Protocol implementation during the COVID-19 pandemic: experiences from a randomized trial of stress ulcer prophylaxis.

BACKGROUND: During the COVID-19 pandemic, many intensive care units (ICUs) halted research to focus on COVID-19-specific studies. OBJECTIVE: To describe the conduct of an international randomized trial of stress ulcer prophylaxis (Re-Evaluating the Inhibition of Stress Erosions in the ICU [REVISE]) during the pandemic, addressing enrolment patterns, center engagement, informed consent processes, data collection, a COVID-specific substudy, patient transfers, and data monitoring. METHODS: REVISE is a randomized trial among mechanically ventilated patients, comparing pantoprazole 40 mg IV to placebo on the primary efficacy outcome of clinically important upper gastrointestinal bleeding and the primary safety outcome of 90-day mortality. We documented protocol implementation status from March 11th 2020-August 30th 2022. RESULTS: The Steering Committee did not change the scientific protocol. From the first enrolment on July 9th 2019 to March 10th 2020 (8 months preceding the pandemic), 267 patients were enrolled in 18 centers. From March 11th 2020-August 30th 2022 (30 months thereafter), 41 new centers joined; 59 were participating by August 30th 2022 which enrolled 2961 patients. During a total of 1235 enrolment-months in the pandemic phase, enrolment paused for 106 (8.6%) months in aggregate (median 3 months, interquartile range 2;6). Protocol implementation involved a shift from the a priori consent model pre-pandemic (188, 58.8%) to the consent to continue model (1615, 54.1%, p < 0.01). In one new center, an opt-out model was approved. The informed consent rate increased slightly (80.7% to 85.0%, p = 0.05). Telephone consent encounters increased (16.6% to 68.2%, p < 0.001). Surge capacity necessitated intra-institutional transfers; receiving centers continued protocol implementation whenever possible. We developed a nested COVID-19 substudy. The Methods Centers continued central statistical monitoring of trial metrics. Site monitoring was initially remote, then in-person when restrictions lifted. CONCLUSION: Protocol implementation adaptations during the pandemic included a shift in the consent model, a sustained high consent rate, and launch of a COVID-19 substudy. Recruitment increased as new centers joined, patient transfers were optimized, and monitoring methods were adapted.

Does This Patient Have Alcohol Use Disorder?: The Rational Clinical Examination Systematic Review.

Importance: The accuracy of screening tests for alcohol use disorder (defined as a problematic pattern of alcohol use leading to clinically significant impairment or distress) requires reassessment to align with the latest definition in the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5). Objective: To assess the diagnostic accuracy of screening tools in identifying individuals with alcohol use disorder as defined in the DSM-5. Data Sources and Study Selection: The databases of MEDLINE and Embase were searched (January 2013-February 2023) for original studies on the diagnostic accuracy of brief screening tools to identify alcohol use disorder according to the DSM-5 definition. Because diagnosis of alcohol use disorder does not include excessive alcohol use as a criterion, studies of screening tools that identify excessive or high-risk drinking among younger (aged 9-18 years), older (aged ≥65 years), and pregnant persons also were retained. Data Extraction and Synthesis: Sensitivity, specificity, and likelihood ratios (LRs) were calculated. When appropriate, a meta-analysis was performed to calculate a summary LR. Results: Of 4303 identified studies, 35 were retained (N = 79 633). There were 11 691 individuals with alcohol use disorder or a history of excessive drinking. Across all age categories, a score of 8 or greater on the Alcohol Use Disorders Identification Test (AUDIT) increased the likelihood of alcohol use disorder (LR, 6.5 [95% CI, 3.9-11]). A positive screening result using AUDIT identified alcohol use disorder better among females (LR, 6.9 [95% CI, 3.9-12]) than among males (LR, 3.8 [95% CI, 2.6-5.5]) (P = .003). An AUDIT score of less than 8 reduced the likelihood of alcohol use disorder similarly for both males and females (LR, 0.33 [95% CI, 0.20-0.52]). The abbreviated AUDIT-Consumption (AUDIT-C) has sex-specific cutoff scores of 4 or greater for males and 3 or greater for females, but was less useful for identifying alcohol use disorder (males: LR, 1.8 [95% CI, 1.5-2.2]; females: LR, 2.0 [95% CI, 1.8-2.3]). The AUDIT-C appeared useful for identifying measures of excessive alcohol use in younger people (aged 9-18 years) and in those older than 60 years of age. For those younger than 18 years of age, the National Institute on Alcohol Abuse and Alcoholism age-specific drinking thresholds were helpful for assessing the likelihood of alcohol use disorder at the lowest risk threshold (LR, 0.15 [95% CI, 0.11-0.21]), at the moderate risk threshold (LR, 3.4 [95% CI, 2.8-4.1]), and at the highest risk threshold (LR, 15 [95% CI, 12-19]). Among persons who were pregnant and screened within 48 hours after delivery, an AUDIT score of 4 or greater identified those more likely to have alcohol use disorder (LR, 6.4 [95% CI, 5.1-8.0]), whereas scores of less than 2 for the Tolerance, Worried, Eye-Opener, Amnesia and Cut-Down screening tool and the Tolerance, Annoyed, Cut-Down and Eye-Opener screening tool identified alcohol use disorder similarly (LR, 0.05 [95% CI, 0.01-0.20]). Conclusions and Relevance: The AUDIT screening tool is useful to identify alcohol use disorder in adults and in individuals within 48 hours postpartum. The National Institute on Alcohol Abuse and Alcoholism youth screening tool is helpful to identify children and adolescents with alcohol use disorder. The AUDIT-C appears useful for identifying various measures of excessive alcohol use in young people and in older adults.

Assessing fragility of statistically significant findings from randomized controlled trials assessing pharmacological therapies for opioid use disorders: a systematic review.

BACKGROUND: The fragility index is a statistical measure of the robustness or "stability" of a statistically significant result. It has been adapted to assess the robustness of statistically significant outcomes from randomized controlled trials. By hypothetically switching some non-responders to responders, for instance, this metric measures how many individuals would need to have responded for a statistically significant finding to become non-statistically significant. The purpose of this study is to assess the fragility index of randomized controlled trials evaluating opioid substitution and antagonist therapies for opioid use disorder. This will provide an indication as to the robustness of trials in the field and the confidence that should be placed in the trials' outcomes, potentially identifying ways to improve clinical research in the field. This is especially important as opioid use disorder has become a global epidemic, and the incidence of opioid related fatalities have climbed 500% in the past two decades. METHODS: Six databases were searched from inception to September 25, 2021, for randomized controlled trials evaluating opioid substitution and antagonist therapies for opioid use disorder, and meeting the necessary requirements for fragility index calculation. Specifically, we included all parallel arm or two-by-two factorial design RCTs that assessed the effectiveness of any opioid substitution and antagonist therapies using a binary primary outcome and reported a statistically significant result. The fragility index of each study was calculated using methods described by Walsh and colleagues. The risk of bias of included studies was assessed using the Revised Cochrane Risk of Bias tool for randomized trials. RESULTS: Ten studies with a median sample size of 82.5 (interquartile range (IQR) 58, 179, range 52-226) were eligible for inclusion. Overall risk of bias was deemed to be low in seven studies, have some concerns in two studies, and be high in one study. The median fragility index was 7.5 (IQR 4, 12, range 1-26). CONCLUSIONS: Our results suggest that approximately eight participants are needed to overturn the conclusions of the majority of trials in opioid use disorder. Future work should focus on maximizing transparency in reporting of study results, by reporting confidence intervals, fragility indexes, and emphasizing the clinical relevance of findings. TRIAL REGISTRATION: PROSPERO CRD42013006507. Registered on November 25, 2013.

Clinical characteristics and prognostic factors among hospitalized patients with substance use disorders: Findings from a retrospective cohort study of a Canadian inpatient addiction medicine service.

INTRODUCTION: Inpatient addiction medicine services (AMS) were developed in response to the growing needs of hospitalized individuals with substance use disorders (SUDs). AMS aim to enable timely initiation of pharmacologic treatment, build hospital capacity to support patients who use substances, and facilitate transition to community services. As an emerging service being adopted in hospitals across North America, the model of care, populations served, substance use trends, and clinical trajectory has not been widely described. This work aims to characterize patients accessing care through the AMS, establishing predictors for clinical trajectories in hospital including patient-initiated discharge (PID) and hospital re-admission. METHODS: Using a retrospective cohort design, we describe all patients seen by the AMS between 2018 and 2022 across four hospitals in Hamilton, Ontario. Patients seen by AMS were hospitalized and qualified for a SUD based on DSM-V criteria. The study used descriptive statistics to describe the cohort, where appropriate adjusted time-to-event survival models were constructed to identify predictors for hospital re-admission. RESULTS: Patients seen by the AMS (n = 695) frequently lacked access to primary care (47.0 %) and less than half (44.3 %) were receiving community addiction services on admission. The majority met criteria for opioid use disorder (OUD), with injecting being the primary consumption route (54.8 %). Patients exhibited high acuity, with 34.2 % requiring critical care measures. Provision of OAT substantially increased to 77.9 % of patients (29 % on admission). PID occurred in 17.8 % of patients and was significantly associated with an admitting diagnosis of suicidal ideation, infection, heart failure, and distinct substance use profiles including methamphetamine, fentanyl, and heroin use (p < 0.05). PID conferred a 66 % increased risk for re-admission (Hazard-Ratio: 1.66; 95 % CI: 1.08, 2.54; p = 0.02). CONCLUSION: Patients served by AMS primarily include individuals with OUD presenting with the associated medical complications and substantial deficits in the social determinants of health (e.g., high housing insecurity, poverty, and disability). PID occurs among 1 in 5 people and is associated with higher rates of re-admission. By identifying individuals at higher risk of adverse outcomes, these results provide an opportunity to improve outcomes in this high-risk, high-vulnerability population.

Total Bilirubin Levels in Nonalcoholic Fatty Liver Disease and All- cause and Cause-specific Mortality in US Adults.

BACKGROUND AND AIMS: Nonalcoholic Fatty Liver Disease (NAFLD) is a chronic progressive illness with a spectrum of disease severity from steatosis to end-stage liver disease. Emerging evidence suggests total serum bilirubin levels are inversely related to the prevalence of metabolic syndrome including NAFLD. We investigated the effects of bilirubin on all-cause and cause-specific mortality stratified by NAFLD status. METHODS: We used the third National Health and Nutrition Examination Survey Cohort (1988-1994) and linked mortality dataset through 2019. Cox-regression models were constructed to assess the association between bilirubin levels categorized by quartile with all-cause and cause-specific mortality. RESULTS: During the median follow-up of 324 months (n=11,078), higher bilirubin levels were associated with a reduction in risk of all-cause mortality in the multivariate model (hazard ratio [HR]: 0.83, 95% confidence interval [CI]: 0.71-0.97 for quarter 4 [highest bilirubin levels] vs. quarter 1 [lowest bilirubin levels], p for trend=0.033). Higher bilirubin levels were associated with a lower risk for all-cause mortality in individuals with NAFLD (HR; 0.68, 95% CI: 0.55-0.86 for quarter 4, p for trend=0.010); however, this protective association with higher bilirubin levels was not noted in those without NAFLD. Higher bilirubin levels were associated with a lower risk for cardiovascular and cancer-related mortality in individuals with NAFLD. CONCLUSIONS: In this large nationally representative sample of American adults, higher bilirubin levels in NAFLD were associated with a lower risk of all-cause mortality, which may be derived from a lower risk of cardiovascular/cancer-related mortality.

Cytisine for smoking cessation: A systematic review and meta-analysis.

BACKGROUND: Cytisine is a smoking cessation medication. This systematic review incorporates recently published randomized controlled trials (RCTs) to provide an updated evidence-based assessment of cytisine's efficacy and safety. METHODS: We searched Cochrane Library, MEDLINE, and EMBASE, for RCTs comparing cytisine to other smoking cessation treatments in adults who smoke. PRIMARY OUTCOME: 6-month biochemically verified continuous abstinence. Other outcomes: abstinence at longest follow-up, adverse events, mortality, and health-related quality of life (HRQOL). We used Grading of Recommendations Assessment, Development and Evaluation (GRADE) to assess evidence certainty. RESULTS: We included 14 RCTs involving 9953 adults. Cytisine was superior to placebo (risk ratio [RR] 2.25, 95% confidence interval [CI] 1.13-4.47; 5 RCTs, 4325 participants), but not varenicline (RR 1.13, 95% CI 0.65-1.95; 2 RCTs, 2131 participants) for the primary outcome. Cytisine was superior to placebo (RR 2.78, 95% CI 1.64-4.70; 8 RCTs, 5762 participants) and nicotine replacement therapy [NRT] (RR 1.39, 95% CI 1.12-1.73; 2 RCTs, 1511 participants), but not varenicline (RR 1.02, 95% CI 0.72-1.44; 4 RCTs, 2708 participants) for abstinence at longest follow-up. Cytisine increased mostly gastrointestinal adverse events compared to placebo (RR 1.15; 95% CI 1.06-1.25; 8 RCTs, 5520 participants) and NRT (RR 1.52, 95% CI 1.26-1.84; 1 RCT, 1310 participants) but less adverse events compared to varenicline (RR 0.67; 95% CI 0.48-0.95; 3 RCTs, 2484 participants). CONCLUSION: Cytisine shows greater efficacy than placebo and NRT, but more adverse events. It is comparable to varenicline, with fewer adverse events. This can inform clinicians and guidelines on cytisine for smoking cessation.

Proton pump inhibitors in critically ill mechanically ventilated patients with COVID-19: protocol for a substudy of the Re-EValuating the Inhibition of Stress Erosions (REVISE) Trial.

BACKGROUND: Critically ill patients commonly receive proton pump inhibitors (PPIs) to prevent gastrointestinal (GI) bleeding from stress-induced ulceration. Despite widespread use in the intensive care unit (ICU), observational data suggest that PPIs may be associated with adverse outcomes in patients with COVID-19 infection. This preplanned study is nested within a large randomized trial evaluating pantoprazole versus placebo in invasively ventilated patients. The 3 objectives are as follows: (1) to describe the characteristics of patients with COVID-19 in terms of demographics, biomarkers, venous thromboembolism, tracheostomy incidence and timing, and other clinical outcomes; (2) to evaluate the impact of COVID-19 infection on clinically important GI bleeding, 90-day mortality, and other outcomes compared to a propensity-matched non-infected cohort; and (3) to explore whether pantoprazole has a differential treatment effect on clinically important GI bleeding, 90-day mortality, and other outcomes in patients with and without COVID-19 infection. METHODS: The ongoing trial Re-EValuating the Inhibition of Stress Erosions (REVISE) compares pantoprazole 40 mg IV to placebo on the primary efficacy outcome of clinically important GI bleeding and the primary safety outcome of 90-day mortality. The protocol described in this report is for a substudy focused on patients with COVID-19 infection that was not in the original pre-pandemic trial protocol. We developed a one-page case report form to characterize these patients including data related to biomarkers, venous thromboembolism, COVID-19 therapies, tracheostomy incidence and timing, duration of mechanical ventilation, and ICU and hospital stay. Our analysis will describe the trajectory of patients with COVID-19 infection, a propensity-matched analysis of infected and non-infected patients, and an extended subgroup analysis comparing the effect of PPI among patients with and without COVID-19 infection. DISCUSSION: Prophylactic acid suppression in invasively ventilated critically ill patients with COVID-19 infection has unknown consequences. The results of these investigations will inform practice, guidelines, and future research. TRIAL REGISTRATION: REVISE Trial [NCT03374800 December 15, 2017], COVID-19 Cohort Study [NCT05715567 February 8, 2023].

Types of Physical Activity in Nonalcoholic Fatty Liver Disease and All-Cause and Cardiovascular Mortality.

The impact of different types of physical activity (PA) on mortality in the context of nonalcoholic fatty liver disease (NAFLD) is not clearly defined and was investigated. This prospective study was performed using the 2007-2014 US National Health and Nutrition Examination Survey with mortality follow-up through 2019. Over a median follow-up of 8.6 years, leisure-time and transportation-related PA that fulfilled the criteria outlined in the PA guidelines (≥150 min/week) in NAFLD were associated with a risk reduction in all-cause mortality (hazard ratio [HR]: 0.76, 95% confidence interval [CI]: 0.59-0.98 for leisure-time PA; HR: 0.62, 95% CI: 0.45-0.86 for transportation-related PA). Leisure-time and transportation-related PA in NAFLD were inversely associated with all-cause mortality in a dose-dependent manner (p for trends <0.01). Furthermore, the risk for cardiovascular mortality was lower in those meeting the PA guidelines for leisure-time PA (HR: 0.63, 95% CI: 0.44-0.91) and transportation-related PA (HR: 0.38, 95% CI: 0.23-0.65). Increasing sedentary behavior was linked to an increased risk of all-cause and cardiovascular mortality (p for trend <0.01). Meeting PA guidelines (≥150 min/week) for leisure-time and transportation-related PA has beneficial health effects on all-cause and cardiovascular mortality among individuals with NAFLD. Sedentary behavior in NAFLD showed harmful effects on all-cause and cardiovascular mortality.

Enhancing end of life care on general internal medical wards: the 3 Wishes Project.

BACKGROUND: Initially developed in the intensive care unit (ICU) at St. Joseph's Healthcare Hamilton (SJHH) the 3 Wishes Project (3WP) provides personalized, compassionate care to dying patients and their families. The objective of this study was to develop and evaluate 3WP expansion strategies for patients cared for on General Internal Medicine (GIM) wards in our hospital. METHODS: From January 2020-November 2021, we developed a phased, multicomponent approach for program expansion. We enrolled patients on the GIM wards who had a high probability of dying in hospital, then elicited, implemented, and documented wishes for them or their families. Data were analyzed descriptively. RESULTS: From March 2020 to November 2020, we implemented staff education and engagement activities, created an Expansion Coordinator position, held strategic consultations, and offered enabling resources. From March 2020 to November 2021, we enrolled 62 patients and elicited 281 wishes (median [1st, 3rd quartiles] 4 [4, 5] wishes/patient). The most common wish categories were personalizing the environment (67 wishes, 24%), rituals and spiritual support (42 wishes, 15%), and facilitating connections (39 wishes, 14%). The median [1st, 3rd] cost/patient was $0 [0, $10.00] (range $0 to $86); 91% of wishes incurred no cost to the program. CONCLUSIONS: The formal expansion of the 3WP on GIM wards has been successful despite COVID-19 pandemic disruptions. While there is still work ahead, these data suggest that implementing the 3WP on the GIM wards is feasible and affordable. Increased engagement of the clinical team during the pandemic suggests that it is positively received.

Association between depression and metabolic dysfunction-associated fatty liver disease/significant fibrosis.

BACKGROUND: An association between depression and metabolic dysfunction-associated fatty liver disease (MAFLD) appears logical on the basis of previous observations linking depression to nonalcoholic fatty liver disease. We aim to investigate the association between depression and MAFLD and significant fibrosis. METHODS: This cross-sectional study was conducted on data from National Health and Nutrition Examination Survey, 2017 to March 2020 Pre-pandemic dataset. Depression and depression-related functional impairment were assessed using the Patient Health Questionnaire (PHQ-9). MAFLD, based on the criteria proposed by an international expert panel, and significant fibrosis were defined by transient elastography. RESULTS: Of the 3327 individuals (mean age: 46.9 years, 50.2 % men), the prevalence of depression and functional impairment due to depression was higher among individuals with MAFLD or significant fibrosis than among those without. Individuals with depression were approximately 70 % more likely to have MAFLD than those without. In multivariable analyses, depression was associated with an increased risk of MAFLD (odds ratio [OR]: 1.77, 95 % confidence interval [CI]:1.33-2.36 for ≥263 dB/m and OR: 1.70, 95 % CI: 1.20-2.41 for ≥285 dB/m). These associations were more pronounced in postmenopausal women than premenopausal women. In terms of significant fibrosis, depression remained an independent predictor of significant fibrosis; however, it attenuated after adjustment for body mass index. LIMITATIONS: Temporal causality and residual confounders could not be entirely investigated due to the study design. CONCLUSIONS: Depression was independently associated with MAFLD and significant fibrosis in a nationally representative sample of adults in the US.

Gallstone Disease and Its Association With Nonalcoholic Fatty Liver Disease, All-Cause and Cause-Specific Mortality.

BACKGROUND & AIMS: Presence of gallstone disease may influence outcomes in patients with nonalcoholic fatty liver disease (NAFLD). We studied the impact of gallstone disease on mortality in individuals with and without NAFLD. METHODS: Prospective cohort study used the Third National Health and Nutrition Examination Survey (1988-1994) with mortality data through 2015. Gallstone disease was defined as ultrasonographic evidence of gallstones or absence of the gallbladder (prior cholecystectomy). NAFLD was defined using standardized ultrasonographic criteria. RESULTS: Gallstone disease and cholecystectomy were independently associated with NAFLD (odds ratio [OR], 1.75; 95% confidence interval [CI], 1.43-2.15 for gallstone disease and OR, 2.77; 95% CI, 2.01-3.83 for cholecystectomy compared with no gallstone disease). During the median follow-up of 23 years, gallstone disease was associated with a higher risk of all-cause mortality (hazard ratio [HR], 1.19; 95% CI, 1.05-1.37) and cause-specific mortality. Gallstone disease was associated with a higher risk of all-cause mortality in non-NAFLD sub-cohort (HR, 1.42; 95% CI, 1.23-1.64) but not in NAFLD (HR, 1.03; 95% CI, 0.87-1.22). Gallstone disease was associated with a higher risk of cardiovascular-related (HR, 1.40; 95% CI, 1.10-1.78) and cancer-related (HR, 1.71; 95% CI, 1.18-2.48) mortality in non-NAFLD sub-cohort. Gallstone disease was associated with increased cardiovascular mortality (HR, 1.36; 95% CI, 1.05-1.77) in NAFLD. CONCLUSIONS: Gallstone disease is an independent risk factor for NAFLD, but gallstone disease is not associated with all-cause mortality in individuals with NAFLD. Screening for gallstone disease in individuals at risk for developing NAFLD may help with risk stratification for all-cause mortality related to gallstone disease.

Chronic liver disease-related mortality in diabetes before and during the COVID-19 in the United States.

BACKGROUND: Global pandemic of COVID-19 represents an unprecedented challenge. COVID-19 has predominantly targeted vulnerable populations with pre-existing chronic medical diseases, such as diabetes and chronic liver disease. AIMS: We estimated chronic liver disease-related mortality trends among individuals with diabetes before and during the COVID-19 pandemic. METHODS: Utilizing the US national mortality database and Census, we determined the quarterly age-standardized chronic liver disease-related mortality and quarterly percentage change (QPC) among individuals with diabetes. RESULTS: The quarterly age-standardized mortality for chronic liver disease and/or cirrhosis among individuals with diabetes remained stable before the COVID-19 pandemic and sharply increased during the COIVD-19 pandemic at a QPC of 8.5%. The quarterly mortality from nonalcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD) increased markedly during the COVID-19 pandemic. Mortality for hepatitis C virus (HCV) infection declined with a quarterly rate of -3.3% before the COVID-19 pandemic and remained stable during the COVID-19 pandemic. While ALD- and HCV-related mortality was higher in men than in women, NAFLD-related mortality in women was higher than in men. CONCLUSIONS: The sharp increase in mortality for chronic liver disease and/or cirrhosis among individuals with diabetes during the COVID-19 pandemic was associated with increased mortality from NAFLD and ALD.

Cannabis use and opioid relapse: An exploratory survival analysis of prospectively collected data.

Importance: It is known that only minority of patients with opioid use disorder (OUD) receive treatment, of which only a fraction successfully complete treatment as intended. Factors associated with poor treatment outcomes remain unclear, and there is emerging but conflicting evidence that cannabis use may mitigate opioid use. Objective: To analyze predictors of relapse amongst patients receiving buprenorphine-naloxone for OUD and identify the association between cannabis use and time to relapse. Design: Data were prospectively collected between May 2018 and October 2020, and patients were followed for 12 months. Setting: Thirty-one outpatient opioid agonist treatment clinics across Ontario, Canada. Participants: All patients 16 years of age or older receiving buprenorphine-naloxone for OUD who had a urine toxicology screen negative for opioids at baseline were eligible for inclusion. Of the 488 patients consecutively sampled, 466 were included. Exposure: Cannabis use. Main outcome and measure: Relapse to opioid use assessed using urine toxicology screens. We employed a multivariable Cox-proportional hazard model for our analyses. Results: We found that cannabis use was not protective against relapse [hazard ratio (HR) = 1.03, 95% confidence interval (CI): 0.78, 1.36, p = 0.84]. We found that participants who have been in treatment for at least two years had a 44% decrease in the hazard of relapse compared to those in treatment for less than a year (HR = 0.56, 95% CI: 0.34, 0.92, p = 0.021). We also found that the hazard of relapse was 2.6 times higher for participants who were intravenous drug users (HR = 2.61, 95% CI: 1.74, 3.91, p < 0.001), and that for every 1mg increase in the participants' buprenorphine-naloxone dose, the hazard of relapse is 2% greater (HR = 1.02, 95% CI: 1.01, 1.03, p < 0.001). Conclusion: Our analysis failed to show cannabis to be protective against relapse to opioid use in patients receiving buprenorphine-naloxone for OUD. We identified that individuals who inject drugs, are on higher doses of buprenorphine-naloxone, or have been in treatment for less than two years have a higher hazard for relapse. The presence of such factors may thus warrant closer patient follow-up and more stringent treatment protocols to mitigate risk of relapse and potential overdose.

Sodium-glucose cotransporter-2 inhibitors improve liver enzymes in patients with co-existing non-alcoholic fatty liver disease: a systematic review and meta-analysis.

Introduction: Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis, inflammation, and fibrosis. While sodium-glucose cotransporter-2 (SGLT-2) inhibitors have been established to improve glycaemic control in type-2 diabetes mellitus (T2DM), evidence of the beneficial effects in diabetics with coexisting NAFLD has yet to be quantitatively summarized. Material and methods: We searched the PubMed, Medline, CINAHL, and Cochrane databases and ClinicalTrial.gov from database inception to July 2020. We included randomized controlled trials assessing the impact of SGLT2 inhibitors on liver enzymes among patients with NAFLD. Our primary outcome included liver inflammation as measured using liver transaminase. Secondary outcomes included drug efficacy on hepatic steatosis and body mass index. Risk differences were calculated using a random model. Results: A total of 10,555 patients were included in this meta-analysis (SGLT2 inhibitor group: n = 7125; control group: n = 3430). The treatment duration ranged from 8 to 52 weeks. Patients with T2DM, who were treated with SGLT2 inhibitor had decrease in ALT (SMD = -0.22, 95% CI: -0.27 to -0.20) and AST levels (SMD = -0.20, 95% CI: -0.31 to -0.08). The SGLT-2 inhibitor did not cause statistically significant weight loss (SMD = -0.21, 95% CI: -0.47 to 0.06), fibrosis regression utilizing FIB-4 score (SMD = -0.12, 95% CI: -0.41 to 0.18), and hepatic steatosis by using MRI-PDFF (SMD = -0.31, 95% CI: -0.68 to 0.07), as compared to controls. Conclusions: The SGLT2 inhibitor treatment may improve liver function, as demonstrated in the statistically significant reduction in transaminase levels. There were also notable trends in improved liver fibrosis and steatosis across the study periods.

A technology assisted precision ketogenic diet intervention for cardio-renal-metabolic health in overweight or obese adults: Protocol for a randomized controlled trial.

BACKGROUND: The obesity epidemic is a public health concern, as it is associated with a variety of chronic conditions. The ketogenic diet has drawn much scientific and public attention. However, implementation is challenging and its effect on cardio-renal-metabolic health is inconclusive. This study will assess the feasibility, acceptability, and preliminary efficacy of a technology-assisted ketogenic diet on cardio-renal-metabolic health. METHODS: This is a single center, 6-month, stratified, randomized controlled trial. A total of 60 overweight/obese adults (18+ years old) will be enrolled, including 20 without type 2 diabetes (T2D) and without chronic kidney disease (CKD); 20 with T2D, but without CKD; and 20 with early-stage CKD. Participants will be stratified based on health conditions and randomized into a ketogenic diet (n = 30) or a low-fat diet group (n = 30). Health education involving diet and physical activity will be delivered both digitally and in-person. Mobile and connected health technologies will be used to track lifestyle behaviors and health indicators, as well as provide weekly feedback. The primary outcome (weight) and the secondary outcomes (e.g., blood pressure, glycemic control, renal health) will be assessed with traditional measurements and metabolomics. DISCUSSION: Mobile and connected health technologies provide new opportunities to improve chronic condition management, health education attendance, planned lifestyle changes and engagement, and health outcomes. The advancement of bioinformatics technology offers the possibility to profile and analyze omics data which may advance our understanding of the underlying mechanisms of intervention effects on health outcomes at the molecular level for personalized and precision lifestyle interventions.

Trends in Etiology-based Mortality From Chronic Liver Disease Before and During COVID-19 Pandemic in the United States.

BACKGROUND & AIMS: During the global coronavirus disease 2019 (COVID-19) pandemic, patients with pre-existing chronic liver disease may represent a vulnerable population. We studied the etiology-based temporal trends in mortality of chronic liver disease and the underlying cause of death in the United States before and during the COVID-19 pandemic. METHODS: Population-based analyses were performed on United States national mortality records (2017-2020). Temporal trends in quarterly age-standardized mortality were obtained by joinpoint analysis with estimates of quarterly percentage change (QPC). RESULTS: Quarterly age-standardized all-cause mortality due to alcohol-related liver disease (ALD) initially increased at a quarterly rate of 1.1% before the COVID-19 pandemic, followed by a sharp increase during the COVID-19 pandemic at a quarterly rate of 11.2%. Likewise, steady increase in mortality of nonalcoholic fatty liver disease before the COVID-19 pandemic (QPC, 1.9%) accelerated during the COVID-19 pandemic (QPC, 6.6%). Although ALD-related mortality increased steeply compared with viral hepatitis-related mortality during the COVID-19 pandemic, the proportion of mortality due to COVID-19 among individuals with ALD was the lowest at 2.5%; more than 50% lower than viral hepatitis. The significant decline in all-cause mortality due to viral hepatitis before the COVID-19 pandemic plateaued during the COVID-19 pandemic due to increase in COVID-19-related mortality in individuals with viral hepatitis. Mortality due to cirrhosis increased markedly during the COVID-19 pandemic, mainly attributable to ALD. CONCLUSION: All-cause mortality for ALD and nonalcoholic fatty liver disease rapidly accelerated during the COVID-19 pandemic compared with the pre-COVID-19 era. There has been a significant decline in viral hepatitis; however, a significant increase in COVID-related death in this population.

Changing trends in aetiology-based hospitalizations with end-stage liver disease in the United States from 2016 to 2019.

BACKGROUNDS AND AIMS: A potent and safe antiviral agent may impact chronic hepatitis C (HCV)-related end-stage liver disease (ESLD). We assess aetiology-based hospitalizations for ESLD in the United States, 2016-2019. METHODS: We utilized the National Inpatient Sample (NIS) from 2016 to 2019. We defined ESLD as either decompensated cirrhosis or hepatocellular carcinoma, criteria obtained from the International Classification of Diseases, Tenth Revision. RESULTS: National hospitalization rates for non-alcoholic fatty liver disease (NAFLD) increased significantly from 67.1/100 000 persons in 2016 to 93.6 in 2019 with an average annual percentage change (AAPC) of 12.1%, while chronic hepatitis C (HCV) decreased significantly from 71.2/100 000 persons in 2016 to 58.5 in 2019 (-6.5% AAPC). Hospitalizations for ESLD in alcohol-related liver disease (ALD) increased as well. CONCLUSIONS: Hospitalization rates for NAFLD- and ALD-related ESLD increased steadily, while those for HCV-related ESLD decreased during the direct-acting antivirals era.

Type 2 Diabetes Independent of Glycemic Control is Associated With Cognitive Impairments: Findings From NHANES.

Examine the association between glycemic control and cognition. Included subjects ≥60 years who participated in the 2013 to 2014 National Health and Nutrition Examination Survey and completed one of the followings: Consortium to Establish a Registry for Alzheimer's Disease Word List (CERAD-WL), Animal Fluency (AF), Digit Symbol Substitution Test (DSST), and CERAD-Delayed Recall (CERAD-DR). Stratified participants into: No type 2 diabetes (T2D; N = 557), Controlled T2D (N = 41), Uncontrolled T2D (N = 120), and Untreated T2D (N = 86). Multiple regression was used to examine the association between variables. After adjusting for demographics and cardiovascular risk factors, Uncontrolled T2D was associated with lower DSST (ß = -3.164, p = .04), and Untreated T2D was associated with a trend for having lower CERAD-DR (ß = -.496, p = .06) scores. T2D, independent of glycemic control, is associated with cognitive impairment and this relationship is influenced by modifiable and non-modifiable risk factors.