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Background: Individuals with diabetes and a learning disability have poorer health outcomes than those without a learning disability. In the UK, the health inequalities faced by people with learning disabilities are often the result of barriers they face in accessing timely, appropriate and effective health care. The aim of the study was to review relevant literature to identify the barriers and enablers to optimal diabetes care for adults with learning disabilities. Methods: Systematic review methodology was used to answer the research question: What barriers and enablers to optimal diabetes care exist for adults with learning disabilities? This review is reported according to PRISMA guidelines. Key databases were searched using relevant terms. Included studies were synthesised using thematic analysis and were quality appraised. Findings: This review identified 12 barriers to optimal diabetes care for adults with learning disabilities and 14 enablers to optimal care from 10 diverse publications. "Low level of diabetes knowledge and understanding" and "systems that do not allow reasonable adjustments" were the barriers considered to have the greatest reliability. The enabler identified to have the highest reliability was "person-centred planning and reasonable adjustments." Conclusion: This work highlights key actions that can be undertaken to address inequalities in diabetes care for people with learning disabilities. With additional research in this field, further progress can be made to improve the lives of those adults living with learning disabilities and diabetes.

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Background: With millions of unscheduled patient contacts every year and increasing call outs clustered around the most deprived communities, it is clear the ambulance sector could have a role to play in improving population health. However, the application and value of a public health approach within the ambulance sector has not been comprehensively explored. A scoping review was undertaken to explore the role of the ambulance sector in the delivery of public health interventions and what impact this has on population health and ambulance sector outcomes. Methods: A search strategy was developed on MEDLINE and translated to other major medical and health related bibliographic databases (Embase; CINAHL; HMIC; Science and Social Sciences Citation Index; Cochrane Library) to identify literature published since 2000 in OECD countries. Targeted grey literature, reference list, and citation searching was also carried out. Search results were downloaded to Microsoft Excel and screened by three reviewers according to pre-determined inclusion / exclusion criteria. Data from included studies, such as the type of activity noted within the paper, the population involved and the public health approach that was utilised, was extracted from within the paper using a data extraction form and narratively synthesised. Results: Fifty-two references were included in the final review (37 database searching; 9 reference list searching; 6 grey literature). Included articles were categorised according to the relevant public health domains and subdomains as articulated by the UK Faculty of Public Health: Health improvement domain: Public health education and advice (Health promotion sub-domain) (n=13) Emergency Services personnel providing vaccines (Disease prevention sub-domain) (n=1) Health care public health domain Paramedicine (Service delivery sub-domain) (n=30) Screening tools and referral pathways used by the ambulance sector (Service delivery sub-domain) (n=28) Health intelligence using ambulance sector data (population health management sub-domain) (n=26) Of note, some domains (e.g. health protection) returned nil results. Discussion: The scoping review demonstrates the breadth of public health related activities in which the ambulance sector is involved. However, an overemphasis on demand management outcomes precludes definitive conclusions on the impact of ambulance sector-led public health initiatives on public health outcomes. Future evaluations of public health initiatives should incorporate wider health system perspectives beyond the immediately apparent remit of the ambulance sector. [ABSTRACT FROM AUTHOR]

Recent clinical evidence showed that breast cancer with low HER2 expression levels responded to trastuzumab deruxtecan therapy. The HER2-low cancers comprise immunohistochemistry (IHC) score 1+ and 2+ ISH non-amplified tumours, currently classified as HER2 negative. Little data exists on the reproducibility of pathologists reporting of HER2-low cancer. Sixteen expert pathologists of the UK National Coordinating Committee for Breast Pathology scored 50 digitally scanned HER2 IHC slides. The overall level of agreement, Fleiss multiple-rater kappa statistics and Cohen's Kappa were calculated. Cases with low concordance were re-scored by the same pathologists after a washout period. Absolute agreement was achieved in 6% of cases, all of which scored 3+. Poor agreement was found in 5/50 (10%) of cases. This was due to heterogeneous HER2 expression, cytoplasmic staining and low expression spanning the 10% cut-off value. Highest concordance (86%) was achieved when scores were clustered as 0 versus others. Improvement in kappa of overall agreement was achieved when scores 1+ and 2+ were combined. Inter-observer agreement was moderate to substantial in the whole cohort but fair to moderate in the HER2-low group. Similarly, consensus-observer agreement was substantial to almost perfect in the whole cohort and moderate to substantial in the HER2-low group. HER2-low breast cancer suffers from lower concordance among expert pathologists. While most cases can reproducibly be classified, a small proportion (10%) remained challenging. Refining the criteria for reporting and consensus scoring will help select appropriate patients for targeted therapy. • Concordance of HER2 low scoring using digital whole slide images was assessed among 16 expert pathologists. • 10% of cases were challenging to classify; all were of the HER2 low and ultralow. • Heterogeneity, cytoplasmic expression and percentage expression around 10% were reasons for discordance. • Clustering of categories (0 versus others) resulted in the highest concordance levels. [ABSTRACT FROM AUTHOR]

• Colistimethate sodium dry powder for inhalation (CMS-DPI) and comparator cohorts generally had similar rates of adverse events. • This study supports the long-term safety profile of CMS-DPI in people with cystic fibrosis (CF). • UK CF Registry data are suitable for long-term drug safety studies. As part of the risk management plan in Europe, a long-term observational study was conducted to monitor the safety of colistimethate sodium dry powder for inhalation (CMS-DPI) compared to other inhaled antibiotics. A cohort of CMS-DPI patients and a matched cohort were identified from the UK Cystic Fibrosis Registry (UKCFR) from 2014-2018. The primary outcome was a composite endpoint, defined as adverse events (AEs) or new cystic fibrosis (CF) complications. Other outcomes included pulmonary exacerbations and treatment discontinuations. Of 1466 and 3503 patients in the CMS-DPI and comparator cohorts, respectively, 82.7% and 79.4% had AEs. Among the most common new CF complications were osteopenia, CF-related diabetes, and increased liver enzymes. The adjusted event rate ratio (ERR) for the primary outcome was 1.25 (95% confidence interval [CI]: 1.18-1.33, p <0.001). After excluding new CF complications, there was no difference between cohorts (ERR=1.04, 95% CI: 0.79-1.38, p =0.785). Pulmonary exacerbations were common in CMS-DPI and comparator cohorts (78.0% and 79.9% of patients, respectively), with adjusted ERR of 1.02 (95% CI: 0.95-1.10, p =0.523). Rates of discontinuation were similar in the CMS-DPI and Tobramycin inhalation powder comparator cohorts (37.8% and 39.8% of patients, respectively). There was no difference in the rate of adverse events between CMS-DPI and comparator cohorts. The safety profile of CMS-DPI is similar to those of other inhaled antibiotics, supporting its long-term safety in people with CF. The UKCFR has developed a successful model for partnership with industry to conduct long-term studies aimed at assessing drug safety. [ABSTRACT FROM AUTHOR]

Background: Hospital emergency departments play a crucial role in the initial assessment and management of suspected COVID-19 infection. This needs to be guided by studies of people presenting with suspected COVID-19, including those admitted and discharged, and those who do not ultimately have COVID-19 confirmed. We aimed to characterise patients attending emergency departments with suspected COVID-19, including subgroups based on sex, ethnicity and COVID-19 test results. Methods and findings: We undertook a mixed prospective and retrospective observational cohort study in 70 emergency departments across the United Kingdom (UK). We collected presenting data from 22445 people attending with suspected COVID-19 between 26 March 2020 and 28 May 2020. Outcomes were admission to hospital, COVID-19 result, organ support (respiratory, cardiovascular or renal), and death, by record review at 30 days. Mean age was 58.4 years, 11200 (50.4%) were female and 11034 (49.6%) male. Adults (age >16 years) were acutely unwell (median NEWS2 score of 4), frequently had limited performance status (46.9%) and had high rates of admission (67.1%), COVID-19 positivity (31.2%), organ support (9.8%) and death (15.5%). Children had much lower rates of admission (27.4%), COVID-19 positivity (1.2%), organ support (1.4%) and death (0.3%). Similar numbers of men and women presented to the ED, but men were more likely to be admitted (72.9% v 61.4%), require organ support (12.2% v 7.7%) and die (18.2% v 13.0%). Black or Asian adults tended to be younger than White adults (median age 54, 50 and 67 years), were less likely to have impaired performance status (43.1%, 26.8% and 51.6%), be admitted to hospital (60.8%, 57.3%, 69.6%) or die (11.6%, 11.2%, 16.4%), but were more likely to require organ support (15.9%, 14.3%, 8.9%) or have a positive COVID-19 test (40.8%, 42.1%, 30.0%). Adults admitted with suspected and confirmed COVID-19 had similar age, performance status and comorbidities (except chronic lung disease) to those who did not have COVID-19 confirmed, but were much more likely to need organ support (22.2% v 8.9%) or die (32.1% v 15.5%). Conclusions: Important differences exist between patient groups presenting to the emergency department with suspected COVID-19. Adults and children differ markedly and require different approaches to emergency triage. Admission and adverse outcome rates among adults suggest that policies to avoid unnecessary ED attendance achieved their aim. Subsequent COVID-19 confirmation confers a worse prognosis and greater need for organ support. Registration: ISRCTN registry, ISRCTN56149622, http://www.isrctn.com/ISRCTN28342533. [ABSTRACT FROM AUTHOR]

Background Demand management defines any method used to monitor, direct, or regulate patient referrals. Strategies have been developed to manage the referral of patients to secondary care, with interventions that target primary care, specialist services, or infrastructure. Aim To review the international evidence on interventions to manage referral from primary to specialist care. Design and setting Systematic review. Method Iterative, systematic searches of published and unpublished sources public health, health management, management, and grey literature databases from health care and other industries were undertaken to identify recent, relevant studies. A narrative synthesis of the data was completed to structure the evidence into groups of similar interventions. Results The searches generated 8327 unique results, of which 140 studies were included. Interventions were grouped into four intervention categories: GP education (n = 50); process change (n = 49); system change (n = 38); and patient-focused (n = 3). It is clear that there is no 'magic bullet' to managing demand for secondary care services: although some groups of interventions may have greater potential for development, given the existing evidence that they can be effective in specific contexts. Conclusions To tackle demand management of primary care services, the focus cannot be on primary care alone; a whole-systems approach is needed because the introduction of interventions in primary care is often just the starting point of the referral process. In addition, more research is needed to develop and evaluate interventions that acknowledge the role of the patient in the referral decision. [ABSTRACT FROM AUTHOR]

Background: Emergency planning in the UK has grown considerably in recent years, galvanised by the threat of terrorism. However, deficiencies in NHS emergency planning were identified and the evidence-base that underpins it is questionable. Inconsistencies in terminologies and concepts also exist. Different models of emergency management exist internationally but the optimal system is unknown. This study examines the evidence-base and evidence requirements for emergency planning in the UK health context. Methods: The study involved semi-structured interviews with key stakeholders and opinion leaders. Purposive sampling was used to obtain a breadth of views from various agencies involved in emergency planning and response. Interviews were then analysed using a grounded approach using standard framework analysis techniques. Results: We conducted 17 key informant interviews. Interviewees identified greater gaps in operational than technical aspects of emergency planning. Social and behavioural knowledge gaps were highlighted with regards to how individuals and organisations deal with risk and behave in emergencies. Evidence-based approaches to public engagement and for developing community resilience to disasters are lacking. Other gaps included how knowledge was developed and used. Conflicting views with regards to the optimal configuration and operation of the emergency management system were voiced. Conclusions: Four thematic categories for future research emerged: (i) Knowledge-base for emergency management: Further exploration is needed of how knowledge is acquired, valued, disseminated, adopted and retained. (ii) Social and behavioural issues: Greater understanding of how individuals approach risk and behave in emergencies is required. (iii) Organisational issues in emergencies: Several conflicting organisational issues were identified; value of planning versus plans, flexible versus standardized procedures, top-down versus bottom-up engagement, generic versus specific planning, and reactive versus proactive approaches to emergencies. (iv) Emergency management system: More study is required of system-wide issues relating to system configuration and operation, public engagement, and how emergency planning is assessed. INSET: `. [ABSTRACT FROM AUTHOR]

Background: Recent terrorist attacks and natural disasters have led to an increased awareness of the importance of emergency planning. However, the extent to which emergency planners can access or use evidence remains unclear. The aim of this study was to identify, analyse and assess the location, source and quality of emergency planning publications in the academic and UK grey literature. Methods: We conducted a scoping review, using as data sources for academic literature Embase, Medline, Medline in Process, Psychinfo, Biosis, Science Citation Index, Cinahl, Cochrane library and Clinicaltrials.gov. For grey literature identification we used databases at the Health Protection Agency, NHS Evidence, British Association of Immediate Care Schemes, Emergency Planning College and the Health and Safety Executive, and the websites of UK Department of Health Emergency Planning Division and UK Resilience. Aggregative synthesis was used to analyse papers and documents against a framework based on a modified FEMA Emergency Planning cycle. Results: Of 2736 titles identified from the academic literature, 1603 were relevant. 45% were from North America, 27% were commentaries or editorials and 22% were event reports. Of 192 documents from the grey literature, 97 were relevant. 76% of these were event reports. The majority of documents addressed emergency planning and response. Very few documents related to hazard analysis, mitigation or capability assessment. Conclusions: Although a large body of literature exists, its validity and generalisability is unclear There is little evidence that this potential evidence base has been exploited through synthesis to inform policy and practice. The type and structure of evidence that would be of most value of emergency planners and policymakers has yet to be identified. [ABSTRACT FROM AUTHOR]

Background Many major public health issues today are not confined by national boundaries. However, the global public health workforce appears unprepared to confront the challenges posed by globalization. We therefore sought to investigate whether the current UK public health training programme adequately prepares its graduates to operate in a globalized world. Methods We used mixed methods involving an online cross-sectional survey of UK public health trainees on the international content of the Faculty of Public Health's written examination, a qualitative review of the Faculty's 2007 training curriculum and a questionnaire survey of all training deaneries in the UK. Results We found that global health issues are not addressed by the current training curriculum or in the written examination despite trainee interest for this. Many of the deaneries were also unreceptive to international placements. Conclusions Despite the recognized educational legitimacy of global health placements and the favourable UK policy context, the opportunities and international content of public health training remain limited. In order to retain its position as a leader in the field of public health, the UK needs to adapt its training programme to better reflect today's challenges. [ABSTRACT FROM PUBLISHER]

The article focuses on the challenges faced by Great Britain government to control the increasing healthcare costs and demand, against a backdrop of financial austerity. It mentions the referral pathway redesign method inorder to control and to monitor, direct, or regulate patient referrals from primary care to specialist, non-emergency care in hospital.

Aim HER2 status is vital for selecting breast cancer patients for trastuzumab treatment. One recommended approach is to assess immunohistochemical staining and then perform in situ hybridisation on those tumours with a borderline (2+) immunohistochemical result. This audit aimed to assess the value of the percentage of immunohistochemical staining in 2+ tumours in selecting tumours for in-situ hybridisation. Methods HER2 immunohistochemistry and in situ hybridisation was performed according to UK guidelines. The percentage of complete membrane staining of invasive carcinoma cells for HER2 was recorded as part of routine reporting. Results 191 (11%) of 1735 invasive carcinomas were scored as 3+. 419 (24%) were scored as 2+. 57 of 413 2+ carcinomas (14%) were amplified (ratio of HER2 to chromosome 17≥2.0). The frequency of amplification was related to the percentage of complete membrane staining: eight of 149 (5%) with 10-19% membrane staining, 11 of 93 (12%) with 20-29% staining, 26 of 150 (17%) with 30-79% staining and 12 of 21 (57%) with 80-100% staining. Conclusions This audit suggests that increasing the threshold for 2+ from 10% to 20% complete membrane staining would reduce the number of in-situ hybridisation tests by 36%, but reduce the detection of amplified tumours by 14%. [ABSTRACT FROM AUTHOR]

This article discusses the role of regulation in the development of sustainable practices in the energy sector. The position of the Great Britain Sustainable Development Commission on effective environmental and social accounting practices is presented. Issues relating to the development of regulations that effectively monitor businesses without harming their ability to operate are assessed. The position of the Great Britain Office of Gas and Electricity Markets (Ofgem) on sustainable development is considered. The competing priorities of saving money on energy generation and promoting sustainability in energy industries are contrasted.

The article analyzes challenges of health care commissioning and health reform in England. The author mentions that despite the desire to have multiple agency commissioning, it is unclear on how it will bbenefit general practice. Moreover, he believes of the need of clinical commissioners to engage with several stakeholders.

A letter to the editor is presented in response to a plan by the coalition government of Great Britain to implement commissioning by consortiums of general practitioners (GPs).

Abstract Background The homeobox B13 (HOXB13) G84E mutation has been recommended for use in genetic counselling for prostate cancer (PCa), but the magnitude of PCa risk conferred by this mutation is uncertain. Objective To obtain precise risk estimates for mutation carriers and information on how these vary by family history and other factors. Design, setting, and participants Two-fold: a systematic review and meta-analysis of published risk estimates, and a kin-cohort study comprising pedigree data on 11 983 PCa patients enrolled during 1993–2014 from 189 UK hospitals and who had been genotyped for HOXB13 G84E. Outcome measurements and statistical analysis Relative and absolute PCa risks. Complex segregation analysis with ascertainment adjustment to derive age-specific risks applicable to the population, and to investigate how these vary by family history and birth cohort. Results and limitations A meta-analysis of case-control studies revealed significant heterogeneity between reported relative risks (RRs; range: 0.95–33.0, p < 0.001) and differences by case selection (p = 0.007). Based on case-control studies unselected for PCa family history, the pooled RR estimate was 3.43 (95% confidence interval [CI] 2.78–4.23). In the kin-cohort study, PCa risk for mutation carriers varied by family history (p < 0.001). There was a suggestion that RRs decrease with age, but this was not significant (p = 0.068). We found higher RR estimates for men from more recent birth cohorts (p = 0.004): 3.09 (95% CI 2.03–4.71) for men born in 1929 or earlier and 5.96 (95% CI 4.01–8.88) for men born in 1930 or later. The absolute PCa risk by age 85 for a male HOXB13 G84E carrier varied from 60% for those with no PCa family history to 98% for those with two relatives diagnosed at young ages, compared with an average risk of 15% for noncarriers. Limitations include the reliance on self-reported cancer family history. Conclusions PCa risks for HOXB13 G84E mutation carriers are heterogeneous. Counselling should not be based on average risk estimates but on age-specific absolute risk estimates tailored to individual mutation carriers' family history and birth cohort. Patient summary Men who carry a hereditary mutation in the homeobox B13 (HOXB13) gene have a higher than average risk for developing prostate cancer. In our study, we examined a large number of families of men with prostate cancer recruited across UK hospitals, to assess what other factors may contribute to this risk and to assess whether we could create a precise model to help in predicting a man's prostate cancer risk. We found that the risk of developing prostate cancer in men who carry this genetic mutation is also affected by a family history of prostate cancer and their year of birth. This information can be used to assess more personalised prostate cancer risks to men who carry HOXB13 mutations and hence better counsel them on more personalised risk management options, such as tailoring prostate cancer screening frequency. Take Home Message Men with a G84E mutation in the HOXB13 gene are at a high risk of developing prostate cancer. The risk is however heterogeneous, and is modified by both family history and birth cohort. Genetic counselling should account for this heterogeneity. [ABSTRACT FROM AUTHOR]

Abstract: Breast needle core biopsy (NCB) is now a standard diagnostic procedure in the triple assessment of screen detected breast lesions. Therefore, it is important to provide robust and up-to-date data on the performance of NCB in the screening setting. However, previous studies of NCB have suffered from either limitation in the number of assessed cases or included a mix of symptomatic and screen detected breast lesions. In this study, we have evaluated the performance of a large series of uniformly assessed NCBs of screen detected lesions (20001 cases) over a period of 10 years (1997–2007). Our results showed a gradual increase in the number of NCBs and an improvement of their performance over the period of the study; absolute sensitivity increased from 84.9% to 96.4% and complete sensitivity increased from 90.9% to 99.7%. There was also a gradual reduction in the number of surgical interventions after benign (B2) and negative (B1) NCB diagnoses. Our study provides data showing variance from the suggested thresholds for the measures of performance of NCB in the United Kingdom which could be used to provide updated evidence-based thresholds for assessment of performance of NCB diagnosis use in the assessment of breast cancer screen detected lesions in the UK and elsewhere. [Copyright &y& Elsevier]

The last UK breast cancer (BC) human epidermal growth factor receptor 2 (HER2) testing guideline recommendations were published in 2015. Since then, new data and therapeutic strategies have emerged. The American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) published a focused update in 2018 that reclassified in situ hybridisation (ISH) Group 2 (immunohistochemistry (IHC) score 2+and HER 2/chromosome enumeration probe 17 ( CEP 17) ratio ≥2.0 and HER 2 copy number <4.0 signals/cell), as well as addressed other concerns raised by previous guidelines. The present article further refines UK guidelines, with specific attention to definitions of HER2 status focusing on eight key areas: (1) HER2 equivocal (IHC 2+) and assignment of the ASCO/CAP ISH group 2 tumours; (2) the definition of the group of BCs with low IHC scores for HER2 with emphasis on the distinction between IHC score 1+ (HER2-Low) from HER2 IHC score 0 (HER2 negative); (3) reporting cases showing HER2 heterogeneity; (4) HER2 testing in specific settings, including on cytological material; (5) repeat HER2 testing, (6) HER2 testing turnaround time targets; (7) the potential role of next generation sequencing and other diagnostic molecular assays for routine testing of HER2 status in BC and (8) use of image analysis to score HER2 IHC. The two tiered system of HER2 assessment remains unchanged, with first line IHC and then ISH limited to IHC equivocal cases (IHC score 2+) but emerging data on the relationship between IHC scores and levels of response to anti-HER2 therapy are considered. Here, we present the latest UK recommendations for HER2 status evaluation in BC, and where relevant, the differences from other published guidelines., Competing Interests: Competing interests: The authors attended meetings sponsored by Roche and AstraZeneca on HER2 low and HER2 positive breast cancer. No other relevant conflict of interests., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The WHO and National Institute for Health and Care Excellence recommend various triage tools to assist decision-making for patients with suspected COVID-19. We aimed to compare the accuracy of triage tools for predicting severe illness in adults presenting to the ED with suspected COVID-19., Methods: We undertook a mixed prospective and retrospective observational cohort study in 70 EDs across the UK. We collected data from people attending with suspected COVID-19 and used presenting data to determine the results of assessment with the WHO algorithm, National Early Warning Score version 2 (NEWS2), CURB-65, CRB-65, Pandemic Modified Early Warning Score (PMEWS) and the swine flu adult hospital pathway (SFAHP). We used 30-day outcome data (death or receipt of respiratory, cardiovascular or renal support) to determine prognostic accuracy for adverse outcome., Results: We analysed data from 20 891 adults, of whom 4611 (22.1%) died or received organ support (primary outcome), with 2058 (9.9%) receiving organ support and 2553 (12.2%) dying without organ support (secondary outcomes). C-statistics for the primary outcome were: CURB-65 0.75; CRB-65 0.70; PMEWS 0.77; NEWS2 (score) 0.77; NEWS2 (rule) 0.69; SFAHP (6-point rule) 0.70; SFAHP (7-point rule) 0.68; WHO algorithm 0.61. All triage tools showed worse prediction for receipt of organ support and better prediction for death without organ support. At the recommended threshold, PMEWS and the WHO criteria showed good sensitivity (0.97 and 0.95, respectively) at the expense of specificity (0.30 and 0.27, respectively). The NEWS2 score showed similar sensitivity (0.96) and specificity (0.28) when a lower threshold than recommended was used., Conclusion: CURB-65, PMEWS and the NEWS2 score provide good but not excellent prediction for adverse outcome in suspected COVID-19, and predicted death without organ support better than receipt of organ support. PMEWS, the WHO criteria and NEWS2 (using a lower threshold than usually recommended) provide good sensitivity at the expense of specificity., Trial Registration Number: ISRCTN56149622., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The cost-effectiveness of population-based panel testing for high- and moderate-penetrance ovarian cancer (OC)/breast cancer (BC) gene mutations is unknown. We evaluate the cost-effectiveness of population-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 mutation testing compared with clinical criteria/family history (FH) testing in unselected general population women., Methods: A decision-analytic model comparing lifetime costs and effects of criteria/FH-based BRCA1/BRCA2 testing is compared with BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing in those fulfilling clinical criteria/strong FH of cancer (≥10% BRCA1/BRCA2 probability) and all women age 30 years or older. Analyses are presented for UK and US populations. Identified carriers undergo risk-reducing salpingo-oophorectomy. BRCA1/BRCA2/PALB2 carriers can opt for magnetic resonance imaging/mammography, chemoprevention, or risk-reducing mastectomy. One-way and probabilistic sensitivity analysis (PSA) enabled model uncertainty evaluation. Outcomes include OC, BC, and additional heart disease deaths. Quality-adjusted life-years (QALYs), OC incidence, BC incidence, and incremental cost-effectiveness ratio (ICER) were calculated. The time horizon is lifetime and perspective is payer., Results: Compared with clinical criteria/FH-based BRCA1/BRCA2 testing, clinical criteria/FH-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing is cost-effective (ICER = £7629.65/QALY or $49 282.19/QALY; 0.04 days' life-expectancy gained). Population-based testing for BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 mutations is the most cost-effective strategy compared with current policy: ICER = £21 599.96/QALY or $54 769.78/QALY (9.34 or 7.57 days' life-expectancy gained). At £30 000/QALY and $100 000/QALY willingness-to-pay thresholds, population-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 panel testing is the preferred strategy in 83.7% and 92.7% of PSA simulations; criteria/FH-based panel testing is preferred in 16.2% and 5.8% of simulations, respectively. Population-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing can prevent 1.86%/1.91% of BC and 3.2%/4.88% of OC in UK/US women: 657/655 OC cases and 2420/2386 BC cases prevented per million., Conclusions: Population-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing is more cost-effective than any clinical criteria/FH-based strategy. Clinical criteria/FH-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing is more cost-effective than BRCA1/BRCA2 testing alone.

Human prion diseases constitute a group of infectious and invariably fatal neurodegenerative disorders associated with misfolding of the prion protein. Variant Creutzfeldt-Jakob disease (vCJD) is a zoonotic prion disease linked to oral exposure to the infectious agent that causes bovine spongiform encephalopathy (BSE) in cattle. The most recent case of definite vCJD was heterozygous (MV) at polymorphic codon 129 of the prion protein gene PRNP while all of the previous 177 definite or probable vCJD cases who underwent genetic analysis were methionine homozygous (MM). Retrospective prevalence studies conducted on lympho-reticular tissue suggest that the number of asymptomatic vCJD carriers in the United Kingdom might be around 1 in 2000 people. In addition, there have been four known cases of the transmission of vCJD infection via blood transfusion. For these reasons, a sensitive, reliable, and fast diagnostic test is currently needed. We describe a rapid and highly sensitive seeding conversion assay that detects disease-associated prion protein in the brain and cerebrospinal fluid in vCJD after 48-96 h of amplification, with 100% sensitivity and specificity. This method can amplify prions from definite, probable, and possible vCJD cases from patients who are either MM or MV at PRNP-codon 129., (© 2017 The Authors The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.)

The UK National Institute for Health and Care Excellence (NICE) is a non-departmental public body accountable to the Department of Health. NICE was established in 1999 in an attempt to reduce variability in the availability and quality of medical services in NHS to end the so-called postcode lottery. Since its establishment NICE has acquired an international reputation for the development of high quality, evidence-based clinical guidelines. NICE also makes cost-benefit assessments of certain technologies on the basis of effectiveness and cost effectiveness. In order to develop a NICE guideline related to psychiatry, the National Collaborating Centre for Mental Health establishes a Guideline Development Group that consists of technical experts, health and/or social care professionals, and lay representatives. The group searches for and evaluates the available evidence and formulates a series of clinical recommen- dations following which stakeholders are consulted and revisions occur. As well as providing treatment recommendations for healthcare professionals, the guidelines are also intended to inform patients, helping them make decisions and improving communication between patients and healthcare staff, and also to direct the focus of research. To date, NICE has published guidance on antenatal and postnatal mental health, antisocial personality disorder, attention deficit hyperactivity disorder, bipolar disorder, borderline personality disorder, dementia, depression, depression in children and young people, drug misuse (opioid detoxification and psychological interventions), eating disorders, obsessive-compulsive disorder, PTSD, schizophrenia, and the management of self-harm. We describe how, both directly through education and effects on clinical pathways, and indirectly through effects on health providers and patient behavior, NICE guidance has had an impact on psychiatrists working in UK.