Are within-person Numerical Rating Scale (NRS) ratings of breathlessness 'on average' valid in advanced disease for patients and for patients' informal carers?

INTRODUCTION: The Numerical Rating Scale (NRS) is frequently used to assess patient-reported breathlessness in both a research and clinical context. A subgroup of patients report average breathlessness as worse than their worst breathlessness in the last 24 hours (paradoxical average). The Peak/End rule describes how the most extreme and current breathlessness influence reported average. This study seeks to highlight the existence of a subpopulation who give 'paradoxical averages using the NRS, to characterise this group and to investigate the explanatory relevance of the 'Peak/End' rule. METHODS: Data were collected within mixed method face-to-face interviews for three studies: the Living with Breathlessness Study and the two subprotocols of the Breathlessness Intervention Service phase III randomised controlled trial. Key variables from the three datasets were pooled (n=561), and cases where participants reported a paradoxical average (n=45) were identified. These were compared with non-cases and interview transcripts interrogated. NRS ratings of average breathlessness were assessed for fit to Peak/End rule. RESULTS: Patients in the paradoxical average group had higher Chronic Respiratory Questionnaire physical domain scores on average p=0.042). Peak/End rule analysis showed high positive correlation (Spearman's rho=0.756, p<0.001). CONCLUSIONS: The NRS requires further standardisation with reporting of question order and construction of scale used to enable informed interpretation. The application of the Peak/End rule demonstrates fallibility of NRS-Average as a construct as it is affected by current breathlessness. Measurement of breathlessness is important for both clinical management and research, but standardisation and transparency are required for meaningful results

Support Needs Approach for Patients (SNAP) tool: a validation study.

OBJECTIVES:Patient-identified need is key to delivering holistic, supportive, person-centred care, but we lack tools enabling patients to express what they need to manage life with a long-term condition. The Support Needs Approach for Patients (SNAP) tool was developed to enable patients with advanced chronic obstructive pulmonary disease (COPD) identify and express their unmet support needs to healthcare professionals (HCPs), but its validity is unknown. This study aimed to establish face, content and criterion validity of the SNAP tool. DESIGN:Two-stage mixed-methods study involving patients with advanced COPD and their carers. Stage 1: Face and content validity assessed though focus groups involving patients and carers considering appropriateness, relevance and completeness of the SNAP tool. Data were analysed using conventional content analysis. Stage 2: Content and criterion validity assessed in a postal survey through patient self-completion of the SNAP tool and disease impact measures (Chronic Respiratory Questionnaire, COPD Assessment Test, and Hospital Anxiety and Depression Scale). Content validity assessed using summary statistics; criterion validity via correlations between tool items and impact measures. SETTINGS AND PARTICIPANTS:Two hundred and forty patients and carers participated. Stage 1 patient and informal carer participants were recruited from two primary care practices and Stage 2 patients from 28 practices. Participating practices located in the East of England were recruited via the NIHR Clinical Research Network: Eastern. RESULTS:Patients and carers found the tool patient-friendly and comprehensive, with potential clinical utility. No tool items were redundant. Clear correlations were found between tool items and the majority of items in the impact measures. CONCLUSIONS:The SNAP tool has good face, content and criterion validity. It has potential to support the delivery of holistic, supportive, person-centred care by enabling patients to identify and express their unmet support needs to HCPs

Impact of the Southwark and Lambeth Integrated Care Older People's Programme on hospital utilisation and costs: controlled time series and cost-consequence analysis.

OBJECTIVES: To estimate the impact on hospital utilisation and costs of a multi-faceted primary care intervention for older people identified as being at risk of avoidable hospitalisation. DESIGN: Observational study: controlled time series analysis and estimation of costs and cost consequences of the Programme. General practitioner (GP)'s practice level data were analysed from 2009 to 2016 (intervention operated from 2012 to 2016). Mixed-effect Poisson regression models of hospital utilisation included comparisons with control practices and background trends in addition to within-practice comparisons. Cost estimation used standard tariff values. SETTING: 94 practices in Southwark and Lambeth and 263 control practices from other parts of England. MAIN OUTCOME MEASURES: Hospital utilisation: emergency department attendance, emergency admissions, emergency admissions for ambulatory sensitive conditions, outpatient attendance, elective admission and length of stay. RESULTS: By the fourth year of the Programme, there were reductions in accident and emergency (A&E) attendance (rate ratio 0.944, 95% CI 0.913 to 0.976), outpatient attendances (rate ratio 0.938, 95% CI 0.902 to 0.975) and elective admissions (rate ratio 0.921, 95% CI 0.908 to 0.935) but there was no evidence of reduced emergency admissions. The costs of the Programme were £149 per resident aged 65 and above but savings in hospital costs were only £86 per resident aged 65 and above, equivalent to a net increase in health service expenditure of £64 per resident though the Programme was nearly cost neutral if set-up costs were excluded. Holistic assessments carried out by GPs and consequent Integrated Care Management (ICM) plans were associated with increases in elective activity and costs; £126 increase in outpatient attendance and £936 in elective admission costs per holistic assessment carried out, and £576 increase in outpatient and £5858 in elective admission costs per patient receiving ICM. CONCLUSIONS: The Older People's Programme was not cost saving. Some aspects of the Programme were associated with increased costs of elective care, possibly through the identification of unmet need

Associations between diagnostic pathways and care experience in colorectal cancer: evidence from patient-reported data.

OBJECTIVE: To examine how different pathways to diagnosis of colorectal cancer may be associated with the experience of subsequent care. DESIGN: Patient survey linked to information on diagnostic route.English patients with colorectal cancer (analysis sample n=6837) who responded to a patient survey soon after their hospital treatment. MAIN OUTCOME MEASURES: Odds Ratios and adjusted proportions of negative evaluation of key aspects of care for colorectal cancer, including the experience of shared decision-making about treatment, specialist nursing and care coordination, by diagnostic route (ie, screening detection, emergency presentation, urgent and elective general practitioner referral). RESULTS: For 14 of 18 questions, there was evidence (p≤0.02) for variation in patient experience by diagnostic route, with 6-31 percentage point differences between routes in adjusted proportions of negative experience. Emergency presenters were more likely to report a negative experience for most questions, including those about adequacy of information about their diagnosis and sufficient explanation before operations. Screen-detected patients were least likely to report negative experiences except for support from primary care. Patients diagnosed through elective primary care referrals were most likely to report worse experience for questions for which overall variation by route was generally small. CONCLUSIONS: Screening-detected patients tend to report the best and emergency presenters the worst experience of subsequent care. Improvement efforts can target care integration for screening-detected patients and provision of information about the diagnosis and treatment of emergency presenters

Reduced Graphene Oxide: Nanotoxicological Profile In Rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)We have previously demonstrated that reduced graphene oxide (rGO) administered intravenously in rats was detected inside the hippocampus after downregulation of the tight and adherens junction proteins of the blood-brain barrier. While down-regulators of junctional proteins could be useful tools for drug delivery through the paracellular pathway, concerns over toxicity must be investigated before clinical application. Herein, our purpose was to trace whether the rGO inside the hippocampus triggered toxic alterations in this brain region and in target organs (blood, liver and kidney) of rats at various time points (15 min, 1, 3 h and 7 days). Results: The assessed rGO-treated rats (7 mg/kg) were clinically indistinguishable from controls at all the time points. Hematological, histopathological (neurons and astrocytes markers), biochemical (nephrotoxicity and hepatotoxicity assessment) and genotoxicological based tests showed that systemic rGO single injection seemed to produce minimal toxicological effects at the time points assessed. Relative to control, the only change was a decrease in the blood urea nitrogen level 3 h post-treatment and increases in superoxide dismutase activity 1 h and 7 days post-treatment. While no alteration in leukocyte parameters was detected between control and rGO-treated animals, time-dependent leukocytosis (rGO-1 h versus rGO-3 h) and leukopenia (rGO-3 h versus rGO-7 days) was observed intra-treated groups. Nevertheless, no inflammatory response was induced in serum and hippocampus at any time. Conclusions: The toxic effects seemed to be peripheral and transitory in the short-term analysis after systemic administration of rGO. The effects were self-limited and non-significant even at 7 days post-rGO administration.14Brazilian funding agency Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2012/24782-5]Brazilian funding agency Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [305099/2011-6, 486142/2012-4]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Oral mucositis in pediatric acute lymphoblastic leukemia patients: evaluation of microbiological and hematological factors

To investigate the associations of oral microbiota, leucocytes count, neutrophil count, platelet counts and hemoglobin level, and the severity of oral mucositis in pediatric patients with acute lymphoblastic leukemia (ALL) receiving chemotherapy. 71 prospective patients were included. Analyses of oral microbiota and blood sample were conducted on days 14 (D14) and 56 (D56) of the Brazilian GBTLI-99 treatment protocol. Herpes simplex virus (HSV) identification was performed by PCR followed by DNA sequencing analysis. Bacteria and fungi identification was obtained by standard microbiological culture tests. 103 episodes of mucositis occurred, being 65 at D14 and 38 at D56. Most cases positive for herpes viral DNA sequences were identified as HSV-1. At D14, we found a significant association between the severity of mucositis and presence of HSV-1 (p = 0.0347), Candida spp. (p = 0.0078), and low platelet count (p = 0.0064). At D56, we found a significant association between the severity of mucositis and the presence of HSV-1 (p = 0.0317), previous HSV-1 presence on D14 (p < 0.0001) and neutrophil count (p = 0.0211). Clinical relevance: the identification of risk factors for mucositis in children and adolescents may contribute to the development of new strategies for prevention and/or treatment, reducing the complications associated with this condition. The presence of HSV, platelet count, and Candida spp. presence at D14 of ALL induction treatment is associated with increased severity of mucositis in children and adolescents. At D56 of ALL treatment, mucositis severity was associated with neutrophil count, HSV presence, and previous presence of HSV (at D14).325322330FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPES

Variation and statistical reliability of publicly reported primary care diagnostic activity indicators for cancer: a cross-sectional ecological study of routine data.

OBJECTIVES: Recent public reporting initiatives in England highlight general practice variation in indicators of diagnostic activity related to cancer. We aimed to quantify the size and sources of variation and the reliability of practice-level estimates of such indicators, to better inform how this information is interpreted and used for quality improvement purposes. DESIGN: Ecological cross-sectional study. SETTING: English primary care. PARTICIPANTS: All general practices in England with at least 1000 patients. MAIN OUTCOME MEASURES: Sixteen diagnostic activity indicators from the Cancer Services Public Health Profiles. RESULTS: Mixed-effects logistic and Poisson regression showed that substantial proportions of the observed variance in practice scores reflected chance, variably so for different indicators (between 7% and 85%). However, after accounting for the role of chance, there remained substantial variation between practices (typically up to twofold variation between the 75th and 25th centiles of practice scores, and up to fourfold variation between the 90th and 10th centiles). The age and sex profile of practice populations explained some of this variation, by different amounts across indicators. Generally, the reliability of diagnostic process indicators relating to broader populations of patients most of whom do not have cancer (eg, rate of endoscopic investigations, or urgent referrals for suspected cancer (also known as 'two week wait referrals')) was high (≥0.80) or very high (≥0.90). In contrast, the reliability of diagnostic outcome indicators relating to incident cancer cases (eg, per cent of all cancer cases detected after an emergency presentation) ranged from 0.24 to 0.54, which is well below recommended thresholds (≥0.70). CONCLUSIONS: Use of indicators of diagnostic activity in individual general practices should principally focus on process indicators which have adequate or high reliability and not outcome indicators which are unreliable at practice level

Ventricular volume expansion in presymptomatic genetic frontotemporal dementia

Objective: To characterize the time course of ventricular volume expansion in genetic frontotemporal dementia (FTD) and identify the onset time and rates of ventricular expansion in presymptomatic FTD mutation carriers. Methods: Participants included patients with a mutation in MAPT, PGRN, or C9orf72, or first-degree relatives of mutation carriers from the GENFI study with MRI scans at study baseline and at 1 year follow-up. Ventricular volumes were obtained from MRI scans using FreeSurfer, with manual editing of segmentation and comparison to fully automated segmentation to establish reliability. Linear mixed models were used to identify differences in ventricular volume and in expansion rates as a function of time to expected disease onset between presymptomatic carriers and noncarriers. Results: A total of 123 participants met the inclusion criteria and were included in the analysis (18 symptomatic carriers, 46 presymptomatic mutation carriers, and 56 noncarriers). Ventricular volume differences were observed 4 years prior to symptom disease onset for presymptomatic carriers compared to noncarriers. Annualized rates of ventricular volume expansion were greater in presymptomatic carriers relative to noncarriers. Importantly, time-intensive manually edited and fully automated ventricular volume resulted in similar findings. Conclusions: Ventricular volume differences are detectable in presymptomatic genetic FTD. Concordance of results from time-intensive manual editing and fully automatic segmentation approaches support its value as a measure of disease onset and progression in future studies in both presymptomatic and symptomatic genetic FTD