The FOXP3+ Pro-Inflammatory T Cell: A Potential Therapeutic Target in Crohn's Disease.

BACKGROUND & AIMS: The incidence of Crohn's disease (CD) continues to increase worldwide. The contribution of CD4+ cell populations remains to be elucidated. We aimed to provide an in-depth transcriptional assessment of CD4+ T cells driving chronic inflammation in CD. METHODS: We performed single-cell RNA-sequencing in CD4+ T cells isolated from ileal biopsies of patients with CD compared with healthy individuals. Cells underwent clustering analysis, followed by analysis of gene signaling networks. We overlapped our differentially expressed genes with publicly available microarray data sets and performed functional in vitro studies, including an in vitro suppression assay and organoid systems, to model gene expression changes observed in CD regulatory T (Treg) cells and to test predicted therapeutics. RESULTS: We identified 5 distinct FOXP3+ regulatory Treg subpopulations. Tregs isolated from healthy controls represent the origin of pseudotemporal development into inflammation-associated subtypes. These proinflammatory Tregs displayed a unique responsiveness to tumor necrosis factor-α signaling with impaired suppressive activity in vitro and an elevated cytokine response in an organoid coculture system. As predicted in silico, the histone deacetylase inhibitor vorinostat normalized gene expression patterns, rescuing the suppressive function of FOXP3+ cells in vitro. CONCLUSIONS: We identified a novel, proinflammatory FOXP3+ T cell subpopulation in patients with CD and developed a pipeline to specifically target these cells using the US Food and Drug Administration-approved drug vorinostat.

Facilitators and barriers to adherence to medical recommendations among adolescents with cancer: A systematic review.

We aimed to systematically review barriers/facilitators of adherence among adolescents with cancer (aged 10-24 years), following a comprehensive approach to adherence that goes beyond medication-taking. Empirical studies published in English exploring determinants of adherence to medical recommendations among adolescents with cancer were identified in MEDLINE, PsycInfo, and Web of Science, up to October 2021. Records and full-text articles were reviewed by two independent reviewers, and results were classified according to the World Health Organization's (WHO) multidimensional adherence model. Eighteen studies were included. Despite heterogeneity in the definition and measurement of adherence, literature supported barriers/facilitators at patient, treatment, condition, healthcare team/system, and social/economic levels. Specifically, patient-related factors (i.e., psychological functioning and beliefs about disease and treatment) and social-related factors (i.e., family functioning) were major determinants of adolescent adherence. Few studies were conducted, and inconsistent findings were displayed for other dimensions (i.e., healthcare team/system, treatment, and condition-related factors). Adherence is a complex and multidetermined phenomenon. More research is needed to provide critical insights for policymakers and healthcare professionals in planning practices and interventions that effectively address meaningful barriers/facilitators of adolescents' adherence.

Active tuberculosis in inflammatory bowel disease patients: a case-control study.

Background/Aims: Anti-tumor necrosis factor (anti-TNF) drugs have been the mainstay therapy for moderate to severe inflammatory bowel disease (IBD) over the past 25 years. Nevertheless, these drugs are associated with serious opportunistic infections like tuberculosis (TB). Brazil is ranked among the 30 countries with the highest incidence of TB in the world. This study aimed at identifying risk factors for the development of active TB and describing clinical characteristics and outcomes in IBD patients followed at a tertiary referral center in Brazil. Methods: We conducted a retrospective, case-control study between January 2010 and December 2021. Active TB cases in IBD patients were randomly matched 1:3 to controls (IBD patients with no previous history of active TB) according to gender, age, and type of IBD. Design: This was a retrospective, case-control study. Results: A total of 38 (2.2%) cases of TB were identified from 1760 patients under regular follow-up at our outpatient clinics. Of the 152 patients included in the analysis (cases and controls), 96 (63.2%) were male, and 124 (81.6%) had Crohn's disease. Median age at TB diagnosis was 39.5 [interquartile range (IQR) 30.8-56.3]. Half of the active TB cases were disseminated (50%). Overall, 36 patients with TB (94.7%) were being treated with immunosuppressive medications. Of those, 31 (86.1%) were under anti-TNF drugs. Diagnosis of TB occurred at a median of 32 months after the first dose of anti-TNF (IQR 7-84). In multivariate analysis, IBD diagnosis older than 17 years and anti-TNF therapy were significantly associated with the development of TB (p < 0.05). After the TB treatment, 20 (52.7%) patients received anti-TNF therapy, and only one developed 'de novo' TB 10 years after the first infection. Conclusions: TB remains a significant health problem in IBD patients from endemic regions, especially those treated with anti-TNFs. In addition, age at IBD diagnosis (>17 years old) was also a risk factor for active TB. Most cases occur after long-term therapy, suggesting a new infection. The reintroduction of anti-TNFs agents after the anti-TB treatment seems safe. These data highlight the importance of TB screening and monitoring in IBD patients living in endemic areas.

Efficacy of Early Optimization of Infliximab Guided by Therapeutic Drug Monitoring during Induction-A Prospective Trial.

Therapeutic drug monitoring (TDM) during induction therapy with anti-tumor necrosis factor drugs has emerged as a strategy to optimize response to these biologics and avoid undesired outcomes related to inadequate drug exposure. This study aimed to describe clinical, biological, and endoscopic remission rates at six months in Brazilian inflammatory bowel disease (IBD) patients following a proactive TDM algorithm guided by IFX trough levels (ITL) and antibodies to IFX (ATI) levels during induction, at week six. A total of 111 IBD patients were prospectively enrolled, excluding those previously exposed to the drug. ITL ≥ 10 µg/mL was considered optimal. Patients with suboptimal ITL (<10 µg/mL) were guided according to ATI levels. Those who presented ATI ≤ 200 ng/mL underwent dose intensification in the maintenance phase, and patients with ATI > 200 ng/mL discontinued IFX. In our study, proactive TDM was associated with persistence in the IFX rate at six months of 82.9%. At that time, rates of clinical, biological, and endoscopic remission in patients under IFX treatment were 80.2%, 73.9%, and 48.1%, respectively. Applying a simplified TDM-guided algorithm during induction seems feasible and can help improve patients' outcomes in clinical practice.

Impacto de uma colônia de férias para adolescentes com diabetes tipo 1: estudo longitudinal / Impacto de una colonia de vacaciones para adolescentes con diabetes tipo 1: estudio longitudinal / Impact of a summer camp for adolescents with type 1 diabetes: longitudinal study

RESUMO Objetivo: caracterizar adolescentes com diabetes tipo 1, frequentadores de uma colônia de férias, e sua evolução nas dimensões do conhecimento acerca da doença, na autoeficácia, qualidade de vida e hemoglobina glicada. Método: estudo quantitativo comparativo antes e após o campo, com seguimento de seis meses. Foram avaliados o conhecimento (teste de conhecimentos acerca da diabetes), aautoeficácia (self-efficacy diabetes scale), a qualidade de vida (disabkids chronic generic measure) e a hemoglobina glicada, em três momentos, de 2018 a 2019, em 30 adolescentes com diabetes dos 15 aos 18 anos, que participaram numacolônia de férias. Resultados: os adolescentes apresentavam inicialmente conhecimento global elevado (>80%) na área do exercício físico, hipoglicemia e complicações da diabetes, e inferior a 60% sobre conservação de insulina, substituição de lanceta, refeições, monitorização de glicose, vômitos, diarréia e consumo de bebidas alcoólicas. Os níveis de autoeficácia social aumentaram após a colônia, contudo não se mantiveram após seis meses. Não se observaram alterações nos valores da hemoglobina glicadae na qualidade de vida após a colônia. Conclusão: acolônia produziu efeito na autoeficácia social, contudo, não se pode afirmar impacto ao nível dos conhecimentos e qualidade de vida dos participantes. Os resultados sugerem a implementação de programas estruturados, com foco na promoção da autogestão da diabetes.

RESUMEN Objetivo: caracterizar adolescentes con diabetes tipo 1, frecuentadores de una colonia de vacaciones, y su evolución en las dimensiones del conocimiento acerca de la enfermedad, en la autoeficacia, calidad de vida y hemoglobina glicosilada. Método: estudio comparativo cuantitativo antes y después del campo, con un seguimiento de seis meses. Fueron evaluados el conocimiento (test de conocimientos acerca de la diabetes), la autoeficacia (self-efficacy diabetes Scale), la calidad de vida (disabkids Chronic Generic Measure) y la hemoglobina glicosilada, en tres momentos, de 2018 a 2019, en 30 adolescentes con diabetes de 15 a 18 años que participaron en una colonia de vacaciones. Resultados: los adolescentes presentaban inicialmente conocimiento global elevado (>80%) en el área del ejercicio físico, hipoglucemia y complicaciones de la diabetes, e inferior a 60% sobre conservación de insulina, sustitución de lanceta, comidas, monitoreo de glucosa, vómitos, diarrea y consumo de alcohol. Los niveles de autoeficacia social aumentaron después de la colonia, pero no se mantuvieron después de seis meses. No se observaron alteraciones en los valores de la hemoglobina glicosilada y en la calidad de vida después de la colonia. Conclusión: la colonia ha producido efecto en la autoeficacia social, sin embargo, no se puede afirmar impacto al nivel de los conocimientos y calidad de vida de los participantes. Los resultados sugieren la implementación de programas estructurados, con enfoque en la promoción de la autogestión de la diabetes.

ABSTRACT Objective: to characterize adolescents with type 1 diabetes, frequenters of a summer camp, and their evolution in the dimensions of knowledge about the disease, self-efficacy, quality of life and glycated hemoglobin. Method: quantitative comparative study before and after the field, with follow-up of six months. Knowledge (test of knowledge about diabetes), self-efficacy (self-efficacy diabetes scale), quality of life (disabkids chronic generic measure) and glycated hemoglobin were evaluated in three moments, from 2018 to 2019, in 30 adolescents with diabetes aged 15 to 18, who participated in a summer camp. Results: the adolescents initially had high overall knowledge (>80%) in the area of physical exercise, hypoglycemia and complications of diabetes, and less than 60% on insulin conservation, lancet replacement, meals, glucose monitoring, vomiting, diarrhea and alcohol consumption. Levels of social self-efficacy increased after the colony, but did not continue after six months. There were no changes in the values of glycated hemoglobin and quality of life after the colony. Conclusion: the colony produced an effect on social self-efficacy, however, there is no impact on the level of knowledge and quality of life of the participants. The results suggest the implementation of structured programs focused on promoting diabetes self-management.

A Novel FGFR1 Missense Mutation in a Portuguese Family with Congenital Hypogonadotropic Hypogonadism.

Congenital hypogonadotropic hypogonadism (CHH) is a rare reproductive endocrine disorder characterized by complete or partial failure of pubertal development and infertility due to deficiency of the gonadotropin-releasing hormone (GnRH). CHH has a significant clinical heterogeneity and can be caused by mutations in over 30 genes. The aim of this study was to investigate the genetic defect in two siblings with CHH. A woman with CHH associated with anosmia and her brother with normosmic CHH were investigated by whole exome sequencing. The genetic studies revealed a novel heterozygous missense mutation in the Fibroblast Growth Factor Receptor 1 (FGFR1) gene (NM_023110.3: c.242T>C, p.Ile81Thr) in the affected siblings and in their unaffected father. The mutation affected a conserved amino acid within the first Ig-like domain (D1) of the protein, was predicted to be pathogenic by structure and sequence-based prediction methods, and was absent in ethnically matched controls. These were consistent with a critical role for the identified missense mutation in the activity of the FGFR1 protein. In conclusion, our identification of a novel missense mutation of the FGFR1 gene associated with a variable expression and incomplete penetrance of CHH extends the known mutational spectrum of this gene and may contribute to the understanding of the pathogenesis of CHH.

Cell Type-Specific Induction of Inflammation-Associated Genes in Crohn's Disease and Colorectal Cancer.

Based on the rapid increase in incidence of inflammatory bowel disease (IBD), the identification of susceptibility genes and cell populations contributing to this condition is essential. Previous studies suggested multiple genes associated with the susceptibility of IBD; however, due to the analysis of whole-tissue samples, the contribution of individual cell populations remains widely unresolved. Single-cell RNA sequencing (scRNA-seq) provides the opportunity to identify underlying cellular populations. We determined the enrichment of Crohn's disease (CD)-induced genes in a publicly available Crohn's disease scRNA-seq dataset and detected the strongest induction of these genes in innate lymphoid cells (ILC1), highly activated T cells and dendritic cells, pericytes and activated fibroblasts, as well as epithelial cells. Notably, these genes were highly enriched in IBD-associated neoplasia, as well as sporadic colorectal cancer (CRC). Indeed, the same six cell populations displayed an upregulation of CD-induced genes in a CRC scRNA-seq dataset. Finally, after integrating and harmonizing the CD and CRC scRNA-seq data, we demonstrated that these six cell types display a gradual increase in gene expression levels from a healthy state to an inflammatory and tumorous state. Together, we identified cell populations that specifically upregulate CD-induced genes in CD and CRC patients and could, therefore, contribute to inflammation-associated tumor development.

Family caregiver grief and post-loss adjustment: A longitudinal cohort study.

OBJECTIVE: In order to better understand the different grieving trajectories of the family caregivers (FCs), this study aims to examine the evolution of prolonged grief disorder (PGD) symptoms and the predictive role of the caregiving-related factors in the FCs' grieving trajectory from pre- to post-death. METHOD: A prospective cohort study was carried out with advanced cancer FCs evaluated before death (T1) and 6-12 months post-loss (T2). RESULTS: Participants in T1 (n = 156) were mostly female, adult child, or spouse of the care recipient, with a mean age of 51.78 (SD = 13.29). At T2, 87 FCs participated in the survey. PGD prevalence was higher pre-death (38.6%) than in bereavement (33.7%). Of those who met the PGD criteria before death, most also met these criteria after death (n = 26, 61.9%). Psychological distress and caregiver burden were highly correlated with pre-death grief, which in turn played a critical role in mediating the link between psychological distress and bereavement outcome. Great emotional closeness in the relationship was predictive of PGD symptoms persistence. In contrast, the long-term consequences of caregiver burden were not confirmed. SIGNIFICANCE OF RESULTS: This study provides evidence for the diversity of individual FC responses and the complex pattern of interactions between caregiving-related factors, relationship quality, and PGD symptoms evolution from pre- to post-death.

Peritoneal Chlamydia trachomatis Infection as a Cause of Ascites: A Diagnosis Not to Be Missed.

Ascites is a common complication of several conditions, but it is rare in cases of Chlamydia trachomatis infection. We report a 36-year-old patient presenting with abdominal swelling for a week prior to hospitalization. An extensive workup excluded liver or heart disease and malignancy. A computed tomography scan demonstrated massive ascites and severe thickening of peritoneal reflections. Laboratory tests showed low serum-ascites albumin gradient, high total protein, and low adenosine. Diagnostic laparoscopy revealed inflammatory signs of both fallopian tubes. The histopathological results from peritoneal biopsy were consistent with lymphoid proliferation with reactive lymphoplasmacytic infiltrate. A gynecological investigation showed a positive DNA for C. trachomatis in the cervical swab. After treatment with doxycycline, there was a complete resolution of ascites.

Late diagnosis of classic congenital adrenal hyperplasia: long-term consequences during adulthood.

SUMMARY: Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders related to enzyme deficiencies in the adrenal steroidogenesis pathway leading to impaired corticosteroid biosynthesis. Depending on the extension of enzyme defect, there may be variable severities of CAH - classic and non-classic. We report the case of a 37-year-old male patient with a previously unknown diagnosis of classic CAH referred to Endocrinology evaluation due to class III obesity and insulin resistance. A high diagnostic suspicion was raised at the first Endocrinology consultation after careful past medical history analysis especially related to the presence of bilateral adrenal myelolipomas and primary infertility. A genetic test confirmed the presence of a variant of the CYP21A2 in homozygous with an enzymatic activity of 0-1%, corresponding to a classic and severe CAH form. Our case represents an unusually late definitive diagnose of classic CAH since the definition was established only during adulthood in the fourth decade of life. The missing diagnosis of classic 21 hydroxylase deficiency during infancy led to important morbidity, with a high impact on patients' quality of life. LEARNING POINTS: Congenital adrenal hyperplasia (CAH) refers to a group of autosomal recessive enzyme disorders responsible for an impaired cortical adrenal hormonal synthesis. CAH may be divided into two major forms: classic and non-classic CAH. If untreated, CAH may be fatal or may be responsible for important multi-organ long-term consequences that can be undervalued during adulthood. Adrenal myelolipomas are associated with chronic exposure to high ACTH levels and continuous androgen hyperstimulation typically found in undertreated CAH patients. Testicular adrenal rest tumours (TART) and primary infertility can be the first manifestation of the disease during adulthood.

Assessing the Relationship between PTSS in Childhood Cancer Survivors and Their Caregivers and Their Quality of Life.

Childhood cancer is a traumatic experience for survivors and their families. The experience of this disease affects survivors' and families' quality of life, even years after it occurs. The purpose of the present study was to assess if the caregivers' posttraumatic stress symptoms mediated the associations between survivors' posttraumatic stress symptoms and caregivers' quality of life, in a sample of 46 dyads of caregivers and childhood cancer survivors. Survivors and caregivers completed the PCL-5, and caregivers completed the WHOQOL-bref. Results showed that survivors' and caregivers' posttraumatic stress symptoms scores and caregivers' quality of life were associated. The caregivers' posttraumatic stress symptoms mediated the relationship between survivors' posttraumatic stress symptoms and caregivers' quality of life. Knowing posttraumatic stress symptoms direct and indirect effects on caregivers' quality of life contributes to understand their experience and to develop intervention strategies with this population.

Microbiota intestinal, prebióticos, probióticos e simbióticos em doenças gastrointestinais e hepáticas: procedimentos de reunião conjunta da Sociedade Brasileira de Hepatologia (SBH), Núcleo Brasileiro de Estudos do Helicobacter pylori e Microbiota (NBEHPM) e Federação Brasileira de Gastroenterologia (FBG) / Gut microbiota, prebiotics, probiotics, and synbiotics in gastrointestinal and liver diseases: proceedings of a joint meeting of the brazilian society of hepatology (sbh), brazilian nucleus for the study of helicobacter pylori and microbiota (nbehpm), and brazilian federation of gastroenterology (fbg)

ABSTRACT Over the last years, there is growing evidence that microorganisms are involved in the maintenance of our health and are related to various diseases, both intestinal and extraintestinal. Changes in the gut microbiota appears to be a key element in the pathogenesis of hepatic and gastrointestinal disorders, including non-alcoholic fatty liver disease, alcoholic liver disease, liver cirrhosis, inflammatory bowel disease, irritable bowel syndrome, and Clostridium difficile - associated diarrhea. In 2019, the Brazilian Society of Hepatology (SBH) in cooperation with the Brazilian Nucleus for the Study of Helicobacter Pylori and Microbiota (NBEHPM), and Brazilian Federation of Gastroenterology (FBG) sponsored a joint meeting on gut microbiota and the use of prebiotics, probiotics, and synbiotics in gastrointestinal and liver diseases. This paper summarizes the proceedings of the aforementioned meeting. It is intended to provide practical information about this topic, addressing the latest discoveries and indicating areas for future studies.

RESUMO Nos últimos anos, um volume crescente de evidências indica que os microrganismos estão envolvidos na manutenção da saúde humana e também estão relacionados a várias doenças, tanto intestinais quanto extraintestinais. Alterações na microbiota intestinal parecem ser um elemento chave na patogênese de doenças hepáticas e gastrointestinais, incluindo doença hepática gordurosa não-alcoólica, doença hepática alcoólica, cirrose hepática, doenças inflamatórias intestinais, síndrome do intestino irritável e diarreia associada ao Clostridium difficile. Em 2019, a Sociedade Brasileira de Hepatologia (SBH) em colaboração com o Núcleo Brasileiro para Estudo do Helicobacter pylori e Microbiota (NBEHPM) e a Federação Brasileira de Gastroenterologia (FBG) realizaram um encontro exclusivamente voltado para a discussão sobre microbiota e uso de prebióticos, probióticos e simbióticos em doenças hepáticas e gastrointestinais. Este texto resume os principais pontos discutidos durante o evento, e tem a intenção de fornecer informações práticas sobre o assunto, abordando as descobertas mais recentes e indicando áreas para estudos futuros.

The use of 5-aminosalicylate for patients with Crohn's disease in a prospective European inception cohort with 5 years follow-up - an Epi-IBD study.

BACKGROUND: The lack of scientific evidence regarding the effectiveness of 5-aminosalicylate in patients with Crohn's disease is in sharp contrast to its widespread use in clinical practice. AIMS: The aim of the study was to investigate the use of 5-aminosalicylate in patients with Crohn's disease as well as the disease course of a subgroup of patients who were treated with 5-aminosalicylate as maintenance monotherapy during the first year of disease. METHODS: In a European community-based inception cohort, 488 patients with Crohn's disease were followed from the time of their diagnosis. Information on clinical data, demographics, disease activity, medical therapy and rates of surgery, cancers and deaths was collected prospectively. Patient management was left to the discretion of the treating gastroenterologists. RESULTS: Overall, 292 (60%) patients with Crohn's disease received 5-aminosalicylate period during follow-up for a median duration of 28 months (interquartile range 6-60). Of these, 78 (16%) patients received 5-aminosalicylate monotherapy during the first year following diagnosis. Patients who received monotherapy with 5-aminosalicylate experienced a mild disease course with only nine (12%) who required hospitalization, surgery, or developed stricturing or penetrating disease, and most never needed more intensive therapy. The remaining 214 patients were treated with 5-aminosalicylate as the first maintenance drug although most eventually needed to step up to other treatments including immunomodulators (75 (35%)), biological therapy (49 (23%)) or surgery (38 (18%)). CONCLUSION: In this European community-based inception cohort of unselected Crohn's disease patients, 5-aminosalicylate was commonly used. A substantial group of these patients experienced a quiescent disease course without need of additional treatment during follow-up. Therefore, despite the controversy regarding the efficacy of 5-aminosalicylate in Crohn's disease, its use seems to result in a satisfying disease course for both patients and physicians.

Health-care costs of inflammatory bowel disease in a pan-European, community-based, inception cohort during 5 years of follow-up: a population-based study.

BACKGROUND: Inflammatory bowel disease (IBD) places a significant burden on health-care systems because of its chronicity and need for expensive therapies and surgery. With increasing use of biological therapies, contemporary data on IBD health-care costs are important for those responsible for allocating resources in Europe. To our knowledge, no prospective long-term analysis of the health-care costs of patients with IBD in the era of biologicals has been done in Europe. We aimed to investigate cost profiles of a pan-European, community-based inception cohort during 5 years of follow-up. METHODS: The Epi-IBD cohort is a community-based, prospective inception cohort of unselected patients with IBD diagnosed in 2010 at centres in 20 European countries plus Israel. Incident patients who were diagnosed with IBD according to the Copenhagen Diagnostic Criteria between Jan 1, and Dec 31, 2010, and were aged 15 years or older the time of diagnosis were prospectively included. Data on clinical characteristics and direct costs (investigations and outpatient visits, blood tests, treatments, hospitalisations, and surgeries) were collected prospectively using electronic case-report forms. Patient-level costs incorporated procedures leading to the initial diagnosis of IBD and costs of IBD management during the 5-year follow-up period. Costs incurred by comorbidities and unrelated to IBD were excluded. We grouped direct costs into the following five categories: investigations (including outpatient visits and blood tests), conventional medical treatment, biological therapy, hospitalisation, and surgery. FINDINGS: The study population consisted of 1289 patients with IBD, with 1073 (83%) patients from western Europe and 216 (17%) from eastern Europe. 488 (38%) patients had Crohn's disease, 717 (56%) had ulcerative colitis, and 84 (6%) had IBD unclassified. The mean cost per patient-year during follow-up for patients with IBD was €2609 (SD 7389; median €446 [IQR 164-1849]). The mean cost per patient-year during follow-up was €3542 (8058; median €717 [214-3512]) for patients with Crohn's disease, €2088 (7058; median €408 [133-1161]) for patients with ulcerative colitis, and €1609 (5010; median €415 [92-1228]) for patients with IBD unclassified (p<0·0001). Costs were highest in the first year and then decreased significantly during follow-up. Hospitalisations and diagnostic procedures accounted for more than 50% of costs during the first year. However, in subsequent years there was a steady increase in expenditure on biologicals, which accounted for 73% of costs in Crohn's disease and 48% in ulcerative colitis, in year 5. The mean annual cost per patient-year for biologicals was €866 (SD 3056). The mean yearly costs of biological therapy were higher in patients with Crohn's disease (€1782 [SD 4370]) than in patients with ulcerative colitis (€286 [1427]) or IBD unclassified (€521 [2807]; p<0·0001). INTERPRETATION: Overall direct expenditure on health care decreased over a 5-year follow-up period. This period was characterised by increasing expenditure on biologicals and decreasing expenditure on conventional medical treatments, hospitalisations, and surgeries. In light of the expenditures associated with biological therapy, cost-effective treatment strategies are needed to reduce the economic burden of inflammatory bowel disease. FUNDING: Kirsten og Freddy Johansens Fond and Nordsjællands Hospital Forskningsråd.

Family Caregivers' Anticipatory Grief: A Conceptual Framework for Understanding Its Multiple Challenges.

The end-of-life trajectory of cancer patients in palliative care (PC) elicits an anticipatory grief (AG) process in family caregivers (FCs). Although widely recognized, AG lacks conceptual clarification. This study aims to qualitatively explore the experience of FCs of patients with terminal cancer to identify the core characteristics and the specific adaptive challenges related to AG in the context of end-of-life caregiving. Data were collected through in-depth semi-structured interviews conducted in a clinical sample of 26 FCs of cancer patients in PC. Findings from thematic analysis suggest that the AG experience is characterized by traumatic distress from being exposed to life-threatening conditions and the separation distress induced by loss anticipation and current relational losses, challenging the FCs to long-term emotional regulation effort demands. These results contribute to the conceptualization of AG and may inform intervention programs for the main challenges the FCs face when adjusting to loss during end-of-life caregiving.

Do parents of children with cancer want to participate in treatment decision-making?

PURPOSE: This study aimed to describe parents' preferences regarding their role in treatment decision-making when a child has cancer and examines whether their preferences were related to parents sociodemographic characteristics (sex and education level), patients' characteristics (age group and treatment status), and healthcare context features (parents' perception of family-centered care). METHODS: Two hundred and twenty-eight parents of children/adolescents with cancer were recruited from two Portuguese pediatric oncology wards. Participants provided sociodemographic and clinical information. The Control Preferences Scale for Pediatrics was used to assess the parents' preferred role in treatment decision-making. The Measure of Process of Care assessed the parents' perception of family-centered care (family-centered services and providing general information subscales). RESULTS: Results showed that parents preferred a passive-collaborative role (45.2%), followed by collaborative (27.2%), passive (21.0%), and active-collaborative (6.6%). None preferred an active role. Chi-square test showed that the group of parents preferring a passive role had a lower proportion of more-educated parents, compared to those preferring active-collaborative or collaborative roles. Additionally, groups did not proportionally differ according to the parents' sex, patients' age, and treatment status. A multivariate analysis of variance showed that parents preferring an active-collaborative role reported lower mean scores on family-centered services compared to those preferring passive-collaborative and passive roles. Finally, no significant differences were found concerning providing general information. CONCLUSIONS: This study's findings may guide professionals in identifying parents' preferences regarding their participation in treatment decision-making process. Mapping their preferences may support professionals in promoting desirable levels of parental involvement in decisions in pediatric oncology context.

Management of inflammatory bowel disease patients in the COVID-19 pandemic era: a Brazilian tertiary referral center guidance

The world is fighting the COVID-19 outbreak and health workers, including inflammatory bowel diseases specialists, have been challenged to address the specific clinical issues of their patients. We hereby summarize the current literature in the management of inflammatory bowel disease (IBD) patients during the COVID-19 pandemic era that support the rearrangement of our IBD unit and the clinical advice provided to our patients.

Preferências dos adolescentes sobre os cuidados de saúde / Adolescents' preferences regarding health care

Resumo Os adolescentes subutilizam os serviços de saúde sobretudo para efeitos de vigilância, o que constitui uma preocupação para os profissionais. Porque a adolescência é uma fase crucial à aquisição de comportamentos saudáveis e de atitudes facilitadoras do acesso a estes serviços, por isso encontrar formas de responder às necessidades específicas dos adolescentes, através da sua participação, constitui um importante investimento no bem-estar das gerações futuras. Este estudo exploratório e descritivo, de natureza qualitativa, com duas fases, teve como objetivos identificar e analisar as ideias e preferências dos adolescentes sobre os cuidados de saúde. Realizaram-se oito entrevistas de grupo com 64 adolescentes dos 13 aos 18 anos: quatro grupos focais (fase 1) e quatro grupos nominais (fase 2). Os dados foram tratados através da análise de conteúdo. Emergiram opiniões favoráveis e desfavoráveis. Nas suas preferências destacaram-se, nas condições dos serviços, haver menos tempo de espera e ambientes mais confortáveis e menos lotados; nas atitudes dos profissionais privilegiaram as competências técnicas, como o saber e a experiência, embora associadas às competências relacionais. Os resultados suportam a necessidade de mudanças nas práticas organizacionais e sobretudo nas atitudes dos profissionais.

Abstract Adolescents underutilize health services, especially for monitoring purposes, which represents a concern for professionals. Since adolescence is a crucial phase in acquiring healthy behaviors and attitudes that facilitate access to these services, finding ways to respond to the specific needs of adolescents through their participation is an important investment in the well-being of future generations. This is an exploratory, descriptive and qualitative study with two phases, seeking to identify and analyze adolescents' ideas and preferences about healthcare. Eight group interviews were conducted with 64 adolescents aged 13 to 18 years: four focus groups (phase 1) and four nominal groups (phase 2). The data was submitted to content analysis. The adolescents revealed both favorable and unfavorable opinions, highlighting a set of preferences regarding service conditions, such as short waiting periods, more comfortable and less crowded settings. Concerning the professionals' attitudes, they emphasized their technical competencies, such as knowledge and experience, although combined with interpersonal skills. These findings support the need for changes in organizational practices, and particularly in the attitudes of the professionals.

Parents' psychological well-being when a child has cancer: Contribution of individual and family factors.

OBJECTIVE: The aim of this study was to examine the contribution of individual (positive reappraisal) and family factors (parenting satisfaction, couple relationship quality, and family life difficulty) to the psychological well-being (PWB) of parents of children/adolescents diagnosed with cancer. METHODS: This cross-sectional study was conducted at two pediatric oncology wards in Portugal. Two-hundred and five parents of pediatric patients with cancer completed self-report questionnaires assessing the use of positive reappraisal as a coping strategy, parenting satisfaction, relationship quality, family life difficulty, and PWB. Sociodemographic and clinical data were also assessed. RESULTS: Standard multiple regression analysis showed a significant contribution of both individual- and family-level factors to parents' PWB. Specifically, the use of positive reappraisal as a coping strategy, parenting satisfaction, and relationship quality were associated with higher PWB; conversely, family life difficulty was linked to lower PWB. Sociodemographic (child's age and family's socioeconomic status) and clinical variables (time since diagnosis and treatment status) were not associated with PWB. CONCLUSIONS: The present study identified potential resources for parents' adaptation to this stressful situation, contributing with insightful conclusions for both research and clinical practice. Screening and addressing both individual- and family-level aspects may be crucial to foster parents' well-being when a child is diagnosed with cancer.

Child and family characteristics are associated with a dietary variety index in 4-year-old children from the Generation XXI cohort.

This study aims to assess dietary variety and adequacy and their associated factors in 4-year-old children. The hypothesis under study is that poor early life characteristics and a deprived family background may be associated with lower dietary variety and adequacy at 4 years of age. The study participants were from a population-based birth cohort: Generation XXI (2005/2006, northern Portugal). Data were collected by trained interviewers at birth (eg, type of delivery, gestational age, birth weight, maternal age, education, smoking during pregnancy, and self-reported weight status before pregnancy) and at 4 years of age (behaviors, family background, and weight status). Diet was assessed by a food frequency questionnaire, and a Healthy Dietary Variety Index was calculated considering variety and adequacy within and among 5 food groups (starchy foods; fruit; vegetables; meat, fish and alternatives; and dairy foods) (score: 0 to 1). General linear models were run (ß̂ coefficients and the respective 95% confidence intervals [CIs], adjusted for child's sex, maternal age, and education) (n = 3962). Lower dietary variety and adequacy at 4 years of age were associated with more screen time (≥120 vs <120 min/d: ß̂ = -0.012, 95% CI: -0.019 to 0.004), no regular participation in sports (ß̂ = -0.022, 95% CI: -0.029 to -0.014), underweight status (ß̂ = -0.081, 95% CI: -0.130 to -0.032), shorter breastfeeding duration (<4 vs ≥6 months: ß̂ = -0.012, 95% CI: -0.019 to -0.005), no siblings (0 vs ≥2: ß̂ = -0.023, 95% CI: -0.034 to -0.011), and a 2-parent family structure (vs single-parent: ß̂ = -0.010, 95% CI: -0.021 to -0.001). Children of less educated and less physically active mothers also had lower dietary variety and adequacy. In conclusion, several factors are associated with lower dietary variety and adequacy, including early life determinants, such as shorter breastfeeding duration, but also poor lifestyle choice and family characteristics appear to play a major role.