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Background: The purpose of this study was to assess impingement-free internal rotation (IR) in a virtual reverse shoulder arthroplasty simulation using a Statistical Shape Model based on scapula size. Methods: A database of over 10,000 scapulae utilized for preoperative planning for shoulder arthroplasty was analyzed with a Statistical Shape Model to obtain 5 scapula sizes including the mean and 2 standard deviations. For each scapula model, one glenosphere size (33-42 mm) was selected as the best fit based on consensus among 3 shoulder surgeons. Virtual implantation variables included 1) lateral offset (0-12 mm in 2-mm increments), 2) inferior eccentricity (0, 2.5, 5, and 7.5 mm), and 3) posterior eccentricity (0, 2.5, and 5 mm). The neck shaft angle was fixed at 135° with an inlay design humeral prosthesis. IR at the side (IR0) and in abduction (IRABD) were then simulated. Results: Maximum impingement-free IR0 was reached with increasing inferior offset in combination with increasing lateralization. Lateralization was the most important variable in increasing impingement-free IRABD. Maximum IRABD was reached at 4-6 mm of lateralization with smaller scapula (−2 to 0 standard deviation). Increasing lateralization up to 12 mm continues to increase IRABD for larger-sized scapula (+1 to +2 standard deviation). Optimal inferior offset and lateralization to maximize IR did have a small loss of external rotation in neutral abduction. There was no loss of external rotation in 60° of abduction. Conclusion: In a virtual model, the glenosphere position required to maximize IR varied by scapula size. For smaller scapulae, maximum IR0 was reached with a combination of 2.5-mm inferior offset and 0- 4 mm of lateralization. For larger scapulae, maximum IR0 was reached with a combination of 2.5 mm of inferior offset and 4 mm of lateralization. The amount of lateralization required to maximize IRABD also varies by scapula size. Maximum IRABD was reached in smaller scapula with 4-6 mm of lateralization and at least 12 mm of lateralization in larger scapula. These findings may be applied in the clinical decision-making process knowing that impingement-free IR and IRABD can be maximized with combinations of inferior offset and lateralization based on scapula size with minimal effect on external rotation and external rotation in 60° of abduction.

Summary: Background: Issues of under-diagnosis and under-coding of dementia in routinely collected health data limit their utility for estimating dementia prevalence and incidence in Aotearoa New Zealand (NZ). Capture-recapture techniques can be used to estimate the number of dementia cases missing from health datasets by modelling the relationships and interactions between linked data sources. The aim of this study was to apply this technique to routinely collected and linked health datasets and more accurately estimate the incidence of dementia in NZ. Methods: All incident cases of dementia in the NZ 60+ population were identified in three linked national health data sets—interRAI, Public hospital discharges, and Pharmacy. Capture-recapture analysis fitted eight loglinear models to the data, with the best fitting model used to estimate the number of cases missing from all three datasets, and thereby estimate the ‘true’ incidence of dementia. Incidence rates were calculated by 5-year age bands, sex and ethnicity. Findings: Modelled estimates indicate 36% of incident cases are not present in any of the datasets. Modelled incidence rates in the 60+ age group were 19.2 (95% CI 17.3–22.0)/1000py, with an incident rate ratio of 1.9 (95% CI 1.9–2.0) per 5-year age band. There was no difference in incidence rates between males and females. Incidence rates in Asian (p < 0.001) but not Māori (p = 0.974) or Pacific peoples (p = 0.110) were significantly lower compared to Europeans, even after inclusion of missing cases. Interpretation: This is the first study to provide estimates of age 60+ dementia incidence in NZ and for the four main ethnic groups and suggests over a third of incident dementia cases are undiagnosed. This highlights the need for better access to dementia assessment and diagnosis so that appropriate supports and interventions can be put in place to improve outcomes for people living with dementia and their families. Funding: Nil.

Abstract Background Although age is the biggest known risk factor for dementia, there remains uncertainty about other factors over the life course that contribute to a person’s risk for cognitive decline later in life. Furthermore, the pathological processes leading to dementia are not fully understood. The main goals of Insight 46—a multi-phase longitudinal observational study—are to collect detailed cognitive, neurological, physical, cardiovascular, and sensory data; to combine those data with genetic and life-course information collected from the MRC National Survey of Health and Development (NSHD; 1946 British birth cohort); and thereby contribute to a better understanding of healthy ageing and dementia. Methods/Design Phase 1 of Insight 46 (2015–2018) involved the recruitment of 502 members of the NSHD (median age = 70.7 years; 49% female) and has been described in detail by Lane and Parker et al. 2017. The present paper describes phase 2 (2018–2021) and phase 3 (2021–ongoing). Of the 502 phase 1 study members who were invited to a phase 2 research visit, 413 were willing to return for a clinic visit in London and 29 participated in a remote research assessment due to COVID-19 restrictions. Phase 3 aims to recruit 250 study members who previously participated in both phases 1 and 2 of Insight 46 (providing a third data time point) and 500 additional members of the NSHD who have not previously participated in Insight 46. Discussion The NSHD is the oldest and longest continuously running British birth cohort. Members of the NSHD are now at a critical point in their lives for us to investigate successful ageing and key age-related brain morbidities. Data collected from Insight 46 have the potential to greatly contribute to and impact the field of healthy ageing and dementia by combining unique life course data with longitudinal multiparametric clinical, imaging, and biomarker measurements. Further protocol enhancements are planned, including in-home sleep measurements and the engagement of participants through remote online cognitive testing. Data collected are and will continue to be made available to the scientific community.

Background: Improvements in pain control after shoulder arthroplasty with a reduction in narcotic use continues to be an important postoperative goal. With the increased utilization of stemless anatomic total shoulder arthroplasty (aTSA), it is relevant to compare between stemmed and stemless arthroplasty to assess if there is any association between this implant design change and early postoperative pain. Methods: Patients from a multicenter, prospectively-maintained database who had undergone a stemless aTSA with a minimum of two year clinical follow-up were retrospectively identified. Patients who underwent aTSA with a short stem were identified in the same registry, and matched to the stemless aTSA patients by age, sex and preoperative pain score. The primary study outcome was the Visual Analog Scale pain score. Secondary pain outcomes were the American Shoulder and Elbow Surgeons shoulder pain subscore, Western Ontario Osteoarthritis of the Shoulder physical symptoms subscore, and the Single Assessment Numeric Evaluation score. Finally, the percentage of patients who could sleep on the affected shoulder was assessed for each group. These pain-related clinical outcomes were assessed and compared preoperatively, and postoperatively at 9 weeks, 26 weeks, one year and two years. For all statistical comparisons, P > .05 was considered significant. Results: 124 patients were included in the study; 62 in each group. At 9 weeks after surgery, statistically significantly improved pain control was reported by patients undergoing stemless aTSA, as assessed by the Visual Analog Scale (stemless: 1.5, stemmed: 2.5, P = .001), American Shoulder and Elbow Surgeons pain subscore (stemless: 42.4, stemmed: 37.3, P

Abstract Background The Live Well with Parkinson’s Self-Management Toolkit is designed for use in the NHS to support people with Parkinson’s, their carers and health professionals in managing motor and non-motor symptoms and promoting well-being. The Toolkit was developed based on theory-based behaviour change and self-management techniques in consultation with people living with Parkinson’s and health and social care practitioners. There are digital (e-Toolkit) and paper (manual) versions. Methods Single-blind two-arm randomised controlled trial RCT of clinical effectiveness and cost-effectiveness of the Toolkit, facilitated by up to six sessions with a trained non-specialist supporter, in improving quality of life. People with Parkinson’s will be assessed at baseline, 6 and 12 months. Assessors will be blind to the treatment group. The primary outcome measure is the Parkinson’s Disease Questionnaire (PDQ-39, Parkinson’s related quality of life) score at 12 months. Secondary outcome measures include the MDS Unified Parkinson’s Disease Rating Scale (Part I, II, III, IV), EQ-5D, and a Client Service Receipt Inventory shortened, adapted for Parkinson’s. Carer outcomes include the Zarit Carer Burden Inventory and Carer Quality of Life Questionnaire for Parkinsonism. A total of 338 people with Parkinson’s, and their carers if appropriate, will be recruited from diverse settings across England. Those with advanced dementia, at end-of-life or with atypical Parkinsonism will be excluded. A parallel mixed methods process evaluation will explore the factors promoting or inhibiting implementation, uptake, use, effectiveness and cost-effectiveness of the Toolkit and sessions. Discussion If successful, the Live Well with Parkinson’s Toolkit could be used as a model for other complex long-term disorders, including dementia. This would bridge existing gaps in the NHS (as shown by the national Parkinson’s audit data), by enabling patients and carers to access personalised information, advice and support on symptom management and ‘living well’ with Parkinson’s. Trial registration ISRCTN92831552. Registered on 26th Oct 2021.

Abstract Background Delirium affects over 20% of all hospitalised older adults. Delirium is associated with a number of adverse outcomes following hospital admission including cognitive decline, anxiety and depression, increased mortality and care needs. Previous research has addressed prevention of delirium in hospitals and care homes, and there are guidelines on short-term treatment of delirium during admission. However, no studies have addressed the problem of longer-term recovery after delirium and it is currently unknown whether interventions to improve recovery after delirium are effective and cost-effective. The primary objective of this feasibility study is to test a new, theory-informed rehabilitation intervention (RecoverED) in older adults delivered following a hospital admission complicated by delirium to determine whether (a) the intervention is acceptable to individuals with delirium and (b) a definitive trial and parallel economic evaluation of the intervention are feasible. Methods The study is a multi-centre, single-arm feasibility study of a rehabilitation intervention with an embedded process evaluation. Sixty participants with delirium (aged > 65 years old) and carer pairs will be recruited from six NHS acute hospitals across the UK. All pairs will be offered the intervention, with follow-up assessments conducted at 3 months and 6 months post-discharge home. The intervention will be delivered in participants’ own homes by therapists and rehabilitation support workers for up to 10 intervention sessions over 12 weeks. The intervention will be tailored to individual needs, and the chosen intervention plan and goals will be discussed and agreed with participants and carers. Quantitative data on reach, retention, fidelity and dose will be collected and summarised using descriptive statistics. The feasibility outcomes that will be used to determine whether the study meets the criteria for progression to a definitive randomised controlled trial (RCT) include recruitment, delivery of the intervention, retention, data collection and acceptability of outcome measures. Acceptability of the intervention will be assessed using in-depth, semi-structured qualitative interviews with participants and healthcare professionals. Discussion Findings will inform the design of a pragmatic multi-centre RCT of the effectiveness and cost-effectiveness of the RecoverED intervention for helping the longer-term recovery of people with delirium compared to usual care. Trial registration The feasibility study was registered: ISRCTN15676570

Abstract Background The prediction of long-term mortality following acute illness can be unreliable for older patients, inhibiting the delivery of targeted clinical interventions. The difficulty plausibly arises from the complex, multifactorial nature of the underlying biology in this population, which flexible, multimodal models based on machine learning may overcome. Here, we test this hypothesis by quantifying the comparative predictive fidelity of such models in a large consecutive sample of older patients acutely admitted to hospital and characterise their biological support. Methods A set of 804 admission episodes involving 616 unique patients with a mean age of 84.5 years consecutively admitted to the Acute Geriatric service at University College Hospital were identified, in whom clinical diagnoses, blood tests, cognitive status, computed tomography of the head, and mortality within 600 days after admission were available. We trained and evaluated out-of-sample an array of extreme gradient boosted trees-based predictive models of incrementally greater numbers of investigational modalities and modelled features. Both linear and non-linear associations with investigational features were quantified. Results Predictive models of mortality showed progressively increasing fidelity with greater numbers of modelled modalities and dimensions. The area under the receiver operating characteristic curve rose from 0.67 (sd = 0.078) for age and sex to 0.874 (sd = 0.046) for the most comprehensive model. Extracranial bone and soft tissue features contributed more than intracranial features towards long-term mortality prediction. The anterior cingulate and angular gyri, and serum albumin, were the greatest intracranial and biochemical model contributors respectively. Conclusions High-dimensional, multimodal predictive models of mortality based on routine clinical data offer higher predictive fidelity than simpler models, facilitating individual level prognostication and interventional targeting. The joint contributions of both extracranial and intracranial features highlight the potential importance of optimising somatic as well as neural functions in healthy ageing. Our findings suggest a promising path towards a high-fidelity, multimodal index of frailty.

Despite extensive studies on the effects of SARS-CoV-2 infection, there is still a lack of understanding of the downstream epigenetic and regulatory alterations in infected cells. In this study, we investigated changes in enhancer acetylation in epithelial lung cells infected with SARS-CoV-2 and their influence on transcriptional regulation and pathway activity. To achieve this, we integrated and reanalyzed data of enhancer acetylation, ex-vivo infection and single cell RNA-seq data from human patients. Our findings revealed coordinated changes in enhancers and transcriptional networks. We found that infected cells lose the WT1 transcription factor and demonstrate disruption of WT1-bound enhancers and of their associated target genes. Downstream targets of WT1 are involved in the regulation of the Wnt signaling and the mitogen-activated protein kinase cascade, which indeed exhibit increased activation levels. These findings may provide a potential explanation for the development of pulmonary fibrosis, a lethal complication of COVID-19. Moreover, we revealed over-acetylated enhancers associated with upregulated genes involved in cell adhesion, which could contribute to cell-cell infection of SARS-CoV-2. Furthermore, we demonstrated that enhancers may play a role in the activation of pro-inflammatory cytokines and contribute to excessive inflammation in the lungs, a typical complication of COVID-19. Overall, our analysis provided novel insights into the cell-autonomous dysregulation of enhancer regulation caused by SARS-CoV-2 infection, a step on the path to a deeper molecular understanding of the disease.

Abstract Introduction Life-space and frailty are closely linked to health-related quality of life and understanding their inter-relationship could indicate potential intervention targets for improving quality of life. We set out to examine the relationship between frailty and life-space and their relative impact on quality of life measures. Methods Using cross-sectional data from a population-representative cohort of people aged ≥ 70 years, we assessed quality of life with the EuroQol Health Index tool (5-levels) (EQ-5D-5L). We also undertook a life-space assessment and derived a frailty index. Linear regression models estimated EQ-5D-5L scores (dependent variable) using life-space assessment, frailty index and interactions between them. All models were adjusted by age, sex, lifestyle, and social care factors. Results A higher EQ-5D Index was associated with higher life-space (0.02 per life-space assessment score, 95%CI: 0.01 to 0.03, p

Abstract Introduction Frailty and socioeconomic position (SEP) are well‐established determinants of health. However, we know less about the contributions of frailty and SEP in older adults, especially in acute settings. We set out to answer how frailty and SEP might influence health outcomes in older people, comparing a population sample and patients managed by a speciality acute frailty service. Methods We used the Delirium and Population Health Informatics Cohort, a population sample of 1510 individuals aged ≥70 years from the London Borough of Camden and 1750 acute frailty patients. SEP was determined using the Index of Multiple Deprivation. Linear and Cox proportional hazard regression models were conducted to assess SEP on frailty, readmission, and mortality outcomes. Results In the population sample, SEP was significantly associated with frailty and mortality with successive increases in rate of death for each IMD quintile (HR = 1.28, 95% CI 1.11 to 1.49, P

Dementia is an important and growing issue in sub-Saharan Africa, but epidemiological data are lacking. Risk factors may differ from other regions due to high stroke incidence and HIV prevalence. Understanding the epidemiology of cognition in older adults in Africa is crucial for informing public health strategies to improve the lives of people with dementia and their carers. The Wellbeing of Older People Study in Uganda is an open cohort of adults aged 50+ with and without HIV, established in 2009. Detailed socio-demographic and health data have been collected at four waves spanning 10 years, including cognitive assessment using internationally validated WHO-recommended tests: verbal recall, digit span, and verbal fluency. Mortality data was collected until the end of the fourth wave (2019). We examined associations of low baseline cognition scores and changes in cognition score over time using random effects modelling, care needs of people with lower cognition scores, and the relationship between cognition score and mortality. Data were collected on 811 participants. Older age, lower educational attainment, lower socio-economic position, and extremes of BMI were associated with lower cognition scores. Cognition scores declined faster at older ages, but rate of decline was not associated with cardiovascular disease or HIV at baseline. People with lower cognition scores required more assistance with Activities of Daily Living, but mortality rates were similar across the range of cognition scores. The crucial next step will be to investigate types and presentation of clinical dementia in this cohort, so we can better understand the clinical relevance of these findings to inform public health planning.

AbstractThe controversial theory of adaptive amplification states gene amplification mutations are induced by selective environments where they are enriched due to the stress caused by growth restriction on unadapted cells. We tested this theory with three independent assays using an Acinetobacter baylyicatcatAcinetobacter

Abstract Background Delirium is a heterogeneous syndrome with inattention as the core feature. There is considerable variation in the presence and degree of other symptom domains such as altered arousal, psychotic features and global cognitive dysfunction. Delirium is independently associated with increased mortality, but it is unclear whether individual symptom domains of delirium have prognostic importance. We conducted a systematic review and meta-analysis of studies in hospitalised adults in general settings to identify the relationship between symptom domains of delirium and outcomes. (PROSPERO: CRD42018093935). Methods We searched MEDLINE, EMBASE, PsycINFO, CINAHL, clinicaltrials.gov and the Cochrane Central Register of Controlled Trials from inception to November 2019. We included studies of hospitalised adults that reported associations between symptom domains of delirium and 30-day mortality (primary outcome), and other outcomes including mortality at other time points, length of stay, and dementia. Reviewer pairs independently screened articles, extracted data, and assessed risk of bias (Risk of Bias Assessment tool for Non-randomized Studies) and quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation framework. We performed random-effects meta-analyses stratified by delirium domain where possible. Results From 7092 citations we included 6 studies (6002 patients, 1112 with delirium). Higher mortality (ranging from in-hospital to follow-up beyond 12 months) was associated with altered arousal (pooled Odds Ratio (OR) 2.80, 95% Confidence Interval (CI) 2.33–3.37; moderate-quality evidence), inattention (pooled OR 2.57, 95% CI 1.74–3.80; low-quality evidence), and in single studies with disorientation, memory deficits and disorganised thoughts. Risk of bias varied across studies but was moderate-to-high overall, mainly due to selection bias, lack of blinding of assessments and unclear risk of selective outcome reporting. We found no studies on the association between psychotic features, visuospatial deficits or affective disturbances in delirium and outcomes, or studies reporting non-mortality outcomes. Conclusions Few studies have related symptom domains of delirium to outcomes, but the available evidence suggests that altered arousal and inattention in delirium are associated with higher mortality than normal arousal and attention in people with or without delirium. Measurable symptom domains of delirium may have value in predicting survival and stratifying patients for treatment. We recommend that future delirium studies report outcomes by symptom domain.

Abstract Background The highest burden of hypertension is found in Sub-Saharan Africa (SSA) with a threefold greater mortality from stroke and other associated diseases. Ethnicity is known to influence the response to antihypertensives, especially in black populations living in North America and Europe. We sought to outline the impact of all commonly used pharmacological agents on both blood pressure reduction and cardiovascular morbidity and mortality in SSA. Methods We used similar criteria to previous large meta-analyses of blood pressure agents but restricted results to populations in SSA. Quality of evidence was assessed using a risk of bias tool. Network meta-analysis with random effects was used to compare the effects across interventions and meta-regression to explore participant heterogeneity. Results Thirty-two studies of 2860 participants were identified. Most were small studies from single, urban centres. Compared with placebo, any pharmacotherapy lowered SBP/DBP by 8.51/8.04 mmHg, and calcium channel blockers (CCBs) were the most efficacious first-line agent with 18.46/11.6 mmHg reduction. Fewer studies assessing combination therapy were available, but there was a trend towards superiority for CCBs plus ACE inhibitors or diuretics compared to other combinations. No studies examined the effect of antihypertensive therapy on morbidity or mortality outcomes. Conclusion Evidence broadly supports current guidelines and provides a clear rationale for promoting CCBs as first-line agents and early initiation of combination therapy. However, there is a clear requirement for more evidence to provide a nuanced understanding of stroke and other cardiovascular disease prevention amongst diverse populations on the continent. Trial registration PROSPERO, CRD42019122490 . This review was registered in January 2019.

Although transcatheter aortic valve implantation (TAVI) has revolutionised the landscape of treatment for aortic stenosis, there exists a cohort of patients where TAVI is deemed futile. Among the pivotal high-risk trials, one-third to half of patients either died or received no symptomatic benefit from the procedure at 1 year. Futility of TAVI results in the unnecessary exposure of risk for patients and inefficient resource utilisation for healthcare services. Several cardiac and extra-cardiac conditions and frailty increase the risk of mortality despite TAVI. Among the survivors, these comorbidities can inhibit improvements in symptoms and quality of life. However, certain conditions are reversible with TAVI (e.g. functional mitral regurgitation), attenuating the risk and improving outcomes. Quantification of disease severity, identification of reversible factors and a systematic evaluation of frailty can substantially improve risk stratification and outcomes. This review examines the contribution of pre-existing comorbidities towards futility in TAVI and suggests a systematic approach to guide patient evaluation.

Background Drug-induced orthostatic hypotension (OH) is common, and its resulting cerebral hypoperfusion is linked to adverse outcomes including falls, strokes, cognitive impairment, and increased mortality. The extent to which specific medications are associated with OH remains unclear. Methods and findings We conducted a systematic review and meta-analysis to evaluate the extent to which specific drug groups are associated with OH. EMBASE, MEDLINE, and Web of Science databases were searched from inception through 23 November 2020. Placebo-controlled randomised controlled trials (RCTs) on any drug reporting on OH as an adverse effect in adults (≥18 years) were eligible. Three authors extracted data on the drug, OH, dose, participant characteristics, and study setting. The revised Cochrane risk-of-bias tool for randomised trials (RoB 2) was used to appraise evidence. Summary odds ratios (ORs) were estimated for OH using fixed effects Mantel–Haenszel statistics. We conducted subgroup analysis on validity of OH measurement, drug dose, risk of bias, age, and comorbidity. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool was used to summarise the certainty of evidence. Of 36,940 citations, 69 eligible RCTs were included in the meta-analysis comprising 27,079 participants. Compared with placebo, beta-blockers and tricyclic antidepressants were associated with increased odds of OH (OR 7.76 [95% CI 2.51, 24.03]; OR 6.30 [95% CI 2.86, 13.91]). Alpha-blockers, antipsychotics, and SGLT-2 inhibitors were associated with up to 2-fold increased odds of OH, compared to placebo. There was no statistically significant difference in odds of OH with vasodilators (CCBs, ACE inhibitors/ARBs, SSRIs), compared to placebo. Limitations of this study are as follows: data limited to placebo-controlled studies, (excluding head-to-head trials), many RCTs excluded older participants; therefore results may be amplified in older patients in the clinical setting. The study protocol is publicly available on PROSPERO (CRD42020168697). Conclusions Medications prescribed for common conditions (including depression, diabetes, and lower urinary tract symptoms) were associated with significantly increased odds of OH. Drugs causing sympathetic inhibition were associated with significantly increased odds of OH, while most vasodilators were associated with small nonsignificant differences in odds of OH, compared to placebo. Drugs targeting multiple parts of the orthostatic blood pressure (BP) reflex pathway (e.g. sympathetic inhibition, vasodilation, cardio-inhibitory effects) may carry cumulative risk, suggesting that individuals with polypharmacy could benefit from postural BP monitoring. Cini Bhanu and colleagues evaluate the extent to which different drug groups are associated with orthostatic hypertension in this systematic review and meta-analysis. Author summary Why was this study done? Orthostatic hypotension (OH) is a common side effect of drugs. It causes a reduction in blood pressure (BP) on standing, which results in reduced cerebral blood flow that is linked to falls, strokes, cognitive impairment, and increased mortality. Over 250 medications are associated with OH. However, there is conflicting evidence on the extent to which different drug groups are associated with OH as a side effect. To our knowledge, there are no systematic reviews providing an overview of which drugs are associated with OH. What did the researchers do and find? We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) comparing a drug to placebo, including 69 trials comprising 27,079 participants, to address the extent to which specific medications are associated with OH. We found that drugs primarily inhibiting sympathetic activity were associated with significantly increased odds of OH, compared to placebo (beta-blockers, TCAs, antipsychotics, alpha-blockers). Drugs primarily causing vasodilation (CCBs, ACE inhibitors/ARBs, SSRIs, SGLT-2 inhibitors) were associated with smaller differences that were not statistically significant, compared to placebo. What do these findings mean? Drugs prescribed widely for common conditions including lower urinary tract symptoms, mental health conditions, pain, and insomnia are associated with significantly increased risk of OH; alternative prescribing, shorter treatment, and postural BP checks should be considered to manage this risk. The relationship between antihypertensives and antidiabetic drugs and OH is more complex. Drugs targeting multiple parts of the BP reflex pathway causing OH may carry cumulative risk, suggesting that individuals with polypharmacy could benefit from routine postural BP monitoring.

Rationale & Objective: Chronic kidney disease (CKD) can progress rapidly, and patients are often unprepared to make kidney failure treatment decisions. We aimed to better understand patients’ preferences for and experiences of shared and informed decision making (SDM) regarding kidney replacement therapy before kidney failure. Study Design: Cross-sectional study. Setting & Participants: Adults receiving nephrology care at CKD clinics in rural Pennsylvania. Predictors: Estimated glomerular filtration rate, 2-year risk for kidney failure, duration and frequency of nephrology care, and preference for SDM. Outcomes: Occurrence and extent of kidney replacement therapy discussions and participants’ satisfaction with those discussions. Analytic Approach: Multivariable logistic regression to quantify associations between participants’ characteristics and whether they had discussions. Results: The 447 study participants had a median age of 72 (IQR, 64-80) years and mean estimated glomerular filtration rate of 33 (SD, 12) mL/min/1.73 m2. Most (96%) were White, high school educated (67%), and retired (65%). Most (72%) participants preferred a shared approach to kidney treatment decision making, and only 35% discussed dialysis or transplantation with their kidney teams. Participants who had discussions (n = 158) were often completely satisfied (63%) but infrequently discussed potential treatment-related impacts on their lives. In multivariable analyses, those with a high risk for kidney failure within 2 years (OR, 3.24 [95% CI, 1.72-6.11]; P < 0.01), longer-term nephrology care (OR, 1.12 [95% CI, 1.05-1.20] per 1 additional year; P < 0.01), and more nephrology visits in the prior 2 years (OR, 1.34 [95% CI, 1.20-1.51] per 1 additional visit; P < 0.01) had higher odds of having discussed dialysis or transplantation. Limitations: Single health system study. Conclusions: Most patients preferred sharing CKD treatment decisions with their providers, but treatment discussions were infrequent and often did not address key treatment impacts. Longitudinal nephrology care and frequent visits may help ensure that patients have optimal SDM experiences.

The use of high-field superconducting magnets has furthered the development of medical diagnosis, fusion research, accelerators, and particle physics. High-temperature superconductors enable magnets more powerful than those possible with Nb-Ti (superconducting transition temperature T_{c} of 9.2 K) and Nb_{3}Sn (T_{c} of 18.4 K) conductors due to their very high critical field B_{c2} of greater than 100 T near 4.2 K. However, the development of high-field accelerator magnets using high-temperature superconductors is still at its early stage. We report the construction of the world’s first high-temperature superconducting Bi_{2}Sr_{2}CaCu_{2}O_{x} (Bi-2212 with T_{c} of ∼82 K) accelerator dipole magnet. The magnet is based on a canted-cosine-theta design with Bi-2212 Rutherford cables. A high critical current was achieved by an overpressure processing heat treatment. The magnet was constructed from a nine-strand Rutherford cable made from industrial 0.8 mm wires. At 4.2 K, it reached a quench current of 3600 A and a dipole field of 1.64 T in a bore of 31 mm. The magnet did not exhibit the undesirable quench training common in Nb-Ti and Nb_{3}Sn accelerator magnets. It quenched a dozen times without degradation. The magnet exhibited low magnetic field hysteresis (

BackgroundWe aimed to estimate multimorbidity trajectories and quantify socioeconomic inequalities based on childhood and adulthood socioeconomic position (SEP) in the risks and rates of multimorbidity accumulation across adulthood.Methods and findingsParticipants from the UK 1946 National Survey of Health and Development (NSHD) birth cohort study who attended the age 36 years assessment in 1982 and any one of the follow-up assessments at ages 43, 53, 63, and 69 years (N = 3,723, 51% males). Information on 18 health conditions was based on a combination of self-report, biomarkers, health records, and prescribed medications. We estimated multimorbidity trajectories and delineated socioeconomic inequalities (based on childhood and adulthood social class and highest education) in multimorbidity at each age and in longitudinal trajectories. Multimorbidity increased with age (0.7 conditions at 36 years to 3.7 at 69 years). Multimorbidity accumulation was nonlinear, accelerating with age at the rate of 0.08 conditions/year (95% CI 0.07 to 0.09, p < 0.001) at 36 to 43 years to 0.19 conditions/year (95% CI 0.18 to 0.20, p < 0.001) at 63 to 69 years. At all ages, the most socioeconomically disadvantaged had 1.2 to 1.4 times greater number of conditions on average compared to the most advantaged. The most disadvantaged by each socioeconomic indicator experienced an additional 0.39 conditions (childhood social class), 0.83 (adult social class), and 1.08 conditions (adult education) at age 69 years, independent of all other socioeconomic indicators. Adverse adulthood SEP was associated with more rapid accumulation of multimorbidity, resulting in 0.49 excess conditions in partly/unskilled compared to professional/intermediate individuals between 63 and 69 years. Disadvantaged childhood social class, independently of adulthood SEP, was associated with accelerated multimorbidity trajectories from age 53 years onwards. Study limitations include that the NSHD cohort is composed of individuals of white European heritage only, and findings may not be generalizable to the non-white British population of the same generation and did not account for other important dimensions of SEP such as income and wealth.ConclusionsIn this study, we found that socioeconomically disadvantaged individuals have earlier onset and more rapid accumulation of multimorbidity resulting in widening inequalities into old age, with independent contributions from both childhood and adulthood SEP.

Background: Transcatheter aortic valve implantation (TAVI) has become the standard-of-care for treatment of severe symptomatic aortic stenosis and is also being increasingly recommended for low-risk patients. While TAVI boasts positive post-procedural outcomes, it is also associated with cognitive complications, namely delirium and cognitive decline. There is a pressing need for accurate risk tools which can identify TAVI patients at risk of delirium and cognitive decline, as risk scores designed for general cardiovascular surgery fall short. The present effect-finding exploratory study will assess the utility of various measures in the context of aging and frailty in predicting who will and who will not develop delirium or cognitive impairment following TAVI. The measures we propose include gait, visual symptoms, voice, swallowing, mood and sleep.Methods: This is an observational prospective cohort study focused on identifying pre-procedural risk factors for the development of delirium and cognitive decline following TAVI. Potential risk factors will be measured prior to TAVI. Primary outcomes will be post-procedure cognitive decline and delirium. Secondary outcomes include activities of daily living, quality of life, and mortality. Delirium presence will be measured on each of the first 2 days following TAVI. All other outcomes will be assessed at 3-, 6-, and 12-months post-operatively. A series of logistic regressions will be run to investigate the relationship between potential predictors and outcomes (presence vs. absence of either delirium or cognitive decline).Discussion: This study will assess the strengths of associations between a range of measures drawn from frailty and aging literature in terms of association with cognitive decline and delirium following TAVI. Identified measures can be used in future development of TAVI risk prediction models, which are essential for the accurate identification of cognitive at-risk patients and successful application of pre-procedural interventions.Clinical Trial Registration: This trial is registered with the Australian New Zealand Clinical Trials Registry. [https://bit.ly/2PAotP5], [ACTRN12618001114235].

Rationale & Objective: Digital health system tools to support shared decision making and preparation for kidney replacement treatments for patients with chronic kidney disease (CKD) are needed. Study Design: Descriptive study of the implementation of digital infrastructure to support a patient-centered health system intervention. Setting & Participants: 4 CKD clinics within a large integrated health system. Exposure: We developed an integrated suite of digital engagement tools to support patients’ shared decision making and preparation for kidney failure treatments. Tools included an automated CKD patient registry and risk prediction algorithm within the electronic health record (EHR) to identify and prioritize patients in need of nurse case management to facilitate shared decision making and preparation for kidney replacement treatments, an electronic patient-facing values clarification tool, a tracking application to document patients’ preparation for treatments, and an EHR work flow to broadcast patients’ treatment preferences to all health care providers. Outcomes: Uptake and acceptability. Analytic Approach: Mixed methods. Results: From July 1, 2017, through June 30, 2018, the CKD registry identified 1,032 patients in 4 nephrology clinics, of whom 243 (24%) were identified as high risk for progressing to kidney failure within 2 years. Kidney Transitions Specialists enrolled 117 (48%) high-risk patients by the end of year 1. The values tool was completed by 30/33 (91%) patients who attended kidney modality education. Nurse case managers used the tracking application for 100% of patients to document 287 planning steps for kidney replacement therapy. Most (87%) high-risk patients had their preferred kidney replacement modality documented and displayed in the EHR. Nurse case managers reported that the tools facilitated their identification of patients needing support and their navigation activities. Limitations: Single institution, short duration. Conclusions: Digital health system tools facilitated rapid identification of patients needing shared and informed decision making and their preparation for kidney replacement treatments. Funding: This work was supported through a Patient-Centered Outcomes Research Institute (PCORI) Project Program Award (IHS-1409-20967). Trial registration: ClinicalTrials.gov NCT02722382.

It is recognised that delirium is common among older adult inpatients and correlated with negative outcomes. The gold standard care for delirium management is achieved using multicomponent interventions. Which components work best is not yet well defined. During the COVID-19 outbreak, a paediatric ward was repurposed to treat adult patients. Paediatric nurses and play specialists remained on the ward. It was observed that the paediatric ward aesthetic and the team’s dedicated approach to cognitive stimulation and sleep promotion improved well-being among older adult patients. We propose that elements of paediatric care, primarily deployment of a play specialist, could be incorporated into a multicomponent intervention for delirium prevention and management.

Rationale & Objective: Chronic kidney disease (CKD) care is often fragmented across multiple health care providers. It is unclear whether patients rely mostly on their nephrologists or non-nephrologist providers for medical care, including CKD treatment and advice. Study Design: Cross-sectional study. Setting & Participants: Adults receiving nephrology care at CKD clinics in Pennsylvania. Predictors: Frequency, duration, and patient-centeredness (range, 1 [least] to 4 [most]) of participants’ nephrology care. Outcome: Participants’ reliance on nephrologists, primary care providers, or other specialists for medical care, including CKD treatment and advice. Analytical Approach: Multivariable logistic regression to quantify associations between participants’ reliance on their nephrologists (vs other providers) and their demographics, comorbid conditions, kidney function, and nephrology care. Results: Among 1,412 patients in clinics targeted for the study, 676 (48%) participated. Among these, 453 (67%) were eligible for this analysis. Mean age was 71 (SD, 12) years, 59% were women, 97% were white, and 65% were retired. Participants were in nephrology care for a median of 3.8 (IQR, 2.0-6.6) years and completed a median of 4 (IQR, 3-5) nephrology appointments in the past 2 years. Half (56%) the participants relied primarily on their nephrologists, while 23% relied on primary care providers, 18% relied on all providers equally, and 3% relied on other specialists. Participants’ adjusted odds of relying on their nephrologists were higher for those in nephrology care for longer (OR, 1.08 [95% CI, 1.02-1.15]; P = 0.02), those who completed more nephrology visits in the previous 2 years (OR, 1.16 [95% CI, 1.05-1.29]; P = 0.005), and those who perceived their last interaction with their nephrologists as more patient-centered (OR, 2.63 [95% CI, 1.70-4.09]; P

Abstract Background To describe the development of polypharmacy and its components in a British birth cohort in its seventh decade and to investigate socioeconomic and gender differences independent of disease burden. Methods Data from the MRC National Survey for Health and Development were analysed to determine the prevalence and composition of polypharmacy at age 69 and changes since ages 60 to 64. Multinomial regression was used to test associations between gender, education and occupational social class and total, cardiological and non-cardiological polypharmacy controlling for disease burden. Results At age 69, 22.8% of individuals were taking more than 5 medications. There was an increase in the use of 5 to 8 medications (+ 2.3%) and over 9 medications (+ 0.8%) between ages 60–64 and 69. The greatest increases were found for cardiovascular (+ 13.4%) and gastrointestinal medications (+ 7.3%). Men experienced greater cardiological polypharmacy, women greater non-cardiological polypharmacy. Higher levels of education were associated with lower polypharmacy independent of disease burden, with strongest effects seen for over five cardiological medications (RRR 0.3, 95% CI 0.2–0.5 p

Abstract Background Delirium affects 25% of older inpatients and is associated with long-term cognitive impairment and future dementia. However, no population studies have systematically ascertained cognitive function before, cognitive deficits during, and cognitive impairment after delirium. Therefore, there is a need to address the following question: does delirium, and its features (including severity, duration, and presumed aetiologies), predict long-term cognitive impairment, independent of cognitive impairment at baseline? Methods The Delirium and Population Health Informatics Cohort (DELPHIC) study is an observational population-based cohort study based in the London Borough of Camden. It is recruiting 2000 individuals aged ≥70 years and prospectively following them for two years, including daily ascertainment of all inpatient episodes for delirium. Daily inpatient assessments include the Memorial Delirium Assessment Scale, the Observational Scale for Level of Arousal, and the Hierarchical Assessment of Balance and Mobility. Data on delirium aetiology is also collected. The primary outcome is the change in the modified Telephone Interview for Cognitive Status at two years. Discussion DELPHIC is the first population sample to assess older persons before, during and after hospitalisation. The cumulative incidence of delirium in the general population aged ≥70 will be described. DELPHIC offers the opportunity to quantify the impact of delirium on cognitive and functional outcomes. Overall, DELPHIC will provide a real-time public health observatory whereby information from primary, secondary, intermediate and social care can be integrated to understand how acute illness is linked to health and social care outcomes.

Laparoscopic sleeve gastrectomy (LSG) is the most common bariatric surgery performed for morbid obesity. Leaks of the vertical staple line can occur in up to 7% of cases and are difficult to manage. Endolumenal vacuum (EVAC) therapy and fistulojejunostomy (FJ) have separate documented uses to heal these complicated leaks. We aim to show the benefit of using EVAC with FJ in the treatment of LSG staple line leaks. The patient presented with an LSG chronic leak. EVAC therapy was initiated but failed to close the fistula after 101 days. EVAC therapy was abandoned, and FJ was performed to resolve the leak. Postoperatively, no leak was encountered requiring any additional procedures. Based on our findings, we conclude that EVAC therapy facilitates in resolving leaks that restore gastrointestinal continuity and maintain source control. It promotes healing and causes reperfusion of ischemic tissue and fistula cavity debridement.

This article argues that 9/11 created a crisis of confidence amongst writers of American fiction by problematizing literary realism’s claims to verisimiltude and so undermining it as a plausible and credible mode of fiction. Surveying the post-9/11 debate over the merits and shortcomings of realism, this article suggests that the unlikely beneficiary of this crisis of confidence has been the contemporary nouveau roman, a mode of fiction that originates from within the literary traditions of continental Europe. The emergence of writers, publishers, reviewers, and readers attracted to the nouveau roman as a mode of literature in opposition to realism—and engaged in its production, evaluation, promotion, and dissemination—seems to signify a widespread dissatisfaction with the predominant American literary response to the crisis of 9/11. Providing a brief history of the emergence of this post-9/11 institutional support for the nouveau roman, this article contends that the nouveau roman requires a place in literary histories of post-9/11 American fiction even if it does not explicitly address the subject of 9/11 itself.

Delirium is increasingly considered to be an important determinant of trajectories of cognitive decline. Therefore, analyses of existing cohort studies measuring cognitive outcomes could benefit from methods to ascertain a retrospective delirium diagnosis. This study aimed to develop and validate such a method for delirium detection using routine medical records in UK and Ireland.A point prevalence study of delirium provided the reference-standard ratings for delirium diagnosis. Blinded to study results, clinical vignettes were compiled from participants' medical records in a standardised manner, describing any relevant delirium symptoms recorded in the whole case record for the period leading up to case-ascertainment. An expert panel rated each vignette as unlikely, possible, or probable delirium and disagreements were resolved by consensus.From 95 case records, 424 vignettes were abstracted by 5 trained clinicians. There were 29 delirium cases according to the reference standard. Median age of subjects was 76.6 years (interquartile range 54.6 to 82.5). Against the original study DSM-IV diagnosis, the chart abstraction method gave a positive likelihood ratio (LR) of 7.8 (95% CI 5.7-12.0) and the negative LR of 0.45 (95% CI 0.40-0.47) for probable delirium (sensitivity 0.58 (95% CI 0.53-0.62); specificity 0.93 (95% CI 0.90-0.95); AUC 0.86 (95% CI 0.82-0.89)). The method diagnosed possible delirium with positive LR 3.5 (95% CI 2.9-4.3) and negative LR 0.15 (95% CI 0.11-0.21) (sensitivity 0.89 (95% CI 0.85-0.91); specificity 0.75 (95% CI 0.71-0.79); AUC 0.86 (95% CI 0.80-0.89)).This chart abstraction method can retrospectively diagnose delirium in hospitalised patients with good accuracy. This has potential for retrospectively identifying delirium in cohort studies where routine medical records are available. This example of record linkage between hospitalisations and epidemiological data may lead to further insights into the inter-relationship between acute illness, as an exposure, for a range of chronic health outcomes.

The electrolytic reduction of CO2 in aqueous media promises a pathway for the utilization of the green house gas by converting it to base chemicals or building blocks thereof. However, the technology is currently not economically feasible, where one reason lies in insufficient reaction rates and selectivities. Current research of CO2 electrolysis is becoming aware of the importance of the local environment and reactions at the electrodes and their proximity, which can be only assessed under true catalytic conditions, i.e. by in operando techniques. In this work, multinuclear in operando NMR techniques were applied in order to investigate the evolution of the electrolyte chemistry during CO2 electrolysis. The CO2 electroreduction was performed in aqueous NaHCO3 or KHCO3 electrolytes at silver electrodes. Based on 13C and 23Na NMR studies at different magnetic fields, it was found that the dynamic equilibrium of the electrolyte salt in solution, existing as ion pairs and free ions, decelerates with increasingly negative potential. In turn, this equilibrium affects the resupply rate of CO2 to the electrolysis reaction from the electrolyte. Substantiated by relaxation measurements, a mechanism was proposed where stable ion pairs in solution catalyze the bicarbonate dehydration reaction, which may provide a new pathway for improving educt resupply during CO2 electrolysis. The electrolytic reduction of CO2 in aqueous media promises a pathway for the utilization of the greenhouse gas by converting it to base chemicals, however, reactions at the electrodes and their proximity remain challenging to elucidate. Here, the authors use multinuclear in operando NMR to study CO2 electrolysis in aqueous media and find that stable ion pairs in solution catalyze the bicarbonate dehydration reaction. [ABSTRACT FROM AUTHOR]