Characterization of Biologic Discontinuation Among Pediatric Patients with Crohn's Disease.

BACKGROUND & AIMS: Biologic therapies may effectively treat Crohn's disease (CD), and pediatric patients who discontinue multiple biologics risk exhausting treatment options. The frequency and context of biologic discontinuation have not been well-characterized. We aimed to determine patterns of biologic use, discontinuation, and evaluation in pediatric patients with CD. METHODS: Pediatric patients with CD at 7 U.S. centers (2010-2020) were identified. Prospective ImproveCareNow registry data were supplemented with medical record abstraction. Biologics included monoclonal antibody and small molecule medications. Therapeutic drug monitoring (TDM) was considered induction if <14 weeks after biologic start, proactive if later during quiescent disease, and reactive during active disease. RESULTS: Of 823 patients included (median age, 13.0 years; 40% female), 86% started biologics (78% infliximab, 21% adalimumab, <1% others). Twenty-six percent used concomitant immunomodulators for ≥12 months. Most (85%) measured TDM including 47% induction, 69% proactive, and 24% reactive. Twenty-nine percent discontinued their first biologic after median 793 days because of inefficacy (34%), anti-drug antibodies (8%), adverse events (8%), or non-adherence (12%). If inefficacy, 86% underwent pre-discontinuation evaluation. If infliximab or adalimumab inefficacy and TDM was done, 62% had levels <10 µg/mL. Proactive TDM and concomitant immunomodulators were associated with 60% and 32% reduced biologic discontinuation. CONCLUSIONS: Most children with CD are treated with biologics; 25%-37% discontinue biologics, resulting in 1 in 12 using >2 biologics during pediatric care. Half of patients discontinued biologics without trial of high-dose therapy and 14% without any evaluation. Concomitant immunomodulator use and proactive TDM decreased risk of biologic discontinuation. Strategies are needed to preserve biologic efficacy and prevent biologic discontinuation.

Review article: exclude or expose? The paradox of conceptually opposite treatments for irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is a heterogeneous disorder of gut-brain interaction (DGBI) maintained by interacting biological, psychological, and social processes. Interestingly, there are two contrasting yet evidence-based treatment approaches for reducing IBS symptoms: exclusion diets such as those low in fermentable oligo-, di-, monosaccharides and polyols (FODMAPs) and exposure-based cognitive-behavioural therapy (CBT). Exclusion diets recommend patients avoid foods thought to be symptom-inducing, whereas exposure-based CBT encourages patients to expose themselves to foods. AIMS: To address the paradox of conceptually opposite exclusion diets and exposure-based CBT for IBS. METHODS: In this conceptual review, we describe the rationale, practical implementation, evidence base and strengths and weaknesses of each treatment. We conducted up-to-date literature search concerning the low FODMAP diet and CBT, and performed a secondary analysis of a previously conducted trial to illustrate a key point in our review. RESULTS: The low FODMAP diet has demonstrated efficacy, but problems with adherence, nutritional compromise, and heightened gastrointestinal-specific anxiety raise caution. Exposure-based CBT has demonstrated efficacy with substantial evidence for gastrointestinal-specific anxiety as a key mechanism of action. Mediation analysis also showed that increased FODMAP intake mediated decreased symptom severity in exposure-based CBT. However, there is minimal evidence supporting which treatment "works best for whom" and how these approaches could be best integrated. CONCLUSIONS: Even though exclusion diets and exposure-based CBT are conceptually opposite, they each have proven efficacy. Clinicians should familiarise themselves with both treatments. Further research is needed on predictors, mechanisms and moderators of treatment outcomes.

The lived experience of irritable bowel syndrome: A focus on dietary management.

BACKGROUND: Irritable bowel syndrome (IBS) is a disorder of the gut-brain axis with a prevalence of 3.5% in Australia. The complexity of mechanisms underlying IBS means patients often respond poorly to treatment. There is encouraging evidence for the successful use of dietary strategies for short- and long-term management of IBS. OBJECTIVE: The aim of this narrative review was to explore the lived experience of IBS from the patient perspective with emphasis on dietary involvement and diet management of the condition. DISCUSSION: There are a number of dietary constituents implicated in IBS, and patients' main concerns are the trial-and-error nature of identifying triggers, uncertainty regarding food choices and reduced enjoyment of food. Despite this, dietary modifications are accepted by patients and healthcare professionals (HCPs) as an efficacious management strategy. A meaningful relationship with their HCP can improve patient adherence, treatment success and overall satisfaction for patients.

Impact of Protein-Losing Enteropathy on Inflammatory Biomarkers and Vascular Dysfunction in Fontan Circulation.

Fontan palliation has improved survival for single ventricle patients, but long-term complications persist including cardiovascular dysfunction, neurohormonal abnormalities, and protein-losing enteropathy (PLE). Although chronic inflammation contributes to morbidity, an association between inflammation and vascular dysfunction has not been studied. We assessed inflammation and vascular function in 31 Fontan-palliated patients (52% male, median age 14.3 years), including 10 PLE+. Fontan circulation was associated with altered inflammatory cytokines (TNF-α: mean 2.5 ± 1.4 vs. 0.7 ± 0.2 pg/ml, p < 0.0001; sTNFR2: 371 ± 108 vs. 2694 ± 884 pg/ml, p < 0.0001) and vascular dysfunction [log-transformed reactive hyperemia index (lnRHI) 0.28 ± 0.19 vs. 0.47 ± 0.26, p < 0.01; augmentation index (AI) -2.9 ± 13.8 vs. -16.3 ± 12.0, p = 0.001; circulating endothelial progenitor cells (cEPCs) 5.0 ± 8.1 vs. 22.8 ± 15.9, p = 0.0002)]. Furthermore, PLE+ patients showed greater inflammation (IFN-γ 6.3 ± 2.2 vs. 11.5 ± 7.9 pg/ml, p = 0.01; sTNFR1: 1181 ± 420 vs. 771 ± 350 pg/ml, p = 0.01) and decreased arterial compliance (AI: 5.4 ± 17.1 vs. -6.8 ± 10.2, p = 0.02) than PLE- patients. Circulating EPCs, but not inflammatory cytokines, were inversely associated with arterial stiffness in Fontan patients. In conclusion, chronic inflammation and vascular dysfunction are observed after Fontan operation, with greater inflammation and arterial stiffness in Fontan patients with active PLE. However, there is no clear association between inflammatory cytokines and vascular dysfunction, suggesting these pathophysiologic processes are not mechanistically linked.

Psychiatric provider comfort and perception regarding psychogenic nonepileptic seizures.

The treatment of psychogenic nonepileptic seizures (PNES) involves psychotherapy: yet there is a gap in the understanding of the perceptions and comfort of therapy providers regarding PNES. In this study, we surveyed providers of therapy, including psychiatrists, psychiatric nurse practitioners, physician assistants, psychologists, and social workers, to collect information regarding their comfort and perceptions in caring for individuals with PNES. This study identified differences between physician and non-physician groups in training about PNES and in exposure to patients with PNES. While 26.7% of non-physician providers describe prior training in PNES, 48.3% endorse feeling comfortable treating PNES, suggesting that comfort is based in areas other than prior training. And while providers (83.8% of physicians and 82.1% of non-physicians) deny concern about patients having an in-appointment episode, 36.1% of physicians and 51.7% of non-physicians are concerned that they would not be able to tell apart a nonepileptic versus epileptic episode. While physicians and non-physician providers were similar in their views regarding chronicity, cyclicality, effect of treatment, and illness coherence of PNES, physicians noted significantly greater perceptions of the negative consequences and patient control ability. While both groups viewed PNES as improving with treatment, 83.8% of physicians and 89.7% of non-physicians agreed or strongly agreed that more training in PNES would increase their comfort.

Therapy of IBS: Is a Low FODMAP Diet the Answer?

Irritable bowel syndrome (IBS) is the most prevalent functional gastrointestinal disorder with a worldwide prevalence of 11%. It is characterized by abdominal pain and altered bowel habits in the absence of underlying unique pathology. The condition is associated with poor quality of life and high use of healthcare resources required for management. The low FODMAP diet (LFD) is a recognized treatment for symptom management of IBS; however, approximately 30% of patients do not respond. The aim of this review was to understand the effectiveness and application of the LFD compared with other dietary and non-dietary interventions. Ten studies were included, eight of which assessed the LFD against other dietary interventions including traditional dietary advice, modified National Institute for Health and Care Excellence guidelines, a high FODMAP diet, gluten-free diet and Mediterranean diet, generalized dietary advice, probiotics, and a sham diet. Two studies compared a LFD to non-diet interventions of gut directed hypnotherapy or yoga. The findings clearly support the LFD as an effective treatment in IBS, and although it highlights the role for microbiota and current psychosocial state, it remains challenging to identify what combination of treatments may be best to ensure a personalized approach and overall higher response rates to IBS therapy.

Use of dietary interventions for functional gastrointestinal disorders.

The role of food in the development of symptoms experienced within functional gastrointestinal disorders (FGIDs) is well recognised. This review aims to describe the evidence base for dietary interventions in the different functional esophageal, duodenal and bowel disorders. Randomised controlled trials are lacking for many of the FGIDs, with the exception of irritable bowel syndrome (IBS). Restricting rapidly fermentable, short-chain carbohydrates (FODMAPs) provides an evidence based dietary approach for the management of symptoms of IBS. Recent evidence shows the upper GI motility response varies between carbohydrates, which gives promise for the potential application of the low FODMAP diet in upper GI disorders. In addition to fine-tuning our FODMAP understanding, other observational data and smaller sized studies create an exciting and optimistic future for dietary management of all FGIDs.

The Benefits of Honoring Patients as Teachers: A Qualitative Study.

INTRODUCTION: Medical training could not occur without the contributions of patients. Few programs are available that recognize patients for their essential role in medical education, and even fewer explore their impact. The Patients as Teachers (PaT) program was developed to provide an opportunity for medical students to formally honor patients for their contributions and to evaluate their effect on students' medical education. METHODS: This qualitative study involved the evaluation of transcripts of audiotaped interviews conducted with students and their honorees following participation in the PaT program in 2015 and 2016. Two different sets of authors independently examined transcripts from each year utilizing a descriptive coding strategy. Consensus was reached on theme selection and relationships between themes explored for theory development. A third author ensured grounding of the concepts in the data analyzed. RESULTS: Four themes emerged: (1) appreciating humanism in medicine, (2) expressing gratitude, (3) connecting patients and students, and (4) experiencing a unique event. CONCLUSION: The Patients as Teachers program provides meaningful benefits to both students and patients and has the potential to infuse elements of humanism into medical training.

Discoidin Domain Receptor 2 as a Potential Therapeutic Target for Development of Disease-Modifying Osteoarthritis Drugs.

Osteoarthritis (OA) is the most common form of arthritis disorders, but the identification of therapeutic targets to effectively prevent OA has been increasingly difficult. The goal of this investigation is to provide experimental evidence that discoidin domain receptor 2 (DDR2) may be an ideal target for the development of disease-modifying OA drugs. Ddr2 was conditionally deleted from articular cartilage of adult mouse knee joints. Aggrecan-CreERT2;floxed Ddr2 mice, which were generated by crossing Aggrecan-CreERT2 mice with floxed Ddr2 mice, then received tamoxifen injections at the age of 8 weeks. The mice were then subjected to destabilization of the medial meniscus (DMM) surgery. At 8 and 16 weeks after DMM, mice were euthanized for the collection of knee joints. In a separate experiment, Aggrecan-CreERT2;floxed Ddr2 mice were subjected to DMM at the age of 10 weeks. The mice then received tamoxifen injections at 8 weeks after DMM. The mice were euthanized for the collection of knee joints at 16 weeks after DMM. The progressive process of articular cartilage degeneration was significantly delayed in the knee joints of Ddr2-deficient mice in comparison to their control littermates. Articular cartilage damage in the knee joints of the mice was associated with increased expression profiles of both Ddr2 and matrix metalloproteinase 13. These findings suggest that DDR2 may be an ideal target for the development of disease-modifying OA drugs.

Perceived stigma and depression among caregivers of patients with bipolar disorder.

This study investigates the associations between perceived stigma, depressive symptoms and coping among caregivers of people with bipolar disorder. Caregivers of 500 people with DSM-IV bipolar disorder responded to measures of these constructs at study entry. Patients' clinical and functional status were evaluated within 30 days of the caregiver assessment. Perceived stigma was positively associated with caregiver depressive symptoms, controlling for patient status and socio-demographic factors. Social support and avoidance coping accounted for 63% of the relationship between caregiver stigma and depression. Results suggest that caregivers' perceptions of stigma may negatively affect their mental health by reducing their coping effectiveness.

The economics of squamous cell carcinoma of the head and neck.

PURPOSE OF REVIEW: The current review presents a brief overview of the recent literature on the costs of squamous cell carcinoma of the head and neck (SCCHN), one of the most common forms of cancer. SCCHN is a relatively deadly disease. Approximately 50% of patients survive to 5 years, and surgery and chemoradiotherapy can leave survivors with pain, disfigurement, and disability that further add to the burden of the disease. RECENT FINDINGS: Earlier diagnosis of SCCHN increases the likelihood of treating with a single modality, lowers the risk of mortality, decreases medical expenditures, and improves patients' quality of life. Unfortunately, more than one-half of new cases of oral cancer are diagnosed at an advanced stage. Patients with SCCHN have been shown to use significantly more healthcare resources than similar patients without SCCHN, with resource use varying by cancer stage. SUMMARY: Although there have been a number of treatment innovations for SCCHN in the past 5 years, the lack of economic data complicates the task of evaluating these new interventions. In this time of mounting concerns over healthcare costs, more emphasis on economic data is clearly warranted.