Characteristics of older unpaid carers in England: a study of social patterning from the English Longitudinal Study of Ageing.

BACKGROUND: A growing number of older people provide unpaid care, but contemporary research evidence on this group is limited. AIM: This study aims to describe the characteristics of older people who provide unpaid care and how these vary by socioeconomic position. METHODS: Using recent information from the English Longitudinal Study of Ageing (ELSA wave 9, 2019), we analysed cross-sectional data on 1,282 unpaid carers aged ≥50. Data on sociodemographics, health, social wellbeing, care intensity and caregiver-recipient relationships were extracted. Total net non-pension wealth quintiles were used as a relative measure of socioeconomic position. Differences between the poorest and richest wealth quintiles were examined through logistic regression. FINDINGS: Most older carers in ELSA were female and looking after another older person. Poor mental and physical health and social isolation were common, and socially patterned. Compared with carers in the middle wealth group, the poorest group were more likely to be living with the person they cared for (odds ratio (OR) 1.56 [95% confidence interval (CI) 1.03-2.36]) and more likely to experience loneliness (OR 2.29 [95% CI 1.42-3.69]), dependency (i.e. the need for help with activities of daily living) (OR 1.62 [95% CI 1.05-2.51]), chronic pain (OR 1.81 [95% CI 1.23-2.67]), a higher number of diseases (OR 1.75 [95% CI 1.15-2.65]) and fair/poor self-rated health (OR 2.59 [95% CI 1.79-3.76]). The poorest carers were also less likely to have a high quality of life (OR 0.51 [95% CI 0.33-0.80]) or be in work (OR 0.33 [95% CI 0.19-0.59]). CONCLUSION: Our findings suggest that financially disadvantaged unpaid carers (and their households) may have the greatest needs for intervention and support. Focussing resources on this group has potential to address social inequalities.

Is polypharmacy associated with difficulty taking medicines in people aged ≥85 living at home? Findings from the Newcastle 85+ Study.

It is unclear whether polypharmacy is associated with difficulty taking medications amongst people aged ≥85 living at home. This is despite the projected decline in availability of family carers, who may support independent living. Using Newcastle 85+ Study data and mixed-effects modelling, we investigated the association between polypharmacy and difficulty taking medications amongst 85-year-olds living at home, over a 10-year time period. Polypharmacy was not associated with difficulty taking medications as either a continuous (OR = 0.99 [0.91-1.08]) or categorical variable (5-9 medications, OR = 0.69 [0.34-1.41]; ≥10 medications, OR = 0.85 [0.34-2.07]). The significant predictors included disability, visual impairment and cognitive impairment. Our results suggest that people aged ≥85 living at home with disability, visual impairment and/or cognitive impairment will have difficulty taking their medications, regardless of how many they are prescribed. Therefore, healthcare professionals should routinely ask about, assess and address problems that these patient groups may have with taking their medicines, independent of the number of drugs taken.

The association between multimorbidity and mobility disability-free life expectancy in adults aged 85 years and over: A modelling study in the Newcastle 85+ cohort.

BACKGROUND: Mobility disability is predictive of further functional decline and can itself compromise older people's capacity (and preference) to live independently. The world's population is also ageing, and multimorbidity is the norm in those aged ≥85. What is unclear in this age group, is the influence of multimorbidity on (a) transitions in mobility disability and (b) mobility disability-free life expectancy (mobDFLE). METHODS AND FINDINGS: Using multistate modelling in an inception cohort of 714 85-year-olds followed over a 10-year period (aged 85 in 2006 to 95 in 2016), we investigated the association between increasing numbers of long-term conditions and (1) mobility disability incidence, (2) recovery from mobility disability and (3) death, and then explored how this shaped the remaining life expectancy free from mobility disability at age 85. Models were adjusted for age, sex, disease group count, BMI and education. We defined mobility disability based on participants' self-reported ability to get around the house, go up and down stairs/steps, and walk at least 400 yards; participants were defined as having mobility disability if, for one or more these activities, they had any difficulty with them or could not perform them. Data were drawn from the Newcastle 85+ Study: a longitudinal population-based cohort study that recruited community-dwelling and institutionalised individuals from Newcastle upon Tyne and North Tyneside general practices. We observed that each additional disease was associated with a 16% increased risk of incident mobility disability (hazard ratio (HR) 1.16, 95% confidence interval (CI): 1.07 to 1.25, p < 0.001), a 26% decrease in the chance of recovery from this state (HR 0.74, 95% CI: 0.63 to 0.86, p < 0.001), and a 12% increased risk of death with mobility disability (HR: 1.12, 95% CI: 1.07- to .17, p < 0.001). This translated to reductions in mobDFLE with increasing numbers of long-term conditions. However, residual and unmeasured confounding cannot be excluded from these analyses, and there may have been unobserved transitions to/from mobility disability between interviews and prior to death. CONCLUSIONS: We suggest 2 implications from this work. (1) Our findings support calls for a greater focus on the prevention of multimorbidity as populations age. (2) As more time spent with mobility disability could potentially lead to greater care needs, maintaining independence with increasing age should also be a key focus for health/social care and reablement services.

Does polypharmacy shape dependency transitions in the very old? Findings from the Newcastle 85+ Study.

BACKGROUND: helping older people to maintain their independence, and identifying risk factors that compromise this, is of high importance. Polypharmacy is common in the very old (aged ≥ 85) but whether it can shape transitions in dependency in this fastest growing subpopulation is unclear. METHODS: using Newcastle 85+ Study data and multi-state modelling, we investigated the association between each additional medication prescribed and the progression of and recovery from dependency states, over 10 years (age 85-95). Participants were defined as either free from care (independent), requiring care less often than daily (low dependency), or requiring care at regular intervals each day or 24 hourly (medium/high dependency). RESULTS: each additional medication prescribed was associated with a 10% decreased chance of recovery from low dependence to independence (hazard ratio (HR): 0.90, 95% confidence interval (CI): 0.82-0.99). DISCUSSION: when a relatively able person visits the GP or clinical pharmacist, careful consideration should be given to whether the potential benefits from adding a new medication outweigh the risk to reduced recovery of independence.

Prescribing at 95 years of age: cross-sectional findings from the Newcastle 85+ study.

BACKGROUND: Previous research has examined prescribing amongst 85-year-olds in English primary care, but less is known about prescribing amongst 95-year-olds in spite of population ageing. AIM: We describe the most commonly prescribed medicines in a cohort of 95-year-olds, using 10-year follow-up data from the Newcastle 85+ Study (n = 90). METHOD: A total of 1040 participants were recruited to the Newcastle 85+ Study through general practices at 85-years of age, and 90 surviving participants were re-contacted and assessed at 95-years of age. Prescribed medications from general practice medical records were examined through cross-tabulations and classified as preventative or for symptom control based on their customary usage. RESULTS: Preventative medications with unclear evidence of benefit such as statins (36.7%), aspirin (21.1%) and bisphosphonates (18.9%) were frequently prescribed. CONCLUSIONS: Future research in a larger clinical dataset could investigate this preliminary trend, which suggests that benefit/risk information for preventive medication, and evidence for deprescribing, is needed in the very old.

Describing transitions in residential status over 10 years in the very old: results from the Newcastle 85+ Study.

BACKGROUND: the very old (aged ≥ 85) are the fastest growing subpopulation of many developed countries but little is known about how their place of residence changes over time. We investigated transitions in residential status in an inception cohort of 85-year-olds over 10 years. METHODS: data were drawn from the Newcastle 85+ Study, a population-based longitudinal study of individuals aged 85 in 2006 (i.e. born in 1921) and permanently registered with a Newcastle or North Tyneside general practice (n = 849). RESULTS: 76.3% lived in standard (non-supported) housing at baseline (age = 85) and few moved into a care home. The majority either remained in standard housing or died over the study period. A significant number who lived in standard housing had dependency and frailty at baseline. DISCUSSION: given the undersupply of care homes, and preference of older people to remain in their own homes as they age, the questions posed by this analysis are how to survive to 85 and remain in standard housing until the age of 85? And how, and by whom, are such a group being supported to remain at home? We need qualitative research to explore the informal-formal care networks of the very old.

Is polypharmacy associated with mortality in the very old: Findings from the Newcastle 85+ Study.

Polypharmacy is common in the very old (≥85 years), where little is known about its association with mortality. We aimed to investigate the association between polypharmacy and all-cause mortality in the very old, over an 11-year time period. Data were drawn from the Newcastle 85+ Study (741), a cohort of people who were born in 1921 and turned 85 in 2006. Survival analysis was performed using Cox proportional hazards models with time-varying covariates, wherein polypharmacy was operationalised continuously. Each additional medication prescribed was associated with a 3% increased risk of mortality (hazard ratio: 1.03, 95% confidence interval: 1.00-1.06). Amongst the very old, the risks and benefits of each additional medication prescribed should be carefully considered.

Characterising polypharmacy in the very old: Findings from the Newcastle 85+ Study.

BACKGROUND: Polypharmacy is potentially harmful and under-researched amongst the fastest growing subpopulation, the very old (aged ≥85). We aimed to characterise polypharmacy using data from the Newcastle 85+ Study-a prospective cohort of people born in 1921 who turned 85 in 2006 (n = 845). METHODS: The prevalence of polypharmacy at baseline (mean age 85.5) was examined using cut-points of 0, 1, 2-4, 5-9 and ≥10 medicines-so-called 'no polypharmacy', 'monotherapy', 'minor polypharmacy', 'polypharmacy' and 'hyperpolypharmacy.' Cross-tabulations and upset plots identified the most frequently prescribed medicines and medication combinations within these categories. Mixed-effects models assessed whether gender and socioeconomic position were associated with prescribing changes over time (mean age 85.5-90.5). Participant characteristics were examined through descriptive statistics. RESULTS: Complex multimorbidity (44.4%, 344/775) was widespread but hyperpolypharmacy was not (16.0%, 135/845). The median medication count was six (interquartile range 4-8). Preventative medicines were common to all polypharmacy categories, and prescribing regimens were diverse. Nitrates and oral anticoagulants were more frequently prescribed for men, whereas bisphosphonates, non-opioid analgesics and antidepressants were more common in women. Cardiovascular medicines, including loop diuretics, tended to be more frequently prescribed for socioeconomically disadvantaged people (<25th centile Index of Multiple Deprivation (IMD)), despite no difference in the prevalence of cardiovascular disease (p = 0.56) and diabetes (p = 0.92) by IMD. CONCLUSION: Considering their complex medical conditions, prescribing is relatively conservative amongst 85-year-olds living in North East England. Prescribing shows significant gender and selected socioeconomic differences. More support for managing preventative medicines, of uncertain benefit, might be helpful in this population.

Coronavirus disease 2019 pandemic: staged management of surgical services for gynecology and obstetrics.

The coronavirus disease 2019 pandemic warrants an unprecedented global healthcare response requiring maintenance of existing hospital-based services while simultaneously preparing for high-acuity care for infected and sick individuals. Hospitals must protect patients and the diverse healthcare workforce by conserving personal protective equipment and redeployment of facility resources. While each hospital or health system must evaluate their own capabilities and surge capacity, we present principles of management of surgical services during a health emergency and provide specific guidance to help with decision making. We review the limited evidence from past hospital and community responses to various health emergencies and focus on systematic methods for adjusting surgical services to create capacity, addressing the specific risks of coronavirus disease 2019. Successful strategies for tiered reduction of surgical cases involve multidisciplinary engagement of the entire healthcare system and use of a structured risk-assessment categorization scheme that can be applied across the institution. Our institution developed and operationalized this approach over 3 working days, indicating that immediate implementation is feasible in response to an unforeseen healthcare emergency.

Adverse Outcomes of Polypharmacy in Older People: Systematic Review of Reviews.

OBJECTIVE: Polypharmacy is widespread among older people, but the adverse outcomes associated with it are unclear. We aim to synthesize current evidence on the adverse health, social, medicines management, and health care utilization outcomes of polypharmacy in older people. DESIGN: A systematic review, of systematic reviews and meta-analyses of observational studies, was conducted. Eleven bibliographic databases were searched from 1990 to February 2018. Quality was assessed using AMSTAR (A Measurement Tool to Assess Systematic Reviews). SETTING AND PARTICIPANTS: Older people in any health care setting, residential setting, or country. RESULTS: Twenty-six reviews reporting on 230 unique studies were included. Almost all reviews operationalized polypharmacy as medication count, and few examined medication classes or disease states within this. Evidence for an association between polypharmacy and many adverse outcomes, including adverse drug events and disability, was conflicting. The most consistent evidence was found for hospitalization and inappropriate prescribing. No research had explored polypharmacy in the very old (aged ≥85 years), or examined the potential social consequences associated with medication use, such as loneliness and isolation. CONCLUSIONS AND IMPLICATIONS: The literature examining the adverse outcomes of polypharmacy in older people is complex, extensive, and conflicting. Until polypharmacy is operationalized in a more clinically relevant manner, the adverse outcomes associated with it will not be fully understood. Future studies should work toward this approach in the face of rising multimorbidity and population aging.

Discovery of deshydroxy bicalutamide derivatives as androgen receptor antagonists.

Deshydroxy propioanilides were synthesised by Michael addition reaction between substituted thiophenols onto four different phenylacrylamide derivatives to give twenty-three novel deshydroxy bicalutamide derivatives lacking the central hydroxyl group. The antiproliferative activities of these compounds were evaluated against human prostate cancer cell lines and thirteen compounds showed better inhibitory activities (IC50 = 2.67-13.19 µM) compared to bicalutamide (IC50 = 20.44 µM) in LNCaP. Remarkably, novel double branched bicalutamide analogues (27 and 28) were isolated as major by-products and found to have the best activity across three human prostate cancer cell lines (LNCaP, VCaP and PC3). The most active compound 28 shows sub-micromolar activity (IC50 = 0.43 µM in LNCaP), which represents more than 40-fold improvement over the clinical anti-androgen bicalutamide (IC50 = 20.44 µM) and a more than 3 fold improvement over enzalutamide (IC50 = 1.36 µM). Moreover, strong reduction of PSA expression in LNCaP cells upon treatment with compounds 27, 28 and 33 was observed during qPCR analysis, confirming their AR antagonist activity. Molecular modelling studies revealed a novel binding mode of these structurally distinct double branched analogues within the ligand binding domain (LBD) of the androgen receptor.

End-of-life discussions: Who's doing the talking?

PURPOSE: To determine, in a tertiary academic medical center, the reported frequency of end-of-life discussions among nurses and the influence of demographic factors on these discussions. METHODS: Survey of nurses on frequency of end-of-life discussions in two urban academic medical centers. Chi-square tests were used to separately assess the relationship between age, gender, specialty, and experience with responses to the question, "Do you regularly talk with your patients about end-of-life wishes?" RESULTS: Overall, more than one-third of respondents reported rarely or never discussing end-of-life wishes with their patients. Only specialty expertise (p<0.001) was statistically significantly associated with discussing end-of-life issues with patients. Over half of nurses specializing in critical care responded that they have these discussion "always" or "most of the time." However, for the specialties of surgery (59%) and anesthesiology (56%), the majority of respondents reported rarely or never having end-of-life discussions with patients. CONCLUSIONS: In a survey conducted in two tertiary care institutions, more than one-third of nurses from all disciplines responded that they never or almost never discuss end-of-life issues with their patients. Specialty influenced the likelihood of discussing end-of-life issues with patients.

Managing Asbestos-Containing Materials in the Built Environment: Report of a Health and Safety Executive and Government Office for Science Workshop.

The duty to manage asbestos in non-domestic premises is described in the Control of Asbestos Regulations 2012. Health and Safety Executive (HSE) policy and guidance on asbestos in the built environment in Great Britain is that asbestos-containing materials (ACMs) that are in good condition and unlikely to be disturbed can be managed in place. Where ACMs are in poor condition or likely to be disturbed they should be repaired, encapsulated or, if necessary, removed. HSE and Government Office for Science hosted a stakeholder workshop to consider evidence on the management of ACMs in public buildings. Invitees attended from a range of backgrounds (including regulatory, government, academic, medical, public interest groups, and professional service providers). Participants considered the evidence, suggested nine evidence gap areas and ranked these according to preference in an anonymous vote. The top three suggested evidence gaps were: (i) the comparative risks of managing ACMs in place versus removal; (ii) improved measurement techniques at lower fibre concentrations; and (iii) building the evidence base on the effectiveness of asbestos management and safe removal. HSE will use the workshop outputs to inform its research planning. It is anticipated that a number of initiatives for shared research will be explored.

Incorporating airway examination photography into the electronic record.

BACKGROUND: Photography of the airway has been used in research to validate preoperative airway assessment and the likelihood of identifying the difficult-to-mask ventilate and/or intubate patient. Up till now, no study has demonstrated the perceived utility of incorporation of airway photographs into the anesthesia preassessment. METHODS: The University of Florida Health Presurgical Clinic routinely incorporates three photographs of all adult patients during their preanesthesia visit. The first is a head-on view of the patient opening the mouth widely as part of a Mallampati examination, and the second and third are side views of the patient prognathing and with the neck in maximal extension, respectively. After IRB approval, providers of anesthesia were surveyed regarding their opinions on the perceived value of the new process. Chi-square tests were used to determine if the responses to each question significantly differed from the distribution that would be predicted by chance. P < 0.05 was considered statistically significant. RESULTS: The survey was emailed to 180 individuals, with 145 responding. The responses significantly (P < 0.0001) indicated that the photographs helped the providers plan care for their patients and improved their satisfaction with the preoperative assessment. Technical and educational barriers were overcome using iterative Plan-Do-Study-Act cycles and coaching, respectively. CONCLUSIONS: Photographs of the airway assessment can successfully be taken and incorporated into an electronic medical record in a busy presurgical clinic. The pictures provide additional perceived value to the traditional written assessment of a patient's airway examination by someone else.

Estrogen increases proteasome activity in murine microglial cells.

During inflammation, microglial cells go through phenotypic and functional changes that include the production and release of large amounts of oxygen and nitrogen radicals. As such, activated microglia are subject to heightened oxidative stress. The multicatalytic proteasome clears oxidized and damaged proteins from cells, and has been shown to be an important aspect of the microglial compensatory response to activation. The female sex steroid estrogen is both cytoprotective and anti-inflammatory, and has been shown to affect microglial signaling in particular. To determine if estrogen might affect the proteasome in microglial cells, we examined the effects of 17 beta-estradiol treatment on proteasome activity in N9 microglial cells. Specifically, we measured ATP-dependent and ATP-independent chymotrypsin-like, trypsin-like, and peptidyl glutamyl peptide hydrolase (PGPH)-like activities in response to both 17 beta-estradiol and interferon gamma. Data indicate that estrogen, but not interferon gamma, significantly increases ATP-dependent chymotrypsin-like and PGPH-like activity. Furthermore, this effect was blocked by the p44/42 MAPK inhibitor PD98059. Hence, these data demonstrate that through the MAPK pathway, estrogen can upregulate proteasome activity, suggesting a possible mechanism for estrogen's cytoprotective effects.