Variation in reported experience of involvement in cancer treatment decision making: Evidence from the National Cancer Patient Experience Survey

This is the final version. Available on open access from Springer Nature via the DOI in this recordBackground: Exploring variation in patients' experiences of involvement in treatment decision making can identify groups needing extra support, such as additional consultation time, when considering treatment options. Methods: We analysed data from the 2010 English National Cancer Patient Experience Survey, a national survey of all patients attending hospitals in England for cancer treatment over a 3-month period, to examine how experience of involvement in decisions about treatment varied between patients with 38 different primary cancers using logistic regression. We analysed responses from 41 411 patients to a single question examining patient experience of involvement in treatment decision making. We calculated unadjusted odds ratios of reporting the most positive experience between patients of different sociodemographic and tumour characteristics and explored the effects of adjusting for age, gender, ethnicity, deprivation, cancer type and hospital of treatment.Results:Of the 41 441 respondents, 29 776 (72%) reported positive experiences of decision-making involvement. Younger patients reported substantially less positive experiences of involvement in decision making (adjusted OR=0.49 16-24 vs 65-74; P<0.001), as did ethnic minorities (adjusted ORs=0.52, 0.62 and 0.73 for Black, Chinese and Asian vs White patients, respectively; P<0.001). Experience varied considerably between patients with different cancers (e.g., OR=0.52 for anal and 1.37 for melanoma vs colon cancer; P<0.001), with ovarian, myeloma, bladder and rectal cancer patients reporting substantially worse experiences compared with other patients with gynaecological, haematological, urological and colorectal cancers, respectively. Clustering of different patient groups within hospitals with outlying performance report scores could not account for observed differences. Conclusion: Efforts to improve involvement in treatment decision making can focus on those who report the worst experience, in particular younger patients, ethnic minorities and patients with rectal, ovarian, multiple myeloma and bladder cancer. © 2013 Cancer Research UK. All rights reserved.National Institute for Health Research (NIHR

Accuracy of routinely recorded ethnic group information compared with self-reported ethnicity: Evidence from the English Cancer Patient Experience survey

This is the final version. Available on open access from BMJ Publishing Group via the DOI in this recordData sharing statement No additional data are available.Objective: To describe the accuracy of ethnicity coding in contemporary National Health Service (NHS) hospital records compared with the 'gold standard' of self-reported ethnicity. Design: Secondary analysis of data from a crosssectional survey (2011). Setting: All NHS hospitals in England providing cancer treatment. Participants: 58 721 patients with cancer for whom ethnicity information (Office for National Statistics 2001 16-group classification) was available from self-reports (considered to represent the 'gold standard') and their hospital record. Methods: We calculated the sensitivity and positive predictive value (PPV) of hospital record ethnicity. Further, we used a logistic regression model to explore independent predictors of discordance between recorded and self-reported ethnicity. Results: Overall, 4.9% (4.7-5.1%) of people had their self-reported ethnic group incorrectly recorded in their hospital records. Recorded White British ethnicity had high sensitivity (97.8% (97.7-98.0%)) and PPV (98.1% (98.0-98.2%)) for self-reported White British ethnicity. Recorded ethnicity information for the 15 other ethnic groups was substantially less accurate with 41.2% (39.7-42.7%) incorrect. Recorded 'Mixed' ethnicity had low sensitivity (12-31%) and PPVs (12- 42%). Recorded 'Indian', 'Chinese', 'Black-Caribbean' and 'Black African' ethnic groups had intermediate levels of sensitivity (65-80%) and PPV (80-89%, respectively). In multivariable analysis, belonging to an ethnic minority group was the only independent predictor of discordant ethnicity information. There was strong evidence that the degree of discordance of ethnicity information varied substantially between different hospitals (p<0.0001). Discussion: Current levels of accuracy of ethnicity information in NHS hospital records support valid profiling of White/non-White ethnic differences. However, profiling of ethnic differences in process or outcome measures for specific minority groups may contain a substantial and variable degree of misclassification error. These considerations should be taken into account when interpreting ethnic variation audits based on routine data and inform initiatives aimed at improving the accuracy of ethnicity information in hospital records. Copyright © 2013 BMJ Publishing Group. All rights reserved.National Institute for Health Research (NIHR

The Pattern Of Neurological Manifestations Of Tuberculosis Among Adult Sudanese Patients

Objective: To study the pattern of neurological manifestations of tuberculosis among adult Sudanese tuberculous patients seen at El-Shaab Teaching Hospital (Sudan). Methods: This study was performed on 179 Sudanese patients with tuberculosis admitted at El-Shaab Teaching Hospital during the period from May 2005 to January 2006. Demographic and clinical data were obtained. Investigations including CXR, sputum for acid alcohol fast bacilli [AAFB], Mantoux test, complete haemogram were done. Screening for HIV, NC Study, EMG, CT, MRI of the brain or spinal cord were performed when indicated. Results: Fifty seven out of 179 tuberculous patients had neurological complications. 22 presented with Pott\'s paraplegia, 18 with peripheral neuropathy, six had tubercloma, three with tuberculous meningitis, three had quadriplegia, two had hemiplegia, two had proximal myopathy and one had multiple cranial nerves palsies CONCULSION: The study revealed high incidence of Potts paraplegia and peripheral neuropathy, this is most probably due to late presentation. Keywords: Pott\'s paraplegia, peripheral neuropathy, tubercloma, tuberculous meningitis, quadriplegia, hemiplegia, proximal myopathy Sudan Journal of Medical Sciences Vol. 3 (3) 2008: pp. 221-22

Accuracy of routinely recorded ethnic group information compared with self-reported ethnicity: evidence from the English Cancer Patient Experience survey.

OBJECTIVE: To describe the accuracy of ethnicity coding in contemporary National Health Service (NHS) hospital records compared with the 'gold standard' of self-reported ethnicity. DESIGN: Secondary analysis of data from a cross-sectional survey (2011). SETTING: All NHS hospitals in England providing cancer treatment. PARTICIPANTS: 58 721 patients with cancer for whom ethnicity information (Office for National Statistics 2001 16-group classification) was available from self-reports (considered to represent the 'gold standard') and their hospital record. METHODS: We calculated the sensitivity and positive predictive value (PPV) of hospital record ethnicity. Further, we used a logistic regression model to explore independent predictors of discordance between recorded and self-reported ethnicity. RESULTS: Overall, 4.9% (4.7-5.1%) of people had their self-reported ethnic group incorrectly recorded in their hospital records. Recorded White British ethnicity had high sensitivity (97.8% (97.7-98.0%)) and PPV (98.1% (98.0-98.2%)) for self-reported White British ethnicity. Recorded ethnicity information for the 15 other ethnic groups was substantially less accurate with 41.2% (39.7-42.7%) incorrect. Recorded 'Mixed' ethnicity had low sensitivity (12-31%) and PPVs (12-42%). Recorded 'Indian', 'Chinese', 'Black-Caribbean' and 'Black African' ethnic groups had intermediate levels of sensitivity (65-80%) and PPV (80-89%, respectively). In multivariable analysis, belonging to an ethnic minority group was the only independent predictor of discordant ethnicity information. There was strong evidence that the degree of discordance of ethnicity information varied substantially between different hospitals (p<0.0001). DISCUSSION: Current levels of accuracy of ethnicity information in NHS hospital records support valid profiling of White/non-White ethnic differences. However, profiling of ethnic differences in process or outcome measures for specific minority groups may contain a substantial and variable degree of misclassification error. These considerations should be taken into account when interpreting ethnic variation audits based on routine data and inform initiatives aimed at improving the accuracy of ethnicity information in hospital records

Type of RNA Packed in VLPs Impacts IgG Class Switching-Implications for an Influenza Vaccine Design

Nucleic acid packed within virus-like particles (VLPs) is shown to shape the immune response and to induce stronger B cell responses in different immunisation models. Here, using a VLP displaying the highly conserved extracellular domain of the M2 protein (M2e) from the influenza viruses as an antigen, we demonstrate that the type of RNA packaged into VLPs can alter the quality of the induced humoral response. By comparing prokaryotic RNA (pRNA), eukaryotic RNA (eRNA) and transfer RNA (tRNA), we find that pRNA induces the most protective IgG subclasses using a murine influenza model. We provide evidence that this process is predominantly dependent on endosomal Toll-like receptor (TLR7), and rule out a role for cytoplasmic mitochondrial antiviral signalling protein (MAVS) and its upstream retinoic acid-inducible gene-I-like receptors (RIG-I). Our findings provide considerations for the rational design of VLP-based vaccines and the immunomodulation exerted by TLR7 ligands packaged within the particles. Based on this work, we conclude that VLPs packing prokaryotic RNA must be preferred whenever a response dominated by IgG2 is desired, while eukaryotic RNA should be employed in order to induce a response dominated by IgG1

Virus-Like Particle (VLP) Plus Microcrystalline Tyrosine (MCT) Adjuvants Enhance Vaccine Efficacy Improving T and B Cell Immunogenicity and Protection against Plasmodium berghei/vivax

Vaccination is the most effective prophylactic tool against infectious diseases. Despite continued efforts to control malaria, the disease still generally represents a significant unmet medical need. Microcrystalline tyrosine (MCT) is a well described depot used in licensed allergy immunotherapy products and in clinical development. However, its proof of concept in prophylactic vaccines has only recently been explored. MCT has never been used in combination with virus-like particles (VLPs), which are considered to be one of the most potent inducers of cellular and humoral immune responses in mice and humans. In the current study we assessed the potential of MCT to serve as an adjuvant in the development of a vaccine against malaria either alone or combined with VLP using Plasmodium vivax thrombospondin-related adhesive protein (TRAP) as a target antigen. We chemically coupled PvTRAP to VLPs derived from the cucumber mosaic virus fused to a universal T-cell epitope of the tetanus toxin (CMVtt), formulated with MCT and compared the induced immune responses to PvTRAP formulated in PBS or Alum. The protective capacity of the various formulations was assessed using Plasmodium berghei expressing PvTRAP. All vaccine formulations using adjuvants and/or VLP increased humoral immunogenicity for PvTRAP compared to the antigen alone. The most proficient responder was the group of mice immunized with the vaccine formulated with PvTRAP-VLP + MCT. The VLP-based vaccine formulated in MCT also induced the strongest T cell response and conferred best protection against challenge with recombinant Plasmodium berghei. Thus, the combination of VLP with MCT may take advantage of the properties of each component and appears to be an alternative biodegradable depot adjuvant for development of novel prophylactic vaccines

Secondary influenza challenge triggers resident memory B cell migration and rapid relocation to boost antibody secretion at infected sites.

Resident memory B (BRM) cells develop and persist in the lungs of influenza-infected mice and humans; however, their contribution to recall responses has not been defined. Here, we used two-photon microscopy to visualize BRM cells within the lungs of influenza -virus immune and reinfected mice. Prior to re-exposure, BRM cells were sparsely scattered throughout the tissue, displaying limited motility. Within 24 h of rechallenge, these cells increased their migratory capacity, localized to infected sites, and subsequently differentiated into plasma cells. Alveolar macrophages mediated this process, in part by inducing expression of chemokines CXCL9 and CXCL10 from infiltrating inflammatory cells. This led to the recruitment of chemokine receptor CXCR3-expressing BRM cells to infected regions and increased local antibody concentrations. Our study uncovers spatiotemporal mechanisms that regulate lung BRM cell reactivation and demonstrates their capacity to rapidly deliver antibodies in a highly localized manner to sites of viral replication

Diagnostic value of cerebrospinal fluid alpha-synuclein seed quantification in synucleinopathies

Several studies have confirmed the α-synuclein real-time quaking-induced conversion (RT-QuIC) assay to have high sensitivity and specificity for Parkinson's disease. However, whether the assay can be used as a robust, quantitative measure to monitor disease progression, stratify different synucleinopathies and predict disease conversion in patients with idiopathic REM sleep behaviour disorder remains undetermined. The aim of this study was to assess the diagnostic value of CSF α-synuclein RT-QuIC quantitative parameters in regard to disease progression, stratification and conversion in synucleinopathies. We performed α-synuclein RT-QuIC in the CSF samples from 74 Parkinson's disease, 24 multiple system atrophy and 45 idiopathic REM sleep behaviour disorder patients alongside 55 healthy controls, analysing quantitative assay parameters in relation to clinical data. α-Synuclein RT-QuIC showed 89% sensitivity and 96% specificity for Parkinson's disease. There was no correlation between RT-QuIC quantitative parameters and Parkinson's disease clinical scores (e.g. Unified Parkinson's Disease Rating Scale motor), but RT-QuIC positivity and some quantitative parameters (e.g. Vmax) differed across the different phenotype clusters. RT-QuIC parameters also added value alongside standard clinical data in diagnosing Parkinson's disease. The sensitivity in multiple system atrophy was 75%, and CSF samples showed longer T50 and lower Vmax compared to Parkinson's disease. All RT-QuIC parameters correlated with worse clinical progression of multiple system atrophy (e.g. change in Unified Multiple System Atrophy Rating Scale). The overall sensitivity in idiopathic REM sleep behaviour disorder was 64%. In three of the four longitudinally followed idiopathic REM sleep behaviour disorder cohorts, we found around 90% sensitivity, but in one sample (DeNoPa) diagnosing idiopathic REM sleep behaviour disorder earlier from the community cases, this was much lower at 39%. During follow-up, 14 of 45 (31%) idiopathic REM sleep behaviour disorder patients converted to synucleinopathy with 9/14 (64%) of convertors showing baseline RT-QuIC positivity. In summary, our results showed that α-synuclein RT-QuIC adds value in diagnosing Parkinson's disease and may provide a way to distinguish variations within Parkinson's disease phenotype. However, the quantitative parameters did not correlate with disease severity in Parkinson's disease. The assay distinguished multiple system atrophy patients from Parkinson's disease patients and in contrast to Parkinson's disease, the quantitative parameters correlated with disease progression of multiple system atrophy. Our results also provided further evidence for α-synuclein RT-QuIC having potential as an early biomarker detecting synucleinopathy in idiopathic REM sleep behaviour disorder patients prior to conversion. Further analysis of longitudinally followed idiopathic REM sleep behaviour disorder patients is needed to better understand the relationship between α-synuclein RT-QuIC signature and the progression from prodromal to different synucleinopathies

Vaccination with nanoparticles combined with micro-adjuvants protects against cancer.

Induction of strong T cell responses, in particular cytotoxic T cells, is a key for the generation of efficacious therapeutic cancer vaccines which yet, remains a major challenge for the vaccine developing world. Here we demonstrate that it is possible to harness the physiological properties of the lymphatic system to optimize the induction of a protective T cell response. Indeed, the lymphatic system sharply distinguishes between nanoscale and microscale particles. The former reaches the fenestrated lymphatic system via diffusion, while the latter either need to be transported by dendritic cells or form a local depot. Our previously developed cucumber-mosaic virus-derived nanoparticles termed (CuMV &lt;sub&gt;TT&lt;/sub&gt; -VLPs) incorporating a universal Tetanus toxoid epitope TT830-843 were assessed for their draining kinetics using stereomicroscopic imaging. A nano-vaccine has been generated by coupling p33 epitope as a model antigen to CuMV &lt;sub&gt;TT&lt;/sub&gt; -VLPs using bio-orthogonal Cu-free click chemistry. The CuMV &lt;sub&gt;TT&lt;/sub&gt; -p33 nano-sized vaccine has been next formulated with the micron-sized microcrystalline tyrosine (MCT) adjuvant and the formed depot effect was studied using confocal microscopy and trafficking experiments. The immunogenicity of the nanoparticles combined with the micron-sized adjuvant was next assessed in an aggressive transplanted murine melanoma model. The obtained results were compared to other commonly used adjuvants such as B type CpGs and Alum. Our results showed that CuMV &lt;sub&gt;TT&lt;/sub&gt; -VLPs can efficiently and rapidly drain into the lymphatic system due to their nano-size of ~ 30 nm. However, formulating the nanoparticles with the micron-sized MCT adjuvant of ~ 5 μM resulted in a local depot for the nanoparticles and a longer exposure time for the immune system. The preclinical nano-vaccine CuMV &lt;sub&gt;TT&lt;/sub&gt; -p33 formulated with the micron-sized MCT adjuvant has enhanced the specific T cell response in the stringent B16F10p33 murine melanoma model. Furthermore, the micron-sized MCT adjuvant was as potent as B type CpGs and clearly superior to the commonly used Alum adjuvant when total CD8 &lt;sup&gt;+&lt;/sup&gt; , specific p33 T cell response or tumour protection were assessed. The combination of nano- and micro-particles may optimally harness the physiological properties of the lymphatic system. Since the nanoparticles are well defined virus-like particles and the micron-sized adjuvant MCT has been used for decades in allergen-specific desensitization, this approach may readily be translated to the clinic