiology (38.9%), then hepatitis C virus (HCV) (25.3%), cryptogenic (18.0%), alcohol-associated liver disease (9.4%), other liver diseases (5.8%) and hepatitis B virus (HBV) at 2.6%. NAFLD patients were the oldest (mean age 71.1± 11.2) and had the highest Charlson Comorbidity Index (CCI) (mean 10.5± 3.9), while HCV were the youngest (mean age 64.2± 9.2 years) and HBV had the lowest CCI (mean 7.2± 4.4) (both P< 0.0001). The overall 5-year survival was 18.8% (95% CI 18.2– 19.3) but was lower in the recent 2014– 2021 period vs 2003– 2013 (18.1% vs 19.5%, P=0.003). The 2014– 2021 cohort (inclusive of HCV treatment advances) was significantly older, with more females, fewer Caucasians, more African Americans, more Hispanics, fewer Asians, more cirrhosis, more NAFLD, and higher CCI (all P< 0.001). On multivariable analysis, males (aHR: 1.13), Caucasians (aHR: 1.46), African Americans (aHR: 1.53) and Hispanics (aHR: 1.28) vs Asians, 2014– 2021 (vs 2003– 2013) cohort (aHR: 1.12), NAFLD (aHR: 1.14) or cryptogenic liver disease (aHR: 1.45) were associated with increased mortality (all P< 0.001).Conclusion: HCC patients in more recent time 2014– 2021 were more likely to be older, more likely to have nonviral etiology, and had worse survival compared to those from 2003 to 2013.Keywords: ethnic disparities, NAFLD, nonviral, epidemiology

Takanori Ito,1 Mindie H Nguyen2,3 1Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan; 2Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, CA, USA; 3Department of Epidemiology and Population Health, Stanford University Medical Center, Palo Alto, CA, USACorrespondence: Mindie H Nguyen, Division of Gastroenterology and Hepatology, Department of Medicine, and Department of Epidemiology and Population Health, Stanford University Medical Center, 780 Welch Road, CJ250K, Palo Alto, CA, 94304, USA, Tel +1 650-498-6084, Fax +1 650-498-5692, Email mindiehn@stanford.eduAbstract: Hepatocellular carcinoma (HCC) continues to be a serious medical problem with poor prognosis worldwide. The distribution of the major etiologies of HCC is changing due to the progress of anti-viral treatments, including hepatitis B virus (HBV) suppression by nucleoside/nucleotide analogues (NAs) and increased sustained virologic response (SVR) rates by direct-acting antivirals (DAAs) for hepatitis C virus (HCV), as well as the rising trend of nonviral liver disease. Although viral hepatitis remains the most common cause of HCC, non-alcoholic liver disease (NAFLD) with metabolic syndrome and alcohol-associated liver disease (ALD) are increasing. Effective and well-tolerated NAs treatment can slow the disease progression of chronic HBV infection to cirrhosis, end-stage liver disease, and reduce HCC risk. Treatment with NAs is also associated with significant improvement in the long-term survival of patients with HBV infection who already have HCC. DAAs have achieved viral elimination in almost all patients with HCV without significant adverse events, even in patients with decompensated liver cirrhosis and HCC. Similarly, DAA therapy can reduce disease progression, liver and non-liver complications, and improve the long-term survival of patients with chronic HCV infection with or without HCC. Meanwhile, NAFLD is a rapidly increasing cause of HCC along with the epidemics of obesity and type 2 diabetes globally. NAFLD-related HCC can occur in patients without cirrhosis and is known to have a lower survival rate than viral hepatitis-related HCC. Since there is currently no specific pharmacotherapy effective for NAFLD, lifestyle modification and prevention of complications are important to improve prognosis. Additionally, ALD is the second fastest-growing cause of HCC-related deaths, especially with an accelerated trend since the COVID-19 pandemic. This review provides an overview of the epidemiologic trends in the etiologies of HCC, and the progress of treatments for each etiology and the impact on outcome in the patients with HCC.Keywords: hepatocellular carcinoma, etiology, hepatitis B, hepatitis C, non-alcoholic fatty liver disease, alcohol-associated liver disease

Phuc Duc Dang,1,2 Minh Hien Nguyen,1,2 Xuan Khan Mai,3,4 Dinh Dai Pham,1,2 Minh Duc Dang,1 Dang Hai Nguyen,1 Van Nam Bui,1 Duy Ton Mai,5 Nhu Binh Do,6,7 Duc Thuan Do1,2 1Department of Stroke, Military Hospital 103, Hanoi, Vietnam; 2Department of Neurology, Vietnam Military Medical University, Hanoi, Vietnam; 3Respiratory Center, Military Hospital 103, Hanoi, Vietnam; 4Department of Tuberculosis and Lung Disease, Vietnam Military Medical University, Hanoi, Vietnam; 5Emergency Department, Bach Mai Hospital, Hanoi, Vietnam; 6Division of Military Science, Military Hospital 103, Hanoi, Vietnam; 7Department of Infectious Disease, Vietnam Military Medical University, Hanoi, VietnamCorrespondence: Duc Thuan Do Tel +84 982275220Email thuandd@vmmu.edu.vnBackground: There have been many scales to predict pneumonia in stroke patients, but they are so complex, making it difficult to apply in practice. Therefore, we conducted this study to assess the role of the National Institutes of Health Stroke Scale (NIHSS) and the Gugging Swallowing Screen (GUSS) in predicting stroke-associated pneumonia (SAP). These scales are routinely used in stroke patients. Therefore, their application in predicting SAP risk will be of high value in clinical practice. There has been no previous study evaluating the effectiveness of SAP risk prediction for each of these scales.Aim: This study aimed to compare the value of NIHSS and GUSS in SAP prediction and their convenience in clinical practice.Methods: It was a cohort study. The receiver operating characteristics (ROC) curves were constructed to assess the sensitivity (Se) and specificity (Sp) of the scales. Area under the curves (AUC) were calculated, and we compared them.Results: NIHSS had a medium value of predictor of SAP with AUC 0.764 (95% CI 0.735– 0.792), 65.4% Se, 76.5% Sp. GUSS had good value in predicting SAP with AUC 0.858 (95% CI 0.833– 0.880), 80.5% Se, 80.1% Sp. Pairwise comparison of ROCs curves demonstrated that the difference between two AUCs was significant (p < 0.01). Performing GUSS required 24.5 ± 6.7 minutes, 2.5 times longer than NIHSS (9.9 ± 2.0 minutes).Conclusion: GUSS had a better predictive value of SAP than NIHSS. But NIHSS was more convenient in clinical practice because of its simple instrument and quick performance.Keywords: stroke-related pneumonia, post-stroke pneumonia, pneumonia after stroke, pneumonia prediction

Eiichi Ogawa,1 Norihiro Furusyo,1 Mindie H Nguyen2 1Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan; 2Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, CA, USA Abstract: Tenofovir alafenamide (TAF), a novel prodrug of tenofovir (TFV), has been approved for the treatment of chronic hepatitis B virus (HBV) infection. TAF has been shown to be a potent inhibitor of HBV replication at a low dose, with high intracellular concentration and more than 90% lower systemic TFV concentration than tenofovir disoproxil fumarate (TDF). In two randomized, double-blind, multinational, Phase 3, non-inferiority trials for hepatitis B e antigen (HBeAg)-positive and -negative patients (primary analysis: 48 weeks), TAF 25 mg orally once-daily was not inferior to TDF 300 mg in achieving an HBV DNA level

Manh Hung Nguyen, Andreas KruseInstitute of Gerontology, Heidelberg University, Heidelberg, GermanyObjective: To evaluate the effects of Tai chi exercise on balance, sleep quality, and cognitive performance in community-dwelling elderly in Vinh city, Vietnam.Design: A randomized controlled trial.Participants: One hundred two subjects were recruited.Intervention: Subjects were divided randomly into two groups. The Tai chi group was assigned 6 months' Tai chi training. The control group was instructed to maintain their routine daily activities.Outcome measures: The Falls Efficacy Scale (FES), Pittsburgh Sleep Quality Index (PSQI), and Trail Making Test (TMT) were used as primary outcome measures.Results: Participants in the Tai chi group reported significant improvement in TMT (part A) (F [1, 71] = 78.37, P < 0.001) and in TMT (part B), (F [1, 71] = 175.00, P < 0.001) in comparison with the control group. Tai chi participants also reported better scores in FES (F [1, 71] = 96.90, P < 0.001) and in PSQI (F [1,71] = 43.69, P = 0.001) than the control group.Conclusion: Tai chi is beneficial to improve balance, sleep quality, and cognitive performance of the elderly.Keywords: Tai chi, sleep, balance

Manh Hung Nguyen, Andreas KruseInstitute of Gerontology, Heidelberg University, Heidelberg, GermanyObjective: Evaluating the effects of Tai Chi exercise on physical fitness, blood pressure, and perceived health in community-dwelling elderly.Design: A randomized controlled trial.Setting: Community-dwelling elderly in Vinh city, Vietnam.Participants: Ninety-six community-dwelling participants aged 60 to 79 years (68.9 ± 5.1 years) were recruited.Intervention: Subjects were divided randomly into two groups: Tai Chi and Control groups. Participants in the Tai Chi group (aged 69.02 ± 5.16 years) attended a 60-minute Tai Chi practice session twice a week for 6 months. The session consisted of a 15-minute warm-up and a 15-minute cool-down period. The Control group (aged 68.72 ± 4.94 years) maintained routine daily activities.Outcome measures: The Senior Fitness Test and Short-Form 36® (SF-36®) are primary outcome measures.Results: After 24 weeks of the Tai Chi training program, the intervention group showed significant decrease in systole of 12 mmHg and heart rate 6.46 bpm. Body mass index and waist–hip ratio were also reduced by 1.23 and 0.04, respectively. The Senior Fitness Test and SF-36 showed significant improvement.Conclusion: In this randomized controlled trial study, Tai Chi is beneficial to improve systole blood pressure, heart rate, body mass index, waist–hip ratio, perceived health, and physical fitness. Assessment of the effects of Tai Chi may be focused more on chronic disease with a long-term training program in the future.Keywords: physical fitness, health, Tai Chi

Introduction'Real-world' data for mold-active triazoles (MATs) in the treatment of invasive fungal infections (IFIs) are lacking. This study evaluated usage of MATs in a disease registry for the management of IFIs.MethodsData were collected for this multicenter, observational, prospective study from 55 US centers, between March 2017 and April 2020. Eligible patients received isavuconazole, posaconazole, or voriconazole as MAT monotherapy (one MAT) or multiple/sequenced MAT therapy (more than one MAT) for prophylaxis or treatment. Patients were enrolled within 60 days of MAT initiation. The primary objective was to characterize patients receiving a MAT and their patterns of therapy. The full analysis set (FAS) included eligible patients for the relevant enrollment protocol, and the safety analysis set (SAF) included patients who received ≥ 1 MAT dose.ResultsOverall, 2009 patients were enrolled in the SAF. The FAS comprised 1993 patients (510 isavuconazole; 540 posaconazole; 491 voriconazole; 452 multiple/sequenced MAT therapies); 816 and 1177 received treatment and prophylaxis at study index/enrollment, respectively. Around half (57.8%) of patients were male, and median age was 59 years. Among patients with IFIs during the study, the most common pathogens were Aspergillus fumigatus in the isavuconazole (18.2% [10/55]) and voriconazole (25.5% [12/47]) groups and Candida glabrata in the posaconazole group (20.9% [9/43]); the lungs were the most common infection site (58.2% [166/285]). Most patients were maintained on MAT monotherapy (77.3% [1541/1993]), and 79.4% (1520/1915) completed their MAT therapies. A complete/partial clinical response was reported in 59.1% (591/1001) of patients with a clinical response assessment. Breakthrough IFIs were reported in 7.1% (73/1030) of prophylaxis patients. Adverse drug reactions (ADRs) were reported in 14.7% (296/2009) of patients (3.9% [20/514] isavuconazole; 11.3% [62/547] posaconazole; 14.2% [70/494] voriconazole).ConclusionsIn this 'real-world' study, most patients remained on their initial therapy and completed their MAT therapy. Over half of patients receiving MATs for IFIs had a successful response, and most receiving prophylaxis did not develop breakthrough IFIs. ADRs were uncommon.

Covid-19, Artificial Intelligence (AI), and Climate Change, have disrupted work education, rendering sustainability of careers and livelihoods a concern. This paper outlines a collaborative response to that challenge, offering opportunities for sustainable livelihoods in a work education cloud collaboration, Project SLiC (Sustainable Livelihoods Collaboration). We have joined forces across nation states in the Global South/North to share cloud resources, focused on teaching a postgraduate course, Sustainable Livelihoods. Online modules are stored in a secure cloud site, from which local courses draw-down, autochthonously, whichever resources fit workforce development in context. We outline modules, and an evaluative process, in a proof-of-concept trial. Finally, we envisage how this initial collaboration may morph into a whole degree, including research supervision. We close with a call to career development professionals to share their unique expertise and experiences at the work education frontline, on how to develop this sustainable careers project, for the greater good. [ABSTRACT FROM AUTHOR]

Posaconazole is a recently approved lipophilic triazole antifungal agent that exhibits potent and broad-spectrum antifungal activity in vitro and in vivo against most Candida spp., Cryptococcus neoformans, Aspergillus spp., many Zygomycetes, endemic fungi and dermatophytes. It has been documented that posaconazole has potency and spectrum of activity similar to those of itraconazole and superior to those of fluconazole against clinically important isolates of Candida spp., C. neoformans and Aspergillus spp. This new triazole has been developed for the treatment of fungal infections, which most often occur in severely immunocompromised patients, such as organ transplant patients or cancer patients undergoing chemotherapy. Since posanconazole has low solubility in aqueous and acidic media, its absorption is dose limited and significantly dependent upon food intake. The time to reach the maximum plasma concentration has been reported to be 5-8 hours following oral administration of a single dose. The relative bioavailability of posaconazole has been estimated to be significantly different among regimens and has been observed to be significantly increased by administration in divided doses. Posaconazole binds predominantly to albumin, and the extent of protein binding is high (>98%). Posaconazole has a large mean apparent volume of distribution after oral administration (V(d)/F), which is approximately 5-25 L/kg, suggesting extensive extravascular distribution and penetration into intracellular spaces. The V(d)/F is influenced by the dosage regimen. Since food significantly increases its bioavailability, posaconazole should be administered with a full meal whenever possible, to ensure optimal absorption. Posaconazole primarily circulates in plasma and then is widely distributed to the tissues and is slowly eliminated. Posaconazole is not metabolized to a significant extent through the cytochrome P450 (CYP) enzyme system and also has no effect on the CYP isoenzymes of 1A2, 2C8, 2C9, 2D6 and 2E1. The limited metabolism of posaconazole is mediated predominantly through phase 2 biotransformations via uridine diphosphate glucuronosyltransferase enzyme pathways. Therefore, inhibitors or inducers of these clearance pathways may affect posaconazole plasma concentrations. Since posaconazole is an inhibitor primarily of CYP3A4, plasma concentrations of drugs that are predominantly metabolized by CYP3A4 may be increased by posaconazole. Posaconazole has a median terminal elimination half-life of 15-35 hours. The renal elimination of posaconazole is less than 1 mL/h, which is negligible compared with the mean total oral clearance of 16.3 L/h. Posaconazole shows potent in vitro activity against yeasts such as Candida spp. and C. neoformans, and against a range of moulds such as Aspergillus spp., as well as many dimorphic fungi and dermatophytes. Posaconazole has been shown to improve survival and/or to reduce the fungal tissue burden in animals infected with Blastomyces dermatitidis, C. neoformans, Aspergillus fumigatus, Aspergillus flavus, Aspergillus terreus, Coccidioides immitis or Pseudallescheria boydii. The predictive pharmacokinetic/pharmacodynamic parameter for posaconazole treatment efficacy--the ratio between the mean free-drug area under the plasma concentration-time curve from 0 to 24 hours and the minimum inhibitory concentration (AUC(24)/MIC)--is about 17, which is similar to the value observed for other azoles in this infection model of disseminated Candida albicans infection. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To evaluate the morbidity and mortality of Candida fungemia and to assess the efficacy of low- vs high-dose amphotericin B and fluconazole vs amphotericin B in patients with candidemia. METHODS: Multicenter, prospective, observational study of 427 consecutive patients with candidemia. RESULTS: The mortality rate for patients with candidemia was 34%. The mortality rate for patients with catheter-related candidemia in whom the catheters were retained was significantly higher than that of patients in whom the catheters were removed (41% vs 21%, P < .001). We found no overall difference in mortality in patients treated with low-dose (total amphotericin B dose of < or = 500 mg) (13%) vs high-dose amphotericin B (total amphotericin B dose of > 500 mg) (15%), but the group treated with a low dose had fewer side effects (40%) than those treated with a high dose (55%) (P = .03). Fluconazole was as efficacious as amphotericin B in the therapy of candidemia, even when stratified by risk factors for mortality. Fewer side effects were seen with fluconazole (12%) compared with amphotericin B (44%) (P < .001). CONCLUSIONS: In selected patients with candidemia, low-dose amphotericin B was as efficacious as high-dose amphotericin B. Based on other studies and ours, fluconazole seems to be an alternative therapeutic option to amphotericin B in selected patients. [ABSTRACT FROM AUTHOR]

We compared the in-vitro activity of fluconazole, itraconazole, ketoconazole and voriconazole against 67 blood isolates of Candida spp. exhibiting a wide range of fluconazole MICs (0.125 to >64 mg/L). Voriconazole was the most potent in vitro, followed by itraconazole, ketoconazole and fluconazole. Itraconazole and voriconazole had in-vitro activity against fluconazole-susceptible and -resistant candida isolates. Higher itraconazole and voriconazole MICs were observed in isolates exhibiting higher fluconazole MICs, suggesting cross-resistance. Itraconazole and voriconazole MICs of ≥16 mg/L were observed only in Candida albicans and Candida tropicalis. Candida krusei and Candida glabrata exhibited itraconazole MICs of 0.5-1 mg/L and voriconazole MICs of 0.25-0.5 mg/L. [ABSTRACT FROM PUBLISHER]

Non-compliance with therapy is a significant problem, particularly when the disease process is chronic and therapeutic regimens are employed for prolonged periods. We assessed the prevalence and variables associated with compliance with antiretroviral therapy in patients with human immunodeficiency virus infection, by means of a longitudinal observational study of 46 patients aged 23 to 68 years, with human immunodeficiency virus infection, followed at the Pittsburgh VA Medical Center. Data on demographics, medical status, physical functioning (Karnofsky performance scores), CD4 lymphocyte count, depression (Beck depression inventory), coping (inventory of coping with illness scale scores), and psychological and emotional stress (profile of mood states scale scores), were prospectively assessed on all patients at baseline and every 6 months. Compliance was assessed at 6 and 12 months: patients taking > or = 80% of antiretroviral therapy were considered compliant. Overall, 63% of patients were compliant with antiretroviral therapy. Age, education, employment, religious support, and perceived quality of life did not correlate with compliance. By univariate analysis, lack of prior intravenous drug use was significantly associated with compliance (p = 0.01). Compliant patients had significantly better adaptive coping (p = 0.03), and less depression (p = 0.04). By multivariate analysis, black race was significantly associated with non-compliance independent of intravenous drug use and educational status. History of prior opportunistic infection (which presumably heightens the perceived severity of illness) (p = 0.02), and lesser psychological disturbance scores (p = 0.02) were associated with compliance. Compliance was observed despite the greater number of prescription medications taken by compliant patients (p = 0.04). At 12 months, Karnofsky scores were better in compliant patients (p = 0.02), although mortality was not different. Besides identifying predictors of compliance, our data suggest that symptoms of depression and psychological stress be sought in patients with non-adherence. [ABSTRACT FROM AUTHOR]

We investigated the interaction between amphotericin B and azithromycin in vitro against 26 clinical isolates of Fusarium. Synergy was demonstrated in all isolates. Amphotericin B MICs were reduced from a mean of 1 mg/L when tested alone to a mean of 0.37 mg/L when tested in combination with azithromycin. Azithromycin demonstrated no activity against Fusarium when tested alone (MIC > 128 mg/L). When combined with amphotericin B the mean MIC was reduced to 5.5 mg/L, a level readily achieved in tissue. Given the resistance of Fusarium to conventional therapy, the in-vitro synergy between amphotericin B and azithromycin might prove to be important in therapy for fusariosis. [ABSTRACT FROM PUBLISHER]

Background/aims: With polarizing income disparities, this study investigated the prevalence and trends of liver disease in a U.S. population-based sample based on income-to-poverty ratio (IPR)., Methods: This cross-sectional study analysed survey data from the 1999-2018 National Health and Nutrition Examination Survey with highest (HIG), middle-income (MIG), and lowest income (LIG) groups defined as IPR ≤ 1, 1 < IPR <5, and IPR ≥ 5, respectively., Results: We analysed 59,204 adult participants with 48.2% male, 39.7% aged 18-39, 36.2% 40-59, and 24.1% ≥60 years. The weighted prevalence of hepatitis C (HCV), B (HBV) infection, non-alcoholic fatty liver disease (NAFLD), alcohol-associated liver disease (ALD), and advanced fibrosis in LIG were 3.9% (n = 276), 7.4% (n = 527), 33.2% (n = 714), 5.2% (n = 401), and 9.0% (n = 694), respectively, compared to lower rates for HIG: 1.0% (n = 82), 3.2% (n = 263), 29.6% (n = 798), 3.9% (n = 354), and 5.0% (n = 638). After adjusting for age, sex, race and ethnicity, education, and birthplace, HIG had the lowest odds of having any liver disease [adjusted odds ratio (aOR) 0.67, p < 0.0001], with similar findings for specific conditions including HCV, HBV, and advanced fibrosis (aOR 0.24, 0.52, and 0.64, all p < 0.0001, respectively). While viraemic HCV prevalence decreased over time for HIG, there were no changes for MIG nor LIG. Similarly, NAFLD prevalence was stable for HIG but increased for MIG and LIG., Conclusion: LIG and MIG in the United States have higher liver disease burdens than HIG, with increasing NAFLD prevalence and lack of decline in current HCV infection prevalence over time as opposed to declining or stable trend in HIG., (© 2024 John Wiley & Sons Ltd.)

Traffic information is crucial for estimating NO 2 concentrations, but it is static and limited in predicting constantly changing NO 2 levels. To overcome these challenges, this study utilized real-time spatial big data to capture both the spatial and temporal fluctuations in traffic. Digital tachograph (DTG) data, sourced from digital devices in all commercial vehicles, are employed to construct a DTG land use regression (LUR) model, and its performance is compared with that of a non-DTG-LUR model. The DTG-LUR model exhibits superior performance, with an explanatory power of 0.46, in contrast to the 0.36 of the non-DTG model. This significant improvement stems from the spatially and temporally dynamic DTG variables such as cargo traffic. This study introduces a novel approach for incorporating DTG data in correlating with NO 2 concentrations. It underscores the advantage of DTG data in predicting daily NO 2 fluctuations at a precise 200-m grid, which is not feasible with conventional data. The findings of the study highlight the immense potential of spatial big data for fine-grained analyses, which could enable hourly predictions of air pollution., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Detailed subgroup incidence rates for steatotic liver disease (SLD)-related hepatocellular carcinoma (HCC) are critical to inform practice and public health interventions but remain sparse. We aimed to fill in this gap., Methods and Findings: In a retrospective cohort study of adults with SLD from the United States (US) Merative Marketscan Research Databases (1/2007 to 12/2021), we estimated HCC incidence stratified by sex, age, cirrhosis, diabetes mellitus (DM), and a combination of all these 4 factors. We excluded patients with significant alcohol use and chronic viral hepatitis. We analyzed data from 741,816 patients with SLD (mean age 51.5 ± 12.8 years, 46% male, 14.7% cirrhosis). During a 2,410,166 person-years (PY) follow-up, 1,740 patients developed HCC. The overall HCC incidence yielded 0.72 per 1,000 PY (95% confidence interval [CI, 0.68, 0.75]). The incidence was higher in males (0.95, 95% CI [0.89, 1.01]) compared to females (0.52, 95% CI [0.48, 0.56]) (p < 0.001). For those with cirrhosis, the incidence was significantly higher at 4.29 (95% CI [4.06, 4.51]) compared to those without cirrhosis (0.14, 95% CI [0.13, 0.16]) (p < 0.001). Additionally, the incidence was higher in patients with DM (1.19, 95% CI [1.12, 1.26]) compared to those without DM (0.41, 95% CI [0.38, 0.44]) (p < 0.001). Chronic kidney disease (CKD) was also associated with a higher HCC incidence of 2.20 (95% CI [2.00, 2.41]) compared to those without CKD (0.58, 95% CI [0.55, 0.62]) (p < 0.001). Similarly, individuals with cardiovascular disease (CVD) had a higher HCC incidence of 1.89 (95% CI [1.75, 2.03]) compared to those without CVD (0.51, 95% CI [0.48, 0.54]) (p < 0.001). Finally, the incidence of HCC was significantly higher in patients with non-liver cancer (3.90, 95% CI [3.67, 4.12]) compared to those without other cancers (0.29, 95% CI [0.26, 0.31]) (p < 0.001). On further stratification, HCC incidence incrementally rose by 10-year age intervals, male sex, cirrhosis, and DM, reaching 19.06 (95% CI [16.10, 22.01]) and 8.44 (95% CI [6.78, 10.10]) in males and females, respectively, but only 0.04 for non-diabetic, noncirrhotic aged <40 years patients in both sexes. The main limitation of this methodology is the potential misclassification of the International Classification of Diseases (ICD) codes inherent in claims database studies., Conclusions: This nationwide study provided robust granular estimates for SLD-related HCC incidence stratified by several key risk factors. In addition to cirrhosis, future surveillance strategies, prevention, public health initiatives, and future research models should also take into account the impact of sex, age, and DM., Competing Interests: I have read the journal’s policy and the author of this manuscript has the following competing interests: MHN: Research support: Pfizer, Enanta, Astra Zeneca, GSK, Delfi, Innogen, Exact Science, CurveBio, Gilead, Vir Biotech, Helio Health, National Cancer Institute, Glycotest, B.K. Kee Foundation. Consulting and/or Advisory Board: Intercept, Exact Science, Gilead, GSK, Eli Lilly. Exelixis. MHN is an Academic Editor on PLOS Medicine’s editorial board. Other authors: no declaration to disclose., (Copyright: © 2024 Lai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)