Outcomes of early vs late treatment initiation in solid organ transplantation from hepatitis C virus nucleic acid test-positive donors to hepatitis C virus-uninfected recipients: Results from the HCV-TARGET study.

Curative hepatitis C virus (HCV) therapy has increased transplantation from HCV-infected nucleic acid test-positive donors to HCV-uninfected recipients (D+/R-). We evaluated outcomes of early and late HCV treatment among D+/R- nonliver organ transplants. Patients received HCV regimens per local standard (n = 10 sites). Outcomes were compared between early and late treatments. Early treatment regimens (ETR) (n = 56) were initiated pretransplantation to day 7 posttransplant. Late treatment regimens (LTRs) (n = 102) began median 31 (range, 8-114) days posttransplant. There were 79 kidney, 50 lung, 23 heart, and 6 mixed transplants, similar between groups. HCV RNA was quantifiable in 98% of LTR versus 44.6% of ETR recipients (P < .001). Mean (range) days on treatment were 28 (7-93) ETR and 81 (51-111) LTR (P < .0001). There were no virological failures with ETR, but relapse (n = 3) and nonresponse (n = 2) in LTR (P = .16), including fibrosing cholestatic hepatitis postrelapse (n = 1). Sustained virological response was 100% (95% confidence interval, 93.4-100.0) in ETR (n = 54) and 94.9% (95% confidence interval, 88.5-98.3) in LTR (n = 98). Acute rejection occurred in 11 (19.6%) ETR and 25 (24.5%) LTR. In total, 11 HCV-unrelated deaths occurred: 8 ETR and 3 LTR. Organ transplantation from HCV-infected nucleic acid test-positive donors to HCV-uninfected recipients was safe. ETR led to fewer virological failures with shorter treatment duration, supporting recommendations to initiate treatment promptly posttransplant.

Examining the evolving landscape of liver cancer burden in the United States from 1990 to 2019.

INTRODUCTION: Liver cancer (LC) is frequently preceded by cirrhosis and poses a significant public health challenge in the United States (US). Recent decades have seen notable shifts in the epidemiological patterns of LC, yet national data guiding the optimal allocation of resources and preventive efforts remain limited. This study aims to investigate the current trends, risk factors, and outcomes of LC in the US. METHODS: This study utilized the Global Burden of Disease (GBD) dataset to collect data on the annual incident cases, deaths, Disability-Adjusted Life Years (DALYs), age-standardized incidence rates (ASIR), age-standardized death rates, and age-standardized DALY rates of primary LC and its etiologies and risk factors, between 1990 and 2019. Percentage changes in incident cases, DALYs, and deaths and the estimated annual percentage change (EAPC) in ASIR and deaths rates of LC were calculated to conduct temporal analysis. Linear regression was applied for the calculation of EAPCs. Correlations of EAPC with socio-demographic index (SDI) were separately evaluated by Pearson correlation analyses. RESULTS: We observed a marked increase in the ASIR of LC, increasing from 2.22 (95% CI: 2.15-2.27) per 100,000 people in 1990 to 5.23 (95% CI: 4.28-6.29) per 100,000 people in 2019, a percentage change of 135.4%. LC due to hepatitis C followed by alcohol use were the primary factors driving this increase. The ASIR and age-standardized death rates of LC showed a significant average annual increase of 3.0% (95% CI: 2.7-3.2) and 2.6% (95% CI: 2.5-2.8), respectively. There was a significant negative correlation between the SDI and the EAPC in ASIR (ρ = -0.40, p = 0.004) and age-standardized death rates (ρ = -0.46, p < 0.001). In 2019, drug and alcohol use, followed by elevated body mass index (BMI) were the primary risk factors for age-standardized DALY rates attributable to LC. CONCLUSION: The increased burden of LC in the US highlights the need for interventions. This is particularly important given that LC is mostly influenced by modifiable risk factors, such as drug and alcohol use, and elevated BMI. Our findings highlight the urgent need for public health interventions targeting socio-economic, lifestyle, and modifiable risk factors to mitigate the escalating burden of LC.

The impact of overweight and obesity on health outcomes in the United States from 1990 to 2021.

AIM: Elevated body mass index (BMI) presents a significant public health challenge in the United States, contributing to considerable morbidity, mortality and economic burden. This study investigates the health burden of overweight and obesity in the United States from 1990 to 2021, leveraging the Global Burden of Disease data set to analyse trends, disparities and potential determinants of high BMI-related health outcomes. MATERIALS AND METHODS: Our study focused on the United States, analysing trends in disability-adjusted life years (DALY) and deaths attributable to high BMI, defined as a BMI of 25 kg/m2 or higher for adults. Statistical analyses included estimated annual percentage change (EAPC) in age-standardized DALY rates and age-standardized death rates. Pearson correlation was performed between EAPCs and the socio-demographic index (SDI), with significance set at p < 0.05. RESULTS: From 1990 to 2021, age-standardized DALY rates attributable to high BMI increased by 24.9%, whereas the age-standardized death rates increased by 5.2%. Age disparities showed DALYs peaking at 60-64 years for males and 65-69 years for females, with deaths peaking at 65-69 years for males and 90-94 years for females. A strong negative correlation was found between the EAPC in age-standardized DALY and death rates and the SDI. CONCLUSIONS: Overweight and obesity significantly impact public health in the United States, especially among older adults and lower socio-demographic regions. Comprehensive public health strategies integrating behavioural, technological and environmental interventions are crucial. Future research should focus on longitudinal studies, personalized interventions and policy-driven approaches to address the multifaceted influences on high BMI.

Determinants and outcomes of acute pancreatitis in patients hospitalized for COVID-19: Early pandemic experience.

OBJECTIVES: To examine the predictors and outcomes associated with the development of acute pancreatitis (AP) in patients hospitalized with Coronavirus Disease 2019 (COVID-19). METHODS: This is an observational analysis of the 2020 National Inpatient Sample Database. The study includes adult patients who were admitted with a confirmed diagnosis of COVID-19 and stratifies them based on the presence or absence of AP during their hospitalization. Predictors of AP development between the two groups and differences in outcomes are examined. Multivariate logistic regression analysis using Stata/BE 17.0 is conducted, with adjustments made for age, sex, race, and Charlson Comorbidity Index (CCI). Statistical significance is determined at a p-value of <0.05. RESULTS: Significant factors associated with an increased risk of AP in COVID-19 patients include Hispanic ethnicity, higher Charlson Comorbidity Index (CCI) score, residence in states located in the southern region, history of chronic kidney disease, chronic liver disease, malnutrition, portal hypertension, and alcohol use. COVID-19 patients who developed AP were also found to be at higher risk of adverse outcomes, including mortality, acute coronary syndrome, acute kidney injury, sepsis, septic shock, in-hospital cardiac arrest, invasive mechanical ventilation, upper gastrointestinal bleeding, prolonged length of stay, and increased healthcare cost. CONCLUSIONS: In hospitalized patients with COVID-19, the presence of AP is associated with increased mortality and morbidity. Risk factors for developing AP in this population include Hispanic ethnicity, residence in the southern region, higher Charlson Comorbidity Index (CCI) score, history of chronic kidney disease, chronic liver disease, malnutrition, portal hypertension, and alcohol use.

Incidence of Hepatitis C Virus Infections Among Users of Human Immunodeficiency Virus Pre-exposure Prophylaxis.

BACKGROUND & AIMS: Sexual transmission of hepatitis C virus (HCV) is well documented among human immunodeficiency virus (HIV)-uninfected individuals. The use of HIV pre-exposure prophylaxis (PrEP) may be associated with engagement in activities that facilitate the transmission of sexually transmitted infections (STIs) and possibly HCV among PrEP users. METHODS: Between 2012 and 2019, the incidence of HCV and bacterial STIs were calculated among HIV-negative indviduals receiving PrEP at the University Health Network HIV Prevention Clinic. Mucosal, anal, and blood samples were taken to test for HIV, syphilis, and anti-HCV antibodies. RESULTS: Among 344 HIV-uninfected patients receiving PrEP, 86% were men having sex with men (MSM). Five individuals were HCV-antibody positive at the time of PrEP initiation. Serologic and virologic follow-up data were available for 109 HCV-negative individuals over 282 patient-years (PY). Two new infections were recorded, yielding an incidence of primary HCV infection of 0.7 per 100 PY. In contrast with HCV, the incidence rates of chlamydia, gonorrhea, and syphilis were 49.2 per 100 PY, 36.3 per 100 PY, and 5.2 per 100 PY, respectively. Both individuals with new HCV diagnoses reported being MSM with a history of unprotected intercourse and 1 individual also reported recreational drug use. Both individuals were asymptomatic at the time of diagnosis and the infections were detected by routine laboratory monitoring. CONCLUSIONS: The low incidence of HCV infections despite significantly higher rates of other STIs suggests that sexual transmission of HCV is uncommon in HIV-negative MSM PrEP users in this community. Performing routine risk-based HCV surveillance among PrEP users should be evaluated. The high incidence of STIs in this population indicates a vital role for periodic STI monitoring in those receiving PrEP.

Pregnancy-Associated Myocardial Infarction: A Review of Current Practices and Guidelines.

PURPOSE OF REVIEW: Pregnancy-associated myocardial infarction is a principal cause of cardiovascular disease with a steadily rising incidence of 4.98 AMI events/100,000 deliveries over the last four decades in the USA. It is also linked with significant maternal and fetal morbidity and mortality, with maternal case fatality rate ranging from 5.1 to 37%. The management of acute myocardial infarction can be challenging in pregnant patients since treatment modalities and medication use are limited by their safety during pregnancy. RECENT FINDINGS: Limited guidelines exist regarding the management of pregnancy-associated myocardial infarction. Routinely used medications in myocardial infarction including angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), and statin therapy are contraindicated during pregnancy. Aspirin use is considered safe in pregnant women, but dual antiplatelet therapy and therapeutic anticoagulation can be associated with increased risk of maternal and fetal complications, and should only be used after a comprehensive benefit-to-risk assessment. The standard approach to revascularization requires additional caution in pregnant women. Percutaneous coronary intervention is generally considered safe but can be associated with high failure rates and poor outcomes depending on the etiology. Fibrinolytic therapy may have significant sequelae in pregnant patients, and hemodynamic management during surgery is complex and adds risk during pregnancy. Understanding the risks and benefits of the different treatment modalities available and their utility depending on the underlying etiology, encompassed with a multidisciplinary team approach, is vital to improve outcomes and minimize maternal and fetal complications.

Burden of delirium on mortality and healthcare resource utilization in geriatric patients hospitalized for inflammatory bowel disease.

Background: Delirium is prevalent in elderly patients, linked to elevated mortality rates, heightened healthcare resource use, and caregiver burden. Inflammatory bowel disease (IBD) poses various delirium risk factors, yet the impact on geriatric IBD patient outcomes remains unexplored. Methods: Using 2016-2019 National Inpatient Sample data, we identified ≥65-year-old patients admitted for IBD (Crohn's, ulcerative colitis) management stratified by delirium presence as a secondary diagnosis. The study aimed to assess delirium's impact on geriatric IBD patient outcomes. Results: Among 67,534 elderly IBD admissions, 0.7% (470) developed delirium. The delirium group had a 4.8-fold increase in in-hospital mortality risk (odds ratio 4.80, P < 0.001, 95% confidence interval [CI] 1.94-11.8). IBD patients with delirium experienced prolonged length of stay (adjusted mean difference 5.15 days, 95% CI 3.24-7.06, P < 0.001) and increased care costs (adjusted mean difference $48,328, 95% CI $26,485-$70,171, P < 0.001) compared to those without delirium. Conclusion: Elderly IBD patients with delirium face higher mortality risk, prolonged hospitalization, and increased healthcare costs. Clinicians should recognize delirium's detrimental effects in this vulnerable group and adhere to preventive protocols for improved care.

Risk of Aspiration Pneumonitis After Elective Esophagogastroduodenoscopy in Patients on Glucagon-Like Peptide-1 Receptor Agonists.

Background Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are gaining popularity in the management of diabetes mellitus and obesity. It has been suggested that this class of medications causes delayed gastric emptying which raised concerns about the potential for aspiration of gastric contents in patients undergoing sedation. This led to a statement by the American Society of Anesthesiologists about their preoperative use. Nevertheless, there is minimal evidence regarding the effects of GLP-1RAs on the risk of aspiration post-esophagogastroduodenoscopy (EGD). In this study, we sought to evaluate the incidence of aspiration and pneumonia in patients receiving GLP-1RAs who underwent EGD. Methodology We performed a retrospective cohort study in TriNetX, a global federated research network of electronic health records. The primary outcome was the development of aspiration post-EGD. Secondary outcomes were the development of aspiration pneumonia and requiring antibiotics post-EGD. One-to-one propensity score matching was performed for age, sex, diabetes mellitus, obesity, and other comorbidities between the cohorts. Results Our analysis showed a small but significant risk of aspiration pneumonitis in patients on GLP-1RAs undergoing elective EGD compared to non-GLP-1RA-receiving patients. However, there was no increased risk of the composite outcome of respiratory failure or intensive care unit (ICU) admission; however, this did not reach statistical significance. Conclusions GLP-1RA use was associated with an increased risk of aspiration in patients undergoing elective upper endoscopy. However, this did not translate to an increased risk of respiratory failure or ICU admission. Our findings highlight the importance of following an individualized approach to preoperative management that takes into consideration GLP-1RA indications and other aspiration risk factors, including advanced age, impaired gag reflex, and gastrointestinal symptoms such as nausea and abdominal distention.

Inflammatory bowel disease and pulmonary embolism: a nationwide perspective.

OBJECTIVE: To examine the characteristics and outcomes of patients with inflammatory bowel disease (IBD) hospitalized with pulmonary embolism (PE). METHODS: This cross-sectional observational study analyzed data from the 2016 to 2019 National Inpatient Sample to investigate hospitalizations for PE in the USA, stratified by the presence or absence of IBD. Adult patients were selected using the International Classification of Diseases, Tenth Revision codes for PE, Crohn's disease, and ulcerative colitis. Data on patient demographics, comorbidities, and hospital characteristics were collected. Statistical analysis included univariable and multivariable logistic regression using Stata/BE 17.0, focusing on in-hospital mortality and complications in PE patients with and without IBD. Adjusted odds ratios (aOR) and their corresponding 95% confidence intervals (CI) were calculated when appropriate. RESULTS: PE/IBD group was younger (mean age 58.3 vs. 62.7 years; P < 0.001), had a higher proportion of white patients (81.2% vs. 70.9%; P < 0.001), and had a greater prevalence of chronic liver disease (7.54% vs. 6.02%; P = 0.002) when compared to PE/non-IBD patients. The PE/IBD group had lower prevalence rates of coronary artery disease, congestive heart failure, obesity, chronic obstructive pulmonary disease, hypertension, and diabetes. Regarding primary outcomes, there was no significant difference in in-hospital mortality between the two groups (aOR, 0.92; 95% CI, 0.77-1.09; P = 0.355). However, the IBD/PE group had a higher risk of acute kidney injury, sepsis, septic shock, cardiac arrhythmias, and deep vein thrombosis. As for secondary outcomes, PE/IBD patients had more extended hospital stays and higher healthcare costs compared with PE/non-IBD patients. CONCLUSION: Hospitalized PE patients with IBD differ demographically and have a different comorbidity profile compared to those without IBD. PE/IBD patients demonstrate greater use of healthcare resources and elevated risk of hospitalization adverse events than PE/non-IBD patients, highlighting the necessity for individualized management approaches in this population.

Peginterferon lambda for the treatment of outpatients with COVID-19: a phase 2, placebo-controlled randomised trial.

BACKGROUND: To date, only monoclonal antibodies have been shown to be effective for outpatients with COVID-19. Interferon lambda-1 is a type III interferon involved in innate antiviral responses with activity against respiratory pathogens. We aimed to investigate the safety and efficacy of peginterferon lambda in the treatment of outpatients with mild-to-moderate COVID-19. METHODS: In this double-blind, placebo-controlled trial, outpatients with laboratory-confirmed COVID-19 were randomly assigned to a single subcutaneous injection of peginterferon lambda 180 µg or placebo within 7 days of symptom onset or first positive swab if asymptomatic. Participants were randomly assigned (1:1) using a computer-generated randomisation list created with a randomisation schedule in blocks of four. At the time of administration, study nurses received a sealed opaque envelope with the treatment allocation number. The primary endpoint was the proportion of patients who were negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA on day 7 after the injection, analysed by a χ2 test following an intention-to-treat principle. Prespecified analysis of the primary endpoint, adjusted for baseline viral load, using bivariate logistic regression was done. The trial is now complete. This trial is registered with ClinicalTrials.gov, NCT04354259. FINDINGS: Between May 18, and Sept 4, 2020, we recruited 30 patients per group. The decline in SARS-CoV-2 RNA was greater in those treated with peginterferon lambda than placebo from day 3 onwards, with a difference of 2·42 log copies per mL at day 7 (p=0·0041). By day 7, 24 (80%) participants in the peginterferon lambda group had an undetectable viral load, compared with 19 (63%) in the placebo group (p=0·15). After controlling for baseline viral load, patients in the peginterferon lambda group were more likely to have undetectable virus by day 7 than were those in the placebo group (odds ratio [OR] 4·12 [95% CI 1·15-16·73; p=0·029). Of those with baseline viral load above 106 copies per mL, 15 (79%) of 19 patients in the peginterferon lambda group had undetectable virus on day 7, compared with six (38%) of 16 in the placebo group (OR 6·25 [95% CI 1·49-31·06]; p=0·012). Peginterferon lambda was well tolerated, and adverse events were similar between groups with mild and transient aminotransferase, concentration increases more frequently observed in the peginterferon lambda group. Two individuals met the threshold of grade 3 increase, one in each group, and no other grade 3 or 4 laboratory adverse events were reported. INTERPRETATION: Peginterferon lambda accelerated viral decline in outpatients with COVID-19, increasing the proportion of patients with viral clearance by day 7, particularly in those with high baseline viral load. Peginterferon lambda has potential to prevent clinical deterioration and shorten duration of viral shedding. FUNDING: The Toronto COVID-19 Action Initiative, University of Toronto, and the Ontario First COVID-19 Rapid Research Fund, Toronto General & Western Hospital Foundation.

Correction: Hypertension guidelines.

In Aleyadeh W, Hutt-Centeno E, Ahmed HM, Shah NP. Hypertension guidelines: treat patients, not numbers. Cleve Clin J Med 2019; 86(1):47-56. doi:10.3949/ccjm.86a.18027, on page 50, the following statement was incorrect: "In 2017, the American College of Physicians (ACP) and the American Academy of Family Physicians (AAFP) recommended a relaxed systolic blood pressure target, ie, below 150 mm Hg, for adults over age 60, but a tighter goal of less than 130 mm Hg for the same age group if they have transient ischemic attack, stroke, or high cardiovascular risk.9" In fact, the ACP and AAFP recommended a tighter goal of less than 140 mm Hg for this higher-risk group. This has been corrected online.

Hypertension guidelines: Treat patients, not numbers.

The updated 2017 American College of Cardiology and American Heart Association (ACC/AHA) guidelines for managing hypertension advocate tighter blood pressure control than previous guidelines. This review summarizes the evidence behind the guidelines, discusses the risks and benefits of stricter blood pressure control, and provides our insights on blood pressure management in clinical practice.

Inter-observer variability in fetal biometric measurements.

OBJECTIVE: To evaluate inter-observer variability and reproducibility of ultrasound measurements for fetal biometric parameters. MATERIALS AND METHODS: A prospective cohort study was implemented in two tertiary care hospitals in Amman, Jordan; Prince Hamza Hospital and Albashir Hospital. 192 women with a singleton pregnancy at a gestational age of 18-36 weeks were the participants in the study. Transabdominal scans for fetal biometric parameter measurement were performed on study participants from the period of November 2014 to March 2015. Women who agreed to participate in the study were administered two ultrasound scans for head circumference, abdominal circumference and femur length. The correlation coefficient was calculated. Bland-Altman plots were used to analyze the degree of measurement agreement between observers. Limits of agreement ± 2 SD for the differences in fetal biometry measurements in proportions of the mean of the measurements were derived. Main outcome measures examine the reproducibility of fetal biometric measurements by different observers. RESULTS: High inter-observer inter-class correlation coefficient (ICC) was found for femur length (0.990) and abdominal circumference (0.996) where Bland-Altman plots showed high degrees of agreement. The highest degrees of agreement were noted in the measurement of abdominal circumference followed by head circumference. The lowest degree of agreement was found for femur length measurement. We used a paired-sample t-test and found that the mean difference between duplicate measurements was not significant (P > 0.05). CONCLUSION: Biometric fetal parameter measurements may be reproducible by different operators in the clinical setting with similar results. Fetal head circumference, abdominal circumference and femur length were highly reproducible. Large organized studies are needed to ensure accurate fetal measurements due to the important clinical implications of inaccurate measurements.