Achieving consensus on psychosocial and physical rehabilitation management for people living with kidney disease

From Crossref journal articles via Jisc Publications RouterHistory: epub 2023-05-19, issued 2023-05-19Article version: AMPublication status: PublishedPelagia Koufaki - ORCID: 0000-0002-1406-3729 https://orcid.org/0000-0002-1406-3729Background People living with chronic kidney disease (CKD) need to be able to live well with their condition. The provision of psychosocial interventions (psychological, psychiatric, and social care) and physical rehabilitation management is variable across England, as well as the rest of the United Kingdom. There is a need for clear recommendations for standards of psychosocial and physical rehabilitation care for people living with CKD, and guidance for the commissioning and measurement of these services. The NHS England Renal Services Transformation Programme (RSTP) supported a programme of work and modified Delphi process to address the management of psychosocial and physical rehabilitation care as part of a larger body of work to formulate a comprehensive commissioning toolkit for renal care services across England. We sought to achieve expert consensus regarding the psychosocial and physical rehabilitation management of people living with CKD in England and the rest of the UK. Method A Delphi consensus method was used to gather and refine expert opinions of senior members of the kidney multi-disciplinary team (MDT) and other key stakeholders in the UK. An agreement was sought on 16 statements reflecting aspects of psychosocial and physical rehabilitation management for people living with CKD. Results Twenty-six expert practitioners and other key stakeholders, including lived experience representatives, participated in the process. The consensus (>80% affirmative votes) amongst the respondents for all 16 statements was high. Nine recommendation statements were discussed and refined further to be included in the final iteration of the ‘Systems’ section of the NHS England RSTP commissioning toolkit. These priority recommendations reflect pragmatic solutions that can be implemented in renal care and include recommendations for a holistic well-being assessment for all people living with CKD who are approaching dialysis, or who are at listing for kidney transplantation, which includes the use of validated measurement tools to assess the need for further intervention in psychosocial and physical rehabilitation management. It is recommended that the scores from these measurement tools be included in the NHS England Renal Data Dashboard. There was also a recommendation for referral as appropriate to NHS Talking therapies, psychology, counselling or psychotherapy, social work or liaison psychiatry for those with identified psychosocial needs. The use of digital resources was recommended to be used in addition to face-to-face care to provide physical rehabilitation, and all healthcare professionals should be educated to recognise psychosocial and physical rehabilitation needs and refer/sign-post people with CKD to appropriate services. Conclusion There was high consensus amongst senior members of the kidney MDT and other key stakeholders, including those with lived experience, in the UK on all aspects of the psychosocial and physical rehabilitation management of people living with CKD. The results of this process will be used by NHS England to inform the ‘Systems’ section of the commissioning toolkit and data dashboard and to inform the National Standards of Care for people living with CKD.inpressinpres

Science Priorities for the Extraction of the Solid MSR Samples from their Sample Tubes NASA-ESA Mars Rock Team

editorial reviewedPreservation of the chemical and structural integrity of samples that will be brought back from Mars is paramount to achieving the scientific objectives of MSR. Given our knowledge of the nature of the samples retrieved at Jezero by Perseverance, at least two options need to be tested for opening the sample tubes: (1) One or two radial cuts at the end of the tube to slide the sample out. (2) Two radial cuts at the ends of the tube and two longitudinal cuts to lift the upper half of the tube and access the sample. Strategy 1 will likely minimize contamination but incurs the risk of affecting the physical integrity of weakly consolidated samples. Strategy 2 will be optimal for preserving the physical integrity of the samples but increases the risk of contamination and mishandling of the sample as more manipulations and additional equipment will be needed. A flexible approach to opening the sample tubes is therefore required, and several options need to be available, depending on the nature of the rock samples returned. Both opening strategies 1 and 2 may need to be available when the samples are returned to handle different sample types (e.g., loosely bound sediments vs. indurated magmatic rocks). This question should be revisited after engineering tests are performed on analogue samples. The MSR sample tubes will have to be opened under stringent BSL4 conditions and this aspect needs to be integrated into the planning

Association of tumor hypoxia with lower survival after radiotherapy for muscle-invasive bladder cancer

292 Background: Hypoxia may influence clinical outcomes in many human tumors, including muscle invasive urothelial carcinoma (UC) of the bladder. Hypoxia inducible factor-1 (HIF1), glucose transporter protein-1 (GLUT1) and carbonic anhydrase IX (CAIX) are all upregulated by hypoxia. This study examined the relationship between biomarkers of hypoxia or proliferation (Ki67) and clinical outcome in UC patients treated with radiotherapy (RT). Methods: 70 patients were treated with curative intent using RT alone or RT plus neoadjuvant or concurrent chemotherapy (RTCT) between 1997 and 2006. Archived, paraffin-embedded, transurethral biopsy material was available for 44 patients (35 men and 9 women). Tumor was clinically confined to the bladder wall (cT2) in 28 patients and involved perivesical tissues or adjacent organs (cT3/T4) in 16. Tissue micro-arrays were constructed and immunohistochemical analyses performed to assess biomarker expression, which was scored independently by 3 observers in a semi-quantitative manner. The biomarker scores were correlated with clinico-pathologic data extracted from the medical record and with patient outcome. Median follow-up was 4.2 years. Results: HIF1, GLUT1 and CAIX expression was seen in 43%, 96% and 65% of tumors respectively. The median Ki67 expression was 60%. There were no correlations between biomarkers expression and clinico-pathologic prognostic factors. The cystoscopic complete response rate was 71% at 2-3 months post-RT. The 4-year actuarial local control (LC) and overall survival (OS) rates were 48% and 55% respectively. High Ki67 expression was strongly predictive of better LC by univariate and multivariate analyses (70% vs 20% at 4 years, HR 0.95, p= 0.002), whereas no hypoxic marker predicted LC. High CAIX expression was predictive of inferior OS by multivariate analysis (HR 1.6, p=0.04). Conclusions: Tumor hypoxia influences the outcome of patients with bladder cancer treated with RT or RTCT and is a potential therapeutic target. High Ki67 has been reported previously to be a marker of sustained LC in the bladder following RTCT but the biologic mechanism underlying this association is unknown and requires further investigation

TMPRSS2-ERG status and biochemical recurrence following radiotherapy for intermediate-risk prostate cancer.

11 Background: Approximately 50% of prostate cancers (PC) contain TMPRSS2-ERG gene fusions leading to ERG overexpression. Pre-clinical data suggest that these fusions are due to altered DNA double-strand break repair status which could have therapeutic ramification for the use of radiotherapy (RT) and PARP inhibitors. The aim of this study was to correlate TMPRSS2-ERG status to biochemical failure following clinical induction of DNA breaks in the form of image-guided radiotherapy (IGRT) in intermediate-risk PC. Methods: Pre-treatment biopsies from two separate cohorts of intermediate-risk PC patients (T1/T2, GS < 8, PSA < 20ng/ml) were analyzed: 1) 126 patients assessed by array Comparative Genomic Hybridization (aCGH) for TMPRSS2:ERG fusion; and 2) 121 patients assessed by tissue microarray (TMA) for ERG expression by immunohistochemistry (IHC). All patients received IGRT with a median dose of 79.8 Gy (60-79.8 Gy). TMPRSS2:ERG status was correlated to Gleason score, T stage, initial PSA and biochemical-free relapse rate (bFRR; Phoenix definition: nadir + 2ng/ml). Results: At a median follow-up time of 6.36 years, the biochemical relapse event rate was 37% and 18% in the aCGH and IHC cohorts, respectively. ERG expression by IHC was found in 49.6% of the 121 PC. TMPRSS2-ERG status was not correlated to increased Gleason score, pre-treatment PSA or T stage. On multivariate analyses in models containing clinical factors, TMPRSS2:ERG status (either using aCGH or IHC) was not prognostic for biochemical outcome (ERG expression: HR=0.78, 95% CI: 0.33-1.85; p= 0.568; TMPRSS2-ERG fusion: HR=0.71, 95% CI: 0.35-1.41; p=0.326). Conclusions: In two separate cohorts, TMPRSS2-ERG status was not prognostic for bRFR after IGRT. Although a trend was observed, these clinical data do not support the hypothesis that these cancers have DNA repair defects that render them significantly more radiosensitive when compared to other PC. Further clinical trials are required to understand the utility of TMPRSS2:ERG status and response to DNA damaging agents, including that of PARP inhibitors. The trans-Canadian PROFIT trial is completing accrual of close to 1200 patients allowing for TMPRSS2:ERG studies in a larger RT cohort

TMPRSS2-ERG status is not prognostic following prostate cancer radiotherapy:Implications for fusion status anddsb repair

Abstract Background: Preclinical data suggest that TMPRSS2-ERG gene fusions, present in about 50% of prostate cancers, may be a surrogate for DNA repair status and therefore a biomarker for DNA-damaging agents. To test this hypothesis, we examined whether TMPRSS2-ERG status was associated with biochemical failure after clinical induction of DNA damage following image-guided radiotherapy (IGRT). Methods: Pretreatment biopsies from two cohorts of patients with intermediate-risk prostate cancer [T1/T2, Gleason score (GS) &amp;lt; 8, prostate-specific antigen (PSA) &amp;lt; 20 ng/mL; &amp;gt;7 years follow-up] were analyzed: (i) 126 patients [comparative genomic hybridization (CGH) cohort] with DNA samples assayed by array CGH (aCGH) for the TMPRSS2-ERG fusion; and (ii) 118 patients [immunohistochemical (IHC) cohort] whose biopsy samples were scored within a defined tissue microarray (TMA) immunostained for ERG overexpression (known surrogate for TMPRSS2-ERG fusion). Patients were treated with IGRT with a median dose of 76 Gy. The potential role of TMPRSS2-ERG status as a prognostic factor for biochemical relapse-free rate (bRFR; nadir + 2 ng/mL) was evaluated in the context of clinical prognostic factors in multivariate analyses using a Cox proportional hazards model. Results: TMPRSS2-ERG fusion by aCGH was identified in 27 (21%) of the cases in the CGH cohort, and ERG overexpression was found in 59 (50%) patients in the IHC cohort. In both cohorts, TMPRSS2-ERG status was not associated with bRFR on univariate or multivariate analysis. Conclusions: In two similarly treated IGRT cohorts, TMPRSS2-ERG status was not prognostic for bRFR, in disagreement with the hypothesis that these prostate cancers have DNA repair defects that render them clinically more radiosensitive. TMPRSS2-ERG is therefore unlikely to be a predictive factor for IGRT response. Clin Cancer Res; 19(18); 5202–9. ©2013 AACR.</jats:p

Achieving consensus on psychosocial and physical rehabilitation management for people living with kidney disease

Background People living with chronic kidney disease (CKD) need to be able to live well with their condition. The provision of psychosocial interventions (psychological, psychiatric and social care) and physical rehabilitation management is variable across England, as well as the rest of the UK. There is a need for clear recommendations for standards of psychosocial and physical rehabilitation care for people living with CKD, and guidance for the commissioning and measurement of these services. The National Health Service (NHS) England Renal Services Transformation Programme (RSTP) supported a programme of work and modified Delphi process to address the management of psychosocial and physical rehabilitation care as part of a larger body of work to formulate a comprehensive commissioning toolkit for renal care services across England. We sought to achieve expert consensus regarding the psychosocial and physical rehabilitation management of people living with CKD in England and the rest of the UK. Methods A Delphi consensus method was used to gather and refine expert opinions of senior members of the kidney multi-disciplinary team (MDT) and other key stakeholders in the UK. An agreement was sought on 16 statements reflecting aspects of psychosocial and physical rehabilitation management for people living with CKD. Results Twenty-six expert practitioners and other key stakeholders, including lived experience representatives, participated in the process. The consensus (>80% affirmative votes) amongst the respondents for all 16 statements was high. Nine recommendation statements were discussed and refined further to be included in the final iteration of the ‘Systems’ section of the NHS England RSTP commissioning toolkit. These priority recommendations reflect pragmatic solutions that can be implemented in renal care and include recommendations for a holistic wellbeing assessment for all people living with CKD who are approaching dialysis, or who are at listing for kidney transplantation, which includes the use of validated measurement tools to assess the need for further intervention in psychosocial and physical rehabilitation management. It is recommended that the scores from these measurement tools be included in the NHS England Renal Data Dashboard. There was also a recommendation for referral as appropriate to NHS Talking Therapies, psychology, counselling or psychotherapy, social work or liaison psychiatry for those with identified psychosocial needs. The use of digital resources was recommended to be used in addition to face-to-face care to provide physical rehabilitation, and all healthcare professionals should be educated to recognize psychosocial and physical rehabilitation needs and refer/sign-post people with CKD to appropriate services. Conclusion There was high consensus amongst senior members of the kidney MDT and other key stakeholders, including those with lived experience, in the UK on all aspects of the psychosocial and physical rehabilitation management of people living with CKD. The results of this process will be used by NHS England to inform the ‘Systems’ section of the commissioning toolkit and data dashboard and to inform the National Standards of Care for people living with CKD.</p

Utz Wachil: Findings from an International Study of Indigenous Perspectives on Health and Environment

This article reports previously unpublished results of a collaborative study undertaken in 2003 by health workers of the UK-based organisation Health Unlimited, and by researchers of the London School of Hygiene and Tropical Medicine. This study marked the first of a series of collaborative activities aimed at highlighting the situation of Indigenous peoples, some in the most isolated ecosystems of the planet. While many researchers focus on quantitative analysis of the health and environmental conditions of Indigenous peoples, our 2003 study aimed at exploring the views of Indigenous peoples in isolated communities in five countries on their environment and their health. In this article we look closely at the web of knowledge and belief that underpins Indigenous peoples' concepts of health and well-being, and their relationship to land and the environment. Although many Indigenous people have been forced off their traditional lands and live in rural settlements, towns, and cities, there are still a large number of people living in very small Indigenous communities in remote areas. This article focuses on 20 such communities in six countries. We explore traditional knowledge and practice and its relationship to Western medicine and services. The research findings highlight the importance of Indigenous knowledge systems for the emerging ecohealth community and suggest that we have much to learn from Indigenous peoples in our pursuit of a more holistic science