bluuebunny/crossref_metadata_2025_split huggingface dataset:
91 To What Extent are Patients’ Future Care Preferences Shared Between Secondary and Primary Care? A Retrospective Chart Review
Authors: Hopkins S A , Athauda P , Halliday A , Honney K , Jakupaj A , Kaneshamoorthy M , Mark H , Pampali C , Van der Poel L , Ondhia D , Balogun A , Vincent M , Fritz Z , Barclay S 
Published: February 2020

Abstract

Introduction
When a doctor is informed of a patient’s future care preferences if they were to lose capacity, there is an ethical and legal obligation to share this information with the treating medical team. In frail older patients, conversations about treatment preferences often occur during hospital admission. We sought to assess the communication of these preferences to the patient’s GP.

Methods
Retrospective chart review of consecutive discharges from acute geriatric wards across seven hospitals. Records were excluded if the patient was admitted for less than 48 hours, was under orthogeriatric care, or died in hospital.

Results
339 notes were included, 41-50 from each hospital. GPs were informed of the resuscitation status of 28% of all patients. 52% of patients had an inpatient DNACPR, the GP was informed of 54% of these. 36% of patients had an inpatient ceiling of treatment documented, of which GPs were informed of 19%. 53% of hospital DNACPRs were converted into community DNACPRs on discharge: GPs were informed of only 24% of new community DNACRPs. 47% of patients discharged with a new community DNACPR lacked capacity to be involved in that decision; for just 6% of these was the GP asked to review the DNACPR order in the community. Inpatient Advance Care Planning (ACP) discussions were held for 9% of patients, of which the GP was informed in 59% of cases. 49% of ACP conversations involved the next-of-kin but not the patient. Among patients who had a new DNACPR decision made during their admission (n=124), there was documentary evidence in only 25% that the patient or next-of-kin was informed whether this was time-limited or indefinite.

Conclusions
Communication from hospitals to GPs about resuscitation, ceiling of care and ACP discussions is very limited. For patients who have expressed ongoing future care preferences, there is a legal obligation to share this information with the treating medical team, which on discharge is the GP.
There is poor documentary evidence of discussions with patients about whether DNACPR decisions are time-limited or indefinite. Furthermore, many hospitalised frail patients lack capacity to make DNACPR decisions but they may subsequently regain capacity, particularly those with delirium. Despite this, GPs are rarely asked to review new community DNACPRs, including those made for patients without capacity.
95 Goals-Of-Care and Advance Care Planning Discussions with Hospitalised Frail Older People: What is the Evidence?
Authors: Hopkins S A , Bentley A , Phillips V , Barclay S 
Published: February 2020

Abstract

Introduction
National guidelines suggest that patients in the last year of life should be identified, their prognosis and future care options discussed, with advance care planning (ACP) recorded. Goals-of-care should be discussed with hospitalised patients at risk of deteriorating or with life-limiting conditions. The stated purpose of ACP and goals-of-care discussions is to increase goal-concordant care (i.e. patients receiving treatments they would wish to receive, and not receiving those they would not want). This literature review investigates the evidence-base for these policies and outcomes.

Review question
What is the evidence for goals-of-care and ACP discussions with hospitalised frail older people?

Methods
Systematic literature review and narrative synthesis. Electronic search of MEDLINE, CINAHL, ASSIA, PsycINFO, and Embase databases from January 1990 to September 2017. An updated search until May 2019 is currently underway.

Results
Of 8077 unique articles identified, 17 met inclusion criteria. There is no evidence that goals-of-care discussions lead to increased goal-concordant care; there is observational evidence that they increase the accuracy of documented preferences. Currently, rates of goals-of-care discussions are variable (38-72%), and there is poor concordance between patients’ actual and documented preferences, with agreement in only 31-33% of cases.
Present rates of ACP are very low (0-3%), with mixed evidence for benefits of ACP. One single-centre randomised controlled trial suggests ACP improves outcomes for patients who die within 6 months of discharge, including increased goal-concordant care and reduced family distress.
There is very limited evidence concerning patients’ and family members’ experiences of these discussions, their reasons for wishing (or not) to participate in discussions, or their perceptions of the important outcomes. Most (80%) patients would like to be involved in decisions about their care; 48% consider these conversations very important. The views and experiences of healthcare professionals have been little studied.

Conclusions
The asserted aim of goals-of-care and ACP discussions is to increase goal-concordant care; the extent to which this reflects patients’ priorities is unknown. In younger patient populations, while 40% of patients consider goal-concordant care the most important outcome, one third of patients consider family-related outcomes to be more important. Further research is needed to understand the perspectives of frail older patients, their families and clinicians, in order to make these discussions and subsequent care truly patient-centred.
97 Complexity In Croydon
Authors: Smith J , Gass N , Huntley M , Nanuck R , Vandendris S , Bell C , Heitz E , Wilson T 
Published: February 2020

Abstract

Introduction
The Complex Care Support Team (CCST) are a newly-formed, integrated service, caring for Croydon residents when existing services decide additional multidisciplinary team input is required.
There is no single definition of healthcare complexity. Most cases encountered by the team have involved many different services and professionals. The team have found that by forging relationships and co-ordinating care across organisational boundaries, some of the “complexities” can be mitigated. We aim to develop our understanding of the needs of this population and the underlying drivers for complexity in Croydon.

Methods
The records on EMIS, CERNER and ePJS were reviewed from the inaugural two months of the service, for:Rockwood Frailty ScoreNumber of medicationsNumber of long-term conditionsED attendances or admissions to hospital over the preceding year.
After team discussion on every case, underlying causes of complexity were assigned to four groups: medical, psychological, social and systems failure.

Results
Of the 57 people accepted by CCST over 2 months, 39 required reviewing in person. 5 records were not completed, so 34 cases were included for evaluation. The age range of this cohort was 49-92, with 17 male and 17 female. Results revealed significant frailty, multimorbidity and polypharmacy. 91% had two or more underlying drivers for complexity, with the largest underlying driver being systems failure, in 85% of cases.

Conclusions
This work improves our understanding of the needs of the population deemed the most “complex” in Croydon. The likelihood of multiple underlying drivers for complexity was high, highlighting how complex health issues are likely to span both professional and organisational boundaries. This can in itself be a significant underlying driver for complexity, illustrated here as “systems failure”. In developing current and future services, this work reinforces the vital benefits of multidisciplinary and cross-organisational working currently occurring in CCST.
109 Hyponatraemia in Older Patients is Often Untreated, Despite Greater Mortality Burden; Results of A Prospective Cohort Study
Authors: Thorpe O , Cuesta M , Tormey W T , Sherlock M , Williams D J , Thompson C J , Garrahy A 
Published: February 2020

Abstract

Introduction
Hyponatraemia is associated with increased morbidity and mortality, and is commoner in elderly patients. The aetiology and outcomes of hyponatraemia in the elderly has not been defined in prospective studies.

Methods
A single-centre 9 month prospective observational study of hyponatraemic (HN) patients (&lt;/= 130 mmol/L) was performed. Clinical outcomes in patients ≥65 years (Elderly patients, EP) and those &lt;65 years (Young Patients, YP) were analysed, and compared with age-matched eunatremic controls, Analysis was performed using Graphpad-Prism 7.

Results
1321 consecutive admissions with hyponatraemia (67% EP, median age of EP 77 (65–98) years) and 1122 eunatremic controls (63% EP, median age of EP 77 (65–99) years) were analysed.
Median nadir plasma sodium was similar in both groups with HN, 128 (107–130) mmol/L EP vs 128(110–130) mmol/L YP (p = 0.62). EP hyponatraemic patients were more likely to have hypovolaemic hyponatraemia (34%) compared with YP with hyponatraemia (28%, p = 0.03). Diuretic-induced hyponatraemia was twice as common in EP (8%) compared with YP (4%, p = 0.01). Malignancy-induced SIAD occurred with similar frequency in both groups (7% in EP SIAD vs 8% in YP SIAD, p = 0.65). Respiratory disease was causative in 10% cases of EP SIAD, compared with 4% in YP SIAD, p = 0.0004.
Hyponatraemia was corrected in 53% of EP, compared with 64% of YP, p = 0.0001. Length of stay and re-admissions rates were similar across hyponatraemia age groups. EP with HN were 2.4 times more likely to die in hospital, compared with eunatremic age-matched controls, (OR 2.4, 95% CI 1.6–3.7, p &lt; 0.0001).

Conclusions
The causation of hyponatraemia is different in elderly patients. Hyponatraemia in EP is often uncorrected, despite increased mortality compared with eunatremic age-matched controls.
111 Rates and Risk Factors for Hospital Admission in People With Dementia: Systematic Review
Authors: Shepherd H , Livingston G , Chan J , Sommerlad A 
Published: February 2020

Abstract

Background
Hospitalisation is often harmful for people with dementia and results in high societal costs, so avoidance of unnecessary admissions is a global priority. However, no intervention has yet reduced admissions of community-dwelling people with dementia. We therefore aimed to examine hospitalisation rates of people with dementia and whether these differ from people without dementia, and to identify socio-demographic and clinical predictors of hospitalisation.

Methods
We searched MEDLINE, Embase and PsycINFO from inception to May 9, 2019. We included observational studies which (1) examined community-dwelling people with dementia of any age or dementia subtype, (2) diagnosed dementia using validated diagnostic criteria, and (3) examined all-cause general (i.e. non-psychiatric) hospital admissions. Two authors screened abstracts for inclusion and independently extracted data and assessed included studies for risk of bias. Three authors graded evidence strength using Cochrane’s GRADE approach, including assessing for evidence of publication bias using Begg’s test. We used random effects meta-analysis to pool estimates for hospitalisation risk in people with and without dementia.

Results
We included 34 studies of 277,432 people with dementia; 17 from US, 15 from Europe and 2 from Asia. Pooled relative risk of hospitalisation for people with dementia compared to those without was 1.42 (95% confidence interval 1.21, 1.66) in studies adjusted for age, sex, and physical comorbidity. Hospitalisation rates in people with dementia was between 0.37 and 1.26/person-year in high-quality studies. There was strong evidence that admission is associated with older age, and moderately strong evidence that multimorbidity, polypharmacy, and lower functional ability are associated with admission. There was strong evidence that dementia severity alone is not associated.

Conclusions
People with dementia are more frequently admitted to hospital than those without dementia, independent of physical comorbidities. Future interventions to reduce unnecessary hospitalisations should target potentially-modifiable factors, such as polypharmacy and functional ability, in high-risk populations.
The Role of Clinical Examination in Midface Volume Correction Using Hyaluronic Acid Fillers: Should Patients Be Stratified by Skin Thickness?
Authors: Nikolis Andreas , Enright Kaitlyn M , Lazarova Desislava , Sampalis John 
Published: February 2020

Abstract

Background
Aesthetic physicians have several hundred injectable products to select from. Due to differences in their manufacturing technology, these products display varying biophysical qualities, such as their cohesivity and lift capacity. Currently, there is no guidance to objectively selecting the best product for a particular patient. Therefore, an algorithmic approach is required to take specific skin characteristics into consideration.

Objectives
To evaluate (1) whether subjects seeking injectable treatments for midfacial volume loss and/or contour deficiency can be stratified based on specific skin characteristics (eg, thickness, fat quantity, bony structure) and (2) whether particular hyaluronic acid fillers perform best when used in such particular strata.

Methods
This was a prospective, Phase IV, open-label, single-center clinical trial. Thirty female patients with midface/cheek volume loss and/or contour deficiency were recruited (mean age, 53.5 years; SD, 12.57; range, 35–75 years). Subjects were treated with either Restylane Lyft (HAL) or Restylane Volyme (HAV) and followed for 4 months post-injection. Treatment allocation was based on the treating physician’s clinical evaluation and compared with ultrasound evaluation. Ultrasound images were used to confirm stratification. Safety and efficacy assessments were performed at each study visit: baseline, week 2, week 4, week 8, and week 16. Subgroup analyses evaluated whether particular strata performed best when treated with specific products.

Results
The 2 investigative products varied in their efficacy, depending on the characteristics of the subject.

Conclusions
The use of a treatment algorithm may improve outcomes for patients seeking injectable treatments for midfacial volume loss and contour deficiencies.

Level of Evidence: 2
Redrawing Wallace’s Line based on the fauna of Christmas Island, eastern Indian Ocean
Authors: Ali Jason R , Aitchison Jonathan C , Meiri Shai 
Published: February 2020

AbstractBased on a comprehensive literature survey, we determined the sources of the terrestrial vertebrate species on Christmas Island, asking where they originated relative to Wallace’s Line (the southern end of the divide lies 1100 km to the east, where the Lombok Strait adjoins the eastern Indian Ocean). The two bats, Pipistrellus murrayi and Pteropus natalis, are from the west. Concerning the endemic and ‘resident’ bird species, one is from the west (Collocalia natalis), four are from the east (Accipiter fasciatus, Egretta novaehollandiae, Falco cenchroides and Ninox natalis) and the other 15 are ambiguous or indeterminate. Most of the land-locked species are also from the east: rodents Rattus macleari and Rattus nativitatis, and squamates Cryptoblepharus egeriae, Emoia nativitatis and Lepidodactylus listeria. Additionally, two have westerly origins (Crocidura trichura and Cyrtodactylus sadleiri), one is ambiguous (Emoia atrocostata) and another is unknown (Ramphotyphlops exocoeti). West-directed surface currents that flow across the eastern Indian Ocean towards Christmas Island would have facilitated most of the land-animal colonizations. We therefore suggest that Wallace’s Line be redrawn such that the landmass is placed on the Australasian side of this fundamental biogeographical boundary.
Sex and Pubertal Status Influence Dendritic Spine Density on Frontal Corticostriatal Projection Neurons in Mice
Authors: Delevich Kristen , Okada Nana J , Rahane Ameet , Zhang Zicheng , Hall Christopher D , Wilbrecht Linda 
Published: February 2020

Abstract
In humans, nonhuman primates, and rodents, the frontal cortices exhibit grey matter thinning and dendritic spine pruning that extends into adolescence. This maturation is believed to support higher cognition but may also confer psychiatric vulnerability during adolescence. Currently, little is known about how specific cell types in the frontal cortex mature or whether puberty plays a role in the maturation of some cell types but not others. Here, we used mice to characterize the spatial topography and adolescent development of cross-corticostriatal (cSTR) neurons that project through the corpus collosum to the dorsomedial striatum. We found that apical spine density on cSTR neurons in the medial prefrontal cortex decreased significantly between late juvenile (P29) and young adult time points (P60), with females exhibiting higher spine density than males at both ages. Adult males castrated prior to puberty onset had higher spine density compared to sham controls. Adult females ovariectomized before puberty onset showed greater variance in spine density measures on cSTR cells compared to controls, but their mean spine density did not significantly differ from sham controls. Our findings reveal that these cSTR neurons, a subtype of the broader class of intratelencephalic-type neurons, exhibit significant sex differences and suggest that spine pruning on cSTR neurons is regulated by puberty in male mice.
T-cell senescence accelerates angiotensin II-induced target organ damage
Authors: Pan Xiao-Xi , Wu Fang , Chen Xiao-Hui , Chen Dong-Rui , Chen Hong-Jin , Kong Ling-Ran , Ruan Cheng-Chao , Gao Ping-Jin 
Published: February 2020

Abstract

Aims
Aging is a risk factor for cardiovascular diseases and adaptive immunity has been implicated in angiotensin (Ang) II-induced target organ dysfunction. Herein, we sought to determine the role of T-cell senescence in Ang II-induced target organ impairment and to explore the underlying mechanisms.

Methods and results
Flow cytometric analysis revealed that T cell derived from aged mice exhibited immunosenescence. Adoptive transfer of aged T cells to immunodeficient RAG1 KO mice accelerates Ang II-induced cardiovascular and renal fibrosis compared with young T-cell transfer. Aged T cells also promote inflammatory factor expression and superoxide production in these target organs. In vivo and in vitro studies revealed that Ang II promotes interferon-gamma (IFN-γ) production in the aged T cells comparing to young T cells. Importantly, transfer of senescent T cell that IFN-γ KO mitigates the impairment. Aged T-cell-conditioned medium stimulates inflammatory factor expression and oxidative stress in Ang II-treated renal epithelial cells compared with young T cells, and these effects of aged T-cell-conditioned medium are blunted after IFN-γ-neutralizing antibody pre-treatment.

Conclusion
These results provide a significant insight into the contribution of senescent T cells to Ang II-induced cardiovascular dysfunction and provide an attractive possibility that targeting T cell specifically might be a potential strategy to treat elderly hypertensive patients with end-organ dysfunction.
Junctophilin-2 tethers T-tubules and recruits functional L-type calcium channels to lipid rafts in adult cardiomyocytes
Authors: Poulet Claire , Sanchez-Alonso Jose , Swiatlowska Pamela , Mouy Florence , Lucarelli Carla , Alvarez-Laviada Anita , Gross Polina , Terracciano Cesare , Houser Steven , Gorelik Julia 
Published: February 2020

Abstract

Aim
In cardiomyocytes, transverse tubules (T-tubules) associate with the sarcoplasmic reticulum (SR), forming junctional membrane complexes (JMCs) where L-type calcium channels (LTCCs) are juxtaposed to Ryanodine receptors (RyR). Junctophilin-2 (JPH2) supports the assembly of JMCs by tethering T-tubules to the SR membrane. T-tubule remodelling in cardiac diseases is associated with downregulation of JPH2 expression suggesting that JPH2 plays a crucial role in T-tubule stability. Furthermore, increasing evidence indicate that JPH2 might additionally act as a modulator of calcium signalling by directly regulating RyR and LTCCs. This study aimed at determining whether JPH2 overexpression restores normal T-tubule structure and LTCC function in cultured cardiomyocytes.

Methods and results
Rat ventricular myocytes kept in culture for 4 days showed extensive T-tubule remodelling with impaired JPH2 localization and relocation of the scaffolding protein Caveolin3 (Cav3) from the T-tubules to the outer membrane. Overexpression of JPH2 restored T-tubule structure and Cav3 relocation. Depletion of membrane cholesterol by chronic treatment with methyl-β-cyclodextrin (MβCD) countered the stabilizing effect of JPH2 overexpression on T-tubules and Cav3. Super-resolution scanning patch-clamp showed that JPH2 overexpression greatly increased the number of functional LTCCs at the plasma membrane. Treatment with MβCD reduced LTCC open probability and activity. Proximity ligation assays showed that MβCD did not affect JPH2 interaction with RyR and the pore-forming LTCC subunit Cav1.2, but strongly impaired JPH2 association with Cav3 and the accessory LTCC subunit Cavβ2.

Conclusions
JPH2 promotes T-tubule structural stability and recruits functional LTCCs to the membrane, most likely by directly binding to the channel. Cholesterol is involved in the binding of JPH2 to T-tubules as well as in the modulation of LTCC activity. We propose a model where cholesterol and Cav3 support the assembly of lipid rafts which provide an anchor for JPH2 to form JMCs and a platform for signalling complexes to regulate LTCC activity.
Inhibition of Histone Deacetylation by MS-275 Alleviates Colitis by Activating the Vitamin D Receptor
Authors: Li Chunxiao , Chen Yi , Zhu Huatuo , Zhang Xiuming , Han Lu , Zhao Zuodong , Wang Jinghua , Ning Longgui , Zhou Weihua , Lu Chao , Xu Lei , Sang Jianzhong , Feng Zemin , Zhang Yuwei , Lou Xinhe , Bo Xiaochen , Zhu Bing , Yu Chaohui , Zheng Min , Li Youming , Sun Jing , Shen Zhe 
Published: February 2020

Abstract

Background
Ulcerative colitis [UC] is a common chronic inflammatory bowel disease without curative treatment.

Methods
We conducted gene set enrichment analysis to explore potential therapeutic agents for UC. Human colon tissue samples were collected to test H3 acetylation in UC. Both in vivo and in vitro colitis models were constructed to verify the role and mechanism of H3 acetylation modification in UC. Intestine-specific vitamin D receptor [VDR]-/- mice and VD [vitamin D]-deficient diet-fed mice were used to explore downstream molecular mechanisms accordingly.

Results
According to the Connectivity Map database, MS-275 [class I histone deacetylase inhibitor] was the top-ranked agent, indicating the potential importance of histone acetylation in the pathogenesis of UC. We then found that histone H3 acetylation was significantly lower in the colon epithelium of UC patients and negatively associated with disease severity. MS-275 treatment inhibited histone H3 deacetylation, subsequently attenuating nuclear factor kappa B [NF-κB]-induced inflammation, reducing cellular apoptosis, maintaining epithelial barrier function, and thereby reducing colitis activity in a mouse model of colitis. We also identified VDR as be a downstream effector of MS-275. The curative effect of MS-275 on colitis was abolished in VDR-/- mice and in VD-deficient diet-fed mice and VDR directly targeted p65. In UC patients, histone H3 acetylation, VDR and zonulin-1 expression showed similar downregulation patterns and were negatively associated with disease severity.

Conclusions
We demonstrate that MS-275 inhibits histone deacetylation and alleviates colitis by ameliorating inflammation, reducing apoptosis, and maintaining intestinal epithelial barrier via VDR, providing new strategies for UC treatment.