Readmission after index hospital discharge among patients with COVID-19: Protocol for a systematic review and meta-analysis.

Background and Aims: Hospital readmissions among COVID-19 patients have increased the load on the healthcare systems and added more pressure to hospital capacity. This affects the ability to accommodate newly diagnosed COVID-19 patients and other non-COVID-19 patients who require hospitalization. Therefore, this systematic review aims to understand the rates of and risk factors for hospital readmissions and all-cause mortality among COVID-19 patients who were hospitalized after being discharged following index hospitalization. Methods: Our systematic review protocol is registered with the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42021232324) and prepared in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) 2015 statement. We will search MEDLINE (Ovid), EMBASE (Ovid), MedRxiv, Web of Science (Science Citation Index), ProQuest Coronavirus research database, Cochrane Covid-19 study register, and WHO COVID-19: Global literature on coronavirus disease will be identified from December 31, 2019, to May 31, 2021. Two investigators will independently screen titles and abstracts and select studies reporting hospital readmissions among COVID-19 patients. Further, data extraction and risk of bias assessment will be carried out separately by these independent reviewers. We will extract data on demographics, readmissions, all-cause mortality, emergency department visits, comorbidities, and factors associated with hospitalization among COVID-19 patients. Random-effect meta-analysis will be performed if homogeneous groups of studies are found. The combined evidence will be further stratified according to important background characteristics if the data allow. Discussion: This systematic review will summarize the available epidemiological evidence regarding rates of hospital readmissions, comorbidities, and related factors among COVID-19 patients who were readmitted after index hospitalization. A better understanding of the relationship between patient profiles and the rate of hospitalization will be helpful in the development of guidelines for patient management

The 'At-risk mental state' for psychosis in adolescents : clinical presentation, transition and remission.

Despite increased efforts over the last decade to prospectively identify individuals at ultra-high risk of developing a psychotic illness, limited attention has been specifically directed towards adolescent populations (<18 years). In order to evaluate how those under 18 fulfilling the operationalised criteria for an At-Risk Mental State (ARMS) present and fare over time, we conducted an observational study. Participants (N = 30) generally reported a high degree of functional disability and frequent and distressing perceptual disturbance, mainly in the form of auditory hallucinations. Seventy percent (21/30) were found to fulfil the criteria for a co-morbid ICD-10 listed mental health disorder, with mood (affective; 13/30) disorders being most prevalent. Overall transition rates to psychosis were low at 24 months follow-up (2/28; 7.1 %) whilst many participants demonstrated a significant reduction in psychotic-like symptoms. The generalisation of these findings may be limited due to the small sample size and require replication in a larger sample

Prehospital score for acute disease: a community-based observational study in Japan

<p>Abstract</p> <p>Background</p> <p>Ambulance usage in Japan has increased consistently because it is free under the national health insurance system. The introduction of refusal for ambulance transfer is being debated nationally. The purpose of the present study was to investigate the relationship between prehospital data and hospitalization outcome for acute disease patients, and to develop a simple prehospital evaluation tool using prehospital data for Japan's emergency medical service system.</p> <p>Methods</p> <p>The subjects were 9,160 consecutive acute disease patients aged ≥ 15 years who were transferred to hospital by Kishiwada City Fire Department ambulance between July 2004 and March 2006. The relationship between prehospital data (age, systolic blood pressure, pulse rate, respiration rate, level of consciousness, SpO₂level and ability to walk) and outcome (hospitalization or non-hospitalization) was analyzed using logistic regression models. The prehospital score component of each item of prehospital data was determined by beta coefficients. Eligible patients were scored retrospectively and the distribution of outcome was examined. For patients transported to the two main hospitals, outcome after hospitalization was also confirmed.</p> <p>Results</p> <p>A total of 8,330 (91%) patients were retrospectively evaluated using a prehospital score with a maximum value of 14. The percentage of patients requiring hospitalization rose from 9% with score = 0 to 100% with score = 14. With a cut-off point score ≥ 2, the sensitivity, specificity, positive predictive value and negative predictive value were 97%, 16%, 39% and 89%, respectively. Among the 6,498 patients transported to the two main hospitals, there were no deaths at scores ≤ 1 and the proportion of non-hospitalization was over 90%. The proportion of deaths increased rapidly at scores ≥ 11.</p> <p>Conclusion</p> <p>The prehospital score could be a useful tool for deciding the refusal of ambulance transfer in Japan's emergency medical service system.</p

Effects of Intracoronary Alteplase on Microvascular Function in Acute Myocardial Infarction

Background—Impaired microcirculatory reperfusion worsens prognosis following acute ST‐segment–elevation myocardial infarction. In the T‐TIME (A Trial of Low‐Dose Adjunctive Alteplase During Primary PCI) trial, microvascular obstruction on cardiovascular magnetic resonance imaging did not differ with adjunctive, low‐dose, intracoronary alteplase (10 or 20 mg) versus placebo during primary percutaneous coronary intervention. We evaluated the effects of intracoronary alteplase, during primary percutaneous coronary intervention, on the index of microcirculatory resistance, coronary flow reserve, and resistive reserve ratio. Methods and Results—A prespecified physiology substudy of the T‐TIME trial. From 2016 to 2017, patients with ST‐segment–elevation myocardial infarction ≤6 hours from symptom onset were randomized in a double‐blind study to receive alteplase 20 mg, alteplase 10 mg, or placebo infused into the culprit artery postreperfusion, but prestenting. Index of microcirculatory resistance, coronary flow reserve, and resistive reserve ratio were measured after percutaneous coronary intervention. Cardiovascular magnetic resonance was performed at 2 to 7 days and 3 months. Analyses in relation to ischemic time (<2, 2–4, and ≥4 hours) were prespecified. One hundred forty‐four patients (mean age, 59±11 years; 80% male) were prospectively enrolled, representing 33% of the overall population (n=440). Overall, index of microcirculatory resistance (median, 29.5; interquartile range, 17.0–55.0), coronary flow reserve(1.4 [1.1–2.0]), and resistive reserve ratio (1.7 [1.3–2.3]) at the end of percutaneous coronary intervention did not differ between treatment groups. Interactions were observed between ischemic time and alteplase for coronary flow reserve (P=0.013), resistive reserve ratio (P=0.026), and microvascular obstruction (P=0.022), but not index of microcirculatory resistance. Conclusions—In ST‐segment–elevation myocardial infarction with ischemic time ≤6 hours, there was overall no difference in microvascular function with alteplase versus placebo

Subanesthetic ketamine treatment promotes abnormal interactions between neural subsystems and alters the properties of functional brain networks

Acute treatment with subanesthetic ketamine, a non-competitive N-methyl-D-aspartic acid (NMDA) receptor antagonist, is widely utilized as a translational model for schizophrenia. However, how acute NMDA receptor blockade impacts on brain functioning at a systems level, to elicit translationally relevant symptomatology and behavioral deficits, has not yet been determined. Here, for the first time, we apply established and recently validated topological measures from network science to brain imaging data gained from ketamine-treated mice to elucidate how acute NMDA receptor blockade impacts on the properties of functional brain networks. We show that the effects of acute ketamine treatment on the global properties of these networks are divergent from those widely reported in schizophrenia. Where acute NMDA receptor blockade promotes hyperconnectivity in functional brain networks, pronounced dysconnectivity is found in schizophrenia. We also show that acute ketamine treatment increases the connectivity and importance of prefrontal and thalamic brain regions in brain networks, a finding also divergent to alterations seen in schizophrenia. In addition, we characterize how ketamine impacts on bipartite functional interactions between neural subsystems. A key feature includes the enhancement of prefrontal cortex (PFC)-neuromodulatory subsystem connectivity in ketamine-treated animals, a finding consistent with the known effects of ketamine on PFC neurotransmitter levels. Overall, our data suggest that, at a systems level, acute ketamine-induced alterations in brain network connectivity do not parallel those seen in chronic schizophrenia. Hence, the mechanisms through which acute ketamine treatment induces translationally relevant symptomatology may differ from those in chronic schizophrenia. Future effort should therefore be dedicated to resolve the conflicting observations between this putative translational model and schizophrenia

Ablation of the androgen receptor from vascular smooth muscle cells demonstrates a role for testosterone in vascular calcification

Vascular calcification powerfully predicts mortality and morbidity from cardiovascular disease. Men have a greater risk of cardiovascular disease, compared to women of a similar age. These gender disparities suggest an influence of sex hormones. Testosterone is the primary and most well-recognised androgen in men. Therefore, we addressed the hypothesis that exogenous androgen treatment induces vascular calcification. Immunohistochemical analysis revealed expression of androgen receptor (AR) in the calcified media of human femoral artery tissue and calcified human valves. Furthermore, in vitro studies revealed increased phosphate (Pi)-induced mouse vascular smooth muscle cell (VSMC) calcification following either testosterone or dihydrotestosterone (DHT) treatment for 9 days. Testosterone and DHT treatment increased tissue non-specific alkaline phosphatase (Alpl) mRNA expression. Testosterone-induced calcification was blunted in VSMC-specific AR-ablated (SM-ARKO) VSMCs compared to WT. Consistent with these data, SM-ARKO VSMCs showed a reduction in Osterix mRNA expression. However, intriguingly, a counter-intuitive increase in Alpl was observed. These novel data demonstrate that androgens play a role in inducing vascular calcification through the AR. Androgen signalling may represent a novel potential therapeutic target for clinical intervention

GRACE risk score: sex-based validity of in-hospital mortality prediction in Canadian patients with acute coronary syndrome

Background: Although there are sex differences in management and outcome of acute coronary syndromes (ACS), sex is not a component of Global Registry of Acute Coronary Events (GRACE) risk score (RS) for in-hospital mortality prediction. We sought to determine the prognostic utility of GRACE RS in men and women, and whether its predictive accuracy would be augmented through sex-based modification of its components. Methods: Canadian men and women enrolled in GRACE and Canadian Registry of Acute Coronary Events were stratified as ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation ACS (NSTE-ACS). GRACE RS was calculated as per original model. Discrimination and calibration were evaluated using the c-statistic and Hosmer-Lemeshow goodness-of-fit test, respectively. Multivariable logistic regression was undertaken to assess potential interactions of sex with GRACE RS components. Results: For the overall cohort (n = 14,422), unadjusted in-hospital mortality rate was higher in women than men (4.5% vs. 3.0%, p &lt; 0.001). Overall, GRACE RS c-statistic and goodness-of-fit test p-value were 0.85 (95%CI 0.83–0.87) and 0.11, respectively. While the RS had excellent discrimination for all subgroups (c-statistics &gt; 0.80), discrimination was lower for women compared to men with STEMI [0.80 (0.75–0.84) vs. 0.86 (0.82–0.89), respectively, p &lt; 0.05]. The goodness-of-fit test showed good calibration for women (p = 0.86), but suboptimal for men (p = 0.031). No significant interaction was evident between sex and RS components (all p &gt; 0.25). Conclusions: The GRACE RS is a valid predictor of in-hospital mortality for both men and women with ACS. The lack of interaction between sex and RS components suggests that sex-based modification is not required

A pragmatic randomised controlled trial of the Welsh National Exercise Referral Scheme: protocol for trial and integrated economic and process evaluation

Background: The benefits to health of a physically active lifestyle are well established and there is evidence that a sedentary lifestyle plays a significant role in the onset and progression of chronic disease. Despite a recognised need for effective public health interventions encouraging sedentary people with a medical condition to become more active, there are few rigorous evaluations of their effectiveness. Following NICE guidance, the Welsh national exercise referral scheme was implemented within the context of a pragmatic randomised controlled trial. Methods/Design: The randomised controlled trial, with nested economic and process evaluations, recruited 2,104 inactive men and women aged 16+ with coronary heart disease (CHD) risk factors and/or mild to moderate depression, anxiety or stress. Participants were recruited from 12 local health boards in Wales and referred directly by health professionals working in a range of health care settings. Consenting participants were randomised to either a 16 week tailored exercise programme run by qualified exercise professionals at community sports centres (intervention), or received an information booklet on physical activity (control). A range of validated measures assessing physical activity, mental health, psycho-social processes and health economics were administered at 6 and 12 months, with the primary 12 month outcome measure being 7 day Physical Activity Recall. The process evaluation explored factors determining the effectiveness or otherwise of the scheme, whilst the economic evaluation determined the relative cost-effectiveness of the scheme in terms of public spending. Discussion: Evaluation of such a large scale national public health intervention presents methodological challenges in terms of trial design and implementation. This study was facilitated by early collaboration with social research and policy colleagues to develop a rigorous design which included an innovative approach to patient referral and trial recruitment, a comprehensive process evaluation examining intervention delivery and an integrated economic evaluation. This will allow a unique insight into the feasibility, effectiveness and cost effectiveness of a national exercise referral scheme for participants with CHD risk factors or mild to moderate anxiety, depression, or stress and provides a potential model for future policy evaluations. Trial registration: Current Controlled Trials ISRCTN4768044

Increased CSF levels of aromatic amino acids in hip fracture patients with delirium suggests higher monoaminergic activity

textabstractBackground: To examine whether delirium in hip fracture patients was associated with changes in the levels of amino acids and/or monoamine metabolites in cerebrospinal fluid (CSF) and serum. Methods: In this prospective cohort study, 77 patients admitted with an acute hip fracture to Oslo University Hospital, Norway, were studied. The concentrations of amino acids in CSF and serum were determined by high performance liquid chromatography. The patients were assessed daily for delirium by the Confusion Assessment Method (pre-operatively and post-operative day 1-5 (all) or until discharge (delirious patients)). Pre-fracture dementia status was decided by an expert panel. Serum was collected pre-operatively and CSF immediately before spinal anesthesia. Results: Fifty-three (71 %) hip fracture patients developed delirium. In hip fracture patients without dementia (n = 39), those with delirium had significantly higher CSF levels of tryptophan (40 % higher), tyrosine (60 % higher), phenylalanine (59 % higher) and the monoamine metabolite 5-hydroxyindoleacetate (23 % higher) compared to those without delirium. The same amino acids were also higher in CSF in delirious patients with dementia (n = 38). The correlations between serum and CSF amino acid levels were poor. Conclusion: Higher CSF levels of monoamine precursors in hip fracture patients with delirium suggest a higher monoaminergic activity in the central nervous system during delirium in this patient group