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Aim Abnormal ankle-brachial index (ABI) is regarded as peripheral artery disease and can be used to predict cardiovascular (CV) outcomes. However, the usefulness of ABI for the prediction of CV outcome in patients with normal ABI is limited. Upstroke time per cardiac cycle (UTCC) is recently reported to be associated with mortality in patients with acute myocardial infarction and the elderly. Therefore, we aimed to evaluate UTCC, left ventricular ejection fraction (LVEF), brachial-ankle pulse wave velocity (baPWV), and ABI for the prediction of mortality in patients with normal ABI. Methods Patients arranged for echocardiographic examinations were enrolled, and 1076 patients with normal ABI were included. ABI, baPWV, and UTCC were measured by an ABI-form device. Results The median follow-up to mortality was 95 months. There were 88 CV and 244 all-cause deaths. After multivariate analysis, UTCC was associated with increased CV and all-cause mortality (P ≤ 0.004). Age, diabetes, heart failure, left ventricular hypertrophy, baPWV, and LVEF were also independent predictors of CV and all-cause mortality, but ABI was not. Furthermore, UTCC had a better additive predictive value than ABI, baPWV, and LVEF for CV mortality (P ≤ 0.012). It also had a better additive predictive value than ABI and LVEF for all-cause mortality (P ≤ 0.013). Conclusions UTCC is an independent predictor for CV and all-cause mortality in patients with normal ABI. It also has a better additive predictive value of CV and all-cause mortality than ABI and LVEF. Therefore, UTCC is a simple, novel, and useful parameter for identifying high-risk patients with normal ABI.

Background: Exercise offers improvement to physical and mental health symptoms as well and cognitive function in patients with psychosis. However, patients with psychosis are often less ready to benefit from exercise intervention because of the difficulties in motivation. This study aimed to examine the effectiveness of adjunctive motivational coaching on exercise intervention in women with psychosis in Hong Kong. Methods: From a community mental health programme for women, patients with a diagnosis of psychotic disorder (within 5 years of first onset) were randomly allocated to receive 12 30-minute sessions of motivational coaching or psychoeducation in a group format. Both groups additionally received exercise intervention sessions consisting of yoga, stretching and high-intensity interval training. Primary outcome was the total physical activity level measured by the International Physical Activity Questionnaire. Results: Fifty-seven patients (mean [SD] age, 34.47 [12.44] years) were randomised into motivational coaching ( n = 30) or psychoeducation ( n = 27) treatment groups. The motivational coaching group had a significantly higher total physical activity level (4601.67 [686.59] vs 2524.82 [723.73] metabolic equivalent task-min/week, r2 = 0.473, p = 0.04) after the intervention and at 6 months post-intervention. Moderate and light physical activity levels were significantly higher in the motivational coaching group after intervention and at 6 months, respectively. Additionally, symptoms of bizarre behaviour were improved in the motivational coaching group at 6 months. Younger, unemployed, unmarried and those with longer durations of untreated psychosis generally showed larger improvements in the motivational coaching group. Conclusion: Motivational coaching may augment the effects of exercise interventions, as reflected by higher physical activity participation. Motivational coaching augmentation has the potential to further improve exercise intervention outcomes.

To compare the extent to which visceral adiposity, as measured by mesenteric fat thickness, contribute to cardiometabolic risk, especially insulin resistance, in women with PCOS and healthy control.This is a cross-sectional study with a total of 190 women with PCOS fulfilling the Rotterdam diagnostic criteria. Women without PCOS were recruited from a previous study, which comprised 416 healthy women controls with normal glucose tolerance. All subjects underwent OGTT, biochemical assessment, and sonographic assessment with measurements of mesenteric, preperitoneal and subcutaneous fat thickness.Mesenteric fat thickness was strongly correlated to cardiometabolic traits including blood pressure, fasting and 2-h glucose, triglycerides, HOMA-IR; and was negatively correlated to HDL-C in both cohorts (all p0.01). In PCOS, positive correlation was observed between mesenteric fat thickness and free androgen index (p0.01). Compared with controls, the regression line between mesenteric fat and HOMA-IR is much steeper in PCOS (p0.01).Women with PCOS remain more insulin resistant compared to controls at any given degree of visceral adiposity.

BackgroundLittle is known about the effects of physical exercise on sleep-dependent consolidation of procedural memory in individuals with schizophrenia. We conducted a randomized controlled trial (RCT) to assess the effectiveness of physical exercise in improving this cognitive function in schizophrenia.MethodsA three-arm parallel open-labeled RCT took place in a university hospital. Participants were randomized and allocated into either the high-intensity-interval-training group (HIIT), aerobic-endurance exercise group (AE), or psychoeducation group for 12 weeks, with three sessions per week. Seventy-nine individuals with schizophrenia spectrum disorder were contacted and screened for their eligibility. A total of 51 were successfully recruited in the study. The primary outcome was sleep-dependent procedural memory consolidation performance as measured by the finger-tapping motor sequence task (MST). Assessments were conducted during baseline and follow-up on week 12.ResultsThe MST performance scored significantly higher in the HIIT (n = 17) compared to the psychoeducation group (n = 18) after the week 12 intervention (p < 0.001). The performance differences between the AE (n = 16) and the psychoeducation (p = 0.057), and between the AE and the HIIT (p = 0.999) were not significant. Yet, both HIIT (p < 0.0001) and AE (p < 0.05) showed significant within-group post-intervention improvement.ConclusionsOur results show that HIIT and AE were effective at reverting the defective sleep-dependent procedural memory consolidation in individuals with schizophrenia. Moreover, HIIT had a more distinctive effect compared to the control group. These findings suggest that HIIT may be a more effective treatment to improve sleep-dependent memory functions in individuals with schizophrenia than AE alone.

Objectives Kabuki syndrome (KS) is a genetic disorder characterized by intellectual disability, facial dysmorphism and congenital anomalies. We aim to investigate the prenatal features of fetuses with KS and to provide a comprehensive review of the literature on prenatal sonographic abnormalities associated with KS. Methods We retrospectively reviewed the prenatal ultrasound findings of all mothers of children with molecularly confirmed KS in Hong Kong, between 1991 and 2019. We also performed systematic review of the literature to identify studies on the prenatal findings in KS. Results We identified 11 cases with KS with detectable fetal ultrasound findings ranging from no detectable abnormalities to a variety of non-specific findings including increased nuchal translucency, pleural effusion, cardiac anomalies, renal anomalies, intrauterine growth restriction, polyhydramnios, oligohydramnios and single umbilical artery. In combining our cases with the 77 cases published, 42 (50.6%) of them had more than one abnormal antenatal ultrasound finding. The most frequent ultrasound features observed were cardiac anomalies (49.4%), followed by polyhydramnios (28.9%), genitourinary anomalies (26.5%), single umbilical artery (15.7%), intrauterine growth restriction (14.5%) and hydrops fetalis/pleural effusion/ascites (12.0%). Conclusions These cases demonstrate the prenatal phenotypic heterogeneity associated with KS. Although the ultrasound abnormalities are non-specific, KS should be considered in the differential diagnosis when these fetal findings following normal microarray analysis/karyotyping.

Purpose The biological mechanisms underlying developmental stuttering remain unclear. In a previous investigation, we showed that there is significant spatial correspondence between regional gray matter structural anomalies and the expression of genes linked to energy metabolism. In the current study, we sought to further examine the relationship between structural anomalies in the brain in children with persistent stuttering and brain regional energy metabolism. Method High-resolution structural MRI scans were acquired from 26 persistent stuttering and 44 typically developing children. Voxel-based morphometry was used to quantify the between-group gray matter volume (GMV) differences across the whole brain. Group differences in GMV were then compared with published values for the pattern of glucose metabolism measured via F 18 fluorodeoxyglucose uptake in the brains of 29 healthy volunteers using positron emission tomography. Results A significant positive correlation between GMV differences and F 18 fluorodeoxyglucose uptake was found in the left hemisphere (ρ = .36, p < .01), where speech-motor and language processing are typically localized. No such correlation was observed in the right hemisphere (ρ = .05, p = .70). Conclusions Corroborating our previous gene expression studies, the results of the current study suggest a potential connection between energy metabolism and stuttering. Brain regions with high energy utilization may be particularly vulnerable to anatomical changes associated with stuttering. Such changes may be further exacerbated when there are sharp increases in brain energy utilization, which coincides with the developmental period of rapid speech/language acquisition and the onset of stuttering during childhood. Supplemental Material https://doi.org/10.23641/asha.14110454

Numerous studies have identified deficits in the self-monitoring system that are associated with schizophrenia. However, the tasks used in the few previous studies generally involved complex cognitive processes and rarely compared between patients with and without passivity experiences (PE). Here, we examined the deficits in internal motor predictive representation in patients with and without PE, and in healthy controls using a novel paradigm which involved minimal cognitive processes. All participants completed a modified joint position matching (mJPM) task, in which they were required to replicate a voluntary, a passive verbally-cued, and a passive tactile-cued movement under blinded conditions. The absolute difference between the target spot and replicated spot was measured and compared. We hypothesised that if there was a failure in the internal motor predictive representation, patients with PEs would replicate less accurately in the voluntary condition, relative to passive conditions while the healthy controls would be more accurate, and, therefore, significant interactions between groups and conditions would be revealed. Both healthy controls and patients without PEs replicated more accurately in the voluntary condition compared with the passive conditions. The patients with PEs were less accurate in the voluntary condition compared with the passive tactile condition. A significant interaction was observed between patients with vs. without PEs × voluntary vs. passive tactile conditions. The findings suggested the relationship between deficits in motor self-monitoring in the prediction process and PEs, thus showing the need to highlight the link between motor performance and PEs.

Background The widespread nature of coronavirus disease 2019 (COVID-19) has been unprecedented. We sought to analyze its global impact with a survey on colorectal cancer (CRC) care during the pandemic. Methods The impact of COVID-19 on preoperative assessment, elective surgery, and postoperative management of CRC patients was explored by a 35-item survey, which was distributed worldwide to members of surgical societies with an interest in CRC care. Respondents were divided into two comparator groups: 1) ‘delay’ group: CRC care affected by the pandemic; 2) ‘no delay’ group: unaltered CRC practice. Results A total of 1,051 respondents from 84 countries completed the survey. No substantial differences in demographics were found between the ‘delay’ (745, 70.9%) and ‘no delay’ (306, 29.1%) groups. Suspension of multidisciplinary team meetings, staff members quarantined or relocated to COVID-19 units, units fully dedicated to COVID-19 care, personal protective equipment not readily available were factors significantly associated to delays in endoscopy, radiology, surgery, histopathology and prolonged chemoradiation therapy-to-surgery intervals. In the ‘delay’ group, 48.9% of respondents reported a change in the initial surgical plan and 26.3% reported a shift from elective to urgent operations. Recovery of CRC care was associated with the status of the outbreak. Practicing in COVID-free units, no change in operative slots and staff members not relocated to COVID-19 units were statistically associated with unaltered CRC care in the ‘no delay’ group, while the geographical distribution was not. Conclusions Global changes in diagnostic and therapeutic CRC practices were evident. Changes were associated with differences in health-care delivery systems, hospital’s preparedness, resources availability, and local COVID-19 prevalence rather than geographical factors. Strategic planning is required to optimize CRC care., Global changes in both diagnostic and therapeutic practices in colorectal cancer care were evident in this survey conducted to analyze the impact of COVID-19 outbreak. The importance of this finding is that changes were associated with differences in health care delivery systems, hospital’s preparedness, resources availability, and local COVID-19 prevalence rather than geographical variations.

PURPOSE We performed a systematic review on 3 major types of scleral-fixated intraocular lens (SFIOL) implantations and conducted subgroup analyses on pediatric population and subjects with Marfan syndrome. DESIGN Systematic review. METHODS We performed a search in PubMed, Ovid MEDLINE, and Embase for English language articles with keywords "(sutured intraocular lens) OR (SFIOL) OR (sutureless intraocular lens) OR (glued intraocular lens) OR (intrascleral intraocular lens) OR (SFIOL)" through October 16, 2019. Articles reporting individual outcomes after SFIOL were included in this systematic review. Recorded outcome measures included intraoperative and postoperative complications, endothelial cell changes, and intraocular lens-related outcomes. RESULTS Our search yielded 217 papers. After removing duplicated and irrelevant reports, we included 57 articles involving 2624 eyes. The mean age at operation was 51.47 ± 25.62 years. Sutured SFIOL was most commonly reported in all subjects with Marfan syndrome and 92.87% of pediatric patients. The pooled intraoperative complication rate was 6.65%. Minor anterior chamber hemorrhage was the most common intraoperative (1.92%) and postoperative complication (13.93%). Optic capture was the top intraocular lens (IOL)-related complication (4.47%). The overall mean endothelial cell loss was 8.95% at 16.77 ± 11.04 months. Overall 11.99% of SFIOLs were decentred with a mean distance of 0.49 ± 0.40 mm and a mean degree of tilt by 4.11 ± 3.03°. CONCLUSIONS Glued SFIOL had the fewest IOL-related complications and the lowest endothelial cell loss. Sutured SFIOL carried the highest IOL-related complications, whereas sutureless, glueless SFIOL was associated with the greatest endothelial cell loss.

No study has investigated the predictive ability of ankle-brachial index (ABI) calculated using diastolic blood pressure (DBP) (ABIdbp) and mean arterial pressure (MAP) (ABImap) for overall and cardiovascular (CV) mortality in hemodialysis (HD) patients. Our study was aimed to investigate the issue. Two hundred and seven routine HD patients were enrolled. ABI values were measured by ABI-form device. During the follow-up period (122 months), 124 of the 207 patients (59.0%) died, and 59 deaths due to CV cause. Multivariate analysis showed that low ABIsbp, ABIdbp, and ABImap were all significantly associated with increased overall (p ≤ 0.015) and CV mortality (p ≤ 0.015) in whole study patients. A subgroup analysis after excluding 37 patients with ABIsbp < 0.9 or > 1.3 found ABIsbp and ABIsbp < 0.9 were not associated with overall and CV mortality. However, ABImap and ABIdbp < 0.87 were significantly associated with overall mortality (p ≤ 0.042). Furthermore, ABIdbp and ABIdbp < 0.87 were significantly associated with CV mortality (p ≤ 0.030). In conclusion, ABIsbp, ABIdbp, and ABImap were all useful in predicting overall and CV mortality in our HD patients. In the subgroup patients with normal ABIsbp, ABIsbp and ABIsbp < 0.9 were not useful to predict overall and CV mortality. Nevertheless, ABImap and ABIdbp < 0.87 could still predict overall mortality, and ABIdbp and ABIdbp < 0.87 could predict CV mortality. Hence, calculating ABI using DBP and MAP may provide benefit in survival prediction in HD patients, especially in the patients with normal ABIsbp.

Background Psychotic disorders are associated with a high rate of relapse. In addition to medication non-adherence, some psychosocial factors have been found to be predictive of relapse (e.g., poor premorbid adjustment, high expressed emotion and substance misuse). Impairments in cognitive functions including general memory functioning, set shifting, attention, processing speed and working memory have also been indicative of a subsequent psychotic episode. As clinical appointments do not always allow for timely or accurate detection of these early warning signs, the ReMind app is developed to explore potential relapse predictors and enhance the process of relapse monitoring. Aim The ReMind app aims (1) to assess whether verbal or visual working memory predicts psychotic relapse in 1 year and (2) to determine whether social factors such as stressful life events, level of expressed emotion and medication adherence also predict relapse in 1 year. Methods This is a one-year prospective follow-up study involving 176 remitted patients diagnosed with schizophrenia or non-affective psychoses. Monthly relapse predictor assessments will be conducted via ReMind throughout the one-year study duration. These assessments include neurocognitive tasks and psychosocial questionnaires. Results Recruitment began in August 2017 and is still ongoing. Preliminary user feedback suggested an overall positive experience with the app. Conclusion The ReMind app presents a step forward to the identification and sensitive detection of reliable psychosis relapse predictors. With its anticipated success, it may offer an alternative means of monitoring relapse for the Chinese-speaking population in the future.

Pulse wave velocity (PWV) was a good marker of arterial stiffness and could predict cardiovascular (CV) outcomes. Recently, estimated PWV (ePWV) calculated by equations using age and mean blood pressure was reported to be an independent predictor of major CV events. However, there was no study comparing ePWV with brachial‐ankle PWV (baPWV) for CV and overall mortality prediction. We included 881 patients arranged for echocardiographic examination. BaPWV and blood pressures were measured by ankle‐brachial index‐form device. The median follow‐up period to mortality was 94 months. Mortality events were documented during the follow‐up period, including CV mortality (n = 66) and overall mortality (n = 184). Both of ePWV and baPWV were associated with increased CV and overall mortality after the multivariable analysis. ePWV had better predictive value than Framingham risk score (FRS) for CV and overall mortality prediction, but baPWV did not. In direct comparison of multivariable analysis using FRS as basic model, ePWV had a superior additive predictive value for CV mortality than baPWV (p = .030), but similar predictive valve for overall mortality as baPWV (p = .540). In conclusion, both ePWV and baPWV were independent predictors for long‐term CV and overall mortality in univariable and multivariable analysis. Besides, ePWV had a better additive predictive value for CV mortality than baPWV and similar predictive value for overall mortality as baPWV. Therefore, ePWV obtained without equipment deserved to be calculated for overall mortality prediction and better CV survival prediction.

KCNQ2 mutations encompass a wide range of phenotypes, ranging from benign familial neonatal seizure to a clinical spectrum of early-onset epileptic encephalopathy that occurs in the early neonatal period. We report an infant with KCNQ2 encephalopathy presenting as neonatal seizure, initially controlled by two anticonvulsants. Electroencephalogram (EEG) showed repetitive multifocal epileptiform discharges, which remained similar after administration of intravenous pyridoxine injection. Seizure recurred at the age of 3 months preceded by an episode of minor viral infection, which occurred multiple times per day. No significant change in seizure frequency was observed after 5-day oral pyridoxine trial, but subsequently, there was dramatic seizure improvement with oral pyridoxal-5′-phosphate (PLP). We hope to alert clinicians that in patients with neonatal epileptic encephalopathy, particularly with known KCNQ2 mutations, intravenous injection of pyridoxine (preferably with EEG monitoring), followed by both oral trial of pyridoxine and PLP should be considered. KCNQ2 mutations should also be considered in vitamin B6-responsive patients.

A low ankle‐brachial index (ABI) calculated using systolic blood pressure (SBP) (ABIsbp) is associated with poor cardiovascular outcome in patients with acute myocardial infarction (AMI). ABI is always calculated using SBP clinically. However, there was no study investigating ABI calculated using mean artery pressure (MAP)(ABImap) and diastolic blood pressure (DBP)(ABIdbp) for mortality prediction in AMI patients. Therefore, our study was aimed to investigate the issue. 199 AMI patients were enrolled. Different ABIs were measured by an ABI‐form device. The median follow‐up to mortality was 64 months. There were 40 cardiovascular and 137 all‐cause mortality. The best cutoff values of ABImbp and ABIdbp for mortality prediction were 0.91 and 0.78, respectively. After multivariate analysis, only ABIdbp and ABIdbp

Mosaic variegated aneuploidy (MVA) is a rare genetic disorder caused by mutations in BUB1B, CEP57, or TRIP13. We describe the prenatal diagnosis, molecular characterization, and clinical management of a long‐lived patient with BUB1B‐related MVA.

This study explored the 10-year trajectories and outcomes of negative symptoms in patients with first-episode schizophrenia-spectrum disorder. Patients were from the historical control study comparing 10-year outcomes between standard care and early intervention services. A total of 298 patients were identified, 214 were successfully interviewed at 10-year follow-up for clinical and functional outcomes and 209 patients were included for final analyses. Information from clinical records were obtained systematically using standardized data entry forms. These information including negative symptoms, hospitalization and employment, monthly for year 1–3 and trimonthly for the year 4–10. Hierarchical cluster analysis was used to explore the 10-year negative symptom clusters. Demographics and early clinical characteristics related to the cluster memberships and different components of negative symptom at 10-year follow-up were further explored. The cluster analysis identified three longitudinal clusters of negative symptoms and 15% of patients were in the relapsed group. There was no difference in cluster membership between the intervention groups. Male gender and duration of hospitalizations in year four were found to be significant determinants of relapse negative symptoms. Lower education level, higher year-one negative symptom score and more months of unemployment during the first 3 years predicted overall negative symptoms at 10-year follow-up. Male gender was found to be a predictor only for avolition and anhedonia and duration of untreated psychosis only predicted anhedonia. These results highlighted the heterogeneity of longitudinal outcomes and the importance of personalized interventions.

Aim Psychiatric comorbidity frequently occurs with at-risk mental state (ARMS) for psychosis. Its relationships with psychopathology, cognition and functioning, however, remain to be further clarified. We aimed to examine prevalence and correlates of psychiatric comorbidity, and its associations with psychosocial functioning and subjective quality-of-life (QoL) in a representative sample of Chinese ARMS individuals. Methods One hundred ten help-seeking participants aged 15 to 40 years with ARMS were recruited from a specialized early psychosis service in Hong Kong. ARMS status was verified by comprehensive assessment of at-risk mental state (CAARMS). Comorbid Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition non-psychotic psychiatric disorders at baseline were ascertained using diagnostic interview and medical record review. Assessments encompassing symptom profiles, psychosocial functioning, subjective QoL and a brief cognitive battery were conducted. Results Forty-nine (44.5%) ARMS participants were diagnosed as having comorbid non-psychotic psychiatric disorders at baseline, primarily depressive and anxiety disorders. Binary multiple logistic regression analysis revealed that female gender, more severe depressive symptoms, higher suicidality and poorer global cognitive functioning were independently associated with comorbid diagnosis status. ARMS participants with psychiatric comorbidity displayed significantly more limited extended social networks and poorer subjective QoL than those without psychiatric comorbidity. Conclusion Comorbid disorders were frequently observed in Chinese ARMS individuals, and were linked to poorer cognition and higher suicide risk. Our findings underscore a potential critical role of psychiatric comorbidity in determining social functioning and subjective QoL in at-risk individuals. Further longitudinal research is required to clarify trajectories of comorbid disorder status and its prospective impact on clinical and functional outcomes in ARMS populations.

Haloperidol remains a frequently prescribed first-generation antipsychotic. However, haloperidol-associated mortality risk by all causes, cardiovascular disease (CVD), and pneumonia compared with other antipsychotics is unknown. This study investigated the mortality risk associated with long-term haloperidol treatment versus that with other antipsychotics. We identified incident antipsychotic users from 2004 to 2014 in the Clinical Data Analysis and Reporting System (CDARS), a population-based clinical database managed by the Hong Kong Hospital Authority. We included patients who were aged ≥ 18 and received antipsychotics for any indication apart from terminal illnesses or management of acute behavioural disturbance. Patients on haloperidol and other antipsychotic agents (risperidone, quetiapine, olanzapine, chlorpromazine, aripiprazole, sulpiride, amisulpride, or trifluoperazine) were matched by propensity score. Hazard ratios (HRs) for all-cause mortality and death due to CVD and pneumonia were estimated with 95% confidence intervals (CIs) using a Cox proportional hazards model. In total, 136,593 users of antipsychotics were included. During a mean follow-up of 3.2 years, the incidence of all-cause mortality ranged from 186.8/1000 person-years for haloperidol to 10.4/1000 person-years for trifluoperazine. The risk of all-cause mortality was lower with non-haloperidol antipsychotics than with haloperidol, with HRs ranging from 0.68 (95% CI 0.64–0.72 [chlorpromazine]) to 0.43 (95% CI 0.36–0.53 [trifluoperazine]). Risperidone, quetiapine, sulpiride, chlorpromazine, aripiprazole, and trifluoperazine were associated with a significantly lower risk of pneumonia-related mortality. A significantly lower risk of CVD mortality was observed for risperidone, sulpiride, chlorpromazine, and quetiapine. Haloperidol was associated with increased overall mortality when compared with other antipsychotics in long-term follow-up. Treatment with haloperidol should be carefully considered, especially in older patients and patients at risk of CVD or pneumonia, since the risk of death appears to be lower with non-haloperidol agents.

Based on clinical presentation, pathophysiology, high infectivity, high cardiovascular involvement, and therapeutic agents with cardiovascular toxicity of coronavirus disease 2019 (COVID-19), regular cardiovascular treatment is being changing greatly. Despite angiotensin-converting enzyme 2 serving as the portal for infection, the continuation of clinically indicated renin-angiotensin-aldosterone blockers is recommended according to the present evidence. Fibrinolytic therapy can be considered a reasonable option for the relatively stable ST segment elevation myocardial infarction (STEMI) patient with suspected or known COVID-19. However, primary percutaneous coronary intervention is still the standard of care in patients with definite STEMI if personal protective equipment is available and cardiac catheterization laboratory has a good infection control. In patients with elevated cardiac enzymes, it is very important to differentiate patients with Type 2 myocardial infarction or myocarditis from those with true acute coronary syndromes because invasive percutaneous intervention management in the former may be unnecessary, especially if they are hemodynamically stable. Finally, patients with baseline QT prolongation or those taking QT prolonging drugs must be cautious when treating with lopinavir/ritonavir and hydroxychloroquine for COVID-19.

Four-limb blood pressure measurement could improve mortality prediction in the elderly. However, there was no study to evaluate whether such measurement was still useful in predicting overall and cardiovascular (CV) mortality in acute myocardial infarction (AMI). Two hundred AMI patients admitted to cardiac care unit were enrolled. The 4-limb blood pressures, inter-limb blood pressure differences, and ankle brachial index (ABI) were measured using an ABI-form device. The median follow-up to mortality was 64 months (25th-75th percentile: 5-174 months). There were 40 and 138 patients documented as CV and overall mortality, respectively. After multivariable adjustment, the ankle diastolic blood pressure (DBP) on the lower side, ABI value, ABI < 0.9, interarm DBP difference, interankle systolic blood pressure (SBP) and DBP differences, interankle SBP difference ≥ 15 mmHg, and interankle DBP difference ≥ 10 mmHg could predict overall mortality (P ≤ 0.025). The ankle DBP on the lower side, interankle DBP difference, and interankle DBP difference ≥ 10 mmHg could predict CV mortality (P ≤ 0.031). In addition, in the Nested Cox model, the model including the ankle DBP on the lower side and the model including interankle DBP difference had the best value for overall and CV mortality prediction, respectively (P ≤ 0.031). In AMI patients, 4-limb blood pressure measurement could generate several useful parameters in predicting overall and CV mortality. Furthermore, ankle DBP on the lower side and interankle DBP difference were the most powerful parameters in prediction of overall and CV mortality, respectively.

Background Mini-sternotomy has been proven superior to full sternotomy in aortic valve replacement by providing better perioperative outcomes. We investigated whether such technique provides better outcomes in patients undergoing aortic root surgery. Methods A comprehensive electronic literature search was undertaken among the four major databases (PubMed, Ovid, Scopus and EMBASE) to identify all published studies up to June 2018. The search terms used related to mini-sternotomy versus full sternotomy, aortic root, valve sparing, Bentall procedure. Only articles that compared mini against full sternotomy were considered in this analysis. After excluding articles based on title or abstract, the full text articles selected had reference lists searched for any potential further articles to be included in this review. Results A total of 2,765 patients were analysed from across eight comparative studies that were included in the quantitative analysis of the parameters of interest that fulfilled the criteria for meta-analysis. Mini-sternotomy aortic root replacement was associated with significantly shorter cardiopulmonary bypass time (p = 0.009), lower rate of blood transfusion (p = 0.01). additionally, they had lower operative mortality (p = 0.02), and shorter stay at intensive care and at hospital (p = 0.0009, p = 0.03 respectively). However, there was no difference between mini-sternotomy and conventional aortic root replacement in terms of aortic cross-clamp time (p = 0.28), total operation time (p = 0.31), re-exploration rate for bleeding (p = 0.28), stroke rate (p = 0.90), wound infection rate (p = 0.96), and length of mechanical ventilation (p = 0.10). Conclusion Mini-sternotomy is a safe, feasible alternative option to full sternotomy in aortic root repair. However, the significant heterogeneity in data points to the need for a larger, well-designed trial to support the currently limited literature evidences.

Stumpless chronic total occlusion is associated with a higher failure rate of recanalization. Intravascular ultrasound (IVUS) is useful for identifying the entry point; however, 8-F guide catheters are necessary for real-time IVUS-guided wiring. This case reports the novel use of the “ping-pong” guide catheter technique to facilitate real-time IVUS-guided wiring for a stumpless chronic total occlusion. (Level of Difficulty: Advanced.), Graphical abstract, Stumpless chronic total occlusion is associated with a higher failure rate of recanalization. Intravascular ultrasound (IVUS) is useful for…

Background: Environmental tobacco smoke (ETS) exposure in children ranks one of the major public health problems in our time. Poor parental knowledge, attitude, and practice (KAP) on ETS often contribute to worse exposure of the kids. Thus, we aimed to document parental KAP regarding tobacco use, smoking cessation and children's ETS exposure, and to analyse how knowledge and attitude relate to practice.Methods: Self-administered KAP questionnaires were distributed to smoking parents recruited from the pediatric unit at the Prince of Wales Hospital, which provides pediatric service to a population of 1.2 million in Hong Kong. The 60-item questionnaire had a range of 0–38 for knowledge, 0–44 for attitude, and 0–40 for practice. Descriptive analyses were performed for KAP response, regression analyses were performed for the exploration of associations and identification of predictive indicators.Results: 145 smoking parents (mean age: 38.0 ± 6.7 yrs.; male: 85.5%) were included. Less than half (39.3%) of them reported a smoke-free policy at home. Among those parents who had private cars, less than half (45.2%) of them had smoke-free policy in their car that they never smoked in the car. Only 25.5% of the participants correctly answered ≥70% of the knowledge questions, and 11.8 % of the participants gave favorable responses to ≥70% of the attitude questions. The total knowledge and the total attitudes score were positively associated (r = 0.49, 95% CI: 0.35–0.79, p < 0.001), yet they were only modestly correlated with parental practice on children's ETS exposure. By multivariate regressions, potential predictive factors for more favorable parental KAP included higher household income, lower parental nicotine dependence level and breastfeeding practice.Conclusions: Parental KAP related to tobacco use and children's ETS exposure needs improvement to address the significant gap between recommended and actual practice. The weak association between knowledge and practice suggested that parental education alone is not adequate to combat ETS exposure in children.

Early childhood marks a period of dynamic neurocognitive development. Preschool-age coincides with the onset of many childhood disorders and is a developmental period that is frequently studied to determine markers of neurodevelopmental disorders. Magnetic resonance imaging (MRI) is often used to explore typical brain development and the neural bases of neurodevelopmental disorders. However, acquiring high-quality MRI data in young children is challenging. The enclosed space and loud sounds can trigger unease and cause excessive head movement. A better understanding of potential factors that predict successful MRI acquisition would increase chances of collecting useable data in children with and without neurodevelopmental disorders. We investigated whether age, sex, stuttering status, and childhood temperament as measured using the Child Behavioral Questionnaire, could predict movement extent during resting-state functional MRI (rs-fMRI) in 76 children aged 3–7 years, including 42 children who stutter (CWS). We found that age, sex, and temperament factors could predict motion during rs-fMRI scans. The CWS were not found to differ significantly from controls in temperament or head movement during scanning. Sex and age were significant predictors of movement. However, age was no longer a significant predictor when temperament, specifically effortful control, was considered. Controlling for age, boys with higher effortful control scores moved less during rs-fMRI procedures. Additionally, boys who showed higher negative affectivity showed a trend for greater movement. Considering temperament factors in addition to age and sex may help predict the success of acquiring useable rs-fMRI (and likely general brain MRI) data in young children in MR neuroimaging.

Patients with chronic kidney disease (CKD) often have cardiac functional and structural abnormalities which can lead to adverse cardiovascular outcomes. In this study, we investigated associations between diabetes mellitus (DM) and cardiac functional and structural parameters in patients with CKD focusing on aortic root diameter (ARD). We also investigated associations of renal outcomes with DM and cardiac functional and structural characteristics. We enrolled 419 patients with CKD stage 3–5 were enrolled. ARD was normalized to body surface area (BSA) (ARD/BSA), and the rate of decline in renal function was assessed by the estimated glomerular filtration rate (eGFR) slope (mL/min/1.73 m2/year). ARD/BSA ≥2.1 cm/m2 in men or ≥2.2 cm/m2 in women was defined as indicating aortic root dilatation. The patients with DM had lower ARD/BSA, higher left atrial dimension (LAD), lower left ventricular ejection fraction, lower ratio of peak early transmitral filling wave velocity to peak late transmitral filling wave velocity, and higher left ventricular relative wall thickness, than those without DM. After multivariable analysis, DM (vs. non-DM, coefficient β, −0.060, p = 0.018) was significantly associated with low ARD/BSA. Significantly fewer patients with DM had aortic root dilatation compared to those without DM (14.3% vs. 23.1%, p = 0.022). In the patients with DM, there were significant associations between a high left ventricular mass index (LVMI) (per 1 g/m2, β, −0.016, p = 0.040) and high LAD (per 1 cm, β, −1.965, p &lt, 0.001) with a low eGFR slope. However, other parameters, including ARD/BSA, were not associated with eGFR slope. Furthermore, there were no associations between eGFR slope and any of the echocardiographic parameters in the patients without DM. Aortic root dilatation was attenuated in the patients with DM, but it was not associated with a decline in renal function. However, high LAD and LVMI were associated with rapid renal function decline in the CKD patients with DM.

(1) Background: The autonomic imbalance plays a role in vasovagal syncope (VVS) diagnosed by head-up tilting test (HUT). neuECG is a new method of recording skin electrical signals to simultaneously analyze skin sympathetic nerve activity (SKNA) and electrocardiogram. We hypothesize that SKNA is higher in subjects with tilt-positive than tilt-negative and the SKNA surges before syncope. (2) Methods: We recorded neuECG in 41 subjects who received HUT (according to the “Italian protocol”), including rest, tilt-up, provocation and recovery phases. Data were analyzed to determine the average SKNA (aSKNA, μV) per digitized sample. Electrocardiogram was used to calculate standard deviation of normal-to-normal beat intervals (SDNN). The “SKNA-SDNN index” was calculated by rest aSKNA multiplied by the ratio of tilt-up to rest SDNN. (3) Results: 16 of 41 (39%) subjects developed syncope. The aSKNA at rest phase is significantly higher in the tilt-positive (1.21 ± 0.27 µV) than tilt-negative subjects (1.02 ± 0.29 µV) (p = 0.034). There are significant surges and withdraw of aSKNA 30 s before and after syncope (both p ≤ 0.006). SKNA-SDNN index is able to predict syncope (p &lt, 0.001). (4) Conclusion: Higher SKNA at rest phase is associated with positive HUT. The SKNA-SDNN index is a novel marker to predict syncope during HUT.

Made available in DSpace on 2021-06-25T10:11:48Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-12-01 National Human Genome Research Institute Rubinstein–Taybi syndrome (RSTS) is an autosomal dominant disorder, caused by loss-of-function variants in CREBBP or EP300. Affected individuals present with distinctive craniofacial features, broad thumbs and/or halluces, and intellectual disability. RSTS phenotype has been well characterized in individuals of European descent but not in other populations. In this study, individuals from diverse populations with RSTS were assessed by clinical examination and facial analysis technology. Clinical data of 38 individuals from 14 different countries were analyzed. The median age was 7 years (age range: 7 months to 47 years), and 63% were females. The most common phenotypic features in all population groups included broad thumbs and/or halluces in 97%, convex nasal ridge in 94%, and arched eyebrows in 92%. Face images of 87 individuals with RSTS (age range: 2 months to 47 years) were collected for evaluation using facial analysis technology. We compared images from 82 individuals with RSTS against 82 age- and sex-matched controls and obtained an area under the receiver operating characteristic curve (AUC) of 0.99 (p

A rapid decline in renal function is associated with high cardiovascular morbidity and mortality, and therefore it is important to identify those at high-risk of rapid renal function decline. The relationship between liver function and renal function is unclear. Therefore, in this longitudinal study, we aimed to investigate associations between liver function and rapid renal function decline. A total of 27,116 participants were enrolled from the Taiwan Biobank and followed for 3.8 years. A rapid decline in renal function was defined as a decline in estimated glomerular filtration rate (eGFR) of ≥25%. Binary logistic regression analysis was used to identify associations between liver function parameters (glutamic-oxalacetic transaminase, glutamic-pyruvic transaminase, albumin, α-fetoprotein [AFP], total bilirubin, and gamma-glutamyl transpeptidase) and eGFR decline ≥ 25%. The rate of eGFR decline of ≥25% was 4.7%. Multivariable analysis showed that low albumin (odds ratio [OR], 0.173, p &lt, 0.001), high AFP (OR, 1.006, p = 0.010), and low total bilirubin (OR, 0.588, 0.001) were significantly associated with eGFR decline ≥ 25% in all study participants. After excluding abnormal liver function, low albumin (OR, 0.189, 0.001), high AFP (OR, 1.007, p = 0.011), and low total bilirubin (OR, 0.569, p = 0.001) were still significantly associated with an eGFR decline of ≥25%. The results of this large population-based cohort study showed associations between low albumin, low bilirubin, and high AFP with a rapid renal function decline. A greater understanding of potential risk factors for a rapid decline in renal function may help to reduce the burden of renal failure in this high-risk population.

Background: Early childhood marks a period of dynamic neurocognitive development. The preschool age coincides with the onset of many childhood disorders and is a developmental period that is frequently studied to determine markers of neurodevelopmental disorders. Magnetic resonance imaging (MRI) is often used to explore typical brain development and the neural bases of neurodevelopmental disorders. One advantage of MRI is that it provides comprehensive imaging data with high spatial resolution that is not possible with “child-friendly” techniques such as electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS). However, acquiring high-quality MRI data in young children is challenging. The enclosed space and loud sounds can trigger unease and cause excessive head movement. A better understanding of potential factors that predict successful MRI acquisition would increase chances of collecting useable data in children with and without neurodevelopmental disorders.Methods: We investigated whether age, sex, stuttering status, and childhood temperament as measured using the Child Behavioral Questionnaire, could predict movement extent during resting-state functional MRI (rs-fMRI) in 76 children aged 3 to 7 years, including 42 children who stutter (CWS). Results: The CWS did not differ significantly from controls in temperament or head movement during scanning. Boys exhibited significantly more movement than girls, and younger age was a consistent predictor of increased movement, unless temperament was considered. Effortful control and negative affectivity significantly predicted movement especially in young boys. Conclusions: Considering temperament, age, and sex may help predict the success of acquiring useable rs-fMRI data in young children and inform future studies developing better desensitization techniques for pediatric MR neuroimaging.

Objective: Co-occurring population-level events, such as social unrest and coronavirus disease 2019, are observed in many societies today. Few studies have explored their combined mental health effects on young people. While self-focused rumination has been suggested to be a key mechanism underlying depression, the role of event-based rumination in mediating the impact of population stressors has yet to be elucidated. Methods: Data were collected from 6988 young people in a large-scale community online survey in Hong Kong. The survey assessed symptoms of post-traumatic stress disorder and depression, direct exposure to social unrest-related traumatic events, coronavirus disease 2019 pandemic-related events, personal stressful life events, event-based rumination and other individual risk factors. Results: High levels of comorbid post-traumatic stress disorder and depressive symptoms were observed. Logistic regression analysis revealed that probable post-traumatic stress disorder was associated with traumatic events (odds ratio = 1.73, 95% confidence interval = [1.64, 1.82]), pandemic-related events (odds ratio = 1.08, confidence interval = [1.01, 1.16]), stressful life events (odds ratio = 1.20, confidence interval = [1.21, 1.37]), high event-based rumination (odds ratio = 3.00, confidence interval = [2.58, 3.48]), lower resilience (odds ratio = 1.18, confidence interval = [1.15, 1.21]), higher smartphone reliance (odds ratio = 1.09, confidence interval = [1.05, 1.13]) and financial concerns (odds ratio = 1.25, confidence interval = [1.18, 1.33]). The odds for probable post-traumatic stress disorder was also significantly higher when two or more traumatic events were experienced (odds ratio = 4.03, confidence interval = [3.52, 4.62]). Factors associated with moderate-to-severe level depressive symptoms were similar. Event-based rumination significantly mediated between different types of external events (traumatic events, pandemic-related events, stressful life events) and both post-traumatic stress disorder and depressive symptoms. Conclusion: These findings suggest that diverse types of stressful events during population-level crises could add to personal stressors to affect mental health outcomes in young people. Among other protective and risk factors, event-based rumination presented as a prominent transdiagnostic mediator for different symptom dimensions which may be a potentially important target for early risk detection and intervention.

Diastolic dysfunction is an emerging challenge among hemodialysis (HD) patients, and the associations between serum zinc with echocardiographic parameters and diastolic function remain uncertain. A total of 185 maintenance HD patients were stratified by the tertiles of serum zinc level to compare their clinical characteristics and echocardiography. Correlations of serum zinc levels with echocardiographic parameters were examined using Pearson’s analysis. Univariate and multivariate logistic regression analyses were performed to investigate the determinants of E/e’ ratio &gt, 15 and left atrial volume index (LAVI) &gt, 34 mL/m2, both indicators of diastolic dysfunction. Patients belonging to the first tertile of serum zinc level had a significantly higher E/e’ ratio and LAVI. Serum zinc levels were negatively correlated with E (r = −0.204, p = 0.005), E/e’ ratio (r = −0.217, p = 0.003), and LAVI (r = −0.197, p = 0.007). In a multivariate analysis, older age, diabetes, coronary artery disease, and lower serum zinc levels (OR = 0.974, 95% CI = 0.950–0.999, p = 0.039) were significantly associated with E/e’ ratio &gt, 15. Furthermore, diabetes and lower serum zinc levels (OR = 0.978, 95% CI = 0.958–0.999, p = 0.041) were significantly associated with LAVI &gt, 34 mL/m2. Reduced serum zinc level was significantly associated with diastolic dysfunction among HD patients. Further prospective studies are warranted to investigate whether zinc supplementation can attenuate cardiac dysfunction in maintenance HD patients.

Purpose We review two recent neuroanatomical studies of children who stutter (CWS), one that examines white matter integrity and the other that focuses on cortical gray matter morphology. In both studies, we sought to examine differences between children whose stuttering persists (“persistent”), children who recovered from stuttering (“recovered”), and their nonstuttering peers (“controls”). Method Both of the reviewed studies use data from a large pediatric sample spanning preschool- to school-age children (3–10 years old at initial testing). Study 1 focused on surface-based measures of cortical size (thickness) and shape (gyrification) using structural magnetic resonance imaging, whereas Study 2 utilized diffusion tensor imaging to examine white matter integrity. Results In both studies, the main difference that emerged between CWS and fluent peers encompassed left hemisphere speech motor areas that are interconnected via the arcuate fasciculus. In the case of white matter integrity, the temporoparietal junction and posterior superior temporal gyrus, both connected via the left arcuate fasciculus, and regions along the corpus callosum that contain fibers connecting bilateral motor regions were significantly decreased in white matter integrity in CWS compared to controls. In the morphometric study, children who would go on to have persistent stuttering specifically had lower cortical thickness in ventral motor and premotor areas of the left hemisphere. Conclusion These results point to aberrant development of cortical areas involved in integrating sensory feedback with speech movements in CWS and differences in interhemispheric connectivity between the two motor cortices. Furthermore, developmental trajectories in these areas seem to diverge between persistent and recovered cases.

Despite convincing evidence of short-term symptom control and functional recovery of patients with psychosis after receiving early intervention (EI) services, little is known about the long-term outcomes of EI for these patients. This review aims to evaluate the effectiveness of EI services in improving long-term outcomes of patients with psychosis. A systematic literature search was conducted on PubMed, PsycINFO, Scopus, Medline, CINAHL, BIOSIS, and EMBASE electronic databases to identify studies that evaluated long-term outcomes of patients with psychosis measured 5 years or beyond after entering the EI service. Of 13,005 articles returned from the search, 14 eligible articles reporting study cohorts from nine EI services in seven countries and regions were identified. Data on study design, patient characteristics, intervention components, and outcomes were extracted and reviewed. Only a few studies reported better longitudinal outcomes for negative symptoms, mortality, employment, and hospitalization in patients received EI services. However, results from cross-sectional measurements provided little evidence for long-term impacts of EI services on clinical and functional outcomes. A dilution effect of benefits over time was also demonstrated in several studies. This review highlights the gap in current EI service provision and suggests possible future directions for service improvement and further research.

Clinical guidelines provide evidence-based recommendations to regulate pharmacological treatment of psychotic disorders. However, the quality of evidence, country of origin, and publication dates of such guidelines vary, which leads to discrepancies between recommendations. This systematic review aimed to examine consensus and disparities between clinical recommendations on the choice, dose, and duration of antipsychotic treatment for first- and multi-episode schizophrenia patients. A literature search through The Cochrane Library, Embase, Medline, PsycINFO, PubMed, Scopus, Web of Sciences, and relevant bibliographies revealed 24 guidelines that met the inclusion criteria. The guidelines indicated mostly consistent recommendations regarding the optimal dose range of antipsychotics, while guidance with regards to the choice and duration of treatment remains somewhat controversial. Current trends in guidelines emphasize that there is simply no 'one-size-fits-all' method to manage schizophrenia patients. Further research is needed not only to address discrepancies between guidelines, but also to justify the gap between theory and practice.

Sternal wound infection (SWI) is one of the potential complications post cardiac surgery, and despite refined surgical techniques such as smaller incisions, antibiotic therapy, and optimised glycaemic control, the incidence rate is between

Objective: To systematically compare clinical outcomes between aortic valve repair and replacement in patients with aortic regurgitation. Methods: A comprehensive literature search was undertaken among the four major databases (PubMed, Embase, Scopus, and Ovid) to identify all published data comparing clinical outcomes of aortic valve repair vs replacement. Database searched from inception to November 2018. Results: A total of 1071 patients were analyzed in eight articles. Mean age was similar in both groups of patients (47.2 ± 12.8 vs 48.3 ± 12.7 years, P = 0.83, aortic valve repair and replacement, respectively). The preoperative left ventricular ejection fraction was better in the repair group (56.7% ± 4.8 vs 53.3% ± 4.2, P = 0.005). The rate of moderate-to-severe regurgitation and bicuspid aortic valve were similar in both cohorts (81% vs 78%, P = 0.90% and 58% vs 55%, P = 0.46). In-hospital and 1-year mortality was lower in repair cohort, although not reaching statistical significance (1.3% vs 3.6%, P = 0.12; 5.9% vs 9.3%, P = 0.77). Reoperation rate was higher in repair patients at 1 year (8.8% vs 3.7%, P = 0.03). Conclusion: Aortic valve repair offers comparable perioperative outcomes to aortic valve replacement in aortic regurgitation patients at the expense of higher late reintervention rate. Larger trials with long-term follow-up are required to confirm the long-term benefits of aortic valve repair. © 2019 Wiley Periodicals, Inc.

The long-term recovery rate of patients with schizophrenia-spectrum disorders has been persistently low despite the implementation of early intervention (EI) services internationally. It is, therefore, important to identify the modifiable factors during the early stage of the illness that predict long-term remission and recovery. The aim of this study is to explore the predictive value of the early stage clinical factors on the clinical remission and functional recovery at 10-year follow-up of patients with schizophrenia-spectrum disorders who received a 2-year EI service. Patients who received the EI service throughout the region of Hong Kong between 1st July 2001 and 30th June 2002 and with a diagnosis of schizophrenia-spectrum disorder were identified from the centralized hospital database (Clinical Management system, CMS). Semi-structured clinical interview was conducted at 10-year follow-up with a successful interview rate of 74.3% (n = 107). Clinical data was systematically retrieved each month for the first three years from the CMS and written clinical records using a standardized data entry form based on operationalized definitions. Results found shorter duration of untreated psychosis (DUP) predicted long-term clinical remission; higher educational level and shorter period of unemployment during the initial three years of the illness predicted functional recovery. Higher educational level, longer period of employment and planned medication discontinuation during the initial three years predicted complete recovery. The current study demonstrates the long-term impact of DUP and suggests improvement of employment during the early stage of illness could be a potential target for further improvement of the service.

PURPOSE Bipolar disorder (BPD) is often an under-addressed mental disorder. Limited studies have investigated its epidemiology and drug utilisation in Hong Kong (HK) and the United Kingdom (UK) and thus local prescribing practices remain unclear. This study aimed to determine the prevalence of BPD and the prescribing of psychotropic medications as maintenance treatment from 2001-2018 in HK and the UK. METHOD A retrospective study using the data from Clinical Data Analysis and Reporting System in HK and IQVIA Medical Research Data in the UK. RESULTS The prevalence of BPD diagnosis in HK and the UK more than doubled during the study period. Some distinct changes in prescribing patterns over time were observed. Lithium use declined by 2.46% and 14.58% in HK and the UK, respectively. By 2018, patients were 4.6 times more likely to receive antidepressant monotherapy in the UK versus HK (15.62% vs. 3.42%). In HK, 38.41% of women of childbearing age were prescribed valproate in 2018 compared with 8.46% in the UK. CONCLUSION The prevalence of BPD diagnosis has been increasing in HK and the UK. The disparity in prescribing patterns of BPD maintenance treatment in two regions reflected three major issues in clinical practice: (1) under-prescribing of lithium in both regions, (2) antidepressant monotherapy in the UK and (3) overprescribing of valproate to women of childbearing age in HK. A review of current clinical treatment guidelines and regulations of prescribing practice by local clinicians should be immediately implemented to ensure the safe use of medications in patients with BPD.

Objective: Subjective quality of life is an important outcome of psychotic disorders. However, longitudinal course of subjective quality of life in the early illness stage is under-studied. We aimed to investigate the patterns and baseline predictors of subjective quality of life trajectories over 3 years in early psychosis patients, utilizing growth mixing modeling analysis, in the context of a 3-year follow-up of a randomized controlled trial comparing 1-year extension of early intervention with step-down psychiatric care for first-episode psychosis. Method: One hundred sixty Chinese patients were recruited from specialized early intervention program for first-episode psychosis in Hong Kong after they had completed this 2-year early intervention service, and underwent 1-year randomized controlled trial as well as 2-year post–randomized controlled trial follow-up (i.e. 3-year follow-up). Assessments on premorbid adjustment, onset profile, psychopathology, functioning and treatment characteristics were conducted. Individual class membership of subjective quality of life trajectory derived from growth mixing modeling was based on the 36-Item Short Form Health Survey mental component summary scores measured at four different time-points (baseline, 1, 2 and 3 years) among 142 participants across 3-year follow-up. Results: Three distinct subjective quality of life trajectories were identified including higher-improving (68.3%, n = 97), lower-stable (24.6%, n = 35) and deteriorating (7%, n = 10) trajectories. Age of onset; duration of untreated psychosis; depressive, positive and negative symptoms; and intervention condition were significantly different between good (higher-improving trajectory) and poor (combined lower-stable and deteriorating trajectories) trajectory groups. Multiple regression analysis revealed that younger age of onset, more severe depression and receipt of step-down care independently predicted poor subjective quality of life trajectory. Conclusion: Approximately one-third of patients displayed poor subjective quality of life trajectory in the early phase of psychotic illness. Our results affirm depression as a critical determinant of prospective subjective quality of life and underscores positive effect of extended early intervention on sustained subjective quality of life improvement. Further longitudinal research is warranted to facilitate better characterization of subjective quality of life course patterns and development of targeted intervention to optimize subjective quality of life in patients with early psychosis.

Objective To perform a systematic review, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, investigating the role of lymph node dissection (LND) during nephroureterectomy (NU) for upper tract urothelial carcinoma (UTUC); focussing on survival and complication outcomes. Methods A comprehensive systematic search was completed using a combination of Medical Subject Headings terms and keywords related to UTUC and LND on multiple databases. Meta-analyses were performed when outcomes were reported under the same definition in two or more studies. Where meta-analysis was not possible, outcomes were reviewed in a narrative manner. Results A total of 21 studies were included in the qualitative analysis and 11 cohort studies in the quantitative analysis. Our review did not detect significant improvement in recurrence-free survival (RFS) (hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.41–1.92), cancer-specific survival (CSS) (HR 0.89, 95% CI 0.54–1.46) and overall survival (OS) (HR 1.10, 95% CI 0.93–1.30). However, when focussing on studies only including patients with pT2/pT3 UTUC, not performing LND significantly worsened RFS (HR 2.83, 95% CI 1.72–4.66). Reports of removing more than eight lymph nodes may also provide prognostic benefits in pN0 patients. The performance of LND was not associated with a higher rate of postoperative complications (risk ratio 1.06, 95% CI 1.00–1.13). Conclusion Overall, LND did not provide additional benefit in RFS, CSS and OS. However, there was a potential benefit in RFS in patients with muscle-invasive and advanced UTUC. LND was also not associated with increased risks of postoperative complications. Abbreviations: CIS: carcinoma in situ; CSS: cancer-specific survival; HR: hazard ratio; LND: lymph node dissection; NU: nephroureterectomy; OS: overall survival; PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses; RFS: recurrence-free survival; RoB, risk of bias; RR: risk ratio; (UT)UC: (upper tract) urothelial carcinoma

Left ventricular systolic function is a good indicator of cardiac function and a powerful predictor of adverse cardiovascular (CV) outcomes. High ratio of pre-ejection period (PEP) to ejection time (ET) is associated with reduced left ventricular systolic function. Brachial PEP (bPEP) and brachial ET (bET) can be automatically calculated from an ankle-brachial index (ABI)-form device and bPEP/bET was recently reported to be a new and useful parameter of cardiac performance. However, there were no studies evaluating the utility of bPEP/bET for prediction of CV and overall mortality in patients with acute myocardial infarction (AMI). We included 139 cases of AMI admitted to our cardiac care unit consecutively. ABI, bPEP, and bET were obtained from the ABI-form device within the 24 hours of admission. There were 87 overall and 22 CV mortality and the median follow-up to mortality event was 98 months. After multivariable analysis, high bPEP/bET was not only associated with increased long-term CV mortality (hazard ratio (HR) = 1.046; 95% confidence interval (CI): 1.005–1.088; P = 0.029), but also associated with long-term overall mortality (HR = 1.023; 95% CI: 1.001–1.045; P = 0.042). In addition, age was also a significant predictor for CV and overall mortality after the multivariable analysis. In conclusion, bPEP/bET was shown to be a significant predictor for CV and overall mortality in AMI patients after multivariable analysis. Therefore, by means of this novel parameter, we could easily find out the high-risk AMI patients with increased CV and overall mortality.

Aims This paper details the impact of COVID-19 on foot and ankle activity in the UK. It describes regional variations and COVID-19 infection rate in patients undergoing foot and ankle surgery before, during and after the first national lock-down. Patients & methods This was a multicentre, retrospective, UK-based, national audit on foot and ankle patients who underwent surgery between 13th January and 31st July 2020. Data was examined pre- UK national lockdown, during lockdown (23rd March to 11th May 2020) and post-lockdown. All adult patients undergoing foot and ankle surgery in an operating theatre during the study period included from 43 participating centres in England, Scotland, Wales and Northern Ireland. Regional, demographic and COVID-19 related data were captured. Results 6644 patients were included. In total 0.53% of operated patients contracted COVID-19 (n = 35). The rate of COVID-19 infection was highest during lockdown (2.11%, n = 16) and lowest after lockdown (0.16%, n = 3). Overall mean activity during lockdown was 24.44% of pre-lockdown activity with decreases in trauma, diabetic and elective foot and ankle surgery; the change in elective surgery was most marked with only 1.73% activity during lock down and 10.72% activity post lockdown as compared to pre-lockdown. There was marked regional variation in numbers of cases performed, but the proportion of decrease in cases during and after lockdown was comparable between all regions. There was also a significant difference between rates of COVID-19 and timing of peak, cumulative COVID-19 infections between regions with the highest rate noted in South East England (3.21%). The overall national peak infection rate was 1.37%, occurring during the final week of lockdown. General anaesthetic remained the most common method of anaesthesia for foot and ankle surgery, although a significant increase in regional anaesthesia was witnessed in the lock-down and post-lockdown periods. Conclusions National surgical activity reduced significantly for all cases across the country during lockdown with only a slow subsequent increase in elective activity. The COVID-19 infection rate and peaks differed significantly across the country. Clinical relevance This paper highlights a significant regional variation in COVID-19 infection rates and peak of COVID-19 infections across the country; this data may be useful in planning response to subsequent waves. The cumulative COVID-19 infection rates suggest that the risk of contracting COVID-19 in patients undergoing foot and ankle surgery is not insignificant. The marked decrease in, and slow recovery of elective activity seen will need to be considered when planning restoration of elective foot and ankle services.

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase 3 randomized trials. The EXPosurE Registry RiociguaT in patients with pulmonary hypertension (EXPERT) study was designed to monitor the long-term safety of riociguat in clinical practice. Methods: EXPERT was an international, multicenter, prospective, uncontrolled, non-interventional cohort study of patients treated with riociguat. Patients were followed for at least 1 year and up to 4 years from enrollment or until 30 days after stopping riociguat treatment. Primary safety outcomes were adverse events (AEs) and serious adverse events (SAEs) coded using Medical Dictionary for Regulatory Activities preferred terms and System Organ Classes version 21.0, collected during routine clinic visits and collated via case report forms. Results: In total, 956 patients with CTEPH were included in the analysis. The most common AEs in these patients were peripheral edema/edema (11.7%), dizziness (7.5%), right ventricular (RV)/cardiac failure (7.7%), and pneumonia (5.0%). The most common SAEs were RV/cardiac failure (7.4%), pneumonia (4.1%), dyspnea (3.6%), and syncope (2.5%). Exposure-adjusted rates of hemoptysis/pulmonary hemorrhage and hypotension were low and comparable to those in the long-term extension study of riociguat (Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase–Stimulator Trial [CHEST-2]). Conclusion: Data from EXPERT show that in patients with CTEPH, the safety of riociguat in routine practice was consistent with the known safety profile of the drug, and no new safety concerns were identified. © 2020 The Authors Eli Lilly and Company; Pfizer; Bayer; GlaxoSmithKline; Merck; Actelion Pharmaceuticals; Meso Scale Diagnostics; United Therapeutics Corporation; Novartis Pharma; Merck Sharp and Dohme; GlaxoSmithKline Australia; Deutsche Forschungsgemeinschaft; Grupo Ferrer Internacional, S.A The EXPERT registry was funded by Bayer AG (Berlin, Germany) and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., Kenilworth, NJ, USA. The authors acknowledge the database administration by Torsten Tille, Dresden, and the project administration of Mrs Romy Hoppenz and Mrs Linda Kottke at GWT-TUD GmbH, Dresden. Medical writing services provided by Richard Murphy PhD of Adelphi Communications Ltd, Macclesfield, UK were funded by Bayer AG in accordance with Good Publication Practice (GPP3) guidelines. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Prof Marius M. Hoeper reports personal fees from Bayer AG, during the conduct of the study; personal fees from Actelion, personal fees from Acceleron, personal fees from MSD, personal fees from Jansen, personal fees from Pfizer, outside the submitted work. Dr Hans Klose reports speaker and consultancy fees from Actelion, Bayer AG, GSK, Novartis, Pfizer, and United Therapeutics and research support from Actelion, Bayer AG, GSK, Pfizer, and MSD. Dr Michael Halank reports personal fees and non-financial support from Actelion, AstraZeneca, Bayer AG, Berlin-Chemie, GSK, OMT, MSD, and Novartis. Dr George Giannakoulas reports speaker and consultancy fees from Actelion, Bayer, ELPEN Pharmaceuticals, GSK, Pfizer, Lilly, and United Therapeutics, and research support from GSK, ELPEN Pharmaceuticals, and Galenica. Dr Henning Gall has received honoraria and/or other support from Actelion, AstraZeneca, Bayer, BMS, GSK, Janssen-Cilag, Lilly, MSD, Novartis, OMT, Pfizer, and United Therapeutics. Dr Pavel Jansa reports consultancy and speaker fees from MSD, AOP Orphan, and Actelion. Prof Ekkehard Grünig reports research grants and speaker honoraria/consultancy fees from Actelion and Bayer/MSD, research grants from GSK, United Therapeutics, Bellerophon, OMT GmbH, Pfizer, Reata, and Novartis, and speaker honoraria from Bial, Medscape, and OrPha Swiss GmbH. Prof David Pittrow reports personal fees from Actelion, Bayer AG, Aspen, Boehringer Ingelheim, Sanofi, Biogen, Shire, and MSD outside the submitted work. Silvia Ulrich reports research grants and personal fees from Actelion, Bayer, MSD, and Orpha Swiss. Tobias J. Lange has received personal fees from Actelion, MSD, Pfizer, and OMT orphan. Dr Iraklis Tsangaris reports speaker and consultancy fees from Actelion, Bayer AG, ELPEN, GSK, MSD, Pfizer, and United Therapeutics. Stephan Rosenkranz reports remunerations for lectures and/or consultancy from Abbott, Actelion, Arena, Bayer, Ferrer, GSK, MSD, Novartis, Pfizer, and United Therapeutics; and research support to his institution from Actelion, Bayer, Novartis, Pfizer, and United Therapeutics. Repke J. Snijder reports grants from Pfizer and Actelion Pharmaceuticals. Prof Iveta Šimková reports consultancy and speaker fees from MSD, AOP Orphan, and Actelion. Dr Marc Humbert reports grants and personal fees from Bayer and GSK, and personal fees from Actelion, Merck, and United Therapeutics. Marion Delcroix has received investigator, speaker, consultant, and steering committee member fees from Actelion, Bayer AG, Bellerophon, Eli Lilly, GlaxoSmithKline, MSD, Pfizer, and Reata, and research grants from Actelion. Joan A. Barberà reports receipt of honoraria for consultation or speaker fees from Actelion and Merck; and research support through his institution from Actelion, Merck, GlaxoSmithKline, and Ferrer. Joanna Pepke-Zaba reports research grants and speaker honoraria/consultancy fees from Actelion, Bayer/MSD, and GSK. Jean-Luc Vachiéry reports ongoing consultancies to Actelion, Sonnivie, Arena Pharma, Bial Portela, and Respira Therapeutics, past consultancies to AstraZeneca, BayerShering, CardioMEMS, GlaxoSmithKline, Pfizer, Merck, and United Therapeutics, and current membership of an advisory board or similar group for Actelion and GlaxoSmithKline. Jean-Luc Vachiéry's institution receives funding from Actelion Pharmaceuticals for performing clinical studies. Regina Steringer-Mascherbauer, Jens Klotsche, and Miguel-Angel Gomez Sanchez have no conflicts of interest relevant to the EXPERT study. Hossein-Ardeschir Ghofrani reports personal fees for advisory board work, and payment for lectures including service on speaker bureaus, from Actelion, Bayer, GSK, Novartis, and Pfizer; consultancy fees from Actelion, Bayer, Bellerophon Pulse Technologies, GSK, MSD, Novartis, and Pfizer; and grants from Deutsche Forschungsgemeinschaft (DFG). Pilar Escribano Subias reports personal fees from Actelion, Bayer AG, GlaxoSmithKline, and Merck Sharp & Dohme, and grants from Actelion, Bayer AG, GlaxoSmithKline, and Ferrer, outside the submitted work. Gérald Simonneau reports personal fees and non-financial support from Actelion, personal fees and non-financial support from Bayer, personal fees and non-financial support from MSD, outside the submitted work. Douglas S. Helmersen reports industry-sponsored research with Bayer AG, United Therapeutics, and Gilead Sciences, Inc., and advisory board/speaker fees from Bayer AG and Actelion. David Langleben reports honoraria, consultation fees, research support, and/or travel expenses from Actelion, Arena, Bayer AG, Northern Therapeutics, PhaseBio, Acceleron, Janssen, and United Therapeutics. Anco Boonstra reports consultancy fees from Pfizer BV and hospitality from Teva Nederland. Lisa M. Mielniczuk reports speaker fees and honoraria from Bayer AG, and speaker fees, consultancy fees, and travel fees from Actelion. Evgenia Williams and Christian Meier are employees of Bayer AG.

Objectives: The co-occurrence of different classes of population-level stressors, such as social unrest and public health crises, is common in contemporary societies. Yet, few studies explored their combined mental health impact. The aim of this study was to examine the impact of repeated exposure to social unrest-related traumatic events (TEs), coronavirus disease 2019 (COVID-19) pandemic-related events (PEs), and stressful life events (SLEs) on post-traumatic stress disorder (PTSD) and depressive symptoms, and the potential mediating role of event-based rumination (rumination of TEs-related anger, injustice, guilt, and insecurity) between TEs and PTSD symptoms. Methods: Community members in Hong Kong who had utilized a screening tool for PTSD and depressive symptoms were invited to complete a survey on exposure to stressful events and event-based rumination. Results: A total of 10,110 individuals completed the survey. Hierarchical regression analysis showed that rumination, TEs, and SLEs were among the significant predictors for PTSD symptoms (all P < 0.001), accounting for 32% of the variance. For depression, rumination, SLEs, and PEs were among the significant predictors (all P < 0.001), explaining 24.9% of the variance. Two-way analysis of variance of different recent and prior TEs showed significant dose-effect relationships. The effect of recent TEs on PTSD symptoms was potentiated by prior TEs ( P = 0.005). COVID-19 PEs and prior TEs additively contributed to PTSD symptoms, with no significant interaction ( P = 0.94). Meanwhile, recent TEs were also potentiated by SLEs ( P = 0.002). The effects of TEs on PTSD symptoms were mediated by rumination (β = 0.38, standard error = 0.01, 95% confidence interval: 0.36 to 0.41), with 40.4% of the total effect explained. All 4 rumination subtypes were significant mediators. Conclusions: Prior and ongoing TEs, PEs, and SLEs cumulatively exacerbated PTSD and depressive symptoms. The role of event-based rumination and their interventions should be prioritized for future research.

Chronic kidney disease (CKD) is a public health issue and is associated with high morbidity and mortality. How to identify the high-risk CKD patients is very important to improve the long-term outcome. CHADS2 and CHA2DS2-VASc scores are clinically useful scores to evaluate the risk of stroke in patients with atrial fibrillation. However, there was no literature discussing about the usefulness of CHADS2 and CHA2DS2-VASc scores for cardiovascular (CV) and all-cause mortality prediction in CKD patients. This longitudinal study enrolled 437 patients with CKD. CHADS2 and CHA2DS2-VASc scores were calculated for each patient. CV and all-cause mortality data were collected for long-term outcome prediction. The median follow-up to mortality was 91 (25th–75th percentile: 59–101) months. There were 66 CV mortality and 165 all-cause mortality. In addition to age and heart rate, CHADS2 and CHA2DS2-VASc scores (both P value 2DS2-VASc score had a better additive predictive value for all-cause mortality than basic model + CHADS2 score (P = 0.031). In conclusion, our study showed both of CHADS2 and CHA2DS2-VASc scores were significant predictors for long-term CV and all-cause mortality in CKD patients and CHA2DS2-VASc score had a better predictive value than CHADS2 score for all-cause mortality in direct comparison of multivariate model. Therefore, using CHADS2 and CHA2DS2-VASc scores to screen CKD patients may be helpful in identifying the high-risk group with increased mortality.

Low ankle-brachial index (ABI) and high ABI difference (ABID) are each associated with poor prognosis. No study has assessed the ability of the combination of low ABI and high ABID to predict survival. We created an ABI score by assigning 1 point for ABI < 0.9 and 1 point for ABID ≥ 0.17 and examine the ability of this ABI score to predict mortality. We included 941 patients scheduled for echocardiographic examination. The ABI was measured using an ABI-form device. ABID was calculated as |right ABI-left ABI|. Among the 941 subjects, the prevalence of ABI < 0.9 and ABID ≥ 0.17 was 6.1% and 6.8%, respectively. Median follow-up to mortality was 93 months. There were 87 cardiovascular and 228 overall deaths. All ABI-related parameters, including ABI, ABID, ABI < 0.9, ABID ≥ 0.17, and ABI score, were significantly associated with overall and cardiovascular mortality in the multivariable analysis (P ≤ 0.009). Further, in the direct comparison of multivariable models, the basic model + ABI score was the best at predicting overall and cardiovascular mortality among the five ABI-related multivariable models (P ≤ 0.049). Hence, the ABI score, a combination of ABI < 0.9 and ABID ≥ 0.17, should be calculated for better mortality prediction.

Drainage of interstitial fluid from the brain occurs via the intramural periarterial drainage (IPAD) pathways along the basement membranes of cerebral capillaries and arteries against the direction of blood flow into the brain. The cerebrovascular smooth muscle cells (SMCs) provide the motive force for driving IPAD, and their decrease in function may explain the deposition of amyloid-beta as cerebral amyloid angiopathy (CAA), a key feature of Alzheimer&rsquo, s disease. The &alpha, adrenoceptor subtype &alpha, 1A is abundant in the brain, but its distribution in the cerebral vessels is unclear. We analysed cultured human cerebrovascular SMCs and young, old and CAA human brains for (a) the presence of &alpha, 1A receptor and (b) the distribution of the &alpha, 1A receptor within the cerebral vessels. The &alpha, 1A receptor was present on the wall of cerebrovascular SMCs. No significant changes were observed in the vascular expression of the &alpha, 1A-adrenergic receptor in young, old and CAA cases. The pattern of vascular staining appeared less punctate and more diffuse with ageing and CAA. Our results show that the &alpha, 1A-adrenergic receptor is preserved in cerebral vessels with ageing and in CAA and is expressed on cerebrovascular smooth muscle cells, suggesting that vascular adrenergic receptors may hold potential for therapeutic targeting of IPAD.