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.

Long noncoding RNAs (CTC-471J1.2, NeST) as epigenetic risk factors of active juvenile lupus nephritis: a case-control study.

BACKGROUND: Measurement of the circulating levels of long-non-coding RNAs (lncRNAs) in lupus nephritis (LN) patients could dramatically explore more insights about the disease pathogenesis. Hence, we aimed to quantify the level of expression of CTC-471J1.2 and NeST in LN patients and to correlate it with the disease activity. METHOD: This case-control study was conducted on a group of children with juvenile LN attending to Mansoura University Children's Hospital (MUCH). Demographics, clinical, and laboratory findings were collected besides the measurement of lncRNAs by quantitative real-time PCR. RESULTS: The expression level of lncRNAs-CTC-471J1.2 was significantly down-regulated in children with active LN versus inactive cases or controls. In contrast, the NeST was significantly up-regulated in active LN cases. A significant correlation was found between CTC-471J1.2 expression and LN activity parameters. Additionally, both lncRNAs showed a reasonable sensitivity and specificity in differentiation of active LN. A regression analysis model revealed that CTC-471J1.2 and NeST were independent predictors of active nephritis. CONCLUSION: The expression level of circulatory lncRNAs-CTC-471J1.2 and NeST can be used as sensitive and specific biomarkers for active LN. Furthermore, both could serve as predictors for nephritis activity.

Profiles of Web-based Portal Users with Inflammatory Bowel Disease.

BACKGROUND: Web-based portals can enhance communication between patients and providers to support IBD self-management and improve care. We aimed to identify portal use patterns of patients with inflammatory bowel disease (IBD) to inform future web portal-based interventions and portal design. METHODS: Patients with IBD receiving care at the University of Michigan between 2012 and 2021 were identified. Meta-data from electronic logs of each patient's most recent year of portal use were abstracted. Portal engagement was characterized in terms of intensity (ie, frequency of use); comprehensiveness (ie, number of portal functions used); and duration (ie, quarters per year of portal use). We used k-means clustering, a machine-learning technique, to identify groupings of portal users defined in terms of engagement features. RESULTS: We found 5605 patients with IBD who had accessed their portal account at least once. The average age was 41.2 years (SD 16.7), 3035 (54.2%) were female, and 2214 (39.5%) received immune-targeted therapies. We identified 3 patterns of portal engagement: (1) low intensity users (29.5%); (2) moderate intensity, comprehensive, and sustained users (63.3%); and (3) high intensity, comprehensive, sustained users (7.2%). Patients with more intense, comprehensive, and sustained use of the portal were older, female, with more comorbidities, and were more likely to receive immune-targeted therapies. CONCLUSION: Understanding distinct patterns of portal use can inform portal-based interventions and portal design. Patient portals may be particularly helpful in delivering assistance to those with comorbidities and those receiving immune-targeted therapies-many of whom demonstrate more intense, comprehensive, and sustained portal use.

Inflammatory bowel disease patients have varying patterns of web-based portal engagement that can be characterized into distinct groupings. Portals-based interventions may be particularly helpful for those with comorbidities or receiving immune-targeted therapies­many of whom demonstrate more intense, comprehensive, and sustained use.

Serum apelin-12 and obesity-related markers in Egyptian children with Down syndrome.

Children with Down syndrome (DS) exhibit higher overweight/obesity rates than their typically developing peers. Apelin-12 is a bioactive adipokine that exerts vital roles in obesity-related cardiometabolic comorbidities. To date, apelin-12 has not been investigated in obese-DS. This study aimed to explore the possible association between serum apelin-12 and obesity-related markers and to evaluate the efficiency of apelin-12 in the prediction of metabolic syndrome (MetS) in obese-DS compared to BMI Z-score matched obese-control. The cross-sectional study included 150 prepubertal children classified into three groups; obese-DS (n = 50), obese-control (n = 50), and normal-weight-control (n = 50). Anthropometric parameters, body adiposity, fasting serum levels of blood glucose (FBG), insulin, lipid profile, and apelin-12 were evaluated. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated from FBG and insulin. MetS was defined using Adult Treatment Panel III criteria modified for the pediatric age group. ROC curves were analyzed to evaluate the efficiency of apelin-12 in predicting MetS in obesity groups. Obese-DS exhibited higher body adiposity with marked central fat distribution, atherogenic lipid profile, and higher HOMA-IR compared to obese-control. Apelin-12 was significantly higher in obese-DS and obese-DS with MetS compared to obese-control and obese-control with MetS respectively (p < 0.001). The increase in apelin-12 with higher obesity grades was pronounced in obese-DS. Apelin-12 strongly correlated with body adiposity, several MetS risk factors, and HOMA-IR in obese-DS. Significantly higher AUC for apelin-12 in the diagnosis of MetS among obese-DS than obese-control (AUC = 0.948 vs. AUC = 0.807; p = 0.04). CONCLUSIONS:  The current study supports the crucial role of apelin-12 in obesity-related clinical and biochemical markers and in MetS in obese-DS and obese-control. Serum apelin-12 is a potential diagnostic biomarker for MetS with greater performance in obese-DS than obese-control raising its potential for clinical and therapeutic applications. WHAT IS KNOWN: • Obese-DS children displayed excess body adiposity, Pronounced central fat distribution, atherogenic lipid profile, higher HOMA-IR, and higher prevalence of MetS than obese-control. WHAT IS NEW: • Higher serum apelin-12 was observed in obese-DS and obese-DS with MetS than obese-control and obese-control with MetS respectively. The increase in apelin-12 level with increasing obesity grades was more pronounced in obese-DS. • Apelin-12 strongly correlated with obesity-related markers and MetS components in obese-DS. Apelin-12 performed better as a diagnostic biomarker for MetS in obese-DS than obese-control.

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.

Design, synthesis and molecular docking study of new pyrimidine-based hydrazones with selective anti-proliferative activity against MCF-7 and MDA-MB-231 human breast cancer cell lines.

Efforts were directed on the design, synthesis and evaluation of the anticancer activity of some pyrimidine-based hydrazones against two breast cancer cell lines, MCF-7 and MDA-MB-231. Preliminary screening results revealed that some candidates scrutinized for their antiproliferative activities exhibited IC50 values of 0.87 µM-12.91 µM in MCF-7 and 1.75 µM-9.46 µM in MDA-MB-231 cells, indicating almost equal activities on both cell lines and better growth inhibition activities than those of the positive control 5-fluorouracil (5-FU) which displayed IC50 values of 17.02 µM and 11.73 µM respectively. Selectivity of the significantly active compounds was estimated against MCF-10A normal breast cells when compounds 7c, 8b, 9a and 10b exhibited superior activity for cancerous cells than for normal cells when compound 10b presented the best selectivity Index (SI) with respect to both MCF-7 and MDA-MB-231 cancer cells in comparison to the reference drug 5-FU. Mechanisms of their actions were explored by inspecting activation of caspase-9, annexin V staining and cell cycle analysis. It was noticed that compounds 7c, 8b, 8c 9a-c and 10b produced an increase in caspase-9 levels in MCF-7 treated cells with 10b inducing the highest elevation (27.13 ± 0.54 ng/mL) attaining 8.26-fold when compared to control MCF-7 which was higher than that of staurosporine (19.011 ± 0.40 ng/mL). The same compounds boosted caspase-9 levels in MDA-MB-231 treated cells when an increase in caspase-9 concentration reaching 20.40 ± 0.46 ng/mL (4.11-fold increase) was observed for compound 9a. We also investigated the role of these compounds for their increasing apoptosis ability against the 2 cell lines. Compounds 7c, 8b and 10b tested on MCF-7 cells displayed pre-G1 apoptosis and arrested cell cycle in particular at the S and G1 phases. Further clarification of their effects was made by modulating their related activities as inhibitors of ARO and EGFR enzymes when 8c and 9b showed 52.4% and 58.9% inhibition activity relative to letrozole respectively and 9b and 10b showed 36% and 39% inhibition activity of erlotinib. Also, the inhibition activity was verified by docking into the chosen enzymes.

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.

Safety and Effectiveness of Carbon Dioxide Contrast Medium in Infra-Inguinal Endovascular Interventions for Patients With Chronic Threatening Lower Limb Ischemia and Renal Impairment: A Multicentric Trial.

PURPOSE: To assess the safety and effectiveness of using carbon dioxide (CO2) contrast in both supra- and infra-genicular endovascular interventions in patients with renal impairment. MATERIAL AND METHODS: This is a multicentric prospective observational study conducted over a period of 3 years from 2017 to 2020; the study included 114 patients presented with chronic threatening limb ischemia (CTLI) and renal impairment (lowest serum creatinine levels ≥1.3 mg/dL) for whom endovascular procedures were done using CO2 as a contrast medium. Endovascular angiography was guided by CO2 either exclusively (zero contrast) or with the aid of small amount of supplementary iodinated contrast media (ICM) injections. The qualitative assessment of the angiographic images in both supra- and infra-genicular fields were reported and scaled. RESULTS: The qualitative diagnostic images were excellent in 86.5% in the supra-genicular and 66.5% in infra-genicular images. There were no significant changes in mean serum creatinine levels from baseline to first and fifth days post procedural (mean 1.8 mg/dL vs mean 1.9 mg/dL and mean 1.7 mg/dL). CONCLUSION: CO2 is a non-nephrotoxic alternative to traditional ICM that could be safely used and well tolerated during endovascular interventions for peripheral arterial disease in patients with renal impairment. Primary safety and efficacy endpoints were achieved in 100% of cases. The use of automated injector system provides adequate delivery, optimizes the dose, and avoids air contamination. For infra-genicular segment opacification, we recommend super-selective injections and some changes in angiographic techniques from contrast preparation to image post-processing. CLINICAL IMPACT: Co2 is a non-nephrotoxic alternative to traditional ICM that could be safely used and well tolerated during peripheral endovascular interventions in patients with renal impairment. The use of automated injector system would provide adequate delivery, optimizes the dose and avoids air contamination. For infra-genicular segment opacification, its recommended to use selective injection as close to the target artery as possible and some changes in angiographic techniques from contrast preparation to image post-processing.

Dual-effects of caffeinated hyalurosomes as a nano-cosmeceutical gel counteracting UV-induced skin ageing.

Caffeine (CAF) is a challenging natural bioactive compound with proven antiaging efficacy. However, being hydrophilic hampers its permeation through the skin. Our aim is to develop a novel CAF-loaded nano-cosmeceutical tool counteracting skin photoaging via improving CAF skin permeation using a bioactive nanocarrier. Caffeinated hyalurosomes are novel biocompatible antiaging nanoplatforms designed by immobilization of phospholipid vesicles with a hyaluronan polymer. Physicochemical properties of the selected hyalurosomes formulation showed nano-sized vesicles (210.10 ± 1.87 nm), with high zeta potential (-31.30 ± 1.19 mv), and high encapsulation efficiency (84.60 ± 1.05%). In vitro release results showed outstanding sustained release profile from caffeinated hyalurosomes compared to the CAF-loaded in conventional gel over 24 h. The in-vivo study revealed a photoprotective effect of caffeinated hyalurosomes, reflected from the intact and wrinkling-free skin. Results of biochemical analyses of oxidative stress, pro-inflammatory mediators, and anti-wrinkling markers further confirmed the efficacy of the prepared hyalurosomes compared to the CAF conventional gel. Finally, histopathological examination demonstrated normal histological structures of epidermal layers with minimal inflammatory cell infiltrates in the caffeinated hyalurosomes group compared to the positive control group. Conclusively, caffeinated hyalurosomes successfully achieved enhanced CAF loading and penetration into the skin besides the hydration effect of hyaluronan. Consequently, the developed delivery system presents a promising skin protection nano-platforms via the double effects of both hyaluronan and CAF, hence it guards against skin photodamage.

How multisystem inflammatory syndrome in children discriminated from Kawasaki disease: a differentiating score based on an inception cohort study.

BACKGROUND: About 25-50% of multisystem inflammatory syndrome in children (MIS-C) patients meet the criteria for diagnosis of Kawasaki disease (KD). The differentiation of both conditions is so challenging on clinical practice as the management of both is time dependant and precise diagnosis is fundamental. METHOD: Data were collected from children < 18 years old hospitalized with MIS-C or KD. Patient demographics, clinical, and laboratory data were compared, and a discrimination score was created to assist in clinical differentiation. RESULTS: 72 patients with MIS-C and 18 with KD were included in the study. Patients with MIS-C had a higher prevalence of abdominal pain (p = 0.02), vomiting (p = 0.03), and cervical lymphadenopathy (p = 0.02) compared with KD cases. MIS-C patients had higher liver enzymes (aspartate aminotransferase (AST) (p = 0.04), alanine aminotransferase (ALT) (p = 0.03), serum creatinine (p = 0.03), and lower platelet count nadir (p = 0.02) than KD. Four variables were detected in the regression analysis model, and the independent predictors were utilized to generate a scoring model that distinguished MIS-C from KD with an area under the curve of 0.70. CONCLUSION: This study constructed a prediction model for differentiation of MIS-C from KD based on clinical and laboratory profiles. This model will be valuable to guide clinicians in the treatment decisions. Key Points • Children with MIS-C are more likely to have gastrointestinal symptoms, cervical lymphadenopathy, and respiratory involvement than KD patients. • Elevated liver enzymes and lower platelet count are more pronounced laboratory findings in MIS-C than KD. • This study constructed a prediction model for differentiation of MIS-C from KD based on clinical and laboratory profiles. This model will be valuable to guide clinicians in the treatment decisions.

Neuroprotective Effect of Artichoke-Based Nanoformulation in Sporadic Alzheimer's Disease Mouse Model: Focus on Antioxidant, Anti-Inflammatory, and Amyloidogenic Pathways.

The vast socio-economic impact of Alzheimer's disease (AD) has prompted the search for new neuroprotective agents with good tolerability and safety profile. With its outstanding role as antioxidant and anti-inflammatory, alongside its anti-acetylcholinesterase activity, the artichoke can be implemented in a multi-targeted approach in AD therapy. Moreover, artichoke agricultural wastes can represent according to the current United Nations Sustainable Development goals an opportunity to produce medicinally valuable phenolic-rich extracts. In this context, the UPLC-ESI-MS/MS phytochemical characterization of artichoke bracts extract revealed the presence of mono- and di-caffeoylquinic acids and apigenin, luteolin, and kaempferol O-glycosides with remarkable total phenolics and flavonoids contents. A broad antioxidant spectrum was established in vitro. Artichoke-loaded, chitosan-coated, solid lipid nanoparticles (SLNs) were prepared and characterized for their size, zeta potential, morphology, entrapment efficiency, release, and ex vivo permeation and showed suitable colloidal characteristics, a controlled release profile, and promising ex vivo permeation, indicating possibly better physicochemical and biopharmaceutical parameters than free artichoke extract. The anti-Alzheimer potential of the extract and prepared SLNs was assessed in vivo in streptozotocin-induced sporadic Alzheimer mice. A great improvement in cognitive functions and spatial memory recovery, in addition to a marked reduction of the inflammatory biomarker TNF-α, ß-amyloid, and tau protein levels, were observed. Significant neuroprotective efficacy in dentate Gyrus sub-regions was achieved in mice treated with free artichoke extract and to a significantly higher extent with artichoke-loaded SLNs. The results clarify the strong potential of artichoke bracts extract as a botanical anti-AD drug and will contribute to altering the future medicinal outlook of artichoke bracts previously regarded as agro-industrial waste.

Real-world Early Outcomes and Retreatment Rates Following Water Vapour Ablative Therapy for Symptomatic Benign Prostatic Hyperplasia.

Background: Rezum water vapour ablation is an effective minimally invasive surgical therapy for the treatment of bladder outflow obstruction. Objective: To present early outcomes and reoperation rates after Rezum, including an analysis of retreatment rates to gain an insight into optimal patient selection and the durability of the procedure. Design setting and participants: Data were prospectively collected for consecutive patients undergoing Rezum for symptomatic benign prostatic hyperplasia between March 2017 and January 2020 at two hospital sites. Intervention: Rezum treatment of the prostate. Outcome measurements and statistical analysis: Patients were reviewed at 6 wk and 3, 6, and 12 mo after their Rezum procedure. We evaluated changes in urinary symptoms and the retreatment rate. Results and limitations: A total of 461 patients undergoing Rezum were analysed. The mean (±standard deviation) follow-up duration was 16.7 ± 10.4 mo. The mean patient age was 67.5 ± 7.8 yr and the mean prostate volume was 56.5 ± 24.0 ml. There was a significant improvement in mean maximum flow rate and postvoid residual volume and in International Prostate Symptom Score and quality-of-life scores (p < 0.0001). During the follow-up period, 21 patients (4.6%) required retreatment, of which 11 cases (2.4%) were within the first year. The retreatments included eight bladder neck incisions or resections, six transurethral resections of the prostate, four Greenlight laser photoselective vaporisations of the prostate, and three Rezum procedures. The median length of time to a further operation was 11.5 mo (range 3-34). The most common findings at reoperation were an inadequately treated median lobe, an obstructing bladder neck, and in some cases asymmetry of the prostate cavity or recesses within the prostate gland. Conclusions: This study demonstrates that the beneficial effects of Rezum observed in the pivotal phase 2 randomised study are transferable to a real-world population with a comparable early retreatment rate. A range of procedures were used for retreatment. The factors dictating which option to select were based on patient concerns regarding side effects, gland volume, symptom profile, and cystoscopy findings. Patient summary: We investigated outcomes for patients undergoing Rezum, a water vapour treatment to reduce the size of the prostate in men with obstruction of the bladder outlet because of benign prostate enlargement. This technique yields significant improvements in symptoms and preserves sexual function. The proportion of men needing retreatment was 2.4% in the first year after their Rezum procedure.

Trends in the Incidence and Treatment of Distal Radius Fractures in the United States in Privately Insured and Medicare Advantage Enrollees.

Background: This study aims to determine the trends in the treatment of distal radius fractures (DRFs) in patients aged 18 years and older. Methods: An administrative claims database of more than 100 million patients was used to identify patients aged 18 years and older with a DRF between 2005 and 2014. A total of 137 130 DRFs were identified in 135 128 patients. Results: The proportion and rate of fractures were more predominant in those aged 55 years and older compared with a decreasing incidence in patients younger than 55 years. Age-adjusted rates of surgical treatment have significantly increased in both women and men by 15.9% (absolute change, 4.8%) and 5.0% (absolute change, 1.7%) change over time, respectively. Conversely, age-adjusted rates of nonsurgical treatment have significantly decreased overtime in both women and men by 6.9% and 2.6%, respectively. Conclusions: These data provide better understanding of the epidemiology of DRF, which is important to develop preventive strategies targeting high-risk populations and to develop effective treatment strategies.

Novel Siprulina platensis Bilosomes for Combating UVB Induced Skin Damage.

The recent interest in bioactive compounds from natural sources has led to the evolution of the skin care industry. Efforts to develop biologically active ingredients from natural sources have resulted in the emergence of enhanced skin care products. Spirulina (SPR), a nutritionally enriched cyanobacteria-type microalga, is rich in nutrients and phytochemicals. SPR possesses antioxidant, immunomodulatory, and anti-inflammatory activities. Spirulina-loaded bilosomes (SPR-BS), a novel antiaging drug delivery system, were designed for the first time by incorporation in a lecithin−bile salt-integrated system for bypassing skin delivery obstacles. The optimized BS had good entrapment efficiency, small particle size, optimal zeta potential, and sustained drug release pattern. Blank and SPR-loaded BS formulations were safe, with a primary irritancy index of <2 based on the Draize test. In vivo tests were conducted, and photoprotective antiaging effects were evaluated visually and biochemically by analyzing antioxidant, anti-inflammatory, and anti-wrinkling markers following ultraviolet (UV) B irradiation. Results of biochemical marker analysis and histopathological examination confirmed the superior antiaging effect of SPR-BS compared with SPR. Thus, SPR-loaded BS is a promising nanoplatform for SPR delivery, can be used for treating UV-induced skin damage, and offers maximum therapeutic outcomes.

Subtitling strategies of swear words and taboo expressions in the movie "Training Day".

Translators face some problems when they translate swear words and taboo expressions, as they belong to different cultures and they have different impacts on the audience. Although some studies examined the problems faced in translating swear words and how to deal with them, little is known about studies that examined the strategies employed in translating such words and expressions from English into Arabic. Therefore, this study examines the strategies employed in translating such words and expressions from English into Arabic in the "Training Day" movie; and to assess the quality of subtitling these expressions. Samples from the movie were selected and analyzed. The results of the study showed that the subtitler used different strategies to subtitle swear and taboo words and expressions. Two of the most common strategies were found to be translating the swear and taboo words euphemistically, and by omission. As regards, the quality of the subtitles, they were found to be of good quality. This study concludes by proposing a model for subtitling swear words and Taboo expressions.

Variations in Health Care Utilization Patterns Among Inflammatory Bowel Disease Patients at Risk for High Medical Service Utilization Enrolled in High Deductible Health Plans.

BACKGROUND: High-deductible health plans (HDHPs) are increasing in prevalence as a cost control device for slowing health care cost growth by reducing nonessential medical service utilization. High cost-sharing associated with HDHPs can lead to significant financial distress and worse disease outcomes. We hypothesize that chronic disease patients are delaying or foregoing necessary medical care due to health care costs. METHODS: A retrospective cohort analysis of IBD patients at risk for high medical service utilization with continuous enrollment in either an HDHP or THP from 2009 to 2016 were identified using the MarketScan database. Health care costs were compared between insurance plan groups by Kruskal-Wallis test. Temporal trends in office visits, colonoscopies, emergency department (ED) visits, and hospitalizations were evaluated using additive decomposition time series analysis. RESULTS: Of 605,862 patients with a diagnosis of IBD, we identified 13,052 eligible patients. Annual out-of-pocket costs were higher in the HDHP group (n = 524) than the THP group (n = 12,458) ($2870 vs $1,864; P < 0.001) without any difference in total health care expenses ($23,029 vs $23,794; P = 0.583). Enrollment in an HDHP influenced colonoscopy, ED visit, and hospitalization utilization timing. Colonoscopies peaked in the fourth quarter, ED visits peaked in the first quarter, and hospitalizations peaked in the third and fourth quarter. CONCLUSIONS: High-deductible health plan enrollment does not change the cost of care; however, it shifts health care costs onto patients and changes the timing of the care they receive. High-deductible health plans are incentivizing delays in obtaining health care with a potential to cause worse disease outcomes and financial distress. Further evaluation is warranted.

Trends of 5-Aminosalicylate Medication Use in Patients With Crohn Disease.

BACKGROUND: 5-aminosalicylate (5-ASA) medications have a long history of use for the treatment of inflammatory bowel disease and continue to be widely prescribed today. The effectiveness of 5-ASAs in ulcerative colitis is clear; however, studies have shown little benefit for induction or maintenance treatment of Crohn disease (CD). We aimed to quantify usage and examine trends in 5-ASA prescription rates in patients with CD. METHODS: Using a retrospective design, we queried a national database of commercially insured patients (Truven-Health databases) between 2009 and 2014 to identify patients with CD aged 18 to 65 years. Prescription rates for 5-ASA medications including sulfasalazine, mesalamine, olsalazine, and balsalazide were calculated for each calendar year. Regression models were used to examine year-to-year trends in prescription rates and identify patient factors associated with 5-ASA use. RESULTS: We identified 132,804 patients with CD, of whom 37.3% (n = 49,529) received a 5-ASA prescription during the study period. From 2009 to 2014, the overall prescription rates of 5-ASAs declined from 42.9% to 30.0% (P < 0.001). Patient factors independently associated with 5-ASA use included younger age, male sex, multimorbidity, and a health maintenance organization insurance plan, while controlling for the region of residence. CONCLUSIONS: About 1 in 3 privately insured patients with CD received 5-ASA prescriptions despite their questionable effectiveness; however, in an encouraging trend, prescription rates significantly decreased from 2009 to 2014. This high prescription rate may reflect a gap in providers' knowledge regarding the available evidence-an opportunity for cost savings with improved health care delivery.

Mapping the relationships between inflammatory bowel disease and comorbid diagnoses to identify disease associations.

BACKGROUND: Massive amounts of patient data are captured daily in electronic medical records (EMR). Utilizing the power of such large data may help identify disease associations and generate hypotheses that can lead to a better understanding of disease associations and mechanisms. We aimed to comprehensively identify and validate associations between inflammatory bowel disease (IBD) and concurrent comorbid diagnoses. METHODS: We performed a cross-sectional study using EMR data collected between 1986 and 2009 at a large tertiary referral center to identify associations with a diagnosis of IBD. The resulting associations were externally validated using the Truven MarketScan database, a large nationwide dataset of private insurance claims. RESULTS: A total of 6225 IBD patients and 31 125 non-IBD controls identified using EMR data were used to abstract 41 comorbid diagnoses associated with an IBD diagnosis. The strongest associations included Clostridiodes difficile infection, pyoderma gangrenosum, parametritis, pernicious anemia, erythema nodosum, and cytomegalovirus infection. Two IBD association clusters were found, including diagnoses of nerve conduction abnormalities and nonspecific inflammatory conditions of organs outside the gut. These associations were validated in a national cohort of 80 907 patients with IBD and 404 535 age- and sex-matched controls. CONCLUSION: We leveraged a big data approach to identify several associations between IBD and concurrent comorbid diagnoses. EMR and big data provide the opportunity to explore disease associations with large sample sizes. Further studies are warranted to refine the characterization of these associations and evaluate their usefulness for increasing our understanding of disease associations and mechanisms.