Long term cause specific mortality among 34 489 five year survivors of childhood cancer in Great Britain:population based cohort study

Objective To determine whether modern treatments for cancer are associated with a net increased or decreased risk of death from neoplastic and non-neoplastic causes among survivors of childhood cancer. Design Population based cohort study. Setting British Childhood Cancer Survivor Study. Participants Nationwide population based cohort of 34 489 five year survivors of childhood cancer with a diagnosis from 1940 to 2006 and followed up until 28 February 2014. Main outcome measures Cause specific standardised mortality ratios and absolute excess risks are reported. Multivariable Poisson regression models were utilised to evaluate the simultaneous effect of risk factors. Likelihood ratio tests were used to test for heterogeneity or trend. Results Overall, 4475 deaths were observed, which was 9.1 (95% confidence interval 8.9 to 9.4) times that expected in the general population, corresponding to 64.2 (95% confidence interval 62.1 to 66.3) excess deaths per 10 000 person years. The number of excess deaths from all causes declined among those treated more recently; those treated during 1990-2006 experienced 30% of the excess number of deaths experienced by those treated before 1970. The corresponding percentages for the decline in excess deaths from recurrence or progression and non-neoplastic causes were 30% and 60%, respectively. Among survivors aged 50-59 years, 41% and 22% of excess deaths were attributable to subsequent primary neoplasms and circulatory conditions, respectively, whereas the corresponding percentages among those aged 60 years or more were 31% and 37%. Conclusions The net effects of changes in cancer treatments, and surveillance and management for late effects, over the period 1940 to 2006 was to reduce the excess number of deaths from both recurrence or progression and non-neoplastic causes among those treated more recently. Among survivors aged 60 years or more, the excess number of deaths from circulatory causes exceeds the excess number of deaths from subsequent primary neoplasms. The important message for the evidence based surveillance aimed at preventing excess mortality and morbidity in survivors aged 60 years or more is that circulatory disease overtakes subsequent primary neoplasms as the leading cause of excess mortality

Aspects of mental health dysfunction among survivors of childhood cancer

BACKGROUND: Some previous studies have reported that survivors of childhood cancer are at an increased risk of developing long-term mental health morbidity, whilst others have reported that this is not the case. Therefore, we analysed 5-year survivors of childhood cancer using the British Childhood Cancer Survivor Study (BCCSS) to determine the risks of aspects of long-term mental health dysfunction. PROCEDURE: Within the BCCSS, 10 488 survivors completed a questionnaire that ascertained mental health-related information via 10 questions from the Short Form-36 survey. Internal analyses were conducted using multivariable logistic regression to determine risk factors for mental health dysfunction. External analyses were undertaken using direct standardisation to compare mental health dysfunction in survivors with UK norms. RESULTS: This study has shown that overall, childhood cancer survivors had a significantly higher prevalence of mental health dysfunction for 6/10 questions analysed compared to UK norms. Central nervous system (CNS) and bone sarcoma survivors reported the greatest dysfunction, compared to expected, with significant excess dysfunction in 10 and 6 questions, respectively; the excess ranged from 4.4–22.3% in CNS survivors and 6.9–15.9% in bone sarcoma survivors. Compared to expected, excess mental health dysfunction increased with attained age; this increase was greatest for reporting ‘limitations in social activities due to health', where the excess rose from 4.5% to 12.8% in those aged 16–24 and 45+, respectively. Within the internal analyses, higher levels of educational attainment and socio-economic classification were protective against mental health dysfunction. CONCLUSIONS: Based upon the findings of this large population-based study, childhood cancer survivors report significantly higher levels of mental health dysfunction than those in the general population, where deficits were observed particularly among CNS and bone sarcoma survivors. Limitations were also observed to increase with age, and thus it is important to emphasise the need for mental health evaluation and services across the entire lifespan. There is evidence that low educational attainment and being unemployed or having never worked adversely impacts long-term mental health. These findings provide an evidence base for risk stratification and planning interventions

The Protein Model Portal

Structural Genomics has been successful in determining the structures of many unique proteins in a high throughput manner. Still, the number of known protein sequences is much larger than the number of experimentally solved protein structures. Homology (or comparative) modeling methods make use of experimental protein structures to build models for evolutionary related proteins. Thereby, experimental structure determination efforts and homology modeling complement each other in the exploration of the protein structure space. One of the challenges in using model information effectively has been to access all models available for a specific protein in heterogeneous formats at different sites using various incompatible accession code systems. Often, structure models for hundreds of proteins can be derived from a given experimentally determined structure, using a variety of established methods. This has been done by all of the PSI centers, and by various independent modeling groups. The goal of the Protein Model Portal (PMP) is to provide a single portal which gives access to the various models that can be leveraged from PSI targets and other experimental protein structures. A single interface allows all existing pre-computed models across these various sites to be queried simultaneously, and provides links to interactive services for template selection, target-template alignment, model building, and quality assessment. The current release of the portal consists of 7.6 million model structures provided by different partner resources (CSMP, JCSG, MCSG, NESG, NYSGXRC, JCMM, ModBase, SWISS-MODEL Repository). The PMP is available at http://www.proteinmodelportal.org and from the PSI Structural Genomics Knowledgebase

Sex differences in the adult human brain:Evidence from 5216 UK Biobank participants

Sex differences in the human brain are of interest for many reasons: for example, there are sex differences in the observed prevalence of psychiatric disorders and in some psychological traits that brain differences might help to explain. We report the largest single-sample study of structural and functional sex differences in the human brain (2750 female, 2466 male participants; mean age 61.7 years, range 44–77 years). Males had higher raw volumes, raw surface areas, and white matter fractional anisotropy; females had higher raw cortical thickness and higher white matter tract complexity. There was considerable distributional overlap between the sexes. Subregional differences were not fully attributable to differences in total volume, total surface area, mean cortical thickness, or height. There was generally greater male variance across the raw structural measures. Functional connectome organization showed stronger connectivity for males in unimodal sensorimotor cortices, and stronger connectivity for females in the default mode network. This large-scale study provides a foundation for attempts to understand the causes and consequences of sex differences in adult brain structure and function

Patient-Reported Measures for Person-Centered Coordinated Care: A Comparative Domain Map and Web-Based Compendium for Supporting Policy Development and Implementation

BACKGROUND: Patient-reported measure (PRM) questionnaires were originally used in research to measure outcomes of intervention studies. They have now evolved into a diverse family of tools measuring a range of constructs including quality of life and experiences of care. Current health and social care policy increasingly advocates their use for embedding the patient voice into service redesign through new models of care such as person-centered coordinated care (P3C). If chosen carefully and used efficiently, these tools can help improve care delivery through a variety of novel ways, including system-level feedback for health care management and commissioning. Support and guidance on how to use these tools would be critical to achieve these goals. OBJECTIVE: The objective of this study was to develop evidence-based guidance and support for the use of P3C-PRMs in health and social care policy through identification of PRMs that can be used to enhance the development of P3C, mapping P3C-PRMs against an existing model of domains of P3C, and integration and organization of the information in a user-friendly Web-based database. METHODS: A pragmatic approach was used for the systematic identification of candidate P3C-PRMs, which aimed at balancing comprehensiveness and feasibility. This utilized a number of resources, including existing compendiums, peer-reviewed and gray literature (using a flexible search strategy), and stakeholder engagement (which included guidance for relevant clinical areas). A subset of those candidate measures (meeting prespecified eligibility criteria) was then mapped against a theoretical model of P3C, facilitating classification of the construct being measured and the subsequent generation of shortlists for generic P3C measures, specific aspects of P3C (eg, communication or decision making), and condition-specific measures (eg, diabetes, cancer) in priority areas, as highlighted by stakeholders. RESULTS: In total, 328 P3C-PRMs were identified, which were used to populate a freely available Web-based database. Of these, 63 P3C-PRMs met the eligibility criteria for shortlisting and were classified according to their measurement constructs and mapped against the theoretical P3C model. We identified tools with the best coverage of P3C, thereby providing evidence of their content validity as outcome measures for new models of care. Transitions and medications were 2 areas currently poorly covered by existing measures. All the information is currently available at a user-friendly web-based portal (p3c.org.uk), which includes all relevant information on each measure, such as the constructs targeted and links to relevant literature, in addition to shortlists according to relevant constructs. CONCLUSIONS: A detailed compendium of P3C-PRMs has been developed using a pragmatic systematic approach supported by stakeholder engagement. Our user-friendly suite of tools is designed to act as a portal to the world of PRMs for P3C, and have utility for a broad audience, including (but not limited to) health care commissioners, managers, and researchers.BACKGROUND: Patient-reported measure (PRM) questionnaires were originally used in research to measure outcomes of intervention studies. They have now evolved into a diverse family of tools measuring a range of constructs including quality of life and experiences of care. Current health and social care policy increasingly advocates their use for embedding the patient voice into service redesign through new models of care such as person-centered coordinated care (P3C). If chosen carefully and used efficiently, these tools can help improve care delivery through a variety of novel ways, including system-level feedback for health care management and commissioning. Support and guidance on how to use these tools would be critical to achieve these goals. OBJECTIVE: The objective of this study was to develop evidence-based guidance and support for the use of P3C-PRMs in health and social care policy through identification of PRMs that can be used to enhance the development of P3C, mapping P3C-PRMs against an existing model of domains of P3C, and integration and organization of the information in a user-friendly Web-based database. METHODS: A pragmatic approach was used for the systematic identification of candidate P3C-PRMs, which aimed at balancing comprehensiveness and feasibility. This utilized a number of resources, including existing compendiums, peer-reviewed and gray literature (using a flexible search strategy), and stakeholder engagement (which included guidance for relevant clinical areas). A subset of those candidate measures (meeting prespecified eligibility criteria) was then mapped against a theoretical model of P3C, facilitating classification of the construct being measured and the subsequent generation of shortlists for generic P3C measures, specific aspects of P3C (eg, communication or decision making), and condition-specific measures (eg, diabetes, cancer) in priority areas, as highlighted by stakeholders. RESULTS: In total, 328 P3C-PRMs were identified, which were used to populate a freely available Web-based database. Of these, 63 P3C-PRMs met the eligibility criteria for shortlisting and were classified according to their measurement constructs and mapped against the theoretical P3C model. We identified tools with the best coverage of P3C, thereby providing evidence of their content validity as outcome measures for new models of care. Transitions and medications were 2 areas currently poorly covered by existing measures. All the information is currently available at a user-friendly web-based portal (p3c.org.uk), which includes all relevant information on each measure, such as the constructs targeted and links to relevant literature, in addition to shortlists according to relevant constructs. CONCLUSIONS: A detailed compendium of P3C-PRMs has been developed using a pragmatic systematic approach supported by stakeholder engagement. Our user-friendly suite of tools is designed to act as a portal to the world of PRMs for P3C, and have utility for a broad audience, including (but not limited to) health care commissioners, managers, and researchers

Measuring quality of life in Duchenne muscular dystrophy : a systematic review of the content and structural validity of commonly used instruments

Duchenne muscular dystrophy (DMD) is an inherited X-linked neuromuscular disorder. A number of questionnaires are available to assess quality of life in DMD, but there are concerns about their validity. This systematic review aimed to appraise critically the content and structural validity of quality of life instruments for DMD. Five databases (EMBASE, MEDLINE, CINAHL, PsycINFO, and Cochrane Library) were searched, with supplementary searches in Google Scholar. We included articles with evidence on the content and/or structural validity of quality of life instruments in DMD, and/or instrument development. Evidence was evaluated against the Consensus-based Standards for the selection of health Measurement INstruments (COSMIN) criteria. Fifty five articles featured a questionnaire assessing quality of life in DMD. Forty instruments were extracted and 26 underwent assessment. Forty-one articles contained evidence on content or structural validity (including 37 development papers). Most instruments demonstrated low quality evidence and unsatisfactory or inconsistent validity in DMD, with the majority not featuring direct validation studies in this population. Only KIDSCREEN received an adequate rating for instrument design and a satisfactory result for content validity based on its development, yet, like the majority of PROMs, the measure has not been directly validated for use in DMD. Further research is needed on the validity of quality of life instruments in DMD, including content and structural validity studies in this population

Global wealth disparities drive adherence to COVID-safe pathways in head and neck cancer surgery

Peer reviewe