Clinical decision aids and computed tomography coronary angiography in patients with suspected acute coronary syndrome.

BACKGROUND: The HEART score, the T-MACS model and the GRACE score support early decision-making for acute chest pain, which could be complemented by CT coronary angiography (CTCA). However, their performance has not been directly compared. METHODS: In this secondary analysis of a multicentre randomised controlled trial of early CTCA in intermediate-risk patients with suspected acute coronary syndrome, C-statistics and performance metrics (using the predefined cut-offs) of clinical decision aids and CTCA, alone and then in combination, for the index hospital diagnosis of acute coronary syndrome and for 30-day coronary revascularisation were assessed in those who underwent CTCA and had complete data. RESULTS: Among 699 patients, 358 (51%) had an index hospital diagnosis of acute coronary syndrome, for which the C-statistic was higher for CTCA (0.80), followed by the T-MACS model (0.78), the HEART score (0.74) and the GRACE score (0.60). The negative predictive value was higher for the absence of coronary artery disease on CTCA (0.90) or a T-MACS estimate of <0.05 (0.83) than a HEART score of <4 (0.81) and a GRACE score of <109 (0.55). For 30-day coronary revascularisation, CTCA had the greatest C-statistic (0.80) with a negative predictive value of 0.96 and 0.92 in the absence of coronary artery disease and obstructive coronary artery disease, respectively. The combination of the T-MACS estimates and the CTCA findings was most discriminative for the index hospital diagnosis of acute coronary syndrome (C-statistic, 0.88) and predictive of 30-day coronary revascularisation (C-statistic, 0.85). No patients with a T-MACS estimate of <0.05 and normal coronary arteries had acute coronary syndrome during index hospitalisation or underwent coronary revascularisation within 30 days. CONCLUSIONS: In intermediate-risk patients with suspected acute coronary syndrome, the T-MACS model combined with CTCA improved discrimination of the index hospital diagnosis of acute coronary syndrome and prediction of 30-day coronary revascularisation. TRIAL REGISTRATION NUMBER: NCT02284191.

Sex differences in coronary atherosclerotic plaque activity using 18F-sodium fluoride positron emission tomography.

INTRODUCTION: There are sex differences in the extent, severity, and outcomes of coronary artery disease. We aimed to assess the influence of sex on coronary atherosclerotic plaque activity measured using coronary 18F-sodium fluoride (18F-NaF) positron emission tomography (PET), and to determine whether 18F-NaF PET has prognostic value in both women and men. METHODS: In a post-hoc analysis of observational cohort studies of patients with coronary atherosclerosis who had undergone 18F-NaF PET CT angiography, we compared the coronary microcalcification activity (CMA) in women and men. RESULTS: Baseline 18F-NaF PET CT angiography was available in 999 participants (151 (15%) women) with 4282 patient-years of follow-up. Compared to men, women had lower coronary calcium scores (116 [interquartile range, 27-434] versus 205 [51-571] Agatston units; p = 0.002) and CMA values (0.0 [0.0-1.12] versus 0.53 [0.0-2.54], p = 0.01). Following matching for plaque burden by coronary calcium scores and clinical comorbidities, there was no sex-related difference in CMA values (0.0 [0.0-1.12] versus 0.0 [0.0-1.23], p = 0.21) and similar proportions of women and men had no 18F-NaF uptake (53.0% (n = 80) and 48.3% (n = 73); p = 0.42), or CMA values > 1.56 (21.8% (n = 33) and 21.8% (n = 33); p = 1.00). Over a median follow-up of 4.5 [4.0-6.0] years, myocardial infarction occurred in 6.6% of women (n = 10) and 7.8% of men (n = 66). Coronary microcalcification activity greater than 0 was associated with a similarly increased risk of myocardial infarction in both women (HR: 3.83; 95% CI:1.10-18.49; p = 0.04) and men (HR: 5.29; 95% CI:2.28-12.28; p < 0.001). CONCLUSION: Although men present with more coronary atherosclerotic plaque than women, increased plaque activity is a strong predictor of future myocardial infarction regardless of sex.

Coronary Atherosclerotic Plaque Activity and Risk of Myocardial Infarction.

BACKGROUND: Total coronary atherosclerotic plaque activity across the entire coronary arterial tree is associated with patient-level clinical outcomes. OBJECTIVES: We aimed to investigate whether vessel-level coronary atherosclerotic plaque activity is associated with vessel-level myocardial infarction. METHODS: In this secondary analysis of an international multicenter study of patients with recent myocardial infarction and multivessel coronary artery disease, we assessed vessel-level coronary atherosclerotic plaque activity using coronary 18F-sodium fluoride positron emission tomography to identify vessel-level myocardial infarction. RESULTS: Increased 18F-sodium fluoride uptake was found in 679 of 2,094 coronary arteries and 414 of 691 patients. Myocardial infarction occurred in 24 (4%) vessels with increased coronary atherosclerotic plaque activity and in 25 (2%) vessels without increased coronary atherosclerotic plaque activity (HR: 2.08; 95% CI: 1.16-3.72; P = 0.013). This association was not demonstrable in those treated with coronary revascularization (HR: 1.02; 95% CI: 0.47-2.25) but was notable in untreated vessels (HR: 3.86; 95% CI: 1.63-9.10; Pinteraction = 0.024). Increased coronary atherosclerotic plaque activity in multiple coronary arteries was associated with heightened patient-level risk of cardiac death or myocardial infarction (HR: 2.43; 95% CI: 1.37-4.30; P = 0.002) as well as first (HR: 2.19; 95% CI: 1.18-4.06; P = 0.013) and total (HR: 2.50; 95% CI: 1.42-4.39; P = 0.002) myocardial infarctions. CONCLUSIONS: In patients with recent myocardial infarction and multivessel coronary artery disease, coronary atherosclerotic plaque activity prognosticates individual coronary arteries and patients at risk for myocardial infarction.

Early computed tomography coronary angiography and preventative treatment in patients with suspected acute coronary syndrome: A secondary analysis of the RAPID-CTCA trial.

BACKGROUND: Computed tomography coronary angiography (CTCA) offers detailed assessment of the presence of coronary atherosclerosis and helps guide patient management. We investigated influences of early CTCA on the subsequent use of preventative treatment in patients with suspected acute coronary syndrome. METHODS: In this secondary analysis of a multicenter randomized controlled trial of early CTCA in intermediate-risk patients with suspected acute coronary syndrome, prescription of aspirin, P2Y12 receptor antagonist, statin, renin-angiotensin system blocker, and beta-blocker therapies from randomization to discharge were compared within then between those randomized to early CTCA or to standard of care only. Effects of CTCA findings on adjustment of these therapies were further examined. RESULTS: In 1,743 patients (874 randomized to early CTCA and 869 to standard of care only), prescription of P2Y12 receptor antagonist, dual antiplatelet, and statin therapies increased more in the early CTCA group (between-group difference: 4.6% [95% confidence interval, 0.3-8.9], 4.5% [95% confidence interval, 0.2-8.7], and 4.3% [95% confidence interval, 0.2-8.5], respectively), whereas prescription of other preventative therapies increased by similar extent in both study groups. Among patients randomized to early CTCA, there were additional increments of preventative treatment in those with obstructive coronary artery disease and higher rates of reductions in antiplatelet and beta-blocker therapies in those with normal coronary arteries. CONCLUSIONS: Prescription patterns of preventative treatment varied during index hospitalization in patients with suspected acute coronary syndrome. Early CTCA facilitated targeted individualization of these therapies based on the extent of coronary artery disease.

Anti-Atopic Dermatitis Activity of Epi-Oxyzoanthamine Isolated from Zoanthid.

Atopic dermatitis (AD, eczema) is a condition that causes dry, itchy, and inflamed skin and occurs most frequently in children but also affects adults. However, common clinical treatments provide limited relief and have some side effects. Therefore, there is a need to develop new effective therapies to treat AD. Epi-oxyzoanthamine is a small molecule alkaloid isolated from Formosan zoanthid. Relevant studies have shown that zoanthamine alkaloids have many pharmacological and biological activities, including anti-lymphangiogenic functions. However, there are no studies on the use of epi-oxyzoanthamine on the skin. In this paper, epi-oxyzoanthamine has been shown to have potential in the treatment of atopic dermatitis. Through in vitro studies, it was found that epi-oxyzoanthamine inhibited the expression of cytokines in TNF-α/IFN-γ-stimulated human keratinocyte (HaCaT) cells, and it reduced the phosphorylation of MAPK and the NF-κB signaling pathway. Atopic dermatitis-like skin inflammation was induced in a mouse model using 2,4-dinitrochlorobenzene (DNCB) in vivo. The results showed that epi-oxyzoanthamine significantly decreased skin barrier damage, scratching responses, and epidermal hyperplasia induced by DNCB. It significantly reduced transepidermal water loss (TEWL), erythema, ear thickness, and spleen weight, while also increasing surface skin hydration. These results indicate that epi-oxyzoanthamine from zoanthid has good potential as an alternative medicine for treating atopic dermatitis or other skin-related inflammatory diseases.

Hybrid and adaptive control of functional electrical stimulation to correct hemiplegic gait for patients after stroke.

Introduction: Gait, as a fundamental human movement, necessitates the coordination of muscles across swing and stance phases. Functional electrical stimulation (FES) of the tibialis anterior (TA) has been widely applied to foot drop correction for patients with post-stroke during the swing phase. Although the gastrocnemius (GAS) during the stance phase is also affected, the Functional electrical stimulation of the gastrocnemius received less attention. Methods: To address this limitation, a timing- and intensity-adaptive Functional electrical stimulation control strategy was developed for both the TA and GAS. Each channel incorporates a speed-adaptive (SA) module to control stimulation timing and an iterative learning control (ILC) module to regulate the stimulation intensity. These modules rely on real-time kinematic or kinetic data during the swing or stance phase, respectively. The orthotic effects of the system were evaluated on eight patients with post-stroke foot drop. Gait kinematics and kinetics were assessed under three conditions: no stimulation (NS), Functional electrical stimulation to the ankle dorsiflexor tibialis anterior (SA-ILC DS) and FES to the tibialis anterior and the ankle plantarflexor gastrocnemius (SA-ILC DPS). Results: The ankle plantarflexion angle, the knee flexion angle, and the anterior ground reaction force (AGRF) in the SA-ILC DPS condition were significantly larger than those in the NS and SA-ILC DS conditions (p < 0.05). The maximum dorsiflexion angle during the swing phase in the SA-ILC DPS condition was similar to that in the SA-ILC DS condition, with both being significantly larger than the angle observed in the NS condition (p < 0.05). Furthermore, the angle error and force error relative to the set targets were minimized in the SA-ILC DPS condition. Discussion: The observed improvements can be ascribed to the appropriate stimulation timing and intensity provided by the SA-ILC DPS strategy. This study demonstrates that the hybrid and adaptive control strategy of functional electrical stimulation system offers a significant orthotic effect, and has considerable potential for future clinical application.

Temporal Changes in Coronary 18F-Fluoride Plaque Uptake in Patients with Coronary Atherosclerosis.

Coronary 18F-sodium fluoride (18F-fluoride) uptake is a marker of both atherosclerotic disease activity and disease progression. It is currently unknown whether there are rapid temporal changes in coronary 18F-fluoride uptake and whether these are more marked in those with clinically unstable coronary artery disease. This study aimed to determine the natural history of coronary 18F-fluoride uptake over 12 mo in patients with either advanced chronic coronary artery disease or a recent myocardial infarction. Methods: Patients with established multivessel coronary artery disease and either chronic disease or a recent acute myocardial infarction underwent coronary 18F-fluoride PET and CT angiography, which was repeated at 3, 6, or 12 mo. Coronary 18F-fluoride uptake was assessed in each vessel by measuring the coronary microcalcification activity (CMA). Coronary calcification was quantified by measuring calcium score, mass, and volume. Results: Fifty-nine patients had chronic coronary artery disease (median age, 68 y; 93% male), and 52 patients had a recent myocardial infarction (median age, 65 y; 83% male). Reflecting the greater burden of coronary artery disease, baseline CMA values were higher in those with chronic coronary artery disease. Coronary 18F-fluoride uptake (CMA > 0) was associated with higher baseline calcium scores (294 Agatston units [AU] [interquartile range, 116-483 AU] vs. 72 AU [interquartile range, 8-222 AU]; P < 0.001) and more rapid progression of coronary calcification scores (39 AU [interquartile range, 10-82 AU] vs. 12 AU [interquartile range, 1-36 AU]; P < 0.001) than was the absence of uptake (CMA = 0). Coronary 18F-fluoride uptake did not markedly alter over the course of 3, 6, or 12 mo in patients with either chronic coronary artery disease or a recent myocardial infarction. Conclusion: Coronary 18F-fluoride uptake is associated with the severity and progression of coronary artery disease but does not undergo a rapid dynamic change in patients with chronic or unstable coronary artery disease. This finding suggests that coronary 18F-fluoride uptake is a temporally stable marker of established and progressive disease.

Coronary Atherosclerotic Plaque Activity and Future Coronary Events.

Importance: Recurrent coronary events in patients with recent myocardial infarction remain a major clinical problem. Noninvasive measures of coronary atherosclerotic disease activity have the potential to identify individuals at greatest risk. Objective: To assess whether coronary atherosclerotic plaque activity as assessed by noninvasive imaging is associated with recurrent coronary events in patients with myocardial infarction. Design, Setting, and Participants: This prospective, longitudinal, international multicenter cohort study recruited participants aged 50 years or older with multivessel coronary artery disease and recent (within 21 days) myocardial infarction between September 2015 and February 2020, with a minimum 2 years' follow-up. Intervention: Coronary 18F-sodium fluoride positron emission tomography and coronary computed tomography angiography. Main Outcomes and Measures: Total coronary atherosclerotic plaque activity was assessed by 18F-sodium fluoride uptake. The primary end point was cardiac death or nonfatal myocardial infarction but was expanded during study conduct to include unscheduled coronary revascularization due to lower than anticipated primary event rates. Results: Among 2684 patients screened, 995 were eligible, 712 attended for imaging, and 704 completed an interpretable scan and comprised the study population. The mean (SD) age of participants was 63.8 (8.2) years, and most were male (601 [85%]). Total coronary atherosclerotic plaque activity was identified in 421 participants (60%). After a median follow-up of 4 years (IQR, 3-5 years), 141 participants (20%) experienced the primary end point: 9 had cardiac death, 49 had nonfatal myocardial infarction, and 83 had unscheduled coronary revascularizations. Increased coronary plaque activity was not associated with the primary end point (hazard ratio [HR], 1.25; 95% CI, 0.89-1.76; P = .20) or unscheduled revascularization (HR, 0.98; 95% CI, 0.64-1.49; P = .91) but was associated with the secondary end point of cardiac death or nonfatal myocardial infarction (47 of 421 patients with high plaque activity [11.2%] vs 19 of 283 with low plaque activity [6.7%]; HR, 1.82; 95% CI, 1.07-3.10; P = .03) and all-cause mortality (30 of 421 patients with high plaque activity [7.1%] vs 9 of 283 with low plaque activity [3.2%]; HR, 2.43; 95% CI, 1.15-5.12; P = .02). After adjustment for differences in baseline clinical characteristics, coronary angiography findings, and Global Registry of Acute Coronary Events score, high coronary plaque activity was associated with cardiac death or nonfatal myocardial infarction (HR, 1.76; 95% CI, 1.00-3.10; P = .05) but not with all-cause mortality (HR, 2.01; 95% CI, 0.90-4.49; P = .09). Conclusions and Relevance: In this cohort study of patients with recent myocardial infarction, coronary atherosclerotic plaque activity was not associated with the primary composite end point. The findings suggest that risk of cardiovascular death or myocardial infarction in patients with elevated plaque activity warrants further research to explore its incremental prognostic implications.

Diaphragmatic ultrasound can help evaluate pulmonary dysfunction in patients with stroke.

Objective: Pulmonary dysfunction after stroke is increasingly gaining attention from clinical and rehabilitation specialists. However, owing to cognitive and motor dysfunction in patients with stroke, determining the pulmonary function of these patients remains challenging. The present study aimed to devise a simple method for an early evaluation of pulmonary dysfunction in patients with stroke. Methods: Overall, 41 patients with stroke in the recovery period (stroke group) and 22 matched healthy controls (control group) were included in the study. We first collected data regarding baseline characteristics for all participants. Furthermore, the participants with stroke were examined using additional scales, such as the National Institutes of Health Stroke Scale (NIHSS), Fugl-Meyer assessment scale (FMA), and modified Barthel Index (MBI). Subsequently, we examined the participants with simple pulmonary function detection and diaphragm ultrasound (B-mode). Ultrasound indices calculated were as follows: the thickness of the diaphragm under the position of functional residual capacity (TdiFRC), the thickness of the diaphragm under the position of forced vital capacity (TdiFVC), thickness fraction, and diaphragmatic mobility. Finally, we compared and analyzed all data to identify group differences, the correlation between pulmonary function and diaphragmatic ultrasound indices, and the correlation between pulmonary function and assessment scale scores in patients with stroke, respectively. Results: Compared with the control group, patients in the stroke group exhibited lower values for indices of pulmonary and diaphragmatic function (p < 0.001), except for TdiFRC (p > 0.05). The majority of the patients with stroke had restrictive ventilatory dysfunction, as indicated by a significantly higher incidence ratio (36 in 41 patients) than that in the control group (0 in 22 patients) (p < 0.001). Moreover, significant correlations were found between pulmonary function and diaphragmatic ultrasound indices (p < 0.05), with the strongest correlation between TdiFVC and pulmonary indices. In the stroke group, pulmonary function indices were negatively correlated with the NIHSS scores (p < 0.001) and positively correlated with the FMA scores (p < 0.001). No (p > 0.05) or weak (p < 0.05) correlation was found between pulmonary function indices and the MBI scores. Conclusion: We found that patients with stroke had pulmonary dysfunction even in the recovery period. Diaphragmatic ultrasound can be used as a simple and effective tool for detecting pulmonary dysfunction in patients with stroke, with TdiFVC being the most effective index.

Intermittent theta burst stimulation vs. high-frequency repetitive transcranial magnetic stimulation for post-stroke cognitive impairment: Protocol of a pilot randomized controlled double-blind trial.

Introduction: Intermittent theta burst stimulation (iTBS), a novel mode of transcranial magnetic stimulation (TMS), has curative effects on patients with post-stroke cognitive impairment (PSCI). However, whether iTBS will be more applicable in clinical use than conventional high-frequency repetitive transcranial magnetic stimulation (rTMS) is unknown. Our study aims to compare the difference in effect between iTBS and rTMS in treating PSCI based on a randomized controlled trial, as well as to determine its safety and tolerability, and to further explore the underlying neural mechanism. Methods: The study protocol is designed as a single-center, double-blind, randomized controlled trial. Forty patients with PSCI will be randomly assigned to two different TMS groups, one with iTBS and the other with 5 Hz rTMS. Neuropsychological evaluation, activities of daily living, and resting electroencephalography will be conducted before treatment, immediately post-treatment, and 1 month after iTBS/rTMS stimulation. The primary outcome is the change in the Montreal Cognitive Assessment Beijing Version (MoCA-BJ) score from baseline to the end of the intervention (D11). The secondary outcomes comprise changes in resting electroencephalogram (EEG) indexes from baseline to the end of the intervention (D11) as well as the Auditory Verbal Learning Test, the symbol digit modality test, the Digital Span Test findings, and the MoCA-BJ scores from baseline to endpoint (W6). Discussion: In this study, the effects of iTBS and rTMS will be evaluated using cognitive function scales in patients with PSCI as well as data from resting EEG, which allows for an in-depth exploration of underlying neural oscillations. In the future, these results may contribute to the application of iTBS for cognitive rehabilitation of patients with PSCI.

Plaque Burden and 1-Year Outcomes in Acute Chest Pain: Results From the Multicenter RAPID-CTCA Trial.

BACKGROUND: In patients with stable chest pain, computed tomography (CT) plaque burden is an independent predictor of future coronary events. OBJECTIVES: The purpose of this study was to determine whether plaque burden and characteristics can predict subsequent death or myocardial infarction in patients with acute chest pain. METHODS: In a post hoc analysis of a multicenter trial of early coronary CT angiography, the authors performed quantitative plaque analysis to assess the association between primary endpoint of 1-year all-cause death or nonfatal myocardial infarction and the GRACE (Global Registry of Acute Coronary Events) score, presence of obstructive coronary artery disease, and plaque burden in 404 patients with suspected acute coronary syndrome. RESULTS: Following the index event, 25 patients had a primary event that was associated with a higher GRACE score (134 ± 44 vs 113 ± 35; P = 0.012), larger burdens of total (46% [IQR: 43%-50%] vs 36% [IQR: 21%-46%]; P < 0.001), noncalcified (41% [IQR: 37%-%47] vs 33% [IQR: 20%-41%]; P < 0.001), and low-attenuation plaque (4.22% [IQR: 3.3%-5.68%] vs 2.14% [IQR: 0.5%-4.88%]; P < 0.001), but not obstructive coronary artery disease (P = 0.065). Total, noncalcified, and low-attenuation plaque burden were the strongest predictors of future events independent of GRACE score and obstructive coronary artery disease (P ≤ 0.002 for all). Patients with a low-attenuation burden above the median had nearly an 8-fold increased risk of the primary endpoint (HR: 7.80 [95% CI: 2.33-26.0]; P < 0.001), outperforming either a GRACE score of >140 (HR: 3.80 [95% CI :1.45-6.98]; P = 0.004) or obstructive coronary artery disease (HR: 2.07 [95% CI: 0.94-4.53]; P = 0.07). CONCLUSIONS: In patients with suspected acute coronary syndrome, low-attenuation plaque burden is a major predictor of 1-year death or recurrent myocardial infarction. (Rapid Assessment of Potential Ischaemic Heart Disease With CTCA [RAPID-CTCA]; NCT02284191).

Lifetime risk, life expectancy, and years of life lost to type 2 diabetes in 23 high-income jurisdictions: a multinational, population-based study.

BACKGROUND: Diabetes is a major public health issue. Because lifetime risk, life expectancy, and years of life lost are meaningful metrics for clinical decision making, we aimed to estimate these measures for type 2 diabetes in the high-income setting. METHODS: For this multinational, population-based study, we sourced data from 24 databases for 23 jurisdictions (either whole countries or regions of a country): Australia; Austria; Canada; Denmark; Finland; France; Germany; Hong Kong; Hungary; Israel; Italy; Japan; Latvia; Lithuania; the Netherlands; Norway; Scotland; Singapore; South Korea; Spain; Taiwan; the UK; and the USA. Our main outcomes were lifetime risk of type 2 diabetes, life expectancy in people with and without type 2 diabetes, and years of life lost to type 2 diabetes. We modelled the incidence and mortality of type 2 diabetes in people with and without type 2 diabetes in sex-stratified, age-adjusted, and calendar year-adjusted Poisson models for each jurisdiction. Using incidence and mortality, we constructed life tables for people of both sexes aged 20-100 years for each jurisdiction and at two timepoints 5 years apart in the period 2005-19 where possible. Life expectancy from a given age was computed as the area under the survival curves and lifetime lost was calculated as the difference between the expected lifetime of people with versus without type 2 diabetes at a given age. Lifetime risk was calculated as the proportion of each cohort who developed type 2 diabetes between the ages of 20 years and 100 years. We estimated 95% CIs using parametric bootstrapping. FINDINGS: Across all study cohorts from the 23 jurisdictions (total person-years 1 577 234 194), there were 5 119 585 incident cases of type 2 diabetes, 4 007 064 deaths in those with type 2 diabetes, and 11 854 043 deaths in those without type 2 diabetes. The lifetime risk of type 2 diabetes ranged from 16·3% (95% CI 15·6-17·0) for Scottish women to 59·6% (58·5-60·8) for Singaporean men. Lifetime risk declined with time in 11 of the 15 jurisdictions for which two timepoints were studied. Among people with type 2 diabetes, the highest life expectancies were found for both sexes in Japan in 2017-18, where life expectancy at age 20 years was 59·2 years (95% CI 59·2-59·3) for men and 64·1 years (64·0-64·2) for women. The lowest life expectancy at age 20 years with type 2 diabetes was observed in 2013-14 in Lithuania (43·7 years [42·7-44·6]) for men and in 2010-11 in Latvia (54·2 years [53·4-54·9]) for women. Life expectancy in people with type 2 diabetes increased with time for both sexes in all jurisdictions, except for Spain and Scotland. The life expectancy gap between those with and without type 2 diabetes declined substantially in Latvia from 2010-11 to 2015-16 and in the USA from 2009-10 to 2014-15. Years of life lost to type 2 diabetes ranged from 2·5 years (Latvia; 2015-16) to 12·9 years (Israel Clalit Health Services; 2015-16) for 20-year-old men and from 3·1 years (Finland; 2011-12) to 11·2 years (Israel Clalit Health Services; 2010-11 and 2015-16) for 20-year-old women. With time, the expected number of years of life lost to type 2 diabetes decreased in some jurisdictions and increased in others. The greatest decrease in years of life lost to type 2 diabetes occurred in the USA between 2009-10 and 2014-15 for 20-year-old men (a decrease of 2·7 years). INTERPRETATION: Despite declining lifetime risk and improvements in life expectancy for those with type 2 diabetes in many high-income jurisdictions, the burden of type 2 diabetes remains substantial. Public health strategies might benefit from tailored approaches to continue to improve health outcomes for people with diabetes. FUNDING: US Centers for Disease Control and Prevention and Diabetes Australia.

Development of an international standard set of outcome measures for patients with venous thromboembolism: an International Consortium for Health Outcomes Measurement consensus recommendation.

The International Consortium for Health Outcomes Measurement assembled an international working group of venous thromboembolism experts and patient representatives to develop a standardised minimum set of outcomes and outcome measurements for integration into clinical practice and potentially research to support clinical decision making and benchmarking of quality of care. 15 core outcomes important to patients and health-care professionals were selected and categorised into four domains: patient-reported outcomes, long term consequences of the disease, disease-specific complications, and treatment-related complications. The outcomes and outcome measures were designed to apply to all patients with venous thromboembolism aged 16 years or older. A measurement tool package was selected for inclusion in the core standard set, with a minimum number of items to be measured at predefined timepoints, which capture all core outcomes. Additional measures can be introduced to the user by a cascade opt-in system that allows for further assessment if required. This set of outcomes and measurement tools will facilitate the implementation of the use of patient-centred outcomes in daily practice.

Computed tomography coronary angiography in non-ST-segment elevation myocardial infarction.

Electrocardiography and high-sensitivity cardiac troponin testing are routinely applied as the initial step for clinical evaluation of patients with suspected non-ST-segment elevation myocardial infarction. Once diagnosed, patients with non-ST-segment elevation myocardial infarction are commenced on antithrombotic and secondary preventative therapies before undergoing invasive coronary angiography to determine the strategy of coronary revascularisation. However, this clinical pathway is imperfect and can lead to challenges in the diagnosis, management, and clinical outcomes of these patients. Computed tomography coronary angiography (CTCA) has increasingly been utilised in the setting of patients with suspected non-ST-segment elevation myocardial infarction, where it has an important role in avoiding unnecessary invasive coronary angiography and reducing downstream non-invasive functional testing for myocardial ischaemia. CTCA is an excellent gatekeeper for the cardiac catheterisation laboratory. In addition, CTCA provides complementary information for patients with myocardial infarction in the absence of obstructive coronary artery disease and highlights alternative or incidental diagnoses for those with cardiac troponin elevation. However, the routine application of CTCA has yet to demonstrate an impact on subsequent major adverse cardiovascular events. There are several ongoing studies evaluating CTCA and its associated technologies that will define and potentially expand its application in patients with suspected or diagnosed non-ST-segment elevation myocardial infarction. We here review the current evidence relating to the clinical application of CTCA in patients with non-ST-segment elevation myocardial infarction and highlight the areas where CTCA is likely to have an increasing important role and impact for our patients.

Comorbid depressive symptoms can aggravate the functional changes of the pain matrix in patients with chronic back pain: A resting-state fMRI study.

Objective: The purposes of this study are to explore (1) whether comorbid depressive symptoms in patients with chronic back pain (CBP) affect the pain matrix. And (2) whether the interaction of depression and CBP exacerbates impaired brain function. Methods: Thirty-two patients with CBP without comorbid depressive symptoms and thirty patients with CBP with comorbid depressive symptoms were recruited. All subjects underwent functional magnetic resonance imaging (fMRI) scans. The graph theory analysis, mediation analysis, and functional connectivity (FC) analysis were included in this study. All subjects received the detection of clinical depressive symptoms and pain-related manifestations. Result: Compared with the CBP group, subjects in the CBP with comorbid depressive symptoms (CBP-D) group had significantly increased FC in the left medial prefrontal cortex and several parietal cortical regions. The results of the graph theory analyses showed that the area under the curve of small-world property (t = -2.175, p = 0.034), gamma (t = -2.332, p = 0.023), and local efficiency (t = -2.461, p = 0.017) in the CBP-D group were significantly lower. The nodal efficiency in the ventral posterior insula (VPI) (t = -3.581, p = 0.0007), and the network efficiency values (t = -2.758, p = 0.008) in the pain matrix were significantly lower in the CBP-D group. Both the topological properties and the FC values of these brain regions were significantly correlated with self-rating depression scale (SDS) scores (all FDR corrected) but not with pain intensity. Further mediation analyses demonstrated that pain intensity had a mediating effect on the relationship between SDS scores and Pain Disability Index scores. Likewise, the SDS scores mediated the relationship between pain intensity and PDI scores. Conclusion: Our study found that comorbid depressive symptoms can aggravate the impairment of pain matrix function of CBP, but this impairment cannot directly lead to the increase of pain intensity, which may be because some brain regions of the pain matrix are the common neural basis of depression and CBP.

Association of Dietary Fish and n-3 Unsaturated Fatty Acid Consumption with Diabetic Nephropathy from a District Hospital in Northern Taiwan.

Nephropathy caused by diabetes mellitus (DM) is the main cause of end-stage renal disease (ESRD). To understand the association of dietary intake with renal function indicators among patients with diabetic nephropathy (DN), this cross-sectional study was conducted at the dietetic consultation clinic of the Taoyuan Armed Forces General Hospital in Taiwan. In total, 317 participants were recruited for this study. Patients with diabetes who had a urinary albumin-creatinine ratio (UACR) of ≥30 mg/g were defined as having DN. The anthropometric characteristics, blood biochemistry, and renal function of the participants were assessed. Furthermore, a semiquantitative food frequency questionnaire (SQFFQ) was administered to investigate the dietary intake of the participants in the DM and DN groups. The result showed that participants in the DN group were older, had longer diabetes duration and poorer glycemic control and renal function than those in the DM group. Logistic regression models revealed that intake of high-fat marine fishes had the lowest odds ratio (OR) for DN risk compared with other fishes (OR: 0.868; 95% CI: 0.781-0.965, p = 0.009). Shellfish, soybean products, and skim milk also provided better protective effects to decrease the risk of DN. A further analysis of polyunsaturated fatty acids revealed that Σn-3 PUFAs significantly reduced DN risk, while Σn-6 PUFAs did not, especially EPA (OR: 0.821; 95% CI: 0.688-0.979, p = 0.029) and DHA (OR: 0.903; 95% CI: 0.823-0.992, p = 0.033) regardless of whether the variables were adjusted, including diabetes duration, age, and HbA1c. Our findings suggest that a diet that incorporates high-fat fish, shellfish, soybean products, and a lower Σn-6/Σn-3 ratio can mitigate DN risk.

Trends in all-cause mortality among people with diagnosed diabetes in high-income settings: a multicountry analysis of aggregate data.

BACKGROUND: Population-level trends in mortality among people with diabetes are inadequately described. We aimed to examine the magnitude and trends in excess all-cause mortality in people with diabetes. METHODS: In this retrospective, multicountry analysis, we collected aggregate data from 19 data sources in 16 high-income countries or jurisdictions (in six data sources in Asia, eight in Europe, one from Australia, and four from North America) for the period from Jan 1, 1995, to Dec 31, 2016, (or a subset of this period) on all-cause mortality in people with diagnosed total or type 2 diabetes. We collected data from administrative sources, health insurance records, registries, and a health survey. We estimated excess mortality using the standardised mortality ratio (SMR). FINDINGS: In our dataset, there were approximately 21 million deaths during 0·5 billion person-years of follow-up among people with diagnosed diabetes. 17 of 19 data sources showed decreases in the age-standardised and sex-standardised mortality in people with diabetes, among which the annual percentage change in mortality ranged from -0·5% (95% CI -0·7 to -0·3) in Hungary to -4·2% (-4·3 to -4·1) in Hong Kong. The largest decreases in mortality were observed in east and southeast Asia, with a change of -4·2% (95% CI -4·3 to -4·1) in Hong Kong, -4·0% (-4·8 to -3·2) in South Korea, -3·5% (-4·0 to -3·0) in Taiwan, and -3·6% (-4·2 to -2·9) in Singapore. The annual estimated change in SMR between people with and without diabetes ranged from -3·0% (95% CI -3·0 to -2·9; US Medicare) to 1·6% (1·4 to 1·7; Lombardy, Italy). Among the 17 data sources with decreasing mortality among people with diabetes, we found a significant SMR increase in five data sources, no significant SMR change in four data sources, and a significant SMR decrease in eight data sources. INTERPRETATION: All-cause mortality in diabetes has decreased in most of the high-income countries we assessed. In eight of 19 data sources analysed, mortality decreased more rapidly in people with diabetes than in those without diabetes. Further longevity gains will require continued improvement in prevention and management of diabetes. FUNDING: US Centers for Disease Control and Prevention, Diabetes Australia Research Program, and Victoria State Government Operational Infrastructure Support Program.

Attention Bias to Pain Words Comes Early and Cognitive Load Matters: Evidence from an ERP Study on Experimental Pain.

Attention bias (AB) is a common cognitive challenge for patients with pain. In this study, we tested at what stage AB to pain occurs in participants with experimental pain (EP) and tested whether cognitive load interferes with it. We recruited 40 healthy adults aged 18-27 years, and randomized them into control and EP groups. We sprayed the participants in the EP group with 10% capsaicin paste to mimic acute pain and those in the control group with water, accessing both groups' behavioral results and event-related potential data. We found that high-load tasks had longer response times and lower accuracies than low-load tasks did and that different neural processing of words occurred between the groups. The EP group exhibited AB to pain at an early stage with both attentional avoidance (N1 latency) and facilitated attention (P2 amplitude) to pain words. The control group coped with semantic differentiation (N1) at first, followed by pain word discrimination (P2). In addition, AB to pain occurred only in low-load tasks. As the cognitive load multiplied, we did not find AB in the EP group. Therefore, our study adds further evidence for AB to pain, suggesting the implementation of cognitive load in future AB therapy.

Effect of Low-Frequency Repetitive Transcranial Magnetic Stimulation on Executive Function and Its Neural Mechanism: An Event-Related Potential Study.

Objective: Executive function refers to the conscious control of thinking and behavior in psychological process. Executive dysfunction widely exists in a variety of neuropsychiatric diseases, and is closely related to the decline of daily living ability and function. This study intends to explore the effect of low-frequency repetitive transcranial magnetic stimulation (rTMS) on executive function and its neural mechanism by using event-related potential (ERP), so as to provide basis for further study on the relationship between cerebral cortex and executive function. Methods: Task switching paradigm was used to study the cognitive flexibility in executive function. Thirty-one healthy subjects were randomly assigned to receive rTMS stimulations (1 Hz rTMS or sham rTMS) to the left dorsolateral prefrontal cortex (DLPFC) twice. The switching task and the electroencephalography EEG recordings were performed before (pre-rTMS/pre-sham rTMS) and immediately after the end of the rTMS application (post-rTMS/post-sham rTMS). Results: The analysis of RTs showed that the main effects of switching and time were statistically significant. Further analysis revealed that the RT of rTMS stimulation was longer than sham rTMS at post-stimulation. ERP analysis showed that there was a significant switching effect in frontal and central scalp location, and the P2 amplitude in switch trials was greater than that in non-switch trials. At post-stimulation, the N2 amplitude of rTMS is more negative than that of sham rTMS at non-switch trials, whereas no such difference was found at switch trials. The P3 amplitude and LPC amplitude are significantly reduced by rTMS at post-stimulation. Conclusion: Low-frequency rTMS of the left DLPFC can cause decline of cognitive flexibility in executive function, resulting in the change of N2 amplitude and the decrease of P3 and LPC components during task switching, which is of positive significance for the evaluation and treatment of executive function.