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This study quantifies the wide-ranging health care costs affecting patients living with IBD, including the annualized direct and indirect costs of care for patients with IBD, the longitudinal drivers of these costs, and the cost of care for newly diagnosed patients.AbstractBackgroundThe Crohn’s & Colitis Foundation’s Cost of Inflammatory Bowel Disease (IBD) Care Initiative seeks to quantify the wide-ranging health care costs affecting patients living with IBD. We aimed to (1) describe the annualized direct and indirect costs of care for patients with Crohn’s disease (CD) or ulcerative colitis (UC), (2) determine the longitudinal drivers of these costs, and (3) characterize the cost of care for newly diagnosed patients.MethodsWe analyzed the Optum Research Database from the years 2007 to 2016, representing commercially insured and Medicare Advantage–insured patients in the United States. Inclusion for the study was limited to those who had continuous enrollment with medical and pharmacy benefit coverage for at least 24 months (12 months before through 12 months after the index date of diagnosis). The value of patient time spent on health care was calculated as number of workplace hours lost due to health care encounters multiplied by the patients’ estimated average wage derived from the Bureau of Labor Statistics. Comparisons between IBD patients and non-IBD patients were analyzed based on demographics, health plan type, and length of follow-up. We used generalized linear models to estimate the association between total annual costs and various patient variables.ResultsThere were 52,782 IBD patients (29,062 UC; 23,720 CD) included in the analysis (54.1% females). On a per-annual basis, patients with IBD incurred a greater than 3-fold higher direct cost of care compared with non-IBD controls ($22,987 vs $6956 per-member per-year paid claims) and more than twice the out-of-pocket costs ($2213 vs $979 per-year reported costs), with all-cause IBD costs rising after 2013. Patients with IBD also experienced significantly higher costs associated with time spent on health care as compared with controls. The burden of costs was most notable in the first year after initial IBD diagnosis (mean = $26,555). The study identified several key drivers of cost for IBD patients: treatment with specific therapeutics (biologics, opioids, or steroids); ED use; and health care services associated with relapsing disease, anemia, or mental health comorbidity.ConclusionThe costs of care for IBD have increased in the last 5 years and are driven by specific therapeutics and disease features. In addition, compared with non-IBD controls, IBD patients are increasingly incurring higher costs associated with health care utilization, out-of-pocket expenditures, and workplace productivity losses. There is a pressing need for cost-effective strategies to address these burdens on patients and families affected by IBD.Video Abstract 10.1093/ibd/izz104_video1Video Abstractizz104.video16039344358001

Tofacitinib is an anti-JAK/STAT small molecule approved for treatment of adults (but not children and adolescents) with moderate to severe ulcerative colitis. Data is limited in children and teens although two major centers have shown efficacy as both mono- and dual - combination therapy using tofacitinib in pediatric patients refractory to anti-TNF agents. We present a 16-year-old female diagnosed with inflammatory ileocolonic Crohn's disease without upper gastrointestinal involvement after presenting with several months of abdominal pain, diarrhea, and unintentional weight loss. Laboratory evaluation was notable for normal inflammatory markers, albumin and complete blood count and an elevated stool lactoferrin. Initial endoscopic evaluation revealed moderate to severe pancolitis and patchy ileitis; biopsies noted mild chronic active ileitis and moderate to severe chronic active pancolitis without dysplastic or atypical changes. She was started on infliximab for induction and maintenance therapy and dosage was increased due to suboptimal levels and marginal symptomatic improvement. However, despite increased dosing plus a course of budesonide (Uceris), she had minimal improvement in her symptoms and ongoing elevation of her lactoferrin. Given an equivocal result on a Clostridium difficile testing (GDH antigen positive only), she was started on oral vancomycin which resulted in mild improvement, but not resolution, of diarrhea and abdominal pain. This was continued after completion of a 14-day course (and subsequent negative testing) due to increased stool frequency with discontinuation of the medication and improvement with reinitiating it. She had severe pancolitis (Mayo 2 - 3) but normal TI on repeat colonoscopy 5 months after diagnosis. Biopsies (reviewed by a panel of adult GI pathologists) were notable for reactive atypia with features concerning for early dysplasia in the ascending and descending colon. Due to disease severity and rapid progression plus histologic changes concerning for possible dysplasia despite optimized therapy with infliximab and repeat negative C. difficile testing, she was started on tofacitinib 10 mg twice daily along with oral vancomycin. She had complete resolution of diarrhea, abdominal pain, and early satiety within a week; repeat fecal lactoferrin was negative (<30). She underwent repeat colonoscopy with chromoendoscopy 5 months after initiation of tofacitinib which revealed mild acute ileitis but no active colonic inflammation, atypia or dysplasia. This is the first report to our knowledge that an adolescent patient with colonic predominant Crohn's disease has complete resolution of atypia and possible early dysplasia with tofacitinib therapy.

Stressor-exposure has been shown to exacerbate inflammation and change the composition of the gastrointestinal microbiota; however stressor-induced effects on microbiota-derived metabolites and their receptors are unknown. Thus, bacterial-produced short chain fatty acids (SCFAs), as well as microbial community composition, were assessed in the colons of mice exposed to stress during infection with Citrobacter rodentium. Mice were exposed to overnight restraint on 7 consecutive nights, or left undisturbed as a control. After the first exposure of restraint, mice were orally challenged with C. rodentium or with vehicle. Microbial community composition was assessed using 16S rRNA gene sequencing and SCFA levels measured using gas chromatography-mass spectrometry (GC-MS). Pathogen levels and colonic inflammation were also assessed 6 days post-infection. Results demonstrated that the microbial community structure and SCFA production were significantly affected by both stressor exposure and C. rodentium-infection. Exposure to prolonged restraint in the absence of infection significantly reduced SCFAs (acetic acid, butyric acid, and propionic acid). Multiple bacterial taxa were affected by stressor exposure, with the relative abundance of Lactobacillus being significantly reduced and directly correlated with propionic acid. Lactobacillus abundances were inversely correlated with colonic inflammation, supporting the contention that Lactobacillus helps to regulate mucosal inflammatory responses. Our data indicates that restraint stressor can have significant effects on pathogen-induced colonic inflammation and suggest that stressor-induced changes in the microbiota, microbial-produced SCFAs and their receptors may be involved.

Abstract Background Anti-tumor necrosis factor (anti-TNF) therapies are effective treatments for inflammatory bowel diseases (IBD). However, infections, psoriasis, and eczema are potential manifestations. Descriptions of these are limited. Our aim was to characterize these skin manifestations in children with IBD on anti-TNF therapy. Methods Our study is a retrospective review of IBD patients ranging in age from 6 to 18 years who were treated with anti-TNFs from 2010-2015. Data collected included demographics, clinical information, anti-TNF therapy used, and whether patients developed skin manifestations and their type of complication, clinical interventions, and outcomes. Results Of the 409 patients analyzed, 47 (11.4%) developed dermatologic manifestations (39 CD, 8 UC/IC). Among these 47 patients, there were 72 manifestations of infections (28/72; 38.9%), psoriasis (33/72; 45.8%), and eczema (10/72; 13.9%). There was no significant difference between patients with CD and UC/IC in the type of manifestation. Children on infliximab experienced an increased risk of psoriasis than those on adalimumab (P = 0.05). A greater percentage of female patients developed a skin manifestation (28/47; 60%). The majority of patients with a skin manifestation were able to continue the current anti-TNF regimen. Amongst the patients that developed psoriasis, 60% did not require change in anti-TNF therapy. Conclusions This is the largest study analyzing anti-TNF related skin manifestations in a pediatric IBD cohort. Psoriasiform lesions were the most prevalent dermatological manifestation, and females experienced more reactions than males. Most patients were able to continue their anti-TNF therapy. However, if a change was required, it was most likely among those who developed psoriasis and required either a dose or interval change, different anti-TNF medication, or a medication class change.

Prior studies have shown that parents of children with inflammatory bowel diseases (IBD) have significantly more symptoms of depression and anxiety, compared to parents with children who do not have a chronic illness (1). The aim of this study is to investigate the occurrence of symptoms of distress, including depression, anxiety, and post-traumatic stress disorder, among parents of children with IBD and associations with disease course and time from diagnosis. We conducted a cross-sectional study with parents with children (2-17 yrs) diagnosed with IBD. There were two cohorts: 1. recently diagnosed cohort (< 6 months from diagnosis); 2. established diagnosis cohort (> 1 year from diagnosis). Parents completed surveys that included demographic information and 3 widely used measures: Patient Health Questionnaire-8 (PHQ-8), Impact of Event Scale Revised (IES-R), and Patient Reported Outcomes Measurement Information System Short Form v1.0-Anxiety 8A (PROMIS-ANX). A total of 212 parents with children with IBD agreed to participate in our project. 52 parents in the recently diagnosed cohort and 103 parents in the established diagnosis cohort completed surveys. 52% of parents in the recently diagnosed cohort had clinically elevated scores on the PROMIS-ANX measure, with no significant difference in the transformed mean scores between the recently diagnosed and established diagnosis cohorts (3.77 vs 3.74, p = 0.220). Similarly, 45% of parents in the recently diagnosed cohort had clinically elevated depression scores, with no significant difference between the mean transformed scores between the recently diagnosed and the established diagnosis cohort (1.426 vs 1.346, p = 0.266). IES-R scores were significantly higher between parents of children recently diagnosed vs. established diagnosed (2.03 vs 1.62, p = 0.017). The cohort was further divided to those diagnosed within 3 months (n = 37) and those diagnosed over 5 years (n = 41) with no statically significant difference between mean transformed PROMIS-ANX (p = 0.371) or PHQ-8 scores (p = 0.605), but a significant increase in mean IES-R scores (p = 0.0478). There was no significant difference between mean transformed parental PROMIS-ANX, PHQ-8, or IES-R scores and patient's IBD phenotypes or patient medications (p > 0.05). In this cohort, we found that a majority of parents with children with IBD had clinically elevated anxiety scores with no significant decrease in mean transformed scores over time. The only measure of distress that did significantly reduce between cohorts was the mean transformed IES-R score. In conclusion, the present study suggests considerable parental distress in parents of children with IBD. Interventions to alleviate parental distress might be considered.

In Canada, more than 2 million people live with osteoporosis, a disease that increases the risk for fractures, which result in excess mortality and morbidity, decreased quality of life and loss of autonomy. This guideline update is intended to assist Canadian health care professionals in the delivery of care to optimize skeletal health and prevent fractures in postmenopausal females and in males aged 50 years and older. This guideline is an update of the 2010 Osteoporosis Canada clinical practice guideline on the diagnosis and management of osteoporosis in Canada. We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework and quality assurance as per Appraisal of Guidelines for Research and Evaluation (AGREE II) quality and reporting standards. Primary care physicians and patient partners were represented at all levels of the guideline committees and groups, and participated throughout the entire process to ensure relevance to target users. The process for managing competing interests was developed before and continued throughout the guideline development, informed by the Guideline International Network principles. We considered benefits and harms, patient values and preferences, resources, equity, acceptability and feasibility when developing recommendations; the strength of each recommendation was assigned according to the GRADE framework. The 25 recommendations and 10 good practice statements are grouped under the sections of exercise, nutrition, fracture risk assessment and treatment initiation, pharmacologic interventions, duration and sequence of therapy, and monitoring. The management of osteoporosis should be guided by the patient’s risk of fracture, based on clinical assessment and using a validated fracture risk assessment tool. Exercise, nutrition and pharmacotherapy are key elements of the management strategy for fracture prevention and should be individualized. The aim of this guideline is to empower health care professionals and patients to have meaningful discussions on the importance of skeletal health and fracture risk throughout older adulthood. Identification and appropriate management of skeletal fragility can reduce fractures, and preserve mobility, autonomy and quality of life.

Purpose of Review Transition of care for pediatric patients with inflammatory bowel diseases (IBD) is a continuous, dynamic process that takes place over several years with a coordinated approach executed by a multidisciplinary team. We review the concepts, tools, and research in effective transitioning and transfer of care for adolescent/young adult patients with IBD. Recent Findings Given the constraints within the healthcare system, effective transitioning can be challenging to implement in everyday clinical practice. Different barriers include resources and expertise in effective transitioning by pediatric and adult gastroenterology healthcare providers and the impact of non-gastrointestinal issues facing young adult patients who are learning to manage and coordinate all aspects of their medical care and health maintenance. Factors that facilitate successful care transitioning and transfer include structured transitioning programs, utilization of validated transition checklists, and IBD medical summaries. Summary Proactive transitioning by pediatric gastroenterologists in partnership with their emerging young adult patients with IBD leads to better clinical and psychosocial outcomes and ultimately, effective transfer of care to adult gastroenterology. By utilizing utilize comprehensive transition assessment tools and medical summaries in partnership with their patients, pediatric and adult gastroenterology teams can better prepare patients as they transfer to independent care and health maintenance.

Efficient RNA extraction methods are needed to study transcript regulation. Such methods must lyse the cell without degrading the genetic material. For cyanobacteria this can be particularly challenging because of the presence of the cyanobacteria cell envelope. The great breath of cyanobacterial shape and size (unicellular, colonial, or filamentous multicellular) created a variety of cell lysis methods. However, there is still a lack of reliable techniques for nucleic acid extraction for several types of cyanobacteria. Here we designed and tested 15 extraction methods using physical, thermic or chemical stress on the filamentous cyanobacteria Planktothrix agardhii. Techniques based on the use of beads, sonication, and heat shock appeared to be too soft to break the Planktothrix agardhii cell envelope, whereas techniques based on the use of detergents degraded the cell envelope but also the RNA. Two protocols allowed to successfully obtain good-quality RNA. The first protocol consisted to manually crush the frozen cell pellet with a pestle and the second was based on the use of high-intensity ultra-sonication. When comparing these two, the high-intensity ultra-sonication protocol was less laborious, faster and allowed to extract 3.5 times more RNA compared to the liquid nitrogen pestle protocol. The high-intensity ultra-sonication protocol was then tested on five Planktothrix strains, this protocol allowed to obtain >8.5 μg of RNA for approximatively 3.5 × 108 cells. The extracted RNA were characterized by 260/280 and 260/230 ratio > to 2, indicating that the samples were devoid of contaminant, and RNA Quality Number > to 7, meaning that the integrity of RNA was preserved with this extraction method. In conclusion, the method we developed based on high-intensity ultra-sonication proved its efficacy in the extraction of Planktothrix RNA and could be helpful for other types of samples.

Precision medicine is part of five focus areas of the Challenges in IBD research document, which also includes preclinical human IBD mechanisms, environmental triggers, novel technologies, and pragmatic clinical research. The Challenges in IBD Research document provides a comprehensive overview of current gaps in inflammatory bowel diseases (IBD) research and delivers actionable approaches to address them. It is the result of a multidisciplinary input from scientists, clinicians, patients, and funders, and represents a valuable resource for patient centric research prioritization. In particular, the precision medicine section is focused on highlighting the main gap areas that must be addressed to get closer to treatments tailored to the biological and clinical characteristics of each patient, which is the aim of precision medicine. The main gaps were identified in: 1) understanding and predicting the natural history of IBD: disease susceptibility, activity, and behavior; 2) predicting disease course and treatment response; and 3) optimizing current and developing new molecular technologies. Suggested approaches to bridge these gaps include prospective longitudinal cohort studies to identify and validate precision biomarkers for prognostication of disease course, and prediction and monitoring of treatment response. To achieve this, harmonization across studies is key as well as development of standardized methods and infrastructure. The implementation of state-of-the-art molecular technologies, systems biology and machine learning approaches for multi-omics and clinical data integration and analysis will be also fundamental. Finally, randomized biomarker-stratified trials will be critical to evaluate the clinical utility of validated signatures and biomarkers in improving patient outcomes and cost-effective care.