6-month consequences of COVID-19 in patients discharged from hospital: a cohort study.

BACKGROUND: The long-term health consequences of COVID-19 remain largely unclear. The aim of this study was to describe the long-term health consequences of patients with COVID-19 who have been discharged from hospital and investigate the associated risk factors, in particular disease severity. METHODS: We did an ambidirectional cohort study of patients with confirmed COVID-19 who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7 and May 29, 2020. Patients who died before follow-up; patients for whom follow-up would be difficult because of psychotic disorders, dementia, or readmission to hospital; those who were unable to move freely due to concomitant osteoarthropathy or immobile before or after discharge due to diseases such as stroke or pulmonary embolism; those who declined to participate; those who could not be contacted; and those living outside of Wuhan or in nursing or welfare homes were all excluded. All patients were interviewed with a series of questionnaires for evaluation of symptoms and health-related quality of life, underwent physical examinations and a 6-min walking test, and received blood tests. A stratified sampling procedure was used to sample patients according to their highest seven-category scale during their hospital stay as 3, 4, and 5-6, to receive pulmonary function test, high resolution CT of the chest, and ultrasonography. Enrolled patients who had participated in the Lopinavir Trial for Suppression of SARS-CoV-2 in China received SARS-CoV-2 antibody tests. Multivariable adjusted linear or logistic regression models were used to evaluate the association between disease severity and long-term health consequences. FINDINGS: In total, 1733 of 2469 discharged patients with COVID-19 were enrolled after 736 were excluded. Patients had a median age of 57·0 years (IQR 47·0-65·0) and 897 (52%) were male and 836 (48%) were female. The follow-up study was done from June 16 to Sept 3, 2020, and the median follow-up time after symptom onset was 186·0 days (175·0-199·0). Fatigue or muscle weakness (52%, 855 of 1654) and sleep difficulties (26%, 437 of 1655) were the most common symptoms. Anxiety or depression was reported among 23% (367 of 1616) of patients. The proportions of 6-min walking distance less than the lower limit of the normal range were 17% for those at severity scale 3, 13% for severity scale 4, and 28% for severity scale 5-6. The corresponding proportions of patients with diffusion impairment were 22% for severity scale 3, 29% for scale 4, and 56% for scale 5-6, and median CT scores were 3·0 (IQR 2·0-5·0) for severity scale 3, 4·0 (3·0-5·0) for scale 4, and 5·0 (4·0-6·0) for scale 5-6. After multivariable adjustment, patients showed an odds ratio (OR) of 1·61 (95% CI 0·80-3·25) for scale 4 versus scale 3 and 4·60 (1·85-11·48) for scale 5-6 versus scale 3 for diffusion impairment; OR 0·88 (0·66-1·17) for scale 4 versus scale 3 and OR 1·76 (1·05-2·96) for scale 5-6 versus scale 3 for anxiety or depression, and OR 0·87 (0·68-1·11) for scale 4 versus scale 3 and 2·75 (1·61-4·69) for scale 5-6 versus scale 3 for fatigue or muscle weakness. Of 94 patients with blood antibodies tested at follow-up, the seropositivity (96·2% vs 58·5%) and median titres (19·0 vs 10·0) of the neutralising antibodies were significantly lower compared with at the acute phase. 107 of 822 participants without acute kidney injury and with an estimated glomerular filtration rate (eGFR) of 90 mL/min per 1·73 m2 or more at acute phase had eGFR less than 90 mL/min per 1·73 m2 at follow-up. INTERPRETATION: At 6 months after acute infection, COVID-19 survivors were mainly troubled with fatigue or muscle weakness, sleep difficulties, and anxiety or depression. Patients who were more severely ill during their hospital stay had more severe impaired pulmonary diffusion capacities and abnormal chest imaging manifestations, and are the main target population for intervention of long-term recovery. FUNDING: National Natural Science Foundation of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, and Peking Union Medical College Foundation.

Gestational diabetes mellitus is associated with greater incidence of dementia during long-term post-partum follow-up.

BACKGROUND: The impact of gestational diabetes mellitus (GDM) on incident dementia is unknown. Our aim was to evaluate the relationship between GDM and all-cause dementia and the mediating effects of chronic diseases on this relationship. METHODS: This prospective cohort study included women from the UK Biobank who were grouped based on GDM history. Multivariate Cox proportional hazard models were used to explore the associations between GDM and dementia. We further analysed the mediating effects of chronic diseases on this relationship and the interactions of covariates. RESULTS: A total of 1292 women with and 204,171 women without a history of GDM were included. During a median follow-up period of 45 years after first birth, 2921 women were diagnosed with dementia. Women with a GDM history had a 67% increased risk of incident dementia (hazard ratio 1.67, 95% confidence interval: 1.03-2.69) compared with those without a GDM history. According to mediation analyses, type 2 diabetes, coronary heart disease, chronic kidney disease and comorbidities (diagnosed with any two of the three diseases) explained 34.5%, 8.4%, 5.2% and 18.8% of the mediating effect on the relationship. Subgroup analyses revealed that physical activity modified the association between GDM history and dementia (p for interaction = 0.030). Among physically inactive women, GDM was significantly associated with incident dementia; however, this association was not observed among physically active women. CONCLUSIONS: A history of GDM was associated with a greater risk of incident dementia. Type 2 diabetes partially mediated this relationship. Strategies for dementia prevention might be considered for women with a history of GDM.

Nonparametric receiver operating characteristic curve analysis with an imperfect gold standard.

This article addresses the challenge of estimating receiver operating characteristic (ROC) curves and the areas under these curves (AUC) in the context of an imperfect gold standard, a common issue in diagnostic accuracy studies. We delve into the nonparametric identification and estimation of ROC curves and AUCs when the reference standard for disease status is prone to error. Our approach hinges on the known or estimable accuracy of this imperfect reference standard and the conditional independent assumption, under which we demonstrate the identifiability of ROC curves and propose a nonparametric estimation method. In cases where the accuracy of the imperfect reference standard remains unknown, we establish that while ROC curves are unidentifiable, the sign of the difference between two AUCs is identifiable. This insight leads us to develop a hypothesis-testing method for assessing the relative superiority of AUCs. Compared to the existing methods, the proposed methods are nonparametric so that they do not rely on the parametric model assumptions. In addition, they are applicable to both the ROC/AUC analysis of continuous biomarkers and the AUC analysis of ordinal biomarkers. Our theoretical results and simulation studies validate the proposed methods, which we further illustrate through application in two real-world diagnostic studies.

Association of Cardiovascular Health With Risk of Incident Depression and Anxiety.

OBJECTIVE: To investigate the association between cardiovascular health (CVH), defined by the American Heart Association's Life's Essential 8 (LE8) score, and incident depression and anxiety. DESIGN: A prospective cohort study using data from UK Biobank. SETTING: Participants were enrolled from March 2006 to October 2010. PARTICIPANTS: Participants without cardiovascular diseases and common mental disorders at baseline and having complete data on metrics of LE8 were included. MEASUREMENTS: CVH was assessed by LE8 score including eight components. The overall CVH was categorized as low (LE8 score <50), moderate (50≤ LE8 score <80), and high (LE8 score ≥80). RESULTS: We included 115,855 participants (mean age: 55.7 years; female: 52.6%). During a median follow-up of 12.4 years, 3,194 (2.8%) and 4,005 (3.5%) participants had incident depression and anxiety, respectively. Compared with participants having low CVH, those having moderate and high CVH had 37% (HR = 0.63, 95% CI: 0.57-0.70) and 52% (HR = 0.48, 95% CI: 0.41-0.55) lower risk of incident depression. Similarly, moderate and high CVH were related to a lower risk of incident anxiety (HR = 0.81, 95% CI: 0.73-0.89 and HR = 0.68, 95% CI: 0.60-0.78). Restricted cubic spline showed that LE8 score was inversely related to incident depression and anxiety in a linear manner, and the risk of incident depression and anxiety decreased by 17% (HR = 0.83, 95% CI: 0.80-0.85) and 10% (HR = 0.90, 95% CI: 0.88-0.92) for 10-point increment in LE8 score, respectively. CONCLUSIONS: Higher CVH, evaluated by LE8 score, is strongly associated with a lower risk of incident depression and anxiety, suggesting the significance of optimizing CVH by adopting LE8.

Real-world effectiveness of nirmatrelvir-ritonavir versus azvudine in hospitalized patients with COVID-19 during the omicron wave in Beijing: a multicenter retrospective cohort study.

BACKGROUND AND AIM: Two oral antivirals (Nirmatrelvir- ritonavir and Azvudine) are widely used in China practice during the Omicron wave of the pandemic. However, little evidence regarding the real-world effectiveness of these two oral antivirals in in-hospital patients. We aimed to evaluate the clinical effectiveness of nirmatrelvir-ritonavir versus azvudine among adult hospitalized patients with COVID-19. METHODS: This retrospective cohort study used data from three Chinese PLA General Hospital medical centres. Hospitalized patients with COVID-19 treated with azvudine or nirmatrelvir-ritonavir from Dec 10, 2022, to February 20, 2023, and did not require invasive ventilation support on admission were eligible for inclusion. RESULTS: After exclusions and propensity-score matching, the final analysis included 486 azvudine recipients and 486 nirmatrelvir-ritonavir recipients. By 28 days of initiation of the antivirus treatment, the crude incidence rate of all-cause death was similar in both types of antivirus treatment (nirmatrelvir-ritonavir group 2.8 events 1000 person-days [95% CI, 2.1-3.6] vs azvudine group 3.4 events/1000 person-days [95% CI, 2.6-4.3], P = 0.38). Landmark analysis showed that all-cause death was lower in the nirmatrelvir-ritonavir (3.5%) group than the azvudine (6.8%, P = 0.029) within the initial 10-day admission period, while no significant difference was observed for results between 10 and 28 days follow-up. There was no significant difference between the nirmatrelvir-ritonavir group and the azvudine group in cumulative incidence of the composite disease progression event (8.6% with nirmatrelvir-ritonavir vs. 10.1% with azvudine, HR, 1.22; 95% CI 0.80-1.86, P = 0.43). CONCLUSION: Among patients hospitalized with COVID-19 during the omicron wave in Beijing, similar in-hospital clinical outcomes on 28 days were observed between patients receiving nirmatrelvir-ritonavir and azvudine. However, it is worth noticing that nirmatrelvir-ritonavir appears to hold an advantage over azvudine in reducing early mortality. Further randomized controlled trials are needed to verify the efficacy of those two antivirus medications especially in early treatment.

Low-dose IL-2 therapy invigorates CD8+ T cells for viral control in systemic lupus erythematosus.

Autoimmune diseases are often treated by glucocorticoids and immunosuppressive drugs that could increase the risk for infection, which in turn deteriorate disease and cause mortality. Low-dose IL-2 (Ld-IL2) therapy emerges as a new treatment for a wide range of autoimmune diseases. To examine its influence on infection, we retrospectively studied 665 patients with systemic lupus erythematosus (SLE) including about one third receiving Ld-IL2 therapy, where Ld-IL2 therapy was found beneficial in reducing the incidence of infections. In line with this clinical observation, IL-2 treatment accelerated viral clearance in mice infected with influenza A virus or lymphocytic choriomeningitis virus (LCMV). Noticeably, despite enhancing anti-viral immunity in LCMV infection, IL-2 treatment exacerbated CD8+ T cell-mediated immunopathology. In summary, Ld-IL2 therapy reduced the risk of infections in SLE patients and enhanced the control of viral infection, but caution should be taken to avoid potential CD8+ T cell-mediated immunopathology.

Sex differences in changes of depressive symptoms among older adults before and during the COVID-19 pandemic: evidence from two longitudinal cohorts.

BACKGROUND: Major concerns about the adverse mental health impact of the rapidly spread COVID-19 pandemic have been raised. Previous studies on changes of depressive symptoms during the COVID-19 pandemic have yielded inconsistent results regarding the sex differences. Since women have higher depressive symptoms even without the pandemic, it is essential to consider the pre-existing change of depressive symptoms of a similar period to discern the effect of the pandemic on depression. This study aimed to evaluate sex differences in depressive symptoms before and during the pandemic. METHODS: Data from the Health and Retirement Study (HRS; waves 13 to 15) and the English Longitudinal Study of Ageing (ELSA; wave 8 to COVID-19 wave 2) were analyzed. Depressive symptoms were assessed by the 8-item Center for Epidemiological Studies Depression (CES-D) scale. According to the time of COVID-19 outbreak in the US and the UK, the intervals from waves 13 to 14 surveys of the HRS and from waves 8 to 9 surveys of the ELSA were employed as pre-pandemic periods to control for the pre-existing depressive symptoms, respectively. Changes of CES-D scores during the pre-pandemic and pandemic periods were assessed by linear mixed models. RESULTS: Nine thousand, seven hundred thirty-seven participants (mean age: 66.7 ± 10.7 years) from the HRS and 5,098 participants (mean age: 68.7 ± 10.0 years) from the ELSA were included. CES-D scores among women were significantly higher than those among men at all waves in both cohorts. During the pre-pandemic period, no significant sex difference on changes of CES-D scores was detected in either the HRS or the ELSA. During the pandemic period, CES-D scores were increased in both men and women and the sex differences in CES-D increments of the two cohorts were both significant. Enlarged sex differences were demonstrated in increments of CES-D scores during the pandemic period. CONCLUSIONS: Our results suggest women suffered from worse depressive symptoms in response to the pandemic, although the changes of depression were similar between men and women before the pandemic. These findings underscore the necessity to support the vulnerable populations, especially women, to manage the distress brought by the pandemic and maintain optimal mental health status.

6-month consequences of COVID-19 in patients discharged from hospital: a cohort study.

BACKGROUND: The long-term health consequences of COVID-19 remain largely unclear. The aim of this study was to describe the long-term health consequences of patients with COVID-19 who have been discharged from hospital and investigate the associated risk factors, in particular disease severity. METHODS: We did an ambidirectional cohort study of patients with confirmed COVID-19 who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7, 2020, and May 29, 2020. Patients who died before follow-up, patients for whom follow-up would be difficult because of psychotic disorders, dementia, or re-admission to hospital, those who were unable to move freely due to concomitant osteoarthropathy or immobile before or after discharge due to diseases such as stroke or pulmonary embolism, those who declined to participate, those who could not be contacted, and those living outside of Wuhan or in nursing or welfare homes were all excluded. All patients were interviewed with a series of questionnaires for evaluation of symptoms and health-related quality of life, underwent physical examinations and a 6-min walking test, and received blood tests. A stratified sampling procedure was used to sample patients according to their highest seven-category scale during their hospital stay as 3, 4, and 5-6, to receive pulmonary function test, high resolution CT of the chest, and ultrasonography. Enrolled patients who had participated in the Lopinavir Trial for Suppression of SARS-CoV-2 in China received severe acute respiratory syndrome coronavirus 2 antibody tests. Multivariable adjusted linear or logistic regression models were used to evaluate the association between disease severity and long-term health consequences. FINDINGS: In total, 1733 of 2469 discharged patients with COVID-19 were enrolled after 736 were excluded. Patients had a median age of 57·0 (IQR 47·0-65·0) years and 897 (52%) were men. The follow-up study was done from June 16, to Sept 3, 2020, and the median follow-up time after symptom onset was 186·0 (175·0-199·0) days. Fatigue or muscle weakness (63%, 1038 of 1655) and sleep difficulties (26%, 437 of 1655) were the most common symptoms. Anxiety or depression was reported among 23% (367 of 1617) of patients. The proportions of median 6-min walking distance less than the lower limit of the normal range were 24% for those at severity scale 3, 22% for severity scale 4, and 29% for severity scale 5-6. The corresponding proportions of patients with diffusion impairment were 22% for severity scale 3, 29% for scale 4, and 56% for scale 5-6, and median CT scores were 3·0 (IQR 2·0-5·0) for severity scale 3, 4·0 (3·0-5·0) for scale 4, and 5·0 (4·0-6·0) for scale 5-6. After multivariable adjustment, patients showed an odds ratio (OR) 1·61 (95% CI 0·80-3·25) for scale 4 versus scale 3 and 4·60 (1·85-11·48) for scale 5-6 versus scale 3 for diffusion impairment; OR 0·88 (0·66-1·17) for scale 4 versus scale 3 and OR 1·77 (1·05-2·97) for scale 5-6 versus scale 3 for anxiety or depression, and OR 0·74 (0·58-0·96) for scale 4 versus scale 3 and 2·69 (1·46-4·96) for scale 5-6 versus scale 3 for fatigue or muscle weakness. Of 94 patients with blood antibodies tested at follow-up, the seropositivity (96·2% vs 58·5%) and median titres (19·0 vs 10·0) of the neutralising antibodies were significantly lower compared with at the acute phase. 107 of 822 participants without acute kidney injury and with estimated glomerular filtration rate (eGFR) 90 mL/min per 1·73 m2 or more at acute phase had eGFR less than 90 mL/min per 1·73 m2 at follow-up. INTERPRETATION: At 6 months after acute infection, COVID-19 survivors were mainly troubled with fatigue or muscle weakness, sleep difficulties, and anxiety or depression. Patients who were more severely ill during their hospital stay had more severe impaired pulmonary diffusion capacities and abnormal chest imaging manifestations, and are the main target population for intervention of long-term recovery. FUNDING: National Natural Science Foundation of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, and Peking Union Medical College Foundation.

Long-term physical activity participation trajectories were associated with subsequent cognitive decline, risk of dementia and all-cause mortality among adults aged ≥50 years: a population-based cohort study.

AIM: to evaluate self-reported physical activity (PA) participation trajectories over a 6-year span and to assess associations with subsequent cognitive decline, incident dementia and all-cause mortality. METHODS: population-based cohort of 8,842 community-dwelling adults aged ≥50 years in England. Group-based trajectory modelling was used to identify 6-year trajectories of PA participation. Cognitive decline, incident dementia and all-cause mortality were outcomes. RESULTS: five trajectories were identified, including persistently low (N = 2,511), initially low then improving (1,651), initially high then declining (249), persistently moderate (2,422) and persistently high (2,009). Compared with persistently low, participants of initially low then improving and persistently high PA participation experienced decelerated global cognitive decline of 0.012 standard deviation (SD)/year (95% confidence interval [CI]: 0.004-0.021, P = 0.004) and 0.021 SD/year (95% CI: 0.013-0.029, P < 0.001). They were also associated with lower dementia risk, with multivariate-adjusted hazard ratios (HRs) of 0.43 (95% CI: 0.31-0.60) and 0.35 (95% CI: 0.27-0.45). A similar pattern was observed for all-cause mortality, with HRs of 0.31 (95% CI: 0.13-0.74) and 0.25 (95% CI: 0.14-0.45). No significant differences were observed between persistently low and initially high then declining trajectories. CONCLUSION: for middle-aged and older adults, both gradually improved and persistently active PA participation were associated with decelerated cognitive decline, lower risk of dementia and all-cause mortality. Strategies focusing on improving and maintaining PA participation could be of significance by attaining considerable neurocognitive and longevity benefits.

Trajectories of depressive symptoms and subsequent cognitive decline in older adults: a pooled analysis of two longitudinal cohorts.

BACKGROUND: the course of depression is variable, but it is unknown how this variability over time affects long-term cognitive decline. OBJECTIVE: to examine the relationship of different trajectories of depressive symptoms on rates of subsequent cognitive decline in older adults. DESIGN: population-based cohort study. SETTING: communities in the USA and England. SUBJECTS: 17,556 older adults from the Health and Retirement Study and the English Longitudinal Study of Ageing. METHODS: depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale, and trajectories were calculated using group-based trajectory modelling. Global cognitive function and three cognitive domains of memory, executive function and temporal orientation were assessed for up to 18 years. RESULTS: five trajectories of depressive symptoms were identified. Compared with the 'non-depressed' trajectory, the 'worsening depressive symptoms' trajectory (pooled ß = -0.016 standard deviation (SD)/year, 95% confidence interval (CI): -0.021 to -0.010), 'persistent depressive symptoms' trajectory (pooled ß = -0.016 SD/year, 95% CI: -0.024 to -0.008), and 'mild depressive symptoms' trajectory (pooled ß = -0.008 SD/year, 95% CI: -0.014 to -0.003) were associated with faster rates of cognitive decline, while no such association was found for the 'improving depressive symptoms' trajectory (pooled ß = 0.001 SD/year, 95% CI: -0.010 to 0.012). CONCLUSIONS: subthreshold depressive symptoms are associated with an increased rate of cognitive decline, while individuals who show improving depressive symptoms do not exhibit accelerated cognitive decline. These findings raise the possibility that maintaining depressive symptoms as low as possible and ignoring the clinical threshold, might mitigate cognitive decline in older adults.

Development and validation of a deep learning algorithm based on fundus photographs for estimating the CAIDE dementia risk score.

BACKGROUND: the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) dementia risk score is a recognised tool for dementia risk stratification. However, its application is limited due to the requirements for multidimensional information and fasting blood draw. Consequently, an effective and non-invasive tool for screening individuals with high dementia risk in large population-based settings is urgently needed. METHODS: a deep learning algorithm based on fundus photographs for estimating the CAIDE dementia risk score was developed and internally validated by a medical check-up dataset included 271,864 participants in 19 province-level administrative regions of China, and externally validated based on an independent dataset included 20,690 check-up participants in Beijing. The performance for identifying individuals with high dementia risk (CAIDE dementia risk score ≥ 10 points) was evaluated by area under the receiver operating curve (AUC) with 95% confidence interval (CI). RESULTS: the algorithm achieved an AUC of 0.944 (95% CI: 0.939-0.950) in the internal validation group and 0.926 (95% CI: 0.913-0.939) in the external group, respectively. Besides, the estimated CAIDE dementia risk score derived from the algorithm was significantly associated with both comprehensive cognitive function and specific cognitive domains. CONCLUSIONS: this algorithm trained via fundus photographs could well identify individuals with high dementia risk in a population setting. Therefore, it has the potential to be utilised as a non-invasive and more expedient method for dementia risk stratification. It might also be adopted in dementia clinical trials, incorporated as inclusion criteria to efficiently select eligible participants.

Effects of group mindfulness-based cognitive therapy and group cognitive behavioural therapy on symptomatic generalized anxiety disorder: a randomized controlled noninferiority trial.

BACKGROUND: Mindfulness-based cognitive therapy (MBCT) is a promising alternative treatment for generalized anxiety disorder (GAD). The objective of this study was to examine whether the efficacy of group MBCT adapted for treating GAD (MBCT-A) was noninferior to group cognitive behavioural therapy (CBT) designed to treat GAD (CBT-A), which was considered one of first-line treatments for GAD patients. We also explored the efficacy of MBCT-A in symptomatic GAD patients compared with CBT-A for a variety of outcomes of anxiety symptoms, as well as depressive symptoms, overall illness severity, quality of life and mindfulness. METHODS: This was a randomized, controlled, noninferiority trial with two arms involving symptomatic GAD patients. Adult patients with GAD (n = 138) were randomized to MBCT-A or CBT-A in addition to treatment as usual (TAU). The primary outcome was the anxiety response rate assessed at 8 weeks after treatment as measured using the Hamilton Anxiety Scale (HAMA). Secondary outcomes included anxiety remission rates, scores on the HAMA, the state-trait anxiety inventory (STAI), the Hamilton Depression Scale (HAMD), the Severity Subscale of the Clinical Global Impression Scale (CGI-S), and the 12-item Short-Form Health Survey (SF-12), as well as mindfulness, which was measured by the Five Facet Mindfulness Questionnaire (FFMQ). Assessments were performed at baseline, 8 weeks after treatment, and 3 months after treatment. Both intention-to-treat (ITT) and per-protocol (PP) analyses were performed for primary analyses. The χ2 test and separate two-way mixed ANOVAs were used for the secondary analyses. RESULTS: ITT and PP analyses showed noninferiority of MBCT-A compared with CBT-A for response rate [ITT rate difference = 7.25% (95% CI: -8.16, 22.65); PP rate difference = 5.85% (95% CI: - 7.83, 19.53)]. The anxiety remission rate, overall illness severity and mindfulness were significantly different between the two groups at 8 weeks. There were no significant differences between the two groups at the 3-month follow-up. No severe adverse events were identified. CONCLUSIONS: Our data indicate that MBCT-A was noninferior to CBT-A in reducing anxiety symptoms in GAD patients. Both interventions appeared to be effective for long-term benefits. TRIAL REGISTRATION: Registered at chictr.org.cn (registration number: ChiCTR1800019150 , registration date: 27/10/2018).

Dose-Response Relationship Between Long-Term Blood Pressure Variability and Cognitive Decline.

Background and Purpose: We aimed to test whether higher long-term blood pressure variability was associated with accelerated rate of cognitive decline and evaluate potential dose-response relationship. Methods: Original survey data from the Health and Retirement Study and the English Longitudinal Study of Ageing were used. Standardized Z score of cognitive function was the main outcome measure. Visit-to-visit blood pressure SD, coefficient of variation, and variation independent of mean were used. Linear mixed model and restricted spline were applied to assess association and explore dose-response pattern. Segmented regression was used to analyze dose-response relationship and estimate turning point. Meta-analysis using random-effects model was conducted to pool results, with I2 used to test heterogeneity. Results: A total of 12 298 dementia-free participants were included (mean age: 64.6±8.6 years). Significant association was observed between blood pressure variability and cognitive decline. Each 10% increment in coefficient of variation of systolic and diastolic blood pressure was associated with accelerated global cognitive decline of 0.026 SD/y (95% CI, 0.016­0.036, P<0.001) and 0.022 SD/y (95% CI, 0.017­0.027, P<0.001), respectively. Nonlinear dose-response relationship was found (P<0.001 for nonlinearity), with clear turning point observed (P<0.001 for change in slopes). Conclusions: Higher long-term blood pressure variability was associated with accelerated cognitive decline among general adults aged ≥50 years, with nonlinear dose-response relationship. Further randomized controlled trials are warranted to evaluate potential benefits of blood pressure variability-lowering strategies from a cognitive health perspective.

Different hypertension thresholds and cognitive decline: a pooled analysis of three ageing cohorts.

BACKGROUND: The 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for high blood pressure (BP) in adults came up with a new definition of hypertension with a threshold BP level of 130/80 mmHg. But the 2018 European Society of Cardiology (ESC)/European Society of Hypertension (ESH) guidelines adhered to a conventional hypertension definition as BP ≥ 140/90 mmHg. We aimed to compare the trajectories of cognitive decline between participants with BP < 130/80 mmHg in all BP measurement waves and others with all BP < 140/90 mmHg. METHODS: This pooled analysis involved middle-aged and older participants from three nationally representative ageing cohorts, including the Health and Retirement Study (HRS), the English Longitudinal Study of Ageing (ELSA), and the China Health Retirement Longitudinal Study (CHARLS). Participants were divided into the Normal (BP < 130/80 mmHg on all occasions throughout the study), the Borderline (BP < 140/90 mmHg on all occasions throughout the study but not in the Normal group), and the High (the rest of participants) BP groups. Global cognitive Z score was calculated from tests on memory, executive function, and orientation. RESULTS: A total of 17,590 participants (HRS 6964, median follow-ups 12 years; ELSA 5334, median follow-ups 16 years; CHARLS 5292, median follow-ups 7 years) were included. No significant difference in global cognitive decline rate was detected between the Normal and the borderline groups (men, pooled ß = - 0.006 standard deviation [SD]/year; 95% confidence interval [CI], - 0.020 to 0.008; P = 0.377; women, pooled ß = 0.006 SD/year; 95% CI - 0.005 to 0.018; P = 0.269). Participants in the High group had a significantly faster cognitive decline (men, pooled ß = - 0.011 SD/year; 95% CI - 0.020 to - 0.002; P = 0.013; women, pooled ß = - 0.017 SD/year; 95% CI - 0.026 to - 0.008; P < 0.001) than that in the Borderline group. CONCLUSIONS: Individuals in the Borderline group did not experience significantly faster cognitive decline compared with those in the Normal group. It might not be necessary for individuals with borderline BP (between 130/80 and 140/90 mmHg) to initiate antihypertension therapy in consideration of cognitive decline.

Anticardiolipin antibody and anti-ß2 glycoprotein I antibody are potential risk markers of ischaemic stroke in Chinese adults.

OBJECTIVES: aCL and anti-ß2 glycoprotein I antibody (aß2GPI) are autoantibodies associated with thromboembolic diseases. Here we investigated whether they are correlated with ischaemic cardiovascular disease in a Chinese population. METHODS: Serum total aCL and aß2GPI isotypes (IgA, IgG or IgM, separately) were measured in 11 015 Chinese adults. Differences of antibody level between disease and non-disease groups were examined by t-test. The correlation between antibody and ischaemic cardiovascular disease was determined by logistic regression analysis. Performance of risk prediction models employed aCL or aß2GPI isotypes was evaluated by C statistic, net reclassification improvement index and integrated discrimination improvement. RESULTS: Total aCL and aß2GPI isotypes maintained low levels and increased with increasing age except total aCL and aß2GPI IgG in participants older than 70 years. When distinguishing ischaemic cardiovascular disease by coronary heart disease (CHD) and ischaemic stroke, the stroke group had higher levels of aCL and aß2GPI isotypes than the non-stroke group, while the CHD group only had a slightly higher aß2GPI IgG than non-CHD groups. aCL and aß2GPI were positively correlated with stroke but not with CHD, and improved the performance of conventional risk factors for stroke risk prediction, with C statistic from 0.769 (95% CI 0.744, 0.793) to 0.777 (95% CI 0.754, 0.800) (aß2GPI IgG, P = 0.0091), and 0.778 (95% CI 0.754, 0.801) (aß2GPI IgA, P = 0.0793). Stroke risk could be better reclassified by aCL and aß2GPI, in association with both net reclassification improvement and integrated discrimination improvement statistics (P < 0.05). CONCLUSION: aCL and aß2GPI are associated with ischaemic stroke and have added value for stroke risk prediction.

Electroencephalography-Guided Anesthetic Delivery for Preventing Postoperative Delirium in Adults: An Updated Meta-analysis.

BACKGROUND: Postoperative delirium is a major debilitating complication for patients and is associated with poor outcomes. Previous studies have suggested that excessive general anesthesia may lead to postoperative delirium. Electroencephalography (EEG)-based monitors have been administered in clinical practice in an attempt to deliver appropriate anesthesia. The aim of this updated meta-analysis was to evaluate the current body of research concerning the effects of EEG-based monitor on postoperative delirium. METHODS: We conducted a meta-analysis of randomized controlled trials of the effect of processed EEG monitor on postoperative delirium as the primary outcome. The search was performed in CENTRAL, MEDLINE, and EMBASE, with no language restrictions from inception until June 23, 2019. Two independent reviewers screened records and full-text articles for inclusion. Data extraction and risk-of-bias assessment were conducted by 3 independent reviewers. Random-effects models were used to calculate combined-effect estimates. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the quality of evidence. RESULTS: Of 5904 records screened, 5 studies met our inclusion criteria, including 3612 patients. Meta-analysis revealed no significant effect of EEG-based monitors on postoperative delirium (risk ratio [RR], 0.79; 95% confidence interval [CI], 0.60-1.05; I = 73%). The results showed a statistically significant reduction in intensive care unit (ICU) length of stay (3 studies, weight mean difference [WMD] -0.29 days; 95% CI, -0.53 to -0.05) in patients with EEG monitored. EEG-guided anesthesia did not have a statistically significant difference in all-cause mortality (3 studies, RR, 0.63; 95% CI, 0.31-1.29) and hospital length of stay (4 studies, WMD -0.61 days; 95% CI, -1.34 to 0.11). Few studies investigated the effects of EEG-guided anesthesia on perioperative major nonneurological complications and did not come up with promising results. CONCLUSIONS: The current evidence is not sufficient to support the prevention effects of EEG monitor on postoperative delirium. More robustly designed and well-conducted studies with emphasis on this matter are warranted.

Depressive Symptoms in Elderly Chinese Primary Care Patients: Prevalence and Sociodemographic and Clinical Correlates.

OBJECTIVE: To estimate the prevalence of depressive symptoms (depression thereafter) and to identify the sociodemographic and clinical correlates of depression in a sample of elderly patients treated in the primary care setting in Wuhan, China. BACKGROUND: Primary care is an opportune setting for the management of late-life depression in China, but there have been no representative studies on the clinical epidemiology of depression in elderly Chinese primary care patients. METHODS: In total, 752 elderly patients (≥ 65 years) were consecutively recruited from 13 primary care centers in Wuhan, China, and interviewed with a standardized questionnaire. Depression was assessed with the 15-item Geriatric Depression Scale (GDS-15). RESULTS: Of the elderly Chinese primary care patients, 30.6% had depression (GDS-15 ≥ 5). Correlates of depression were an education level of primary school or less (odds ratio [OR]: 1.94, 95% confidence interval [CI]: 1.36-2.77, P < .001), poor financial status (OR: 2.19, 95% CI: 1.16-4.15, P = .016), lack of an exercise habit (OR: 1.40, 95% CI: 1.06-1.74, P = .023), 2 or more chronic medical conditions (OR: 1.90, 95% CI: 1.34-2.69, P < .001), and loneliness (OR: 3.53, 95% CI: 2.46-5.08, P < .001). CONCLUSIONS: Depression is prevalent among elderly Chinese primary care patients, indicating that elderly patients treated in primary care have a high level of need for mental health services in China. There is an urgent need to integrate mental health services into primary health care.

Comparison of vascular-related diseases in their associations with carotid femoral pulse wave velocity: From the Beijing Vascular Disease Patients Evaluation Study (BEST Study).

AIMS: Carotid femoral pulse wave velocity (CF-PWV) is associated with vascular-related diseases. However, this association has rarely been compared in the same study population, which would improve our understanding of the role of these diseases in developing arteriosclerosis. This study was designed to assess arterial function in different vascular-related diseases and the potential interrelationships between these diseases and arteriosclerosis. METHODS: There were 13 798 participants with or without established vascular-related diseases, including hypertension, diabetes, coronary artery disease (CAD), stroke and peripheral artery disease (PAD), enrolled into the study from 2010 to 2016, comprising 6648 males and 7150 females. The odds ratio (OR) of arteriosclerosis (defined as CF-PWV >12 m/s) in associations with the vascular-related diseases was modelled using multivariable logistic regression analyses to adjust for possible confounders. RESULTS: Compared with participants without vascular-related diseases, those presenting the diseases showed a significantly higher prevalence and age- and sex-adjusted OR of arteriosclerosis (all P < .001). After further adjustment for hypertension, the ORs became much smaller and not significant for CAD or stroke. Compared with apparently healthy participants, participants with each of the diseases showed a significantly higher adjusted OR (range: 2.46-3.30, all P < .001); participants with each vascular-related disease only showed much smaller and non-significant ORs, except for hypertension (OR = 2.73, 95% CI: 2.46, 3.04). After further adjustment for hypertension, these ORs became non-significant (range: 0.81-1.36, all P > .05). CONCLUSIONS AND CLINICAL IMPLICATIONS: The associations between arteriosclerosis and diseases other than hypertension were largely explained by the association with hypertension, indicating that hypertension could be the single most important factor that leads to arteriosclerosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT02569268.

HbA1c, diabetes and cognitive decline: the English Longitudinal Study of Ageing.

AIMS/HYPOTHESIS: The aim of the study was to evaluate longitudinal associations between HbA1c levels, diabetes status and subsequent cognitive decline over a 10 year follow-up period. METHODS: Data from wave 2 (2004-2005) to wave 7 (2014-2015) of the English Longitudinal Study of Ageing (ELSA) were analysed. Cognitive function was assessed at baseline (wave 2) and reassessed every 2 years at waves 3-7. Linear mixed models were used to evaluate longitudinal associations. RESULTS: The study comprised 5189 participants (55.1% women, mean age 65.6 ± 9.4 years) with baseline HbA1c levels ranging from 15.9 to 126.3 mmol/mol (3.6-13.7%). The mean follow-up duration was 8.1 ± 2.8 years and the mean number of cognitive assessments was 4.9 ± 1.5. A 1 mmol/mol increment in HbA1c was significantly associated with an increased rate of decline in global cognitive z scores (-0.0009 SD/year, 95% CI -0.0014, -0.0003), memory z scores (-0.0005 SD/year, 95% CI -0.0009, -0.0001) and executive function z scores (-0.0008 SD/year, 95% CI -0.0013, -0.0004) after adjustment for baseline age, sex, total cholesterol, HDL-cholesterol, triacylglycerol, high-sensitivity C-reactive protein, BMI, education, marital status, depressive symptoms, current smoking, alcohol consumption, hypertension, CHD, stroke, chronic lung disease and cancer. Compared with participants with normoglycaemia, the multivariable-adjusted rate of global cognitive decline associated with prediabetes and diabetes was increased by -0.012 SD/year (95% CI -0.022, -0.002) and -0.031 SD/year (95% CI -0.046, -0.015), respectively (p for trend <0.001). Similarly, memory, executive function and orientation z scores showed an increased rate of cognitive decline with diabetes. CONCLUSIONS/INTERPRETATION: Significant longitudinal associations between HbA1c levels, diabetes status and long-term cognitive decline were observed in this study. Future studies are required to determine the effects of maintaining optimal glucose control on the rate of cognitive decline in people with diabetes.

Persistent depressive symptoms and cognitive decline in older adults.

BACKGROUND: Little is known about the effect of persistent depressive symptoms on the trajectory of cognitive decline.AimsWe aimed to investigate the longitudinal association between the duration of depressive symptoms and subsequent cognitive decline over a 10-year follow-up period. METHOD: The English Longitudinal Study of Ageing cohort is a prospective and nationally representative cohort of men and women living in England aged ≥50 years. We examined 7610 participants with two assessments of depressive symptoms at wave 1 (2002-2003) and wave 2 (2004-2005), cognitive data at wave 2 and at least one reassessment of cognitive function (wave 3 to wave 7, 2006-2007 to 2014-2015). RESULTS: The mean age of the 7610 participants was 65.2 ± 10.1 years, and 57.0% were women. Of these, 1157 (15.2%) participants had episodic depressive symptoms and 525 participants (6.9%) had persistent depressive symptoms. Compared with participants without depressive symptoms at wave 1 and wave 2, the multivariable-adjusted rates of global cognitive decline associated with episodic depressive symptoms and persistent depressive symptoms were faster by -0.065 points/year (95% CI -0.129 to -0.000) and -0.141 points/year (95% CI -0.236 to -0.046), respectively (P for trend < 0.001). Similarly, memory, executive and orientation function also declined faster with increasing duration of depressive symptoms (all P for trend < 0.05). CONCLUSIONS: Our results demonstrated that depressive symptoms were significantly associated with subsequent cognitive decline over a 10-year follow-up period. Cumulative exposure of long-term depressive symptoms in elderly individuals could predict accelerated subsequent cognitive decline in a dose-response pattern.Declaration of interestNone.