Notes

Medical Crops from the Management of Depression. 2: Evidence from Clinical studies.
Fewer than half received pain medications (n=76, 30%), anxiolytics (n=35, 14%), antidepressants (n=64, 25%) or sleep medications (n=65, 26%). Eight patients spoke with a psychologist or psychologist (3%). One had an advanced directive and 16 (6%) had a record of discussions with their family caregivers. Three (1%) had end-of-life discussions with their healthcare providers. Most healthcare providers responded 'no' to the 'surprise question' (n=160, 63%). Sensitivity and specificity of the gold standards framework was poor.

Few community dwelling heart failure patients received most aspects of palliative care. The gold standards framework was not a good indicator of those who should receive palliative care.
Few community dwelling heart failure patients received most aspects of palliative care. The gold standards framework was not a good indicator of those who should receive palliative care.
Frailty is an important consideration in the assessment of transcatheter aortic valve implantation patients. The documentation of a patient photograph to augment the objective measurement of frailty has been adopted by some transcatheter aortic valve implantation multidisciplinary (TAVI) programmes.

We used a prospective two-part multimethod study design. In part A, we examined the concordance between the Essential Frailty Toolset (EFT) and the score attributed by healthcare professionals based on visual rating of photographs using kappa estimates and linear regression. In part B, we conducted a content analysis qualitative study to elicit information about how the TAVI multidisciplinary team used photographs to form impressions about frailty.

Part A 94 healthcare professionals (registered nurses/allied health 65%; physicians 35%) rated 40 representative photographs (women 42.5%; mean age 83.4±7.5; mobility aid 40%) between 0 (robust) and 5 (very frail). The estimate of weighted kappa was 0.2575 (95% confidence interval 0.082-0.433), indicating fair agreement between median healthcare professional visual and EFT score, especially when the EFT was 1 or 4. There was significant discordance among raters (kappa estimate 0.110, 95% confidence interval 0.079-0.141). Age, sex and mobility aid did not have a significant effect on score discordance. Part B 12 members of the TAVI multidisciplinary team (registered nurses 27.5%; physicians 72.5%) were shown a series of six representative patient photographs. The following themes emerged from the data (a) looking at the outside; (b) thinking about the inside; (c) use but with caution; and (d) a better approach.

A patient photograph offers complementary information to the multimodality assessment of TAVI patients.
A patient photograph offers complementary information to the multimodality assessment of TAVI patients.Transcriptional enhanced associate domain (TEAD) is a family of transcription factors that plays a significant role during embryonic developmental processes, and its dysregulation is responsible for tumour progression. TEAD is considered as druggable targets in various diseases, namely cancer, cardiovascular diseases and neurodegenerative disorders. Previous structural studies revealed the importance of the central hydrophobic pocket of TEAD as a potential target for small-molecule inhibitors and demonstrated flufenamic acid (FLU) (a COX-2 enzyme inhibitor) to bind and inhibit TEAD2 functions. However, to date, no drug candidates that bind specifically to TEAD2 with high selectivity and efficacy have been developed or proposed. Imatinib Bcr-Abl inhibitor Within this framework, we present here a case study where we have identified potential TEAD2 inhibitor candidates by integrating multiple computational approaches. Among the candidates, the top two ranked compounds ZINC95969481 (LG1) which is a fused pyrazole derivative and ZINC05203789 (LG2), a fluorene derivative resulted in much favourable binding energy scores than the reference ligand, FLU. The drug likeliness of the best compounds was also evaluated in silico to ensure the bioavailability of these compounds particularly LG1 as compared to FLU thus providing a strong rationale for their development as leads against TEAD. Molecular dynamics simulations results highlighted the role of key residues contributing to favourable interactions in TEAD2-LG1 complex with much favourable interaction and binding free energy values with respect to the reference compound. Altogether, this study provides a starting platform to be more exploited by future experimental research towards the development of inhibitors against TEAD, a persuasive strategy for therapeutic intervention in cancer treatment.
The purpose of this study was to identify factors associated with time delay to emergency medical services for patients with suspected ST-elevation myocardial infarction.

This observational study involved 1994 suspected ST-elevation myocardial infarction patients presenting to the emergency medical services in Melbourne, Australia, between October 2011-January 2014. Factors associated with delays to emergency medical services call of >1 h and emergency medical services self-referral were analyzed using multivariable logistic regression.

The time of symptom onset was reported for 1819 patients (91.2%), the median symptom onset-to-call time was 52 min (interquartile range=17-176). Of all emergency medical services calls, 17% were referred by healthcare professionals. Compared to self-referred patients, patients who presented to a general practitioner or hospital had higher odds of delay >1 h to emergency medical services activation (adjusted odds ratio 7.76; 95% confidence interval 5.10-11.83; and 8n myocardial infarction were healthcare referrals, and this was associated with increased delays. A wide range of factors could influence a patient's decision to directly and rapidly seek emergency medical services. More efforts are needed to educate at-risk populations about early self-referral to the emergency medical services.Myocarditis is an important cause of arrhythmias and sudden cardiac death (SCD) in both physically active individuals and athletes. Elite athletes seem to have an increased risk for viral infection and subsequent myocarditis due to increased exposure to pathogens (worldwide traveling/international competition) or impaired immune system (continuing training during infections/resuming training early thereafter, strenuous exercise training or competition, and exercising in extreme weather conditions). Initial clinical presentation is variable, but athletes characteristically express non-specific symptoms of fatigue, muscle soreness, increased heart rate at rest, as well as during exercise and reduced overall exercise capacity. Beyond resting electrocardiogram (ECG), cardiac biomarkers, echocardiography, and 24-hour Holter ECG, diagnostic work-up should include cardiac magnetic resonance imaging (CMR) assessing inflammation, oedema, and fibrosis by late gadolinium enhancement (LGE), respectively, as these measures are crucial for prognosis and sports eligibility. For patients with insufficient cardiac recovery, endomyocardial biopsy is recommended to clarify differential diagnoses and initiate specific treatment options. In uncomplicated cases with normal left ventricular function during acute phase and absent LGE, eligibility for sports can be attested to three months after clinical recovery. In those with persistent pathological findings, even after six months, the risk for SCD remains increased and resuming exercise beyond recreational activities can only be recommended individually based on course of disease, left ventricular function, arrhythmias, pattern of LGE in CMR, as well as intensity and volume of exercise performed during training and competition. For all athletes, follow-up examination should be performed yearly.
To develop and externally validate a risk score for all-cause hospital admissions in patients with atrial fibrillation.

We used a prospective cohort of 2387 patients with established atrial fibrillation as derivation cohort. Independent risk factors were selected from a broad range of variables using the least absolute shrinkage and selection operator method fit to a Cox model. The risk score was validated in a separate prospective cohort of 1300 atrial fibrillation patients. The incidence of all-cause hospital admission was 19.1 per 100 person-years in the derivation cohort and it was 26.1 per 100 person-years in the validation cohort. The most important predictors for admission were age (75-79 years adjusted hazard ratio (aHR), 1.34; 95% confidence interval (CI), 1.01-1.78; 80-84 years aHR, 1.50; 95% CI, 1.11-2.03; ≥85 years aHR, 1.88; 95% CI, 1.36-2.62), prior pulmonary vein isolation (aHR, 0.72; 95% CI, 0.58-0.88), hypertension (aHR, 1.16; 95% CI, 0.99-1.36), diabetes (aHR, 1.38; 95% CI, 1.17-1.62), coronary heart disease (aHR, 1.17; 95% CI, 1.02-1.36), prior stroke/transient ischaemic attack (aHR, 1.26; 95% CI, 1.18-1.47), heart failure (aHR, 1.19; 95% CI, 1.03-1.39), peripheral artery disease (aHR, 1.35; 95% CI, 1.08-1.67), cancer (aHR, 1.33; 95% CI, 1.12-1.57), renal failure (aHR, 1.17; 95% CI, 0.99-1.37) and previous falls (aHR, 1.40; 95% CI, 1.13-1.74). A risk score with these variables was well calibrated, and achieved a C-index of 0.64 in the derivation and 0.59 in the validation cohort.

Multiple risk factors were associated with hospital admissions in atrial fibrillation patients. This prediction tool selects high-risk patients who may benefit from preventive interventions.
Multiple risk factors were associated with hospital admissions in atrial fibrillation patients. This prediction tool selects high-risk patients who may benefit from preventive interventions.Motor planning and execution require a representational map of our body. Since the body can assume different postures, it is not known how it is represented in this map. Moreover, is the generation of the motor command favored by some body configurations? We investigated the existence of a centrally favored posture of the hand for action, in search of physiological and behavioral advantages due to central motor processing. We tested two opposite hand pinch grips, equally difficult and commonly used forearm pronated, thumb-down, index-up pinch against the same grip performed with thumb-up. The former revealed faster movement onset, sign of faster neural computation, and faster target reaching. It induced increased corticospinal excitability, independently on pre-stimulus tonic muscle contraction. Remarkably, motor excitability also increased when thumb-down pinch was only observed, imagined, or prepared, actually keeping the hand at rest. Motor advantages were independent of any concurrent modulation due to somatosensory input, as shown by testing afferent inhibition. Results provide strong behavioral and physiological evidence for a preferred hand posture favoring brain motor control, independently by somatosensory processing. This suggests the existence of a baseline postural representation that may serve as an a priori spatial reference for body-space interaction.
While mechanical stress caused by blood flow, e.g. wall shear stress (WSS), and related parameters, e.g. oscillatory shear index (OSI), are increasingly being recognized as key moderators of various cardiovascular diseases, studies on valves have been limited because of a lack of appropriate imaging modalities. We investigated the influence of aortic root geometry on WSS and OSI on the aortic valve (AV) leaflet.

We applied our novel approach of intraoperative epi-aortic echocardiogram to measure the haemodynamic parameters of WSS and OSI on the AV leaflet. Thirty-six patients were included, which included those who underwent valve-sparing aortic root replacement (VSARR) with no significant aortic regurgitation (n = 17) and coronary artery bypass graft (CABG) with normal AV (n = 19). At baseline, those who underwent VSARR had a higher systolic WSS (0.52 ± 0.12 vs. 0.32 ± 0.08 Pa, respectively, P < 0.001) and a higher OSI (0.37 ± 0.06 vs. 0.29 ± 0.04, respectively, P < 0.001) on the aortic side of the AV leaflet than those who underwent CABG.
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