Frailty, the determinants of health and the new evidence base.

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Seizure pathways change on circadian and slower timescales in individual patients with focal epilepsy.

Personalized medicine requires that treatments adapt to not only the patient but also changing factors within each individual. Although epilepsy is a dynamic disorder characterized by pathological fluctuations in brain state, surprisingly little is known about whether and how seizures vary in the same patient. We quantitatively compared within-patient seizure network evolutions using intracranial electroencephalographic (iEEG) recordings of over 500 seizures from 31 patients with focal epilepsy (mean 16.5 seizures per patient). In all patients, we found variability in seizure paths through the space of possible network dynamics. Seizures with similar pathways tended to occur closer together in time, and a simple model suggested that seizure pathways change on circadian and/or slower timescales in the majority of patients. These temporal relationships occurred independent of whether the patient underwent antiepileptic medication reduction. Our results suggest that various modulatory processes, operating at different timescales, shape within-patient seizure evolutions, leading to variable seizure pathways that may require tailored treatment approaches

The second national audit of intermediate care

Intermediate care services have developed internationally to expedite discharge from hospital and to provide an alternative to an emergency hospital admission. Inconsistencies in the evidence base and under-developed governance structures led to concerns about the care quality, outcomes and provision of intermediate care in the NHS. The National Audit of Intermediate Care was therefore established by an interdisciplinary group. The second national audit reported in 2013 and included crisis response teams, home-based and bed-based services in approximately a half of the NHS. The main findings were evidence of weak local strategic planning, considerable under-provision, delays in accessing the services and lack of mental health involvement in care. There was a very high level of positive patient experience reported across all types of intermediate care, though reported involvement with care decisions was less satisfactory

The Association of Geriatric Syndromes with Hospital Outcomes.

BACKGROUND: Frailty, history of dementia (HoD), and acute confusional states (ACS) are common in older patients admitted to hospital. OBJECTIVE: To study the association of frailty (≥6 points in the Clinical Frailty Scale [CFS]), HoD, and ACS with hospital outcomes, controlling for age, gender, acute illness severity (measured by a Modified Early Warning Score in the emergency department), comorbidity (Charlson Comorbidity Index), and discharging specialty (general medicine, geriatric medicine, surgery). DESIGN: Retrospective observational study. SETTING: Large university hospital in England. PATIENTS: We analyzed 8202 first nonelective inpatient episodes of people aged 75 years and older between October 2014 and October 2015. MEASUREMENTS: The outcomes studied were prolonged length of stay (LOS ≥10 days), inpatient mortality, delayed discharge, institutionalization, and 30-day readmission. Statistical analyses were based on multivariate regression models. RESULTS: Independently of controlling variables, prolonged LOS was predicted by CFS ≥6: odds ratio (OR) =1.55; 95% confidence interval [CI], 1.36-1.77; P ⟨ 0.001; HoD: OR = 2.16; 95% CI, 1.79-2.61; P ⟨ 0.001; and ACS: OR = 3.31; 95% CI, 2.64-4.15; P ⟨ 0.001. Inpatient mortality was predicted by CFS ≥6: OR = 2.29; 95% CI, 1.79-2.94; P ⟨ 0.001. Delayed discharge was predicted by CFS ≥6: OR = 1.46; 95% CI, 1.27-1.67; P ⟨ 0.001; HoD: OR = 2.17; 95% CI, 1.80-2.62; P ⟨ 0.001; and ACS: OR = 2.29; 95% CI: 1.83-2.85; P ⟨ 0.001. Institutionalization was predicted by CFS ≥6: OR = 2.56; 95% CI, 2.09-3.14; P ⟨ 0.001; HoD: OR = 2.51; 95% CI, 2.00-3.14; P ⟨ 0.001; and ACS: OR 1.93; 95% CI, 1.46-2.56; P ⟨ 0.001. Readmission was predicted by ACS: OR = 1.36; 95% CI, 1.09-1.71; P = 0.006. CONCLUSIONS: Routine screening for frailty, HoD, and ACS in hospitals may aid the development of acute care pathways for older adults. Journal of Hospital Medicine 2017;12:83-89.This is the author accepted manuscript. The final version is available from Wiley via http://www.journalofhospitalmedicine.com/jhospmed/article/130058/hospital-medicine/association-geriatric-syndromes-hospital-outcome

The Weaklaw Vent, SE Scotland:Metasomatism of eruptive products by carbo-hydro-fluids of probable mantle origin

This is the author accepted manuscript. The final version is available from CUP via the DOI in this record The Weaklaw vent in SE Scotland (East Lothian coast), inferred to be Namurian, produced lava spatter and volcanic bombs. The latter commonly contained ultramafic xenoliths. All were metasomatised by carbonic fluids rich in incompatible elements. The lavas and xenoliths are inferred to have been basanites and lherzolites prior to metasomatism. The abundance and size of (carbonated) peridotite xenoliths at Weaklaw denotes unusual rapidity of magma ascent and high-energy eruption making Weaklaw exceptional in the British Isles. The lavas and xenoliths were altered subsequently by low-temperature (<200°C) carbo-hydrous fluids to carbonate, clay and quartz assemblages. A small irregular tuffisite 'dyke' that transects the ejecta is also composed dominantly of carbonates and clays. The peridotitic xenoliths are typically foliated, interpreted as originating as pre-entrainment mantle shear-planes. Analyses of the relic spinels shows them to be compositionally similar to spinels in local unaltered lherzolites from near-by basanitic occurrences. Chromium showed neither significant loss nor gain but was concentrated in a di-octahedral smectite allied to volkonskoite. It is in the complex association of smectite with other clays, chlorite and possibly fuchsite that the diverse incompatible elements are concentrated. We conclude that late Palaeozoic trans-tensional fault movement caused mantle shearing. Rapid ascent of basanite magma entrained large quantities of sheared lithospheric mantle. This was followed by ascent of an aggressive carbonate-/ hydroxyl-rich fluid causing pervasive metasomatism. The vent is unique in several ways: in its remarkable clay mineralogy and in displaying such high Cr-clays in a continental intra-plate setting; in being more productive in terms of its 'cargo' of peridotite xenoliths; in presenting an essentially un-eroded sequence of Namurian extrusives; and, not least, for giving evidence for post-eruptive, surface release of small-melt, deep-source fluids

Attenuated reovirus displays oncolysis with reduced host toxicity

Background: Although the naturally occurring reovirus causes only mild symptoms in humans, it shows considerable potential as an oncolytic agent because of its innate ability to target cancer cells. In immunocompromised hosts, however, wild-type reovirus can target healthy tissues, including heart, liver, pancreas and neural structures. Methods: We characterized an attenuated form of reovirus (AV) derived from a persistently infected cell line through sequence analysis, as well as western blot and in vitro transcription and translation techniques. To examine its pathogenesis and oncolytic potential, AV reovirus was tested on healthy embryonic stem cells, various non-transformed and transformed cell lines, and in severe combined immunodeficiency (SCID) mice with tumour xenografts. Results: Sequence analysis of AV reovirus revealed a premature STOP codon in its sigma 1 attachment protein. Western blot and in vitro translation confirmed the presence of a truncated ?1. In comparison to wild-type reovirus, AV reovirus did not kill healthy stem cells or induce black tail formation in SCID mice. However, it did retain its ability to target cancer cells and reduce tumour size. Conclusion: Despite containing a truncated attachment protein, AV reovirus still preferentially targets cancer cells, and compared with wild-type reovirus it shows reduced toxicity when administered to immunodeficient hosts, suggesting the potential use of AV reovirus in combination cancer therapy

Video game intervention for sexual risk reduction in minority adolescents : randomized controlled trial

BACKGROUND : Human immunodeficiency virus (HIV) disproportionately impacts minority youth. Interventions to decrease HIV sexual risk are needed. OBJECTIVE : We hypothesized that an engaging theory-based digital health intervention in the form of an interactive video game would improve sexual health outcomes in adolescents. METHODS : Participants aged 11 to 14 years from 12 community afterschool, school, and summer programs were randomized 1:1 to play up to 16 hours of an experimental video game or control video games over 6 weeks. Assessments were conducted at 6 weeks and at 3, 6, and 12 months. Primary outcome was delay of initiation of vaginal/anal intercourse. Secondary outcomes included sexual health attitudes, knowledge, and intentions. We examined outcomes by gender and age. RESULTS : A total of 333 participants were randomized to play the intervention (n=166) or control games (n=167): 295 (88.6%) were racial/ethnic minorities, 177 (53.2%) were boys, and the mean age was 12.9 (1.1) years. At 12 months, for the 258 (84.6%) participants with available data, 94.6% (122/129) in the intervention group versus 95.4% (123/129) in the control group delayed initiation of intercourse (relative risk=0.99, 95% CI 0.94-1.05, P=.77). Over 12 months, the intervention group demonstrated improved sexual health attitudes overall compared to the control group (least squares means [LS means] difference 0.37, 95% CI 0.01-0.72, P=.04). This improvement was observed in boys (LS means difference 0.67, P=.008), but not girls (LS means difference 0.06, P=.81), and in younger (LS means difference 0.71, P=.005), but not older participants (LS means difference 0.03, P=.92). The intervention group also demonstrated increased sexual health knowledge overall (LS means difference 1.13, 95% CI 0.64-1.61, P<.001), in girls (LS means difference 1.16, P=.001), boys (LS means difference 1.10, P=.001), younger (LS means difference 1.18, P=.001), and older (LS means difference=1.08, P=.002) participants. There were no differences in intentions to delay the initiation of intercourse between the two groups (LS means difference 0.10, P=.56). CONCLUSIONS : An interactive video game intervention improves sexual health attitudes and knowledge in minority adolescents for at least 12 months.Grant R01HD062080 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development.http://www.jmir.orgam2017Psycholog

Characteristics of Early Paget's Disease in SQSTM1 Mutation Carriers: Baseline Analysis of the ZiPP Study Cohort

Mutations in SQSTM1 are strongly associated with Paget's disease of bone (PDB), but little is known about the clinical characteristics of those with early disease. Radionuclide bone scans, biochemical markers of bone turnover, and clinical characteristics were analyzed in SQSTM1 mutation carriers who took part in the Zoledronic acid in the Prevention of Paget's disease (ZiPP) study. We studied 222 individuals, of whom 54.9% were female, with mean ± SE age of 50.1 ± 0.6 years. Twelve SQSTM1 mutations were observed, including p.Pro392Leu, which was present in 141 of 222 (63.5%) subjects. Bone scan examination revealed evidence of PDB in 20 subjects (9.0%), ten of whom (50%) had a single affected site. Participants with lesions were older than those without lesions but the difference was not significant (53.6 ± 9.1 versus 49.8 ± 8.9; p =.07). The mean age of participants with lesions was not significantly different from the age at which their parents were diagnosed with PDB (55 years versus 59 years, p =.17). All individuals with lesions were asymptomatic. Serum concentrations of total alkaline phosphatase (ALP) normalized to the upper limit of normal in each center were higher in those with lesions (0.75 ± 0.69 versus 0.42 ± 0.29 arbitary units; p &lt;.0001). Similar findings were observed for other biochemical markers of bone turnover, but the sensitivity of ALP and other markers in detecting lesions was poor. Asymptomatic PDB is present in about 9% of SQSTM1 mutation carriers by the fifth decade. Further follow-up of this cohort will provide important information on the natural history of early PDB and its response to treatment. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research