What are the key elements of educational interventions for lay carers of patients with advanced disease? A systematic literature search and narrative review of structural components, processes and modes of delivery

Context: Educating carers about symptom management may help meet patient and carer needs in relation to distressing symptoms in advanced disease. Reviews of the effectiveness of carer interventions exist, but few have focused on educational interventions and none on the key elements that comprise them but which could inform evidence-based design. Objectives: To identify the key elements (structural components, processes, and delivery modes) of educational interventions for carers of patients with advanced disease. Methods: We systematically searched seven databases, applied inclusion and exclusion criteria, conducted quality appraisal, extracted data, and performed a narrative analysis. Results: We included 62 articles related to 49 interventions. Two main delivery modes were identified: personnel-delivered interventions and stand-alone resources. Personnel-delivered interventions targeted individuals or groups, the former conducted at single or multiple time points, and the latter delivered as series. Just more than half targeted carers rather than patient-carer dyads. Most were developed for cancer; few focused purely on symptom management. Stand-alone resources were rare. Methods to evaluate interventions ranged from postintervention evaluations to fully powered randomized controlled trials but of variable quality. Conclusion: Published evaluations of educational interventions for carers in advanced disease are limited, particularly for non-cancer conditions. Key elements for consideration in developing such interventions were identified; however, lack of reporting of reasons for nonparticipation or dropout from interventions limits understanding of the contribution of these elements to interventions' effectiveness. When developing personnel-delivered interventions for carers in advanced disease, consideration of the disease (and, therefore, caring) trajectory, intervention accessibility (timing, location, and transport), and respite provision may be helpful

When Frail Older People Relocate in Very Old Age, Who Makes the Decision?

Older people are likely to transition to a new home closer to family who can provide assistance or to long-term residential care as their health declines and their care needs increase. A minority choose to move to "age-friendly" housing before the onset of disability, but the majority prefer to "age in place" and defer moving until health crises compel a transition. Older people living with dementia are likely to move into residential care, but not much is known about the role they play in decision making around these moves. This qualitative study addresses this gap in knowledge by examining how a rare cohort of "older old" people, most with some level of cognitive impairment, were involved in decisions surrounding assistance seeking and moving to a care home. Thematic analysis of qualitative interview data from Cambridge City over-75s Cohort (CC75C) study participants aged 95 years and older, who had moved in later life, and their proxy informants (n = 26). Moves at such an old age were made due to a complexity of push and pull factors which had layered dynamics of decision making. In most cases (n = 22), decision making involved other people with varying degrees of decision ownership. Only four older people, who moved voluntarily, had full ownership of the decision to move. Many relatives reported being traumatized by events leading up to the move. "Older old" people are sometimes unable to make their own decisions about moving due to the urgency of health crisis and cognitive decline. There is a need to support relatives to discuss moving and housing options at timely junctures before health crises intervene in an effort to optimize older people's participation in decision making

Evidence of prokineticin dysregulation in fallopian tube from women with ectopic pregnancy

OBJECTIVE: To demonstrate expression and regulation of prokineticins (PROKs) and their receptors (PROKRs) in Fallopian tube (FT) from non-pregnant women and women with ectopic pregnancy (EP). DESIGN: Tissue analysis. SETTING: Large UK teaching hospital PATIENTS: Women undergoing hysterectomy for benign gynecological conditions (n=15) and surgery for EP (n=16). INTERVENTIONS: Quantitative RT-PCR and immunohistochemistry were used to determine FT PROK/PROKR mRNA expression and protein localization, respectively. PROK/PROKR levels were measured in tubal explant cultures stimulated with estrogen and progestogen. MAIN OUTCOME MEASURES: Differential expression of PROK and PROKR. RESULTS: FT PROK2 and PROKR1 mRNA levels were upregulated during the progesterone-dominant mid-luteal phase of the menstrual cycle. Increased PROKR1 expression was observed in tubal explant cultures treated with medroxyprogesterone acetate. PROK and PROKR proteins were localized to the epithelium and smooth muscle layers of the FT. PROKR1 and PROKR2 mRNA levels were lower in FT from women with EP compared to non-pregnant FT from the mid-luteal phase. CONCLUSION: These data suggest a potential role for PROKs in FT function. PROKs are known to affect smooth muscle contraction in the gut. Dysregulated PROK expression in FT could affect FT smooth muscle contractility and embryo-tubal transport, providing a potential cause for EP

Short‐term psychosocial outcomes of adding a non‐contrast abdominal computed tomography (CT) scan to the thoracic CT within lung cancer screening

Objectives To evaluate psychological, social, and financial outcomes amongst individuals undergoing a non-contrast abdominal computed tomography (CT) scan to screen for kidney cancer and other abdominal malignancies alongside the thoracic CT within lung cancer screening. Subjects and Methods The Yorkshire Kidney Screening Trial (YKST) is a feasibility study of adding a non-contrast abdominal CT scan to the thoracic CT within lung cancer screening. A total of 500 participants within the YKST, comprising all who had an abnormal CT scan and a random sample of one-third of those with a normal scan between 14/03/2022 and 24/08/2022 were sent a questionnaire at 3 and 6 months. Outcomes included the Psychological Consequences Questionnaire (PCQ), the short-form of the Spielberger State–Trait Anxiety Inventory, and the EuroQoL five Dimensions five Levels scale (EQ-5D-5L). Data were analysed using regression adjusting for participant age, sex, socioeconomic status, education, baseline quality of life (EQ-5D-5L), and ethnicity. Results A total of 380 (76%) participants returned questionnaires at 3 months and 328 (66%) at 6 months. There was no difference in any outcomes between participants with a normal scan and those with abnormal scans requiring no further action. Individuals requiring initial further investigations or referral had higher scores on the negative PCQ than those with normal scans at 3 months (standardised mean difference 0.28 sd, 95% confidence interval 0.01–0.54; P = 0.044). The difference was greater in those with anxiety or depression at baseline. No differences were seen at 6 months. Conclusion Screening for kidney cancer and other abdominal malignancies using abdominal CT alongside the thoracic CT within lung cancer screening is unlikely to cause significant lasting psychosocial or financial harm to participants with incidental findings

Prion protein-specific antibodies that detect multiple TSE agents with high sensitivity

This paper describes the generation, characterisation and potential applications of a panel of novel anti-prion protein monoclonal antibodies (mAbs). The mAbs were generated by immunising PRNP null mice, using a variety of regimes, with a truncated form of recombinant ovine prion protein spanning residues 94–233. Epitopes of specific antibodies were mapped using solid-phase Pepscan analysis and clustered to four distinct regions within the PrP molecule. We have demonstrated the utility of these antibodies by use of Western blotting and immunohistochemistry in tissues from a range of different species affected by transmissible spongiform encephalopathy (TSE). In comparative tests against extensively-used and widely-published, commercially available antibodies, similar or improved results can be obtained using these new mAbs, specifically in terms of sensitivity of detection. Since many of these antibodies recognise native PrPC, they could also be applied to a broad range of immunoassays such as flow cytometry, DELFIA analysis or immunoprecipitation. We are using these reagents to increase our understanding of TSE pathogenesis and for use in potential diagnostic screening assays

The physiological responses of cacao to the environment and the implications for climate change resilience. A review

Cacao (Theobroma cacao L.) is a tropical perennial crop which is of great economic importance to the confectionary industry and to the economies of many countries of the humid tropics where it is grown. Some recent studies have suggested climate change could severely impact cacao production in West Africa. It is essential to incorporate our understanding of the physiology and genetic variation within cacao germplasm when discussing the implications of climate change on cacao productivity and developing strategies for climate resilience in cacao production. Here we review the current research on the physiological responses of cacao to various climate factors. Our main findings are 1) water limitation causes significant yield reduction in cacao but genotypic variation in sensitivity is evident, 2) in the field cacao experiences higher temperatures than is often reported in the literature, 3) the complexity of the cacao/ shade tree interaction can lead to contradictory results, 4) elevated CO2 may alleviate some negative effects of climate change 5) implementation of mitigation strategies can help reduce environmental stress, 6) significant gaps in the research need addressing to accelerate the development of climate resilience. Harnessing the significant genetic variation apparent within cacao germplasm is essential to develop modern varieties capable of high yields in non-optimal conditions. Mitigation strategies will also be essential but to use shading to best effect shade tree selection is crucial to avoid resource competition. Cacao is often described as being sensitive to climate change but genetic variation, adaptive responses, appropriate mitigation strategies and interactive climate effects should all be considered when predicting the future of cacao production. Incorporating these physiological responses to various environmental conditions and developing a deeper understanding of the processes underlying these responses will help to accelerate the development of a more resource use efficient tree ensuring sustainable production into the future

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Key elements carers educational interventions

CONTEXT: Educating carers about symptom management may help meet patient and carer needs in relation to distressing symptoms in advanced disease. Reviews of the effectiveness of carer interventions exist, but few have focused on educational interventions and none on the key elements that comprise them but which could inform evidence-based design. OBJECTIVES: To identify the key elements (structural components, processes, and delivery modes) of educational interventions for carers of patients with advanced disease. METHODS: We systematically searched seven databases, applied inclusion and exclusion criteria, conducted quality appraisal, extracted data, and performed a narrative analysis. RESULTS: We included 62 articles related to 49 interventions. Two main delivery modes were identified: personnel-delivered interventions and stand-alone resources. Personnel-delivered interventions targeted individuals or groups, the former conducted at single or multiple time points, and the latter delivered as series. Just more than half targeted carers rather than patient-carer dyads. Most were developed for cancer; few focused purely on symptom management. Stand-alone resources were rare. Methods to evaluate interventions ranged from postintervention evaluations to fully powered randomized controlled trials but of variable quality. CONCLUSION: Published evaluations of educational interventions for carers in advanced disease are limited, particularly for non-cancer conditions. Key elements for consideration in developing such interventions were identified; however, lack of reporting of reasons for nonparticipation or dropout from interventions limits understanding of the contribution of these elements to interventions' effectiveness. When developing personnel-delivered interventions for carers in advanced disease, consideration of the disease (and, therefore, caring) trajectory, intervention accessibility (timing, location, and transport), and respite provision may be helpful.Macmillan Cancer Support for Post-Doctoral Fellowship funding for MF and the review consumables. CP’s work was part-funded by NIHR CLAHRC East of England. FMW’s work was undertaken during her NIHR Clinical Lectureship then NIHR Clinician Scientist award.This is the author accepted manuscript. It is currently embargoed pending publication

Historical overview: Kraepelin's impact on psychiatry

This paper reviews the importance Emil Kraepelin put on disease course as a classificatory principle. It then outlines the academic reception of Kraepelin's disease entities outside Germany, charts the uptake of his diagnostic concepts within clinical practice in Britain, and compares data on admissions for bipolar disorders, involutional melancholia and postpartum psychoses to the North Wales asylum during the period Kraepelin was working to data on contemporary admissions in an effort to shed further light on the validity of his diagnostic concepts

The experience of transitions in care in very old age: implications for general practice.

BACKGROUND: It can be challenging for general practitioners to support their oldest old patients through the complex process of relocation. OBJECTIVE: To provide a typology of the experiences of moving in very old age that is clinically useful for practitioners navigating very old people's relocation. METHODS: Qualitative analysis of data from a mixed-methods UK population-based longitudinal study, Cambridge City over-75s Cohort (CC75C), from Year 21 follow-up onwards. Interviews with participants aged ≥95 years old and proxy informants (Year 21: 44/48, 92%, subsequent attrition all deaths). Thematic analysis of qualitative data available from 26/32 participants who moved before they died. RESULTS: Individuals who moved voluntarily in with family experienced gratitude, and those who moved into sheltered house or care homes voluntarily had no regrets. One voluntary move into care was experienced with regret, loss and increased isolation as it severed life-long community ties. Regret and loss were key experiences for those making involuntary moves into care, but acceptance, relief and appreciation of increased company were also observed. The key experience of family members was trauma. Establishing connections with people or place ahead of moving, for example through previous respite care, eased moving. A checklist for practitioners based on the resulting typology of relocation is proposed. CONCLUSIONS: Most of the sample moved into residential care. This study highlights the importance of connections to locality, people and place along with good family relationships as the key facilitators of a healthy transition into care for the oldest old. The proposed checklist may have clinical utility