A Repurposing Programme Evaluating Transdermal Oestradiol Patches for the Treatment of Prostate Cancer Within the PATCH and STAMPEDE Trials: Current Results and Adapting Trial Design.

AIMS: Androgen deprivation therapy (ADT), usually achieved with luteinising hormone releasing hormone analogues (LHRHa), is central to prostate cancer management. LHRHa reduce both testosterone and oestrogen and are associated with significant long-term toxicity. Previous use of oral oestrogens as ADT was curtailed because of cardiovascular toxicity. Transdermal oestrogen (tE2) patches are a potential alternative ADT, supressing testosterone without the associated oestrogen-depletion toxicities (osteoporosis, hot flushes, metabolic abnormalities) and avoiding cardiovascular toxicity, and we here describe their evaluation in men with prostate cancer. MATERIALS AND METHODS: The PATCH (NCT00303784) adaptive trials programme (incorporating recruitment through the STAMPEDE [NCT00268476] platform) is evaluating the safety and efficacy of tE2 patches as ADT for men with prostate cancer. An initial randomised (LHRHa versus tE2) phase II study (n = 251) with cardiovascular toxicity as the primary outcome measure has expanded into a phase III evaluation. Those with locally advanced (M0) or metastatic (M1) prostate cancer are eligible. To reflect changes in both management and prognosis, the PATCH programme is now evaluating these cohorts separately. RESULTS: Recruitment is complete, with 1362 and 1128 in the M0 and M1 cohorts, respectively. Rates of androgen suppression with tE2 were equivalent to LHRHa, with improved metabolic parameters, quality of life and bone health indices (mean absolute change in lumbar spine bone mineral density of -3.0% for LHRHa and +7.9% for tE2 with an estimated difference between arms of 9.3% (95% confidence interval 5.3-13.4). Importantly, rates of cardiovascular events were not significantly different between the two arms and the time to first cardiovascular event did not differ between treatment groups (hazard ratio 1.11, 95% confidence interval 0.80-1.53; P = 0.54). Oncological outcomes are awaited. FUTURE: Efficacy results for the M0 cohort (primary outcome measure metastases-free survival) are expected in the final quarter of 2023. For M1 patients (primary outcome measure - overall survival), analysis using restricted mean survival time is being explored. Allied translational work on longitudinal samples is underway.

Strengthening the equity focus of applied public health research: introducing the FOR EQUITY platform.

OBJECTIVES: Much applied health research pays insufficient attention to potential unequal impacts across social groups or is typically focused on a single dimension (e.g. socio-economic status), rarely considering the intersecting social processes driving inequalities (e.g. racism, sexism, classism). All health research needs a strong intersectional equity focus in order to inform action to reduce health inequalities as well as improve population health. STUDY DESIGN: Focus On Research and Equity (FOR EQUITY) is a new Web-based platform aiming to strengthen the intersectional equity focus of applied health research. METHODS: The platform was developed in collaboration with members of the public, practitioners and researchers working internationally. The development involved a systematic review of academic and grey literature, a series of workshops and user testing. RESULTS: FOR EQUITY encompasses (1) a Health Inequalities Assessment Tool, with an intersectional perspective on inequalities; (2) a FOR EQUITY Guidance Inventory providing access to a range of international research toolkits and guidance; and (3) a FOR EQUITY Library including case studies illustrating how researchers have attempted to integrate an equity lens into the research process and more general resources on health inequalities. CONCLUSION: FOR EQUITY can support researchers to strengthen the equity lens in their studies to make research evidence more relevant for action to reduce social and health inequalities. However, a single focus on toolkits is unlikely to sufficiently address the barriers to embedding equity in research. A mainstreaming strategy to transform the very roots of the 'institution of research' is required.

Developing and testing a case-management intervention to support the return to work of health care workers with common mental health disorders.

BACKGROUND: To assess the feasibility and acceptability of conducting a trial of the clinical effectiveness and cost-effectiveness of a new case-management intervention to facilitate the return to work of health care workers, on sick leave, having a common mental disorder (CMD). METHODS: A mixed methods feasibility study. RESULTS: Systematic review examined 40 articles and 2 guidelines. Forty-nine National Health Service Occupational Health (OH) providers completed a usual care survey. We trained six OH nurses as case managers and established six recruitment sites. Forty-two out of 1938 staff on sick leave with a CMD were screened for eligibility, and 24 participants were recruited. Out of them, 94% were female. Eleven participants received the intervention and 13 received usual care. Engagement with most intervention components was excellent. Return-to-work self-efficacy improved more in the intervention group than in the usual care group. Qualitative feedback showed the intervention was acceptable. CONCLUSIONS: The intervention was acceptable, feasible and low cost to deliver, but it was not considered feasible to recommend a large-scale effectiveness trial unless an effective method could be devised to improve the early OH referral of staff sick with CMD. Alternatively, the intervention could be trialled as a new stand-alone OH intervention initiated at the time of usual OH referral.

The Phenotypic Spectrum of New-onset IBD in Canadian Children of South Asian Ethnicity: A Prospective Multi-Centre Comparative Study.

BACKGROUND: Canadian-born children of South Asian [SA] ethnicity develop inflammatory bowel disease [IBD] at similar rates to those among Caucasian children. We evaluated the variation in phenotypic spectrum of IBD in SA and Caucasian children in a national paediatric inception cohort of new-onset IBD. METHODS: Patients aged <17 years, enrolled in a Canadian nationwide inception cohort study, were included. Baseline demographic and IBD phenotypic features were compared between SA and Caucasian children. Longitudinal outcomes through 18 months of follow-up were compared matched by propensity scores. RESULTS: Of 1156 children enrolled over 2014 to 2019, 623 were Caucasian [98% and 88% parents Canadian born] and 114 SA [79% Canadian born, 87% parents SA born]. Fewer SAs have a first-degree relative with IBD, 6% vs 19% in Caucasians, p = 0.002. SAs present at a younger age, median age 11.4 years (interquartile range [IQR] 9.2-14.3) vs 13 years [IQR 10.9-15 years], p = 0.03 and more commonly with a UC/IBD-U [ulcerative colitis/IBD-unclassified] subtype [ratio of UC/IBD-U to CD 1.2:1 vs 1:1.8 for Caucasians, p <0.001]. Additionally, a greater proportion of SA CD patients present with colonic-only disease [colonic-only CD/UC/IBD-U in SAs 67% vs 57% for Caucasians, p = 0.001], and among those with CD, colonic CD in SAs 31% vs 23% in Caucasians, p = 0.20]. Perianal fistulising disease was also numerically more common in SAs (14 [27%] vs 64 [18%], p = 0.06]. Adjusting for differences in phenotypic presentation, anti-tumour necrosis factor [TNF] exposure, and time to initiation was similar, and two-thirds of children, whether anti-TNF exposed or naïve, were in corticosteroid-free clinical remission at 18 months irrespective of ethnicity. CONCLUSIONS: The phenotypic spectrum of new-onset IBD in SA children differs from that of Caucasian children, but treatment and clinical course are similar within phenotypic subgroups.

Evidence-based orthopaedic trauma care in the United Kingdom: Guidelines, registries, carrots and sticks.

In the United Kingdom (UK), orthopaedic trauma surgeons utilise evidence-based practice through distillation of high-quality primary research, interrogation of registries and implementation of evidence-based guidelines. Concurrent with this ambition of providing exemplar care based on robust patient centred research, there has evolved a culture of remuneration 'by results'. Therefore, there is a drive for excellence combined with a system of collation and validation of data input as well as remuneration where care excels. There are several organisations involved in each stage of this process, the output of which has much that is pertinent to the globally similar consequences of physical injury. However, their relevance and impact within the UK is magnified as they are written against the backdrop of a unified healthcare system. In this article, we will describe the roles of the different organisations guiding and regulating trauma practice across the UK and discuss how the interplay of these impacts on clinical care.

2,4-Dinitrophenol overdose - Everything old is new again.

A complete case example of a fatal 2,4-dinitrophenol (DNP) overdose involving a 23-year-old male is described. Included are details of not only the patient's presentation symptoms and treatment, but also the subsequent findings of the coronial investigation process including the autopsy, post-mortem computed tomography (PMCT) scanning and toxicological analysis and results. The patient presented with elevated temperature, heart rate and blood pressure. Multiple treatments were conducted to counteract these symptoms, however the patient died approximately 1.5 hours after hospital admission and some 4.5 hours after the DNP was initially consumed. Autopsy revealed the presence of cardiovascular disease that was contributory to death and post-mortem computed tomography showed evidence of decompositional intravascular gas in the neck, head, face, lower abdomen, heart and hepatic systems. Toxicological analysis was completed by protein precipitation with methanol and subsequent instrumental analysis by LC/MS/MS in negative ion mode. The antemortem blood specimen showed the presence of tadalafil, two anabolic steroids and a DNP concentration of 110 mg/kg which is consistent with other reported DNP fatalities. Despite the small amount of time between the antemortem specimen collection and death, the DNP concentration identified in the femoral blood post-mortem specimen was comparably low (5.5 mg/kg). DNP concentrations also reduced during an extended period of specimen storage prior to analysis indicating some instability in biological specimens even when refrigerated or frozen. DNP was found to be distributed primarily in the aqueous tissues (blood, vitreous, bile) rather than solid matrices (liver, kidney, muscle).

Evaluation of a dementia awareness programme in UK schools: a qualitative study.

OBJECTIVES: 'Dementia Friends' is a programme used to raise awareness of dementia, developed by the Alzheimer's Society, which has been delivered across the UK to diverse populations, including adolescents. However, there is little evidence available with regards to adolescents' perceptions of the programme and its impact. This study aims to explore this in a group of adolescents from the south of England. STUDY DESIGN: Focus group discussions. METHODS: Thirty adolescents aged between 11 and 16 years were recruited from two schools in East Sussex, England. All had participated in a Dementia Friends session in the past month. Focus group discussions were transcribed, coded and themes were created using inductive thematic analysis. RESULTS: Four themes were identified: (1) perceptions and experiences of dementia, (2) outcomes and learning from Dementia Friends session, (3) reactions to the Dementia Friends session and (4) identified future learning needs. CONCLUSIONS: Adolescents had generally positive opinions about Dementia Friends, particularly the interactive nature of the session. Whilst they felt participating in Dementia Friends improved their attitudes and knowledge, they were often left wanting to learn more. Future research needs to empirically evaluate the extent to which Dementia Friends may improve attitudes and knowledge of dementia.

The influence of care home managers on the implementation of a complex intervention: findings from the process evaluation of a randomised controlled trial of dementia care mapping.

BACKGROUND: Many people with dementia live in care homes, where staff can struggle to meet their complex needs. Successful practice improvement interventions in these settings require strong managerial support, but little is known about how managers can support implementation in practice, or what factors support or hinder care home managers in providing this support. Using Dementia Care Mapping™ (DCM) as an example, this study explored how care home managers can support the implementation of complex interventions, and identified factors affecting their ability to provide this support. METHODS: We undertook interviews with 48 staff members (managers and intervention leads) from care homes participating in the intervention arm of the DCM EPIC trial of DCM implementation. RESULTS: Managerial support played a key role in facilitating the implementation of a complex intervention in care home settings. Managers could provide practical and financial support in many forms. However, managerial support and leadership approaches towards implementation were highly variable in practice, and implementation was easily de-stabilised by management changes or competing managerial priorities. How well managers understood, valued and engaged with the intervention, alongside the leadership style they adopted to support implementation, were key influences on implementation success. CONCLUSIONS: For care home managers to effectively support interventions they must fully understand the proposed intervention and its potential value. This is especially important during times of managerial or practice changes, when managers lack the skills required to effectively support implementation, or when the intervention is complex. It may be unfeasible to successfully implement new interventions during times of managerial or practice instability. TRIAL REGISTRATION: Current Controlled Trials ISRCTN82288852 , registered 16/01/2014.

Direct integration of micro-LEDs and a SPAD detector on a silicon CMOS chip for data communications and time-of-flight ranging.

We present integration of singulated micron-sized light emitting diodes (micro-LEDs) directly onto a silicon CMOS drive chip using a transfer printing method. An 8x8 micro-LED device array with individual control over each pixel is demonstrated with modulation bandwidths up to 50 MHz, limited by the large modulation depth of the driver chip. The 2 kHz frame rate CMOS driver also incorporates a Single Photon Avalanche Diode device thus allowing detection and transmission functionality on a single integrated chip. Visible light communications at data rates up to 1 Mbps, and time-of-flight ranging with cm-scale resolution are demonstrated using this hybrid integrated system.

Gallium nitride micro-light-emitting diode structured light sources for multi-modal optical wireless communications systems.

Gallium nitride-based light-emitting diodes (LEDs) have revolutionized the lighting industry with their efficient generation of blue and green light. While broad-area (square millimetre) devices have become the dominant LED lighting technology, fabricating LEDs into micro-scale pixels (micro-LEDs) yields further advantages for optical wireless communications (OWC), and for the development of smart-lighting applications such as tracking and imaging. The smaller active areas of micro-LEDs result in high current density operation, providing high modulation bandwidths and increased optical power density. Fabricating micro-LEDs in array formats allows device layouts to be tailored for target applications and provides additional degrees of freedom for OWC systems. Temporal and spatial control is crucial to use the full potential of these micro-scale sources, and is achieved by bonding arrays to pitch-matched complementary metal-oxide-semiconductor control electronics. These compact, integrated chips operate as digital-to-light converters, providing optical signals from digital inputs. Applying the devices as projection systems allows structured light patterns to be used for tracking and self-location, while simultaneously providing space-division multiple access communication links. The high-speed nature of micro-LED array devices, combined with spatial and temporal control, allows many modes of operation for OWC providing complex functionality with chip-scale devices. This article is part of the theme issue 'Optical wireless communication'.

Nurses' illness perceptions during presenteeism and absenteeism.

BACKGROUND: Presenteeism has been linked with lost productivity, impaired health and absence. Whilst much research has focused on types of diseases associated with presenteeism and absenteeism, there has been little investigation into the role of individuals' illness perceptions in these episodes. AIMS: To assess how illness perceptions vary between presenteeism and absenteeism episodes. METHODS: A cross-sectional questionnaire was distributed to ward-based nurses working with older adults. Data on illness perceptions during presenteeism and absenteeism episodes were collected. Data were analysed via the Paired-Samples t-test, Wilcoxon test and McNemar test. RESULTS: Two hundred and seventy cases were analysed (88% response rate). Compared with presenteeism, illnesses during absenteeism were thought to affect lives more (P < 0.001), to have more serious symptoms (P < 0.001), to be more concerning (P = 0.003), more likely to be treated (P = 0.009), more infectious (P < 0.001) and perceived as more legitimate reasons for absenteeism (P < 0.001). Treatment was considered more effective during absenteeism (P < 0.001), whilst workability was better during presenteeism (P < 0.001). Presenteeism was perceived as harmful and absenteeism beneficial for illness. Individuals attended work when presenteeism was expected to be less harmful (P < 0.001) and avoided work when absenteeism was expected to be more beneficial for illness (P < 0.001). CONCLUSIONS: Illness perceptions varied significantly between presenteeism and absenteeism episodes and should be included in models of illness behaviour. Findings also highlight that policy may influence illness behaviour and that nurses may attend work despite concerning levels of illness.

Phenotypic Variation in Paediatric Inflammatory Bowel Disease by Age: A Multicentre Prospective Inception Cohort Study of the Canadian Children IBD Network.

BACKGROUND AND AIMS: Incidence of paediatric inflammatory bowel disease [IBD] in Canada is among the highest worldwide, and age of onset may be decreasing. In a multicentre nationwide inception cohort study, we examined variation in phenotype of IBD throughout the paediatric age spectrum. METHODS: Children aged ≥2 years [y] and <17y [A1 age at diagnosis], with new onset IBD, were systematically evaluated at sites of the Canadian Children IBD Network. Prospectively recorded phenotypic data were compared between age groups. RESULTS: Among 1092 children (70% Caucasian; 64% Crohn's disease [CD], 36% ulcerative colitis/inflammatory bowel disease unclassified [UC/IBD-U]; median age 13 y, interquartile range [IQR] 11-15 y), 210 [19%] were diagnosed before the age of age 10 y [Paris A1a] and 43 [4%] before age 6 y (very-early-onset [VEO-IBD]). CD was less common in younger children [42%, 56%, 66%, respectively, of VEO-IBD, A1a; A1b]. Colon-only IBD [UC/IBDU or CD-colon] was present in 81% of VEO-IBD and 65% of A1a; ileal disease increased progressively, reaching plateau at age 10 y. CD location was ileocolonic [L3] in 53% overall. Ileitis [L1] increased with age [6% of VEO-IBD; 13% of A1a; 21% of A1b], as did stricturing/penetrating CD [4% of A1a; 11% of A1b]. At all ages UC was extensive [E3/E4] in >85%, and disease activity moderate to severe according to Physician's Global Assessment [PGA] and weighted Paediatric Crohn's Disease Activity Index/Paediatric Ulcerative Colitis Activity Index [wPCDAI/PUCAI] in >70%. Heights were modestly reduced in CD [mean height z score -0.30 ± 1.23], but normal in UC/IBD-U. CONCLUSIONS: Paris classification of age at diagnosis is supported by age-related increases in ileal disease until age 10 years. Other phenotypic features, including severity, are similar across all ages. Linear growth is less impaired in CD than in historical cohorts, reflecting earlier diagnosis.

Attrition at the final donor stage among unrelated haematopoietic stem cell donors: the British Bone Marrow Registry experience.

OBJECTIVES: To investigate attrition at the finally selected donor stage among British Bone Marrow Registry (BBMR) donors, all recruited from blood donors. BACKGROUND: The success of searches for unrelated stem cell donors relies on the existence of large international donor registries and the availability of registered donors when matched with a patient. Withdrawal of donors may adversely affect patient outcomes. MATERIALS/METHODS: Data on 2942 planned donations were analysed to assess donor-related deferral rates and associated factors. RESULTS: Overall, 20·2% of requests were cancelled. Transplant centres activated more than half of the cancellations (52·6%). Donor reasons accounted for 46·7% of cancellations (9·4% of requests), of which 61·7% happened for medical and 38·3% for personal reasons. Medical ineligibility of the donor was associated with increasing age (odds ratio [OR] = 1·36, P = 0·011) and peripheral blood stem cell source (OR = 2·22, P = 0·006), and there was some evidence of association with low blood donation reliability (OR = 1·52, P = 0·054). The blood donor reliability score relates to blood donation, and the score worsens if donors consistently fail to attend a donation session when invited. Withdrawal on personal grounds showed associations with donor age (OR = 1·72, P = 0·017, 30-40 years vs other ages), peripheral blood stem cell source (OR = 2·43, P = 0·010) and low blood donor reliability (OR = 1·94, P = 0·007). CONCLUSIONS: To our knowledge, this is the first report on all-cause cancellation at the finally-selected donor stage for international stem cell donor provision, showing 9·4% donor-related cancellation rate. Scores associated with blood donation reliability may be useful to predict stem cell donor withdrawal.

Tumoración frontal que aumenta de tamaño con maniobra de Valsalva / Frontal Tumor that Increased in Size with the Valsalva Maneuver

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Managing employees with dementia: a systematic review.

BACKGROUND: The experience of developing dementia while in employment has been explored from the point of view of the employee, but less is known about the perspectives, experiences and needs of employers. AIMS: To review systematically literature about the management of employees who develop dementia whilst in employment. METHODS: Databases searched included MEDLINE, EMBASE, PsycINFO, CINAHL, BNI, ABI Inform, ISI Web of Science, Open Grey and dementia journals database; 44 documents were identified for inclusion in the review: 22 journal papers, one PhD thesis and 21 articles, reports and webpages from the grey literature. As all documents were qualitative in nature a thematic synthesis of their content was undertaken. RESULTS: Three main themes and ten sub-themes were identified. The main themes concerned early presentation and identification in the workplace; reasonable adjustments for people with working age dementia; and the provision of information to raise awareness and facilitate informed choice. The evidence suggested that there is a lack of awareness about working age dementia and that this may impact negatively on employees. Guidance for employers offered suggestions for good practice. CONCLUSIONS: Guidance for employers is increasingly available although it rarely refers to the evidence base. There is a need for future studies that explore the effectiveness of guidance and training initiatives for employers. Examples of good practice where employees with dementia have been well supported in the workplace and who have been able to leave the workforce with dignity, would be helpful.

Menopause and work: an overview of UK guidance.

BACKGROUND: Recent evidence suggests that some women experience menopausal symptoms that impact on their working lives, and that work environments can impact upon the experience of menopause. As a result, guidance for employers and other key stakeholders about this potential occupational health issue has emerged. To date there has not been a review of these documents to identify their main recommendations for policy and practice. AIMS: To provide a narrative overview of such guidance and summary of content. METHODS: Documents published in the UK and available in a major UK trade union library were searched systematically to identify guidance on the topic of menopause and work. An inductive thematic analysis was performed to identify the main themes addressed. RESULTS: Twenty-five relevant documents, on average eight pages long, were identified. A minority indicated that the use of scientific evidence informed the content. Five overarching themes were identified: (i) legislation; (ii) policy; (iii) information and training needs; (iv) workplace support; and (v) the physical work environment. CONCLUSIONS: This overview of UK guidance revealed common areas of concern about reducing and managing difficulties experienced by working menopausal women. Possible areas for action were identified. Some recommendations were common across much of the guidance, whereas others were exclusive. Future guidance might include consideration of all these issues, while making reference both to the evidence base and sources of further information.

Perspective of Family Members of Transitions to Alternative Levels of Care in Anglo-Saxon Countries.

This scoping review explores circumstances surrounding the decision about, and eventual experience of, transitioning older adults into alternative levels of housing (ALH), such as long-term care. This topic is examined from a family member perspective, given their exposure and involvement in the care of older adult relatives during this transitional period. The scoping review methodology is based on the framework of Arksey and O'Malley and subsequent recommendations from Levac, Colquhoun, and O'Brien. Approximately 470 articles were reviewed covering the period between 2000 and November 2014; 37 articles met inclusion criteria. A temporal organization of themes was used to describe the experiences of family members in the pretransition, active transition, and posttransition periods of moving older adult relatives into ALH. This paper highlights the transitional period as a time of crisis, with a lack of planning, support, and transparent discussion. This study identifies a need for future research on the potential benefits of family support groups, interim transitional housing options, different models of ALH, changing roles in the posttransition period, and the need for a comprehensive list of housing options for older adults. Results have the potential to inform policy/practice and improve the lives of older adults and their family.