Incorporation of quantitative imaging data using artificial intelligence improves risk prediction in veterans with liver disease.

BACKGROUND AND AIMS: Utilization of electronic health records data to derive predictive indexes such as the electronic Child-Turcotte-Pugh (eCTP) Score can have significant utility in health care delivery. Within the records, CT scans contain phenotypic data which have significant prognostic value. However, data extractions have not traditionally been applied to imaging data. In this study, we used artificial intelligence to automate biomarker extraction from CT scans and examined the value of these features in improving risk prediction in patients with liver disease. APPROACH AND RESULTS: Using a regional liver disease cohort from the Veterans Health System, we retrieved administrative, laboratory, and clinical data for Veterans who had CT scans performed for any clinical indication between 2008 and 2014. Imaging biomarkers were automatically derived using the analytic morphomics platform. In all, 4614 patients were included. We found that the eCTP Score had a Concordance index of 0.64 for the prediction of overall mortality while the imaging-based model alone or with eCTP Score performed significantly better [Concordance index of 0.72 and 0.73 ( p <0.001)]. For the subset of patients without hepatic decompensation at baseline (n=4452), the Concordance index for predicting future decompensation was 0.67, 0.79, and 0.80 for eCTP Score, imaging alone, or combined, respectively. CONCLUSIONS: This proof of concept demonstrates that the potential of utilizing automated extraction of imaging features within CT scans either alone or in conjunction with classic health data can improve risk prediction in patients with chronic liver disease.

Impact of lung cancer screening on stage migration and mortality among the national Veterans Health Administration population with lung cancer.

BACKGROUND: Despite randomized trials demonstrating a mortality benefit to low-dose computed tomography screening to detect lung cancer, uptake of lung cancer screening (LCS) has been slow, and the benefits of screening remain unclear in clinical practice. METHODS: This study aimed to assess the impact of screening among patients in the Veterans Health Administration (VA) health care system diagnosed with lung cancer between 2011 and 2018. Lung cancer stage at diagnosis, lung cancer-specific survival, and overall survival between patients with cancer who did and did not receive screening before diagnosis were evaluated. We used Cox regression modeling and inverse propensity weighting analyses with lead time bias adjustment to correlate LCS exposure with patient outcomes. RESULTS: Of 57,919 individuals diagnosed with lung cancer in the VA system between 2011 and 2018, 2167 (3.9%) underwent screening before diagnosis. Patients with screening had higher rates of stage I diagnoses (52% vs. 27%; p ≤ .0001) compared to those who had no screening. Screened patients had improved 5-year overall survival rates (50.2% vs. 27.9%) and 5-year lung cancer-specific survival (59.0% vs. 29.7%) compared to unscreened patients. Among screening-eligible patients who underwent National Comprehensive Cancer Network guideline-concordant treatment, screening resulted in substantial reductions in all-cause mortality (adjusted hazard ratio [aHR], 0.79; 95% confidence interval [CI], 0.67-0.92; p = .003) and lung-specific mortality (aHR, 0.61; 95% CI, 0.50-0.74; p < .001). CONCLUSIONS: While LCS uptake remains limited, screening was associated with earlier stage diagnoses and improved survival. This large national study corroborates the value of LCS in clinical practice; efforts to widely adopt this vital intervention are needed.

Loneliness and Depressive Symptoms Are High Among Older Adults With Digestive Disease and Associated With Lower Perceived Health.

BACKGROUND & AIMS: Current approaches to managing digestive disease in older adults fail to consider the psychosocial factors contributing to a person's health. We aimed to compare the frequency of loneliness, depression, and social isolation in older adults with and without a digestive disease and to quantify their association with poor health. METHODS: We conducted an analysis of Health and Retirement Study data from 2008 to 2016, a nationally representative panel study of participants 50 years and older and their spouses. Bivariate analyses examined differences in loneliness, depression, and social isolation among patients with and without a digestive disease. We also examined the relationship between these factors and health. RESULTS: We identified 3979 (56.0%) respondents with and 3131 (44.0%) without a digestive disease. Overall, 60.4% and 55.6% of respondents with and without a digestive disease reported loneliness (P < .001), 12.7% and 7.5% reported severe depression (P < .001), and 8.9% and 8.7% reported social isolation (P = NS), respectively. After adjusting for covariates, those with a digestive disease were more likely to report poor or fair health than those without a digestive disease (odds ratio [OR], 1.25; 95% CI, 1.11-1.41). Among patients with a digestive disease, loneliness (OR, 1.43; 95% CI, 1.22-1.69) and moderate and severe depression (OR, 2.93; 95% CI, 2.48-3.47; and OR, 8.96; 95% CI, 6.91-11.63, respectively) were associated with greater odds of poor or fair health. CONCLUSIONS: Older adults with a digestive disease were more likely than those without a digestive disease to endorse loneliness and moderate to severe depression and these conditions are associated with poor or fair health. Gastroenterologists should feel empowered to screen patients for depression and loneliness symptoms and establish care pathways for mental health treatment.

Predicting Incident Adenocarcinoma of the Esophagus or Gastric Cardia Using Machine Learning of Electronic Health Records.

BACKGROUND & AIMS: Tools that can automatically predict incident esophageal adenocarcinoma (EAC) and gastric cardia adenocarcinoma (GCA) using electronic health records to guide screening decisions are needed. METHODS: The Veterans Health Administration (VHA) Corporate Data Warehouse was accessed to identify Veterans with 1 or more encounters between 2005 and 2018. Patients diagnosed with EAC (n = 8430) or GCA (n = 2965) were identified in the VHA Central Cancer Registry and compared with 10,256,887 controls. Predictors included demographic characteristics, prescriptions, laboratory results, and diagnoses between 1 and 5 years before the index date. The Kettles Esophageal and Cardia Adenocarcinoma predictioN (K-ECAN) tool was developed and internally validated using simple random sampling imputation and extreme gradient boosting, a machine learning method. Training was performed in 50% of the data, preliminary validation in 25% of the data, and final testing in 25% of the data. RESULTS: K-ECAN was well-calibrated and had better discrimination (area under the receiver operating characteristic curve [AuROC], 0.77) than previously validated models, such as the Nord-Trøndelag Health Study (AuROC, 0.68) and Kunzmann model (AuROC, 0.64), or published guidelines. Using only data from between 3 and 5 years before index diminished its accuracy slightly (AuROC, 0.75). Undersampling men to simulate a non-VHA population, AUCs of the Nord-Trøndelag Health Study and Kunzmann model improved, but K-ECAN was still the most accurate (AuROC, 0.85). Although gastroesophageal reflux disease was strongly associated with EAC, it contributed only a small proportion of gain in information for prediction. CONCLUSIONS: K-ECAN is a novel, internally validated tool predicting incident EAC and GCA using electronic health records data. Further work is needed to validate K-ECAN outside VHA and to assess how best to implement it within electronic health records.

Legalization of Cannabis Does Not Reduce Opioid Prescribing in Patients With Inflammatory Bowel Disease: A Difference-in-Difference Analysis.

INTRODUCTION: Cannabis may provide inflammatory bowel disease (IBD) patients with an alternative to opioids for pain. METHODS: We conducted a difference-in-difference analysis using MarketScan. Changes over time in rates of opioid prescribing were compared in states with legalized cannabis to those without. RESULTS: We identified 6,240 patients with IBD in states with legalized cannabis and 79,272 patients with IBD in states without legalized cannabis. The rate of opioid prescribing decreased over time in both groups and were not significantly different (attributed differential = 0.34, confidence interval -13.02 to 13.70, P = 0.96). DISCUSSION: Opioid prescribing decreased from 2009 to 2016 among patients with IBD in both states with legalized and state without legalized cannabis, similar to what has been observed nationally across a variety of diseases. Cannabis legalization was not associated with a lower rate of opioid prescribing for patients with IBD.

Health Data Sciences and Cardiovascular Disease in Africa: Needs and the Way Forward.

PURPOSE OF REVIEW: The rising burden of cardiovascular disease (CVD) in Africa is of great concern. Health data sciences is a rapidly developing field which has the potential to improve health outcomes, especially in low-middle income countries with burdened healthcare systems. We aim to explore the current CVD landscape in Africa, highlighting the importance of health data sciences in the region and identifying potential opportunities for application and growth by leveraging health data sciences to improve CVD outcomes. RECENT FINDINGS: While there have been a number of initiatives aimed at developing health data sciences in Africa over the recent decades, the progress and growth are still in their early stages. Its maximum potential can be leveraged through adequate funding, advanced training programs, focused resource allocation, encouraging bidirectional international partnerships, instituting best ethical practices, and prioritizing data science health research in the region. The findings of this review explore the current landscape of CVD and highlight the potential benefits and utility of health data sciences to address CVD challenges in Africa. By understanding and overcoming the barriers associated with health data sciences training, research, and application in the region, focused initiatives can be developed to promote research and development. These efforts will allow policymakers to form informed, evidence-based frameworks for the prevention and management of CVDs, and ultimately result in improved CVD outcomes in the region.

Efficacy and Safety of Sphingosine 1-Phosphate Receptor Modulators for Ulcerative Colitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND AND AIMS: Sphingosine 1-phosphate receptor modulators (S1PRMs) are an effective treatment for ulcerative colitis (UC). This review summarizes all available randomized trial data on the efficacy and safety of S1PRM therapy. METHODS: Multiple publication databases were systematically searched for randomized control trials (RCTs) of adults with moderate to severe UC treated with S1PRMs. Random effects meta-analysis was performed. The risk of bias was assessed using the Cochrane Risk-of-Bias 2 tool, and the overall quality of evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. RESULTS: We identified 7 RCTs (1737 patients) involving the use of S1PRMs for moderate to severe UC. During induction, S1PRM therapy was efficacious when compared with placebo for clinical remission [RR: 2.65 (95% CI: 2.00, 3.53)], clinical response [RR: 1.68 (95% CI: 1.48, 1.91)], endoscopic improvement [RR: 2.17 (95% CI: 1.76, 2.68)], endoscopic normalization [RR: 2.56 (95% CI: 1.58, 3.83)], mucosal healing [RR: 2.88 (95% CI: 1.94, 4.26)], and histologic remission [RR: 2.42 (95% CI: 1.60, 3.66)]. Similar results were seen throughout the maintenance peroid, although fewer data were available to pool; notably, both sustained [RR: 3.57 (95% CI: 1.23, 10.35)] and steroid-free [RR: 2.92 (95% CI: 1.35, 6.33)] remission were significantly increased by S1PRM. There were no significant differences in adverse events [RR: 1.02 (95% CI: 0.90, 1.15)] and infections [RR: 1.15 (95% CI: 0.82, 1.60)] between S1PRM and placebo. CONCLUSION: Pooling of RCT data confirms that S1PRM therapy is both effective and safe for patients with moderate to severe UC.

Self-Efficacy, Patient Activation, and the Burden of Inflammatory Bowel Disease on Patients' Daily Lives.

BACKGROUND: The effective management of inflammatory bowel disease (IBD) requires complex self-management behaviors. Both patient activation (the degree to which patients are willing and able to engage in care) and self-efficacy (one's confidence in performing certain behaviors) are thought to play an important role in chronic disease self-management, but patient activation is a broad concept that can be more difficult to precisely target than self-efficacy. We aimed to describe the relationship between patient activation, self-efficacy, and the burden of IBD on patients' daily lives. METHODS: Patients with IBD were recruited from a single center to complete a survey including the Patient Activation Measure (PAM-13®), the IBD Self-Efficacy Scale (IBD-SES), and an IBD-specific patient-reported outcome measure. Using multivariable linear regression, we examined the relationship between IBD burden, self-efficacy, and patient activation, adjusting a priori for age, gender, IBD type, IBD medications, active corticosteroid use, anxiety, and depression. We performed a post-hoc mediation analysis to examine self-efficacy as a potential mediator in the relationship between patient activation and the burden of IBD on patient's daily lives. RESULTS: A total of 132 patients with IBD completed the survey (59% Crohn's disease, 41% ulcerative colitis, 52% female). Higher levels of patient activation and higher levels of self-efficacy were each associated with lower IBD burden (patient activation: ß = - 1.9, p < 0.001, self-efficacy: ß = - 2.6, p < 0.001). Post hoc mediation analysis confirmed that the relationship between patient activation and daily IBD burden was mediated by self-efficacy (Average Causal Mediation Effect = - 1.00, p < 0.001, proportion mediated = 0.62, p < 0.001). DISCUSSION: The relationship between patient activation and IBD burden is highly mediated by self-efficacy, suggesting that self-efficacy could be a more precise target for intervention. Future studies could focus on targeting self-efficacy to build individuals' confidence in IBD self-management and testing of IBD-tailored self-management programs to ultimately improve disease outcomes.

Public deliberation to assess patient views on biosimilar medication switching for the treatment of inflammatory bowel disease.

BACKGROUND: Biosimilars are highly similar, but not identical, versions of originator biologic medications. Switching patients to biosimilars presents an opportunity to mitigate rising drug costs and expand patient access to important biologic therapies. However, decreased patient acceptance and adherence to biosimilar medications have been reported, which can lead to loss of treatment response, adverse reactions, and inefficient resource utilization. Understanding patient perceptions of biosimilars and biosimilar switching is needed to inform patient-centered care strategies that promote efficient resource utilization. METHODS: We used democratic deliberation methods to solicit the informed and considered opinions of patients regarding biosimilar switching. Patients with inflammatory bowel disease (IBD; n = 29) from the Veterans Health Administration (VHA) participated in 5-hour deliberation sessions over two days. Following educational presentations with experts, participants engaged in facilitated small group discussions. Transcripts and facilitators' notes were used to identify key themes. Participants completed surveys pre- and post-deliberation to collect sociodemographic and clinical features as well as to assess IBD treatment knowledge and attitudes toward care and approaches to biosimilar switching. RESULTS: Five major themes emerged from the small group discussions in the context of biosimilar switching: 1) concerns about adverse consequences and unclear risk-benefit balance; (2) importance of communication and transparency; (3) desire for shared decision making and patient involvement in treatment decisions; (4) balancing cost-saving with competing priorities; and (5) advocating for individualized care and prioritization based on risk levels. These views led participants to favor approaches that prioritize switching the sickest patients last (i.e., those with poorly controlled disease) and that offer patients control and choices around biosimilar switching. Participants also expressed preferences for combining elements of different approaches to maximize fairness. CONCLUSIONS: Approaches to biosimilar switching should consider patients' desires for transparency and effective communication about biosimilar switching and engagement in their medical decision-making as part of patient-centered care. Incorporating patient preferences around biosimilar switching is critical when navigating the quality and affordability of care in resource constrained settings, both within the VHA and in other healthcare systems.

Racial Disparity in Esophageal Squamous Cell Carcinoma Treatment and Survival in the United States.

INTRODUCTION: Esophageal squamous cell carcinoma (ESCC) has a higher incidence and prevalence than esophageal adenocarcinoma among Black individuals in the United States. Black individuals have lower ESCC survival. These racial disparities have not been thoroughly investigated. We examined the disparity in treatment and survival stratified by ESCC stage at diagnosis. METHODS: The Surveillance, Epidemiology, and End Results database was queried to identify patients with ESCC between 2000 and 2019. The identified cohort was divided into subgroups by race. Patient and cancer characteristics, treatment received, and survival rates were compared across the racial subgroups. RESULTS: A total of 23,768 patients with ESCC were identified. Compared with White individuals, Black individuals were younger and had more distant disease during diagnosis (distant disease: 26.7% vs 23.8%, P < 0.001). Black individuals had lower age-standardized 5-year survival for localized (survival % [95% confidence interval]: 19.3% [16-22.8] vs 27.6% [25.1-30.2]), regional (14.3% [12-16.7] vs 21.1% [19.6-22.7]), and distant (2.9% [1.9-4.1] vs 6.5% [5.5-7.5]) disease. Black individuals were less likely to receive chemotherapy (54.7% vs 57.5%, P = 0.001), radiation (58.5% vs 60.4%, P = 0.03), and surgery (11.4% vs 16.3%, P < 0.0001). DISCUSSION: Black individuals with ESCC have a lower survival rate than White individuals. This could be related to presenting at a later stage but also disparities in which treatments they receive even among individuals with the same stage of disease. To what extent these disparities in receipt of treatment is due to structural racism, social determinants of health, implicit bias, or patient preferences deserves further study.

Characteristics of Facilities With Early and Rapid Ustekinumab Adoption for Patients With Inflammatory Bowel Disease.

INTRODUCTION: To examine which facility characteristics, including teamwork, are associated with early or rapid inflammatory bowel disease-related ustekinumab adoption. METHODS: We examined the association between ustekinumab adoption and the characteristics of 130 Veterans Affairs facilities. RESULTS: Mean ustekinumab adoption increased by 3.9% from 2016 to 2018 and was higher in urban compared with rural facilities (ß = 0.03, P = 0.033) and among facilities with more teamwork (ß = 0.11, P = 0.041). Compared with nonearly adopters, early adopters were more likely be high-volume facilities (46% vs 19%, P = 0.001). DISCUSSION: Facility variation in medication adoption provides an opportunity for improving inflammatory bowel disease care through targeted dissemination strategies to improve medication uptake.

Yield of Repeat Endoscopy for Barrett's Esophagus After Normal Index Endoscopy.

INTRODUCTION: Guidelines suggest 1-time screening with esophagogastroduodenoscopy (EGD) for Barrett's esophagus (BE) in individuals at an increased risk of esophageal adenocarcinoma (EAC). We aimed to estimate the yield of repeat EGD performed at prolonged intervals after a normal index EGD. METHODS: We conducted a national retrospective analysis within the U S Veterans Health Administration, identifying patients with a normal index EGD between 2003 and 2009 who subsequently had a repeat EGD. We tabulated the proportion with a new diagnosis of BE, EAC, or esophagogastric junction adenocarcinoma (EGJAC) and conducted manual chart review of a sample. We fitted logistic regression models for the odds of a new diagnosis of BE/EAC/EGJAC. RESULTS: We identified 71,216 individuals who had a repeat EGD between 1 and 16 years after an index EGD without billing or cancer registry codes for BE/EAC/EGJAC. Of them, 4,088 had a new billing or cancer registry code for BE/EAC/EGJAC after the repeat EGD. On manual review of a stratified sample, most did not truly have new BE/EAC/EGJAC. A longer duration between EGD was associated with greater odds of a new diagnosis (adjusted odds ratio [aOR] for each 5 years 1.31; 95% confidence interval [CI] 1.19-1.44), particularly among those who were younger during the index EGD (ages 19-29 years: aOR 3.92; 95% CI 1.24-12.4; ages 60-69 years: aOR 1.19; 95% CI 1.01-1.40). DISCUSSION: The yield of repeat EGD for BE/EAC/EGJAC seems to increase with time after a normal index EGD, particularly for younger individuals. Prospective studies are warranted to confirm these findings.

Association between antenatal corticosteroid treatment and severe adverse events in pregnant women.

BACKGROUND: Antenatal corticosteroids are considered the standard of care for pregnant women at risk for preterm birth, but studies examining their potential risks are scarce. We aimed to estimate the associations of antenatal corticosteroids with three severe adverse events: sepsis, heart failure, and gastrointestinal bleeding, in pregnant women. METHODS: Of 2,157,321 pregnant women, 52,119 at 24 weeks 0/7 days to 36 weeks 6/7 days of gestation were included in this self-controlled case series study during the study period of 2009-2018. We estimated incidence rates of three severe adverse events: sepsis, heart failure, and gastrointestinal bleeding. Conditional Poisson regression was used to calculate incidence rate ratios (IRRs) for comparing incidence rates of the adverse events in each post-treatment period compared to those during the baseline period among pregnant women exposed to a single course of antenatal corticosteroid treatment. RESULTS: Among 52,119 eligible participants who received antenatal corticosteroid treatment, the estimated incidence rates per 1000 person-years were 0.76 (95% confidence interval (CI): 0.69-0.83) for sepsis, 0.31 (95% CI: 0.27-0.36) for heart failure, and 11.57 (95% CI: 11.27-11.87) for gastrointestinal bleeding. The IRRs at 5 ~ 60 days after administration of antenatal corticosteroids were 5.91 (95% CI: 3.10-11.30) for sepsis and 4.45 (95% CI: 2.63-7.55) for heart failure, and 1.26 (95% CI: 1.02-1.55) for gastrointestinal bleeding; and the IRRs for days 61 ~ 180 were 2.00 (95% CI: 1.01-3.96) for sepsis, 3.65 (95% CI: 2.14-6.22) for heart failure, and 1.81 (95% CI: 1.56-2.10) for gastrointestinal bleeding. CONCLUSIONS: This nationwide population-based study suggests that a single course of antenatal corticosteroids is significantly associated with a 1.3- to 5.9-fold increased risk of sepsis, heart failure, and gastrointestinal bleeding in pregnant women. Maternal health considerations, including recommendations for adverse event monitoring, should be included in future guidelines for antenatal corticosteroid treatment.

Optimizing hepatitis B virus screening in the United States using a simple demographics-based model.

BACKGROUND AND AIMS: Chronic hepatitis B (CHB) affects >290 million persons globally, and only 10% have been diagnosed, presenting a severe gap that must be addressed. We developed logistic regression (LR) and machine learning (ML; random forest) models to accurately identify patients with HBV, using only easily obtained demographic data from a population-based data set. APPROACH AND RESULTS: We identified participants with data on HBsAg, birth year, sex, race/ethnicity, and birthplace from 10 cycles of the National Health and Nutrition Examination Survey (1999-2018) and divided them into two cohorts: training (cycles 2, 3, 5, 6, 8, and 10; n = 39,119) and validation (cycles 1, 4, 7, and 9; n = 21,569). We then developed and tested our two models. The overall cohort was 49.2% male, 39.7% White, 23.2% Black, 29.6% Hispanic, and 7.5% Asian/other, with a median birth year of 1973. In multivariable logistic regression, the following factors were associated with HBV infection: birth year 1991 or after (adjusted OR [aOR], 0.28; p < 0.001); male sex (aOR, 1.49; p = 0.0080); Black and Asian/other versus White (aOR, 5.23 and 9.13; p < 0.001 for both); and being USA-born (vs. foreign-born; aOR, 0.14; p < 0.001). We found that the ML model consistently outperformed the LR model, with higher area under the receiver operating characteristic values (0.83 vs. 0.75 in validation cohort; p < 0.001) and better differentiation of high- and low-risk persons. CONCLUSIONS: Our ML model provides a simple, targeted approach to HBV screening, using only easily obtained demographic data.

Promoting data harmonization to evaluate vaccine hesitancy in LMICs: approach and applications.

BACKGROUND: Factors influencing the health of populations are subjects of interdisciplinary study. However, datasets relevant to public health often lack interdisciplinary breath. It is difficult to combine data on health outcomes with datasets on potentially important contextual factors, like political violence or development, due to incompatible levels of geographic support; differing data formats and structures; differences in sampling procedures and wording; and the stability of temporal trends. We present a computational package to combine spatially misaligned datasets, and provide an illustrative analysis of multi-dimensional factors in health outcomes. METHODS: We rely on a new software toolkit, Sub-National Geospatial Data Archive (SUNGEO), to combine data across disciplinary domains and demonstrate a use case on vaccine hesitancy in Low and Middle-Income Countries (LMICs). We use data from the World Bank's High Frequency Phone Surveys (HFPS) from Kenya, Indonesia, and Malawi. We curate and combine these surveys with data on political violence, elections, economic development, and other contextual factors, using SUNGEO. We then develop a stochastic model to analyze the integrated data and evaluate 1) the stability of vaccination preferences in all three countries over time, and 2) the association between local contextual factors and vaccination preferences. RESULTS: In all three countries, vaccine-acceptance is more persistent than vaccine-hesitancy from round to round: the long-run probability of staying vaccine-acceptant (hesitant) was 0.96 (0.65) in Indonesia, 0.89 (0.21) in Kenya, and 0.76 (0.40) in Malawi. However, vaccine acceptance was significantly less durable in areas exposed to political violence, with percentage point differences (ppd) in vaccine acceptance of -10 (Indonesia), -5 (Kenya), and -64 (Malawi). In Indonesia and Kenya, although not Malawi, vaccine acceptance was also significantly less durable in locations without competitive elections (-19 and -6 ppd, respectively) and in locations with more limited transportation infrastructure (-11 and -8 ppd). CONCLUSION: With SUNGEO, researchers can combine spatially misaligned and incompatible datasets. As an illustrative example, we find that vaccination hesitancy is correlated with political violence, electoral uncompetitiveness and limited access to public goods, consistent with past results that vaccination hesitancy is associated with government distrust.

Interventions Increase Vaccination Rates in Inflammatory Bowel Disease and Rheumatoid Arthritis: A Systematic Review and Meta-Analysis.

BACKGROUND: Patients with immune-mediated conditions such as IBD and RA are at risk for vaccine-preventable infections. Despite guideline recommendations, prior studies have shown suboptimal vaccination rates. AIM: We conducted a systematic review and meta-analysis to compare the different interventions intended to increase vaccination rates. METHODS: A systematic search was conducted of MEDLINE/PubMed, Embase, CINAHL, and Cochrane Library up to 2020 for studies with interventions intended to increase vaccination rates. We performed a random-effects meta-analysis to generate pooled odds ratios (ORs) to assess all interventions against no interventions. Our primary outcome was pneumococcal vaccination (PCV) rate. RESULTS: Our review found 8580 articles, for which 15 IBD and 8 RA articles met the inclusion criteria; 21 articles were included in the analysis. PCV was the predominant vaccination (91%). In our analysis of patients with IBD, almost all interventions (patient-oriented, physician-oriented, or barrier-oriented) increased PCV uptake [OR, 4.74; 95% CI, 2.44-6.56, I2 = 90%] compared to no intervention. The greatest effect was seen in barrier-oriented studies [OR, 12.68; 95% CI, 2.21-72.62, I2 = 92%]. For RA data, all interventions had increased PCV uptake compared to no interventions (OR 2.74; 95% CI, 1.80-4.17, I2 = 95%). CONCLUSION: Our data suggest that many different interventions can increase PCV rates. It appears that barrier-oriented interventions may have the greatest positive effect on increasing PCV uptake. However, clinicians should be encouraged to implement measures best suited to their practice. Future high-quality randomized controlled trials are needed to determine the best approach to optimize vaccination rates.

Efficacy and Safety of Dual Targeted Therapy for Partially or Non-responsive Inflammatory Bowel Disease: A Systematic Review of the Literature.

BACKGROUND: Dual targeted therapy (DTT) has emerged as an attractive therapeutic option for select patients with active inflammatory bowel disease (IBD) who are unable to achieve remission with biologic or small molecule monotherapy. We conducted a systematic review of specific DTT combinations in patients with IBD. METHODS: We conducted a systematic search of MEDLINE, EMBASE, Scopus, CINAHL Complete, Web of Science Core Collection, and Cochrane Library to identify articles related to the use of DTT for the treatment of Crohn Disease (CD) or ulcerative colitis (UC) published before February 2021. RESULTS: Twenty-nine studies were identified comprising 288 patients started on DTT for partially or non-responsive IBD. We identified 14 studies with 113 patients receiving anti-tumor necrosis factor (TNF) and anti-integrin therapies (i.e., vedolizumab and natalizumab), 12 studies with 55 patients receiving vedolizumab and ustekinumab, nine studies with 68 patients receiving vedolizumab and tofacitinib, five studies with 24 patients receiving anti-TNF therapy and tofacitinib, six studies with 18 patients receiving anti-TNF therapy and ustekinumab, and three studies with 13 patients receiving ustekinumab and tofacitinib. CONCLUSION: DTT is a promising approach to improve IBD treatment for patients with incomplete responses to targeted monotherapy. Larger prospective clinical studies are needed to confirm these findings as is additional predictive modeling to identify the patient subgroups most likely to require and benefit from this approach.

HCC surveillance improves early detection, curative treatment receipt, and survival in patients with cirrhosis: A meta-analysis.

BACKGROUND & AIMS: There is controversy regarding the overall value of hepatocellular carcinoma (HCC) surveillance in patients with cirrhosis given the lack of data from randomized-controlled trials. To address this issue, we conducted a systematic review and meta-analysis of cohort studies evaluating the benefits and harms of HCC surveillance in patients with cirrhosis. METHODS: We performed a search of the Medline and EMBASE databases and national meeting abstracts from January 2014 through July 2020 for studies reporting early-stage HCC detection, curative treatment receipt, or overall survival, stratified by HCC surveillance status, among patients with cirrhosis. Pooled risk ratios (RRs) and hazard ratios, according to HCC surveillance status, were calculated for each outcome using the DerSimonian and Laird method for random effects models. RESULTS: We identified 59 studies including 145,396 patients with HCC, which was detected by surveillance in 41,052 (28.2%) cases. HCC surveillance was associated with improved early-stage detection (RR 1.86, 95% CI 1.73-1.98; I2 = 82%), curative treatment receipt (RR 1.83, 95% CI 1.69-1.97; I2 = 75%), and overall survival (hazard ratio 0.67, 95% CI 0.61-0.72; I2 = 78%) after adjusting for lead-time bias; however, there was notable heterogeneity in all pooled estimates. Four studies examined surveillance-related physical harms due to false positive or indeterminate surveillance results, but no studies examined potential financial or psychological harms. The proportion of patients experiencing surveillance-related physical harms ranged from 8.8% to 27.5% across studies, although most harms were mild in severity. CONCLUSION: HCC surveillance is associated with improved early detection, curative treatment receipt, and survival in patients with cirrhosis, although there was heterogeneity in pooled estimates. Available data suggest HCC surveillance is of high value in patients with cirrhosis, although continued rigorous studies evaluating benefits and harms are still needed. LAY SUMMARY: There has been ongoing debate about the overall value of hepatocellular carcinoma (HCC) screening in patients with cirrhosis given the lack of data from randomized-controlled trials. In a systematic review of contemporary cohort studies, we found that HCC screening is associated with improved early detection, curative treatment receipt, and survival in patients with cirrhosis, although there were fewer data quantifying potential screening-related harms. Available data suggest HCC screening is of high value in patients with cirrhosis, although continued studies evaluating benefits and harms are still needed.

Novel Application of Predictive Modeling: A Tailored Approach to Promoting HCC Surveillance in Patients With Cirrhosis.

OBJECTIVE: There has been increased interest in interventions to promote hepatocellular carcinoma (HCC) surveillance given low utilization and high proportions of late stage detection. Accurate prediction of patients likely versus unlikely to respond to interventions could allow a cost-effective approach to outreach and facilitate targeting more intensive interventions to likely non-responders. DESIGN: We conducted a secondary analysis of a randomized clinical trial evaluating a mailed outreach strategy to promote HCC surveillance among 1200 cirrhosis patients at a safety-net health system between December 2014 and March 2017. We developed regularized logistic regression (RLR) and gradient boosting machine (GBM) algorithm models to predict surveillance completion during each of the 3 screening rounds in a training set (n = 960). Model performance was assessed using multiple performance metrics in an independent test set (n = 240). RESULTS: Among 1200 patients, surveillance was completed in 41-47% of patients over the three rounds. The RLR and GBM models demonstrated good discriminatory accuracy, with area under receiver operating characteristic (AUROC) curves of 0.67 and 0.66 respectively in the first surveillance round and improved to 0.77 by the third surveillance round after incorporating prior screening behavior as a feature. Additional performance characteristics including the Brier score, Hosmer-Lemeshow test and reliability diagrams were also evaluated. The most important variables for the predictive model were prior screening completion status and past primary care contact. CONCLUSIONS: Predictive models can help stratify patients' likelihood to respond to surveillance outreach invitations, facilitating tailored strategies to maximize effectiveness and cost-effectiveness of HCC surveillance population health programs.

Comparative Effectiveness of Surveillance Colonoscopy Intervals on Colorectal Cancer Outcomes in a National Cohort of Patients with Inflammatory Bowel Disease.

BACKGROUND & AIMS: Surveillance colonoscopy is recommended to reduce colorectal cancer (CRC)-related morbidity and mortality in patients with inflammatory bowel disease (IBD). The comparative effectiveness of varying colonoscopy intervals on CRC outcomes among patients with IBD is unknown. METHODS: We performed a retrospective cohort study of patients with confirmed CRC within a cohort of 77,824 patients with IBD during 2000 to 2015 in the National Veterans Health Administration. We examined the association between colonoscopy surveillance intervals on CRC stage, treatment, or all-cause and cancer-specific mortality. The interval of colonoscopy prior to CRC diagnosis was categorized as those performed within <1 year, 1 to 3 years, 3 to 5 years, or none within 5 years. RESULTS: Among 566 patients with CRC-IBD, most (69.4%) did not have colonoscopy within 5 years prior to CRC diagnosis, whereas 9.7% had colonoscopy within 1 year prior to diagnosis, 17.7% within 1 to 3 years, and 3.1% between 3 and 5 years. Compared with no surveillance, colonoscopy within 1 year (adjusted odds ratio, 0.40; 95% confidence interval [CI], 0.20-0.82), and 1 to 3 years (adjusted odds ratio, 0.56; 95% CI, 0.32-0.98) were less likely to be diagnosed at late stage. Regardless of IBD type and duration, colonoscopy within 1 year was associated with a lower all-cause mortality (adjusted hazard ratio, 0.56; 95% CI, 0.36-0.88). CONCLUSIONS: In a national cohort of patients with CRC-IBD, colonoscopy within 3 years prior to CRC diagnosis was associated with early tumor stage at diagnosis, and colonoscopy within 1 year was associated with a reduced all-cause mortality compared with no colonoscopy. Our findings support colonoscopy intervals of 1 to 3 years in patients with IBD to reduce late-stage CRC and all-cause mortality.