Background
Rapid weight gain is common with antipsychotic medication. Lost confidence, low mood and medication non‐adherence often follow. Yet, the dynamic interactions between the physical and ...psychological consequences of weight gain, and implications for intervention, are unknown.
Objectives
We examined first‐person accounts of weight gain to identify preferences for weight change interventions.
Design
A qualitative design was used to explore patients’ experiences of weight change in the context of psychosis.
Method
Semi‐structured interviews, analysed using grounded theory, were conducted with 10 patients with psychosis. Sample validation was conducted with peer researchers with lived experience of psychosis.
Results
Patients described that initially the extent and speed of weight gain was overshadowed by psychotic experiences and their treatment. This led to a shocking realisation of weight gain. The psychological impact of weight gain, most strikingly on the self‐concept, was profound. Loss of self‐worth and changed appearance amplified a sense of vulnerability. There were further consequences on mood, activity and psychotic experiences, such as voices commenting on appearance, that were additional obstacles in the challenging process of weight loss. Sedative effects of medication also contributed. Unsuccessful weight loss left little hope and few preferences for interventions. Early information about common weight gain trajectories and working with experts‐by‐experience were valued. Rebuilding self‐confidence, efficacy and worth may be a necessary first step.
Conclusions
The journey of weight gain in patients with psychosis is characterised by loss of self‐worth, agency and hope. There are multiple stages in the journey, each with different psychological reactions, that may need different treatment responses.
Evidence for the effectiveness of treatments in early-onset psychosis is sparse. Current guidance for the treatment of early-onset psychosis is mostly extrapolated from trials in adult populations. ...The UK National Institute for Health and Care Excellence has recommended evaluation of the clinical effectiveness and cost-effectiveness of antipsychotic drugs versus psychological intervention (cognitive behavioural therapy CBT and family intervention) versus the combination of these treatments for early-onset psychosis. The aim of this study was to establish the feasibility of a randomised controlled trial of antipsychotic monotherapy, psychological intervention monotherapy, and antipsychotics plus psychological intervention in adolescents with first-episode psychosis.
We did a multicentre pilot and feasibility trial according to a randomised, single-blind, three-arm, controlled design. We recruited participants from seven UK National Health Service Trust sites. Participants were aged 14–18 years; help-seeking; had presented with first-episode psychosis in the past year; were under the care of a psychiatrist; were showing current psychotic symptoms; and met ICD-10 criteria for schizophrenia, schizoaffective disorder, or delusional disorder, or met the entry criteria for an early intervention for psychosis service. Participants were assigned (1:1:1) to antipsychotics, psychological intervention (CBT with optional family intervention), or antipsychotics plus psychological intervention. Randomisation was via a web-based randomisation system, with permuted blocks of random size, stratified by centre and family contact. CBT incorporated up to 26 sessions over 6 months plus up to four booster sessions, and family intervention incorporated up to six sessions over 6 months. Choice and dose of antipsychotic were at the discretion of the treating consultant psychiatrist. Participants were followed up for a maximum of 12 months. The primary outcome was feasibility (ie, data on trial referral and recruitment, session attendance or medication adherence, retention, and treatment acceptability) and the proposed primary efficacy outcome was total score on the Positive and Negative Syndrome Scale (PANSS) at 6 months. Primary outcomes were analysed by intention to treat. Safety outcomes were reported according to as-treated status, for all patients who had received at least one session of CBT or family intervention, or at least one dose of antipsychotics. The study was prospectively registered with ISRCTN, ISRCTN80567433.
Of 101 patients referred to the study, 61 patients (mean age 16·3 years SD 1·3) were recruited from April 10, 2017, to Oct 31, 2018, 18 of whom were randomly assigned to psychological intervention, 22 to antipsychotics, and 21 to antipsychotics plus psychological intervention. The trial recruitment rate was 68% of our target sample size of 90 participants. The study had a low referral to recruitment ratio (around 2:1), a high rate of retention (51 84% participants retained at the 6-month primary endpoint), a high rate of adherence to psychological intervention (defined as six or more sessions of CBT; in 32 82% of 39 participants in the monotherapy and combined groups), and a moderate rate of adherence to antipsychotic medication (defined as at least 6 consecutive weeks of exposure to antipsychotics; in 28 65% of 43 participants in the monotherapy and combined groups). Mean scores for PANSS total at the 6-month primary endpoint were 68·6 (SD 17·3) for antipsychotic monotherapy (6·2 points lower than at randomisation), 59·8 (13·7) for psychological intervention (13·1 points lower than at randomisation), and 62·0 (15·9) for antipsychotics plus psychological intervention (13·9 points lower than at randomisation). A good clinical response at 6 months (defined as ≥50% improvement in PANSS total score) was achieved in four (22%) of 18 patients receiving antipsychotic monotherapy, five (31%) of 16 receiving psychological intervention, and five (29%) of 17 receiving antipsychotics plus psychological intervention. In as-treated groups, serious adverse events occurred in eight 35% of 23 patients in the combined group, two 13% of 15 in the antipsychotics group, four 24% of 17 in the psychological intervention group, and four 80% of five who did not receive any treatment. No serious adverse events were considered to be related to participation in the trial.
This trial is the first to show that a head-to-head clinical trial comparing psychological intervention, antipsychotics, and their combination is safe in young people with first-episode psychosis. However, the feasibility of a larger trial is unclear because of site-specific recruitment challenges, and amendments to trial design would be needed for an adequately powered clinical and cost-effectiveness trial that provides robust evidence.
National Institute for Health Research.
Onset of psychosis commonly occurs in adolescence, and long-term prognosis can be poor. There is growing evidence, largely from adult cohorts, that Cognitive Behavioural Therapy for Psychosis (CBTp) ...and Family Interventions (FI) can play a role in managing symptoms and difficulties associated with psychosis. However, adolescents have distinct developmental needs that likely impact their engagement and response to talking therapy. There is limited guidance on adapting CBTp to meet the clinical needs of under-eighteens experiencing psychosis.
This educational clinical practice article details learnings from therapists and supervisors working with young people (aged 14-18 years) with psychosis during the Managing Adolescent first-episode Psychosis: a feasibility Study (MAPS) randomised clinical treatment trial, supplemented by findings from nested qualitative interviews with young people receiving CBTp.
Suggested are given for tailoring CBTp assessment, formulation and interventions to meet the developmental and clinical needs of adolescents with psychosis. Developmentally appropriate techniques and resources described.
Early indications from MAPS study indicate this developmentally tailored approach is an acceptable, safe and helpful treatment for young people with psychosis. Further research is needed to develop empirically grounded and evaluated CBTp for adolescents.
Chromoblastomycosis is an implantation mycosis of the skin caused by certain species of melanised fungi. A man in his 50s, born in Kerala but living in England for 14 years, presented with a nodular ...lesion on his left buttock, which had been present for 20 years. Biopsy revealed muriform cells and fungal culture isolated
, consistent with a diagnosis of chromoblastomycosis. Treatment with oral terbinafine was initiated and changed to itraconazole based on results of antifungal susceptibility. Drug intolerance and low drug levels of itraconazole necessitated change to voriconazole and topical terbinafine. Despite long-term combined therapy, the lesions worsened, and the patient opted for surgical excision abroad. Recurrence was evident at surgical sites and combined therapy continues. Chromoblastomycosis is an insidious and burdensome neglected tropical disease. Within non-endemic countries, diagnosis remains challenging. A travel history and appropriate fungal investigations are vital.
Cancer cells must overcome anoikis (detachment-induced death) to successfully metastasize. Using proteomic screens, we found that distinct oncoproteins upregulate IL1 receptor accessory protein ...(IL1RAP) to suppress anoikis. IL1RAP is directly induced by oncogenic fusions of Ewing sarcoma, a highly metastatic childhood sarcoma. IL1RAP inactivation triggers anoikis and impedes metastatic dissemination of Ewing sarcoma cells. Mechanistically, IL1RAP binds the cell-surface system X
transporter to enhance exogenous cystine uptake, thereby replenishing cysteine and the glutathione antioxidant. Under cystine depletion, IL1RAP induces cystathionine gamma lyase (CTH) to activate the transsulfuration pathway for
cysteine synthesis. Therefore, IL1RAP maintains cyst(e)ine and glutathione pools, which are vital for redox homeostasis and anoikis resistance. IL1RAP is minimally expressed in pediatric and adult normal tissues, and human anti-IL1RAP antibodies induce potent antibody-dependent cellular cytotoxicity of Ewing sarcoma cells. Therefore, we define IL1RAP as a new cell-surface target in Ewing sarcoma, which is potentially exploitable for immunotherapy. SIGNIFICANCE: Here, we identify cell-surface protein IL1RAP as a key driver of metastasis in Ewing sarcoma, a highly aggressive childhood sarcoma. Minimal expression in pediatric and adult normal tissues nominates IL1RAP as a promising target for immunotherapy.
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Medication adherence and growth in children with CKD Akchurin, Oleh M; Schneider, Michael F; Mulqueen, Lucy ...
Clinical journal of the American Society of Nephrology,
2014-Sep-05, Letnik:
9, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Poor growth is a consequence of CKD, but can often be partially or fully prevented or corrected with the use of a number of medications. The extent of nonadherence with medications used to treat or ...mitigate growth failure in CKD has not been examined prospectively in children with CKD.
The prevalence of both prescription of and nonadherence to recombinant human growth hormone (rhGH), phosphate binders, alkali, active vitamin D, nutritional vitamin D, iron, and erythrocyte-stimulating agents was summarized over the first seven visits of the Chronic Kidney Disease in Children cohort study. The association between self-reported nonadherence to each medication group and the mean annual change in age- and sex-specific height z score was quantified using seven separate linear regression models with generalized estimating equations.
Of 834 participants, 597 reported use of at least one of these medication groups and had adherence data available. Nonadherence ranged from 4% over all visits for erythrocyte-stimulating agents to 22% over all visits for nutritional vitamin D. Of the study participants, 451 contributed data to at least one of the analyses of adherence and changes in height z score. Children nonadherent to rhGH had no change in height z score, whereas those adherent to rhGH had a significant improvement of 0.16 SDs (95% confidence interval, 0.05 to 0.27); the effect size was slightly larger and remained significant after adjustment. Among participants with height≤3rd percentile and after adjustment, adherence to rhGH was associated with a 0.33 SD (95% confidence interval, 0.10 to 0.56) greater change in height z score. Nonadherence with other medication groups was not significantly associated with a change in height z score.
Self-reported nonadherence to rhGH was associated with poorer growth velocity in children with CKD, suggesting an opportunity for intervention and improved patient outcome.
Atypical hemolytic uremic syndrome (aHUS) is a rare, lifethreatening, chronic, genetic disease of uncontrolled alternative pathway complement activation. The understanding of the pathophysiology and ...genetics of this disease has expanded over recent decades and promising new developments in the management of aHUS have emerged. Regardless of the cause of aHUS, with or without a demonstrated mutation or autoantibody, blockade of terminal complement activation through C5 is of high interest as a mechanism to ameliorate the disease. Eculizumab, an existing monoclonal antibody directed against C5 with high affinity, prevents the perpetuation of the downstream activation of the complement cascade and the damage caused by generation of the anaphylotoxin C5a and the membrane attack complex C5b-9, by blocking C5 cleavage. We report the successful use of eculizumab in a patient after kidney transplantation and discuss the disease aHUS.
Objective To assess depression in children with chronic kidney disease and to determine associations with patient characteristics, intellectual and educational levels, and health-related quality of ...life (HRQoL). Study design Subjects aged 6-17 years from the Chronic Kidney Disease in Children cohort study completed the Children's Depression Inventory (CDI), Wechsler Abbreviated Scales of Intelligence, Wechsler Individual Achievement Test-II-Abbreviated, and the Pediatric Inventory of Quality of Life Core Scales 4.0. Regression analyses determined associations of CDI score and depression status with subject characteristics, intellectual and educational levels, and HRQoL. A joint linear mixed model and Weibull model were used to determine the effects of CDI score on longitudinal changes in glomerular filtration rate and time to renal replacement therapy. Results A total of 344 subjects completed the CDI. Eighteen (5%) had elevated depressive symptoms, and another 7 (2%) were being treated for depression. In adjusted analyses, maternal education beyond high school was associated with 5% lower CDI scores (estimate, 0.95; 95% CI, 0.92-0.99). Depression status was associated with lower IQ (99 vs 88; P = .053), lower achievement (95 vs 77.5; P < .05), and lower HRQoL by parent and child reports (effect estimates, −15.48; 95% CI, −28.71 to −2.24 and −18.39; 95% CI, −27.81 to −8.96, respectively). CDI score was not related to change in glomerular filtration rate. Conclusion Children with depression had lower psychoeducational skills and worse HRQoL. Identifying and treating depression should be evaluated as a means of improving the academic performance and HRQoL of children with chronic kidney disease.
The primary hyperoxalurias Bobrowski, Amy E; Langman, Craig B
Seminars in nephrology,
03/2008, Letnik:
28, Številka:
2
Journal Article
Recenzirano
The primary hyperoxalurias (PHs) are rare autosomal-recessive inborn errors of metabolism. In the most severe form (type 1), recurrent kidney stones and progressive nephrocalcinosis lead to the loss ...of kidney function, accompanied by systemic oxalosis, and often requires dialysis and/or transplantation. The variety of genetic mutations leading to PH increasingly are being defined, resulting in the ability to diagnose most patients accurately via minimally invasive means. During and after definitive diagnosis, supportive therapies with pyridoxine supplementation, urinary crystallization inhibitors, and hydration should be used, but have varying success. Emerging information about the renal tubular and intestinal transport of oxalate is leading to increasing evidence to support the use of oxalate-degrading bacteria (probiotics) and enzymes in the treatment of PH. Organ transplantation historically has offered the only potential cure for PH, and may include kidney-alone, combined liver-kidney, or pre-emptive liver-alone transplantation. Exciting new approaches in the treatment of type 1 PH, however, are under investigation. These include the restoration of defective enzymatic activity through the use of chemical chaperones, hepatocyte cell transplantation, or enzyme replacement by recombinant gene therapy. These novel approaches illustrate the goal for the ideal treatment of PH: correcting the genetic defect without exposing patients to the life-long risks associated with organ transplantation.
Accurate detection of hypertension is crucial for clinical management of pediatric chronic kidney disease (CKD). The 2017 American Academy of Pediatrics (AAP) clinical practice guideline for ...childhood hypertension included new normative blood pressure (BP) values and revised definitions of BP categories. In this study, we examined the effect of applying the AAP guideline’s normative data and definitions to the Chronic Kidney Disease in Children (CKiD) cohort compared with use of normative data and definitions from the 2004 Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents.
Observational cohort study.
Children and adolescents in the CKiD cohort.
Clinic BP measurements.
BP percentiles and hypertension stages calculated using the 2017 AAP guideline and the Fourth Report from 2004.
Agreement analysis compared the estimated percentile and prevalence of high BP based on the 2017 guideline and 2004 report to clinic and combined ambulatory BP readings.
The proportion of children classified as having normal clinic BP was similar using the 2017 and 2004 systems, but the use of the 2017 normative data classified more participants as having stages 1-2 hypertension (22% vs 11%), with marginal reproducibility (κ=0.569 95% CI, 0.538-0.599). Those identified as having stage 2 hypertension by the 2017 guideline had higher levels of proteinuria compared with those identified using the 2004 report. Comparing use of the 2017 guideline and the 2004 report in terms of ambulatory BP monitoring categories, there were substantially more participants with white coat (3.5% vs 1.5%) and ambulatory (15.5% vs 7.9%) hypertension, but the proportion with masked hypertension was lower (40.2% vs 47.8%, respectively), and the percentage of participants who were normotensive was similar (40.9% vs 42.9%, respectively). Overall, there was good reproducibility (κ=0.799 95% CI, 0.778-0.819) of classification by ambulatory BP monitoring.
Relationship with long-term progression and target organ damage was not assessed.
A greater percentage of children with CKD were identified as having hypertension based on both clinic and ambulatory BP when using the 2017 AAP guideline versus the Fourth Report from 2004, and the 2017 guideline better discriminated those with higher levels of proteinuria. The substantial differences in the classification of hypertension when using the 2017 guideline should inform clinical care.
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