The role of 'familiarity' and 'normality' in supporting transition to end of life care in paediatric oncology: A qualitative study.

AIM: The aim of this study was to explore factors that helped when a child with cancer transitioned to end of life care in a hospital setting. DESIGN: Qualitative exploratory design using reflexive thematic analysis. METHODS: In-depth, semi-structured interviews were carried out with 7 sets of bereaved parents and 10 health professionals from one specialist paediatric oncology centre. Results were shared with professionals to help shape services in a new children's hospital. RESULTS: Three themes were identified: 'change and facing the unknown', 'the comfort of feeling normal' and 'knowing and being known'. Bereaved parents described a gradual awareness of the deterioration of their child's condition and the need for trust in health professionals. Professionals described the process as challenging but were guided by the needs of children and parents. Supportive and trusting relationships with professionals helped parents to cope with the transition. CONCLUSION: We identified practices that helped create a culture that supported parents and professionals involved in caring for children facing death from cancer. These were rooted in feeling supported and working to provide the best end of life care for children. SUMMARY STATEMENT: Given that the death of a child is a uniquely challenging event, this study indicates that the clinical setting can assist via the promotion of familiarity (supporting families over time) and normality (allowing family-focused activities). These were helpful to parents and to professionals. However, professionals need emotional support when working with these families. REPORTING METHOD: The study adhered to the Consolidated Criteria for Reporting Qualitative Research. PATIENT OR PUBLIC CONTRIBUTION: The project steering group included one bereaved parent (who was not involved in the study), one consultant paediatric oncologist and one hospital chaplain.

Reciprocal Regulation of HSD11B1 and HSD11B2 Predicts Glucocorticoid Sensitivity in Childhood Acute Lymphoblastic Leukemia.

There are few biomarkers to predict efficacy of glucocorticoid treatment in childhood acute lymphoblastic leukemia (ALL) at diagnosis. Here, we demonstrate reciprocal regulation of 11beta-hydroxysteroid dehydrogenase (11ß-HSD), may predict the apoptotic response of ALL to glucocorticoid treatment. Our data may be useful to refine glucocorticoid treatment, to retain benefit while minimizing side effects.

'Just gripping my heart and squeezing': Naming and explaining the emotional experience of receiving bad news in the paediatric oncology setting.

OBJECTIVE: To explore recipients' perspectives on the range and origins of their emotional experiences during their 'bad news' consultations. METHODS: Participants were four bereaved families of children who had changed from active treatment to palliative care in paediatric oncology. Data was collected using emotional touchpoint storytelling. The names (descriptors) given to the emotional experiences were linguistically classified. Explanations of their perceived origins were examined using applied thematic analysis. RESULTS: 26 descriptors were given, relating to bodily sensations, affective states, evaluations and cognitive conditions. Three themes were identified in the origins of these experiences - 'becoming aware', 'the changes' and 'being in this situation'. Parents described strong emotional displays during the consultation including physical collapse. These related to the internal process of 'becoming aware'. Three descriptors were given as originating from the clinicians and their delivery of the news - 'supported', 'included', 'trusting'. CONCLUSIONS: Recipients perceive their emotional experiences as mainly originating from the news itself, and perceived consequences of it, rather than its delivery. Strong emotional reactions during the interaction are not necessarily an indicator of ineffectual delivery. PRACTICE IMPLICATIONS: Findings offer a thematic framing that may support and deepen practitioners understanding of recipients' emotional reactions during bad news consultations.

Prevalence, Risk Factors, and Comorbidities of Hidradenitis Suppurativa.

It is challenging to estimate a true prevalence of hidradenitis suppurativa (HS) because it is underdiagnosed and misdiagnosed. Prevalences have been reported from 0.00033% to 4.1%. The incidence seems to be rising. In addition to dermatologic symptoms, HS is associated with metabolic syndrome, and increased cardiovascular risk. The majority of HS patients are smokers. Additional somatic comorbidities complicating HS include autoimmune conditions, follicular syndromes, rheumatologic conditions, and malignancies. HS patients are troubled by psychological comorbidities. When treating HS patients it is imperative not only to treat the skin symptoms, but also address the screening and treatment of possible comorbidities.

Emerging Oral Immunomodulators for the Treatment of Psoriasis: A Review of Phase III Clinical Trials for Apremilast and Tofacitinib.

BACKGROUND: Increased knowledge of the molecular regulatory mechanisms that contribute to the pathogenesis of psoriasis and other inflammatory diseases has created new opportunities for the development of targeted drug therapy for inflammatory conditions. Two new oral medications, apremilast and tofacitinib, have been developed for their immunomodulatory properties, and their potential efficacy in treating psoriasis is being evaluated. METHODS: We reviewed phase III randomized, placebo-controlled clinical trial results for apremilast and tofacitinib for efficacy and safety in psoriasis. RESULTS: Psoriasis Area and Severity Index (PASI) 75 after 16 weeks for apremilast was between 28.8% and 33.1%. PASI 75 was 39.5% after 12 weeks on tofacitinib 5 mg, and 63.6% after 12 weeks on tofacitinib 10 mg. Common side effects for both drugs included nasopharyngitis and upper respiratory tract infections. Gastrointestinal disturbance was common for apremilast. Dyslipidemia and infections were more common with tofacitinib than placebo. CONCLUSION: Both new oral medications, apremilast and tofacitinib, appear to be effective in treating psoriasis

Narrowband UV-B Phototherapy for Steroid-Refractory Sclerotic Chronic Cutaneous Graft-vs-Host Disease.

IMPORTANCE: Chronic graft-vs-host disease (GVHD) affects 50% to 70% of patients who receive allogeneic hematopoietic cell transplants (HCTs), and the skin is the most common site of involvement. Chronic cutaneous GVHD can present with sclerotic or nonsclerotic changes of the skin and often requires treatment with systemic immunosuppressants, extracorporeal photopheresis, or phototherapy. We describe the first reported case, to our knowledge, of the effective treatment of sclerotic chronic cutaneous GVHD with narrowband UV-B (NB UV-B) phototherapy. OBSERVATIONS: A woman in her 40s presented with sclerotic chronic GVHD of the skin 6 years after HCT for treatment of chronic myelogenous leukemia. The patient's cutaneous disease progressed despite treatment with prednisone and oral tacrolimus. The patient was initiated on NB UV-B phototherapy 3 times per week, resulting in clinically significant improvement of cutaneous lesions over the first 2 months. The NB UV-B regimen allowed for a reduction of prednisone dose and continued control of cutaneous GVHD over 6 months of therapy. CONCLUSIONS AND RELEVANCE: Our case report describes the successful use of NB UV-B phototherapy for the treatment of sclerotic chronic cutaneous GVHD. Further study should be performed to evaluate the effectiveness of this therapeutic modality for patients with sclerotic chronic cutaneous GVHD.

Interleukin-15 enhances cellular proliferation and upregulates CNS homing molecules in pre-B acute lymphoblastic leukemia.

Genome-wide association studies have consistently implicated the interleukin-15 (IL-15) gene in acute lymphoblastic leukemia (ALL) biology, including associations with disease susceptibility, and increased risk of central nervous system (CNS) involvement. However, whether pre-B ALL blasts directly respond to IL-15 is unknown. Here, we show that most pre-B ALL primary samples and cell lines express IL-15 and components of its receptor and that primary pre-B ALL cells show increased growth in culture in response to IL-15. Investigation of mechanisms of action using IL-15-responsive SD-1 cells shows this growth advantage is maximal under low-serum conditions, mimicking those found in cerebrospinal fluid. IL-15 also upregulates PSGL-1 and CXCR3, molecules associated with CNS trafficking. Investigation of downstream signaling pathways indicates that IL-15 induces signal transducer and activator of transcription 5 (STAT5), extracellular signal-regulated kinase (ERK) 1/2, and to a lesser extent phosphatidylinositol 3-kinase (PI3K) and nuclear factor κB (NF-κB) phosphorylation. The IL-15-mediated growth advantage is abolished by mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK), PI3K, and NF-κB inhibitors but preserved in the presence of STAT5 inhibition. Together, these observations provide a mechanistic link between increased levels of IL-15 expression and leukemogenesis, high-risk disease, and CNS relapse and suggest potential therapeutic targets.