Do Differential Response Rates to Patient Surveys Between Organizations Lead to Unfair Performance Comparisons?: Evidence From the English Cancer Patient Experience Survey.

BACKGROUND: Patient surveys typically have variable response rates between organizations, leading to concerns that such differences may affect the validity of performance comparisons. OBJECTIVE: To explore the size and likely sources of associations between hospital-level survey response rates and patient experience. RESEARCH DESIGN, SUBJECTS, AND MEASURES: Cross-sectional mail survey including 60 patient experience items sent to 101,771 cancer survivors recently treated by 158 English NHS hospitals. Age, sex, race/ethnicity, socioeconomic status, clinical diagnosis, hospital type, and region were available for respondents and nonrespondents. RESULTS: The overall response rate was 67% (range, 39% to 77% between hospitals). Hospitals with higher response rates had higher scores for all items (Spearman correlation range, 0.03-0.44), particularly questions regarding hospital-level administrative processes, for example, procedure cancellations or medical note availability.From multivariable analysis, associations between individual patient experience and hospital-level response rates were statistically significant (P<0.05) for 53/59 analyzed questions, decreasing to 37/59 after adjusting for case-mix, and 25/59 after further adjusting for hospital-level characteristics.Predicting responses of nonrespondents, and re-estimating hypothetical hospital scores assuming a 100% response rate, we found that currently low performing hospitals would have attained even lower scores. Overall nationwide attainment would have decreased slightly to that currently observed. CONCLUSIONS: Higher response rate hospitals have more positive experience scores, and this is only partly explained by patient case-mix. High response rates may be a marker of efficient hospital administration, and higher quality that should not, therefore, be adjusted away in public reporting. Although nonresponse may result in slightly overestimating overall national levels of performance, it does not appear to meaningfully bias comparisons of case-mix-adjusted hospital results

Do Differential Response Rates to Patient Surveys between Organizations Lead to Unfair Performance Comparisons? Evidence from the English Cancer Patient Experience Survey

This is the final published version. Available from Lippincott Williams & Wilkins via the DOI in this record.Background: Patient surveys typically have variable response rates between organizations, leading to concerns that such differences may affect the validity of performance comparisons. Objective: To explore the size and likely sources of associations between hospital-level survey response rates and patient experience. Research Design, Subjects, and Measures: Cross-sectional mail survey including 60 patient experience items sent to 101,771 cancer survivors recently treated by 158 English NHS hospitals. Age, sex, race/ethnicity, socioeconomic status, clinical diagnosis, hospital type, and region were available for respondents and nonrespondents. Results: The overall response rate was 67% (range, 39% to 77% between hospitals). Hospitals with higher response rates had higher scores for all items (Spearman correlation range, 0.03-0.44), particularly questions regarding hospital-level administrative processes, for example, procedure cancellations or medical note availability. From multivariable analysis, associations between individual patient experience and hospital-level response rates were statistically significant (P < 0.05) for 53/59 analyzed questions, decreasing to 37/59 after adjusting for case-mix, and 25/59 after further adjusting for hospital-level characteristics. Predicting responses of nonrespondents, and re-estimating hypothetical hospital scores assuming a 100% response rate, we found that currently low performing hospitals would have attained even lower scores. Overall nationwide attainment would have decreased slightly to that currently observed. Conclusions: Higher response rate hospitals have more positive experience scores, and this is only partly explained by patient casemix. High response rates may be a marker of efficient hospital administration, and higher quality that should not, therefore, be adjusted away in public reporting. Although nonresponse may result in slightly overestimating overall national levels of performance, it does not appear to meaningfully bias comparisons of case-mixadjusted hospital results.Cancer Research U

Development and validation of the Cambridge Multimorbidity Score

BACKGROUND: Health services have failed to respond to the pressures of multimorbidity. Improved measures of multimorbidity are needed for conducting research, planning services and allocating resources. METHODS: We modelled the association between 37 morbidities and 3 key outcomes (primary care consultations, unplanned hospital admission, death) at 1 and 5 years. We extracted development (n = 300 000) and validation (n = 150 000) samples from the UK Clinical Practice Research Datalink. We constructed a general-outcome multimorbidity score by averaging the standardized weights of the separate outcome scores. We compared performance with the Charlson Comorbidity Index. RESULTS: Models that included all 37 conditions were acceptable predictors of general practitioner consultations (C-index 0.732, 95% confidence interval [CI] 0.731-0.734), unplanned hospital admission (C-index 0.742, 95% CI 0.737-0.747) and death at 1 year (C-index 0.912, 95% CI 0.905-0.918). Models reduced to the 20 conditions with the greatest combined prevalence/weight showed similar predictive ability (C-indices 0.727, 95% CI 0.725-0.728; 0.738, 95% CI 0.732-0.743; and 0.910, 95% CI 0.904-0.917, respectively). They also predicted 5-year outcomes similarly for consultations and death (C-indices 0.735, 95% CI 0.734-0.736, and 0.889, 95% CI 0.885-0.892, respectively) but performed less well for admissions (C-index 0.708, 95% CI 0.705-0.712). The performance of the general-outcome score was similar to that of the outcome-specific models. These models performed significantly better than those based on the Charlson Comorbidity Index for consultations (C-index 0.691, 95% CI 0.690-0.693) and admissions (C-index 0.703, 95% CI 0.697-0.709) and similarly for mortality (C-index 0.907, 95% CI 0.900-0.914). INTERPRETATION: The Cambridge Multimorbidity Score is robust and can be either tailored or not tailored to specific health outcomes. It will be valuable to those planning clinical services, policymakers allocating resources and researchers seeking to account for the effect of multimorbidity

Germline DNA Repair Gene Mutations in Young-onset Prostate Cancer Cases in the UK: Evidence for a More Extensive Genetic Panel

Background Rare germline mutations in DNA repair genes are associated with prostate cancer (PCa) predisposition and prognosis. Objective To quantify the frequency of germline DNA repair gene mutations in UK PCa cases and controls, in order to more comprehensively evaluate the contribution of individual genes to overall PCa risk and likelihood of aggressive disease. Design, setting, and participants We sequenced 167 DNA repair and eight PCa candidate genes in a UK-based cohort of 1281 young-onset PCa cases (diagnosed at ≤60 yr) and 1160 selected controls. Outcome measurements and statistical analysis Gene-level SKAT-O and gene-set adaptive combination of p values (ADA) analyses were performed separately for cases versus controls, and aggressive (Gleason score ≥8, n = 201) versus nonaggressive (Gleason score ≤7, n = 1048) cases. Results and limitations We identified 233 unique protein truncating variants (PTVs) with minor allele frequency <0.5% in controls in 97 genes. The total proportion of PTV carriers was higher in cases than in controls (15% vs 12%, odds ratio [OR] = 1.29, 95% confidence interval [CI] 1.01–1.64, p = 0.036). Gene-level analyses selected NBN (pSKAT-O = 2.4 × 10−4) for overall risk and XPC (pSKAT-O = 1.6 × 10−4) for aggressive disease, both at candidate-level significance (p < 3.1 × 10−4 and p < 3.4 × 10−4, respectively). Gene-set analysis identified a subset of 20 genes associated with increased PCa risk (OR = 3.2, 95% CI 2.1–4.8, pADA = 4.1 × 10−3) and four genes that increased risk of aggressive disease (OR = 11.2, 95% CI 4.6–27.7, pADA = 5.6 × 10−3), three of which overlap the predisposition gene set. Conclusions The union of the gene-level and gene-set-level analyses identified 23 unique DNA repair genes associated with PCa predisposition or risk of aggressive disease. These findings will help facilitate the development of a PCa-specific sequencing panel with both predictive and prognostic potential. Patient summary This large sequencing study assessed the rate of inherited DNA repair gene mutations between prostate cancer patients and disease-free men. A panel of 23 genes was identified, which may improve risk prediction or treatment pathways in future clinical practice

Screening and assessment tools for gaming disorder: A comprehensive systematic review

The inclusion of gaming disorder (GD) as an official diagnosis in the ICD-11 was a significant milestone for the field. However, the optimal measurement approaches for GD are currently unclear. This comprehensive systematic review aimed to identify and evaluate all available English-language GD tools and their corresponding evidence. A search of PsychINFO, PsychArticles, ScienceDirect, Scopus, Web of Science, and Google Scholar identified 32 tools employed in 320 studies (N = 462,249 participants). The evaluation framework examined tools in relation to: (1) conceptual and practical considerations; (2) alignment with DSM-5 and ICD-11 criteria; (3) type and quantity of studies and samples; and (4) psychometric properties. The evaluation showed that GD instrumentation has proliferated, with 2.5 tools, on average, published annually since 2013. Coverage of DSM-5 and ICD-11 criteria was inconsistent, especially for the criterion of continued use despite harm. Tools converge on the importance of screening for impaired control over gaming and functional impairment. Overall, no single tool was found to be clearly superior, but the AICA-Sgaming, GAS-7, IGDT-10, IGDS9-SF, and Lemmens IGD-9 scales had greater evidential support for their psychometric properties. The GD field would benefit from a standard international tool to identify gaming-related harms across the spectrum of maladaptive gaming behaviors.Peer reviewedFinal Accepted Versio

Why business angels reject investment opportunities: Is it personal?

A major focus of research on business angels has examined their decision-making processes and investment criteria. As business angels reject most of the opportunities that they receive, this article explores the reasons informing such decisions. In view of angel heterogeneity, investment opportunities might be expected to be rejected for differing reasons. Two sources of data are used to examine this issue. Face-to-face interviews with 30 business angels in Scotland and Northern Ireland provided information on typical ‘deal killers’. This was complemented by an Internet survey of United Kingdom that attracted responses from 238 UK business angels. The findings confirm that the main reason for rejection relates to the entrepreneur/management team. However, angel characteristics do not explain the number of reasons given for opportunity rejection nor do they predict the reasons for rejecting investment opportunities. This could be related to the increasing trend for business angels to join organised groups which, in turn, leads to the development of a shared repertoire of investment approaches. We suggest the concept of ‘communities-of-practice’ as an explanation for this finding

Colloidal Single-Layer Photocatalysts for Methanol-Storable Solar H₂ Fuel

Molecular surfactants are widely used to control low-dimensional morphologies, including 2D nanomaterials in colloidal chemical synthesis, but it is still highly challenging to accurately control single-layer growth for 2D materials. A scalable stacking-hinderable strategy to not only enable exclusive single-layer growth mode for transition metal dichalcogenides (TMDs) selectively sandwiched by surfactant molecules but also retain sandwiched single-layer TMDs' photoredox activities is developed. The single-layer growth mechanism is well explained by theoretical calculation. Three types of single-layer TMDs, including MoS2 , WS2 , and ReS2 , are successfully synthesized and demonstrated in solar H2 fuel production from hydrogen-stored liquid carrier-methanol. Such H2 fuel production from single-layer MoS2 nanosheets is COx -free and reliably workable under room temperature and normal pressure with the generation rate reaching ≈617 µmole g-1 h-1 and excellent photoredox endurability. This strategy opens up the feasible avenue to develop methanol-storable solar H2 fuel with facile chemical rebonding actualized by 2D single-layer photocatalysts

Controlled dendrimersome nanoreactor system for localised hypochlorite-induced killing of bacteria

Antibiotic resistance is a serious global health problem necessitating new bactericidal approaches such as nanomedicines. Dendrimersomes (DSs) have recently become a valuable alternative nanocarrier to polymersomes and liposomes due to their molecular definition and synthetic versatility. Despite this, their biomedical application is still in its infancy. Inspired by the localized antimicrobial function of neutrophil phagosomes and the versatility of DSs, a simple three-component DS-based nanoreactor with broad-spectrum bactericidal activity is presented. This was achieved by encapsulation of glucose oxidase (GOX) and myeloperoxidase (MPO) within DSs (GOX-MPO-DSs), self-assembled from an amphiphilic Janus dendrimer, that possesses a semipermeable membrane. By external addition of glucose to GOX-MPO-DS, the production of hypochlorite (−OCl), a highly potent antimicrobial, by the enzymatic cascade was demonstrated. This cascade nanoreactor yielded a potent bactericidal effect against two important multidrug resistant pathogens, Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa), not observed for H2O2 producing nanoreactors, GOX-DS. The production of highly reactive species such as –OCl represents a harsh bactericidal approach that could also be cytotoxic to mammalian cells. This necessitates the development of strategies for activating –OCl production in a localized manner in response to a bacterial stimulus. One option of locally releasing sufficient amounts of substrate using a bacterial trigger (released toxins) was demonstrated with lipidic glucose-loaded giant unilamellar vesicles (GUVs), envisioning, e.g., implant surface modification with nanoreactors and GUVs for localized production of bactericidal agents in the presence of bacterial growth

MicroRNAs in cardiac arrhythmia: DNA sequence variation of MiR-1 and MiR-133A in long QT syndrome.

Long QT syndrome (LQTS) is a genetic cardiac condition associated with prolonged ventricular repolarization, primarily a result of perturbations in cardiac ion channels, which predisposes individuals to life-threatening arrhythmias. Using DNA screening and sequencing methods, over 700 different LQTS-causing mutations have been identified in 13 genes worldwide. Despite this, the genetic cause of 30-50% of LQTS is presently unknown. MicroRNAs (miRNAs) are small (∼ 22 nucleotides) noncoding RNAs which post-transcriptionally regulate gene expression by binding complementary sequences within messenger RNAs (mRNAs). The human genome encodes over 1800 miRNAs, which target about 60% of human genes. Consequently, miRNAs are likely to regulate many complex processes in the body, indeed aberrant expression of various miRNA species has been implicated in numerous disease states, including cardiovascular diseases. MiR-1 and MiR-133A are the most abundant miRNAs in the heart and have both been reported to regulate cardiac ion channels. We hypothesized that, as a consequence of their role in regulating cardiac ion channels, genetic variation in the genes which encode MiR-1 and MiR-133A might explain some cases of LQTS. Four miRNA genes (miR-1-1, miR-1-2, miR-133a-1 and miR-133a-2), which encode MiR-1 and MiR-133A, were sequenced in 125 LQTS probands. No genetic variants were identified in miR-1-1 or miR-133a-1; but in miR-1-2 we identified a single substitution (n.100A> G) and in miR-133a-2 we identified two substitutions (n.-19G> A and n.98C> T). None of the variants affect the mature miRNA products. Our findings indicate that sequence variants of miR-1-1, miR-1-2, miR-133a-1 and miR-133a-2 are not a cause of LQTS in this cohort