Tumor-associated changes in intestinal epithelial cells cause local accumulation of KLRG1(+) GATA3(+) regulatory T cells in mice

CD4(+) Foxp3(+) regulatory T cells (Treg) include differentiated populations of effector Treg characterized by the expression of specific transcription factors. Tumors, including intestinal malignancies, often present with local accumulation of Treg that can prevent tumor clearance, but how tumor progression leads to Treg accumulation is incompletely understood. Here using genetically modified mouse models we show that ablation of E-cadherin, a process associated with epithelial to mesenchymal transition (EMT) and tumor progression, promotes the accumulation of intestinal Treg by the specific accumulation of the KLRG1(+) GATA3(+) Treg subset. Epithelial E-cadherin ablation activates the β-catenin pathway, and we find that increasing β-catenin signals in intestinal epithelial cells also boosts Treg frequencies through local accumulation of KLRG1(+) GATA3(+) Treg. Both E-cadherin ablation and increased β-catenin signals resulted in epithelial cells with higher levels of IL-33, a cytokine that preferentially expands KLRG1(+) GATA3(+) Treg. Tumors often present reduced E-cadherin expression and increased β-catenin signaling and IL-33 production. Accordingly, Treg accumulation in intestinal tumors from APC(min/+) mice was exclusively due to the increase in KLRG1(+) GATA3(+) Treg. Our data identify a novel axis through which epithelial cells control local Treg cell subsets, which may be activated during intestinal tumorigenesis

Health-related quality of life and chronic wound characteristics among patients with chronic wounds treated in primary care: A cross-sectional study in Singapore.

Chronic wounds commonly decrease patients' quality of life. Understanding how chronic wounds impact a patient's health-related quality of life (HRQoL) is important for healthcare service delivery and treatment management. This study explored HRQoL among patients suffering from chronic wounds and investigated associations with patients' socio-demographics and wound characteristics. Two hundred and thirty-three patients across six primary care clinics were assessed and responded to a survey that collected information on socio-demographic, wound characteristics, and HRQoL using the EQ-5D-5L instrument. Data were analysed by descriptive statistics and generalised linear models. The mean age of patients was 61.2 (SD: 14.6) years; 68.2% were males; and 61.8% were of Chinese origin. Arterial ulcers had the greatest negative impact on HRQoL related to mobility, self-care, pain/discomfort and anxiety/depression, and the lowest VAS mean score 62.31 (SD: 28.3; range: 0-100) indicating the worst health. HRQoL related to mobility was significantly associated with age (β = 0.008, P < .001), non-Chinese ethnicity (β = 0.25, P = .001), mixed ulcers (β = -0.41, P = .022), atypical hard-to-heal wounds (β = -0.38, P = .021), wounds with low (β = 0.24, P = .044) to moderate (β = 0.29, P = .018) exudate level, and a wound duration ≥6 months (β = 0.19, P = .033). The findings can be used to improve healthcare delivery for patients with chronic wound to optimise their HRQoL

The humanistic and economic burden of chronic wounds: a protocol for a systematic review

Background: Chronic non-healing wounds present a substantial economic burden to healthcare system; significant reductions in quality of life for those affected, and precede often serious events such as limp amputations or even premature deaths. This burden is also likely to increase with a larger proportion of elderly and increasing prevalence of life-style diseases such as obesity and diabetes. Reviews of the evidence on the burden of illness associated with chronic wounds have not been comprehensive in scope and have not provided an assessment of the distribution of the health care costs across categories of resource use. Methods/design: This study is a systematic review of multiple databases for studies on adult patients with chronic wounds and with the primary objective to assess the impact on health-related quality of life by category of ulcers, and associated direct and indirect costs. Eligible studies will primary be empirical studies evaluating, describing or comparing measurement of quality of life and economic impact. Two reviewers will independently screen titles and abstracts and select studies involving adults with chronic wounds. These investigators will also independently extract data using a pre-designed data extraction form. Differences in applied methodologies and uncertainties will clearly be accounted for. Conservative valuations of costs and impact on health-related quality of life will be prioritised. Variations that may depend on age distribution, the categorisation of ulcer, healthcare system etc. will be described clearly. Discussion: The proposed systematic review will yield a comprehensive assessment of the humanistic and economic burden of chronic wounds in an adult population. A better understanding of the humanistic and economic burden of chronic wounds is essential for policy and planning purposes, to monitor trends in disease burden and not at least in order to estimate the real-world cost-effectiveness of new treatments and therapies. Systematic review registration: PROSPERO CRD4201603749

The cost of childhood atopic dermatitis in a multi-ethnic Asian population: a cost-of-illness study.

BACKGROUND: Childhood atopic dermatitis can often have a negative impact on quality of life for affected children and their caregivers. The condition contributes to increased healthcare costs and can pose heavy economic burdens on healthcare systems and societies. OBJECTIVES: The objective of this study is to provide a comprehensive estimate of the economic burden of childhood atopic dermatitis in a Singaporean sample and to investigate associated factors. METHODS: This cross-sectional cost-of-illness study applied a societal perspective. Data was collected between December 2016 and December 2017 in Singapore. Caregivers to children below 16 years of age with physician-confirmed diagnosis of atopic dermatitis were recruited and socio-demographics, clinical characteristics, health service utilisation data and time spent on caregiving were collected from all eligible participants. RESULTS: The average annual cost per child with atopic dermatitis was estimated at US$7,943 (mild US$6,651, moderate US$7,935 and severe US$14,335) in 2017 prices. The major cost was for informal caregiving (46% of the total cost) followed by out-of-pocket expenses (37%). Healthcare utilisation contributed to 17% of the total cost of which 43% was for medications. CONCLUSIONS: Childhood atopic dermatitis imposes substantial costs with a large proportion arising from informal caregiving and out-of-pocket expenses. The cost for atopic dermatitis is also strongly related to disease severity. This information is important for policymakers and other health planners when considering how to better support affected families. This article is protected by copyright. All rights reserved

Factors Influencing Family Burden of Paediatric Patients with Atopic Dermatitis: A Cross-sectional Study

Atopic dermatitis (AD) is a chronic, recurrent inflammatory skin condition that affects about 10–20% of children and 2-15% of adults in developed countries (1). In Singapore, the prevalence among children and adolescents is 20.8% (2). Itchiness, the most common complaint, results in behavioural and social impairments among paediatric AD patients, which in turn impacts on the wellbeing of caregivers, particularly family members (3, 4). A sick child can markedly affect normal family life and the mental and social wellbeing of other family members (5). Their family members, namely parents, may experience feelings of helplessness and stress as they struggle to treat their child’s symptoms, and this can lead to feelings of guilt as they feel they are failing in their duty to care for their offspring (6). In return, family quality of life can greatly influence patient-related outcomes. Previous studies have demonstrated that paediatric atopic eczema can significantly affect family life; however, they provide limited quantitative data on the factors influencing family life and functions (6). Therefore, we conducted this study in an effort to gain in-depth insights into the family burden caused by paediatric AD, and to explore the social and clinical factors potentially impacting family life and function

Societal Burden of Clinically Anxious Youth Referred for Treatment: A Cost-of-illness Study

A prevalence-based cost-of-illness study using a societal perspective was conducted to investigate the cost-of-illness in clinically anxious youth aged 8–18 in The Netherlands. Discriminant validity of the cost diary used was obtained by comparing costs of families with an anxious child (n = 118) to costs of families from the general population (n = 41). To examine the convergent validity, bottom-up acquired costs derived from cost diaries were compared to top-down acquired costs obtained from national registrations. Bottom-up acquired costs measured by means of cost diaries amounted to €2,748 per family of a clinically referred anxious child per annum. Societal costs of families with clinically anxious children were almost 21 times as high compared to families from the general population. With respect to convergent validity, total health care costs using the bottom-up approach from clinically anxious children were quite comparable to those of top-down data of anxious children, although costs within the subcategories differed considerably. Clinical anxiety disorders in childhood cost the Dutch society more than 20 million euros a year. Based on results of discriminate and convergent validity, the cost diary seems a valid method in establishing cost-of-illness in childhood anxiety disorders

Sick Leave and Work Participation Among Parents of Children with Autism Spectrum Disorder in the Stockholm Youth Cohort: A Register Linkage Study in Stockholm, Sweden

This population-based register study explored the association between having a child with/without autism spectrum disorder (ASD) and parental sick leave and work participation. Parents of children with ASD living in Stockholm, Sweden in 2006 were more likely to be on sick leave, not in the labor force, or earning low income when compared to parents who did not have a child with ASD and these results remained after adjusting for familial socioeconomic factors and parental psychiatric care. Sick leave among parents was associated with having a child with ASD without intellectual disability (ID) but not ASD with ID. Although Sweden has policies helping families with children with ASD this study suggests that there exist unmet needs among these parents