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Brief measurements of the subjective experience of stress with good predictive capability are important in a range of community mental health and research settings. The potential for large-scale implementation of such a measure for screening may facilitate early risk detection and intervention opportunities. Few such measures however have been developed and validated in epidemiological and longitudinal community samples. We designed a new single-item measure of the subjective level of stress (SLS-1) and tested its validity and ability to predict long-term mental health outcomes of up to 12 months through two separate studies.
We first examined the content and face validity of the SLS-1 with a panel consisting of mental health experts and laypersons. Two studies were conducted to examine its validity and predictive utility. In study 1, we tested the convergent and divergent validity as well as incremental validity of the SLS-1 in a large epidemiological sample of young people in Hong Kong (n = 1445). In study 2, in a consecutively recruited longitudinal community sample of young people (n = 258), we first performed the same procedures as in study 1 to ensure replicability of the findings. We then examined in this longitudinal sample the utility of the SLS-1 in predicting long-term depressive, anxiety and stress outcomes assessed at 3 months and 6 months (n = 182) and at 12 months (n = 84).
The SLS-1 demonstrated good content and face validity. Findings from the two studies showed that SLS-1 was moderately to strongly correlated with a range of mental health outcomes, including depressive, anxiety, stress and distress symptoms. We also demonstrated its ability to explain the variance explained in symptoms beyond other known personal and psychological factors. Using the longitudinal sample in study 2, we further showed the significant predictive capability of the SLS-1 for long-term symptom outcomes for up to 12 months even when accounting for demographic characteristics.
The findings altogether support the validity and predictive utility of the SLS-1 as a brief measure of stress with strong indications of both concurrent and long-term mental health outcomes. Given the value of brief measures of mental health risks at a population level, the SLS-1 may have potential for use as an early screening tool to inform early preventative intervention work.
The emphasis on team science in clinical and translational research increases the importance of collaborative biostatisticians (CBs) in healthcare. Adequate training and development of CBs ensure appropriate conduct of robust and meaningful research and, therefore, should be considered as a high-priority focus for biostatistics groups. Comprehensive training enhances clinical and translational research by facilitating more productive and efficient collaborations. While many graduate programs in Biostatistics and Epidemiology include training in research collaboration, it is often limited in scope and duration. Therefore, additional training is often required once a CB is hired into a full-time position. This article presents a comprehensive CB training strategy that can be adapted to any collaborative biostatistics group. This strategy follows a roadmap of the biostatistics collaboration process, which is also presented. A TIE approach (Teach the necessary skills, monitor the Implementation of these skills, and Evaluate the proficiency of these skills) was developed to support the adoption of key principles. The training strategy also incorporates a “train the trainer” approach to enable CBs who have successfully completed training to train new staff or faculty.
Adherence problems are an inherent issue with any bio-psycho-social-spiritual prescription for any disease or behvaioural entity. It is all the more important in a patient with severe mental illness like Schizophrenia with limited insight. In several countries various interventions have been studied to address adherence problems in psychosis. Such as compliance therapy, family and psycho educational interventions, telephonic prompting and also legislative measures like Community Treatment Orders (CTO) have to date shown inconsistent and only modest benefits. Incentives based interventions have been tested for both preventive measures and also for adherence problems in chronic diseases. The Institute of Mental Health, Singapore has implemented a Pilot Supervision Programme (PSP) that incentivise patient engagement through quarterly vouchers as well as minimising barriers to accessing service by waiving off certain treatment fees whilst also offering them intensive intervention for one year. Our Pilot Programme, that focused on high risk patients with diagnosis of severe mental illness needing involuntary admission with history of either prolonged or repeated admissions, has begun recruiting patients since October 2012. The comparison was done between pre and post intervention phase. Total of 58 patients (95% suffering from schizophrenia or schizoaffective disorder) accepted into the treatment programme and of that nearly half of them have completed 6 months interventions. The results are promising with more than 50% improvemnt in length of stay, number of admissions and psychiatric emergency room visits, making significant impact on our high risk patients with severe mental illness.
Abnormal effort-based decision-making represents a potential mechanism underlying motivational deficits (amotivation) in psychotic disorders. Previous research identified effort allocation impairment in chronic schizophrenia and focused mostly on physical effort modality. No study has investigated cognitive effort allocation in first-episode psychosis (FEP).
Cognitive effort allocation was examined in 40 FEP patients and 44 demographically-matched healthy controls, using Cognitive Effort-Discounting (COGED) paradigm which quantified participants’ willingness to expend cognitive effort in terms of explicit, continuous discounting of monetary rewards based on parametrically-varied cognitive demands (levels N of N-back task). Relationship between reward-discounting and amotivation was investigated. Group differences in reward-magnitude and effort-cost sensitivity, and differential associations of these sensitivity indices with amotivation were explored.
Patients displayed significantly greater reward-discounting than controls. In particular, such discounting was most pronounced in patients with high levels of amotivation even when N-back performance and reward base amount were taken into consideration. Moreover, patients exhibited reduced reward-benefit sensitivity and effort-cost sensitivity relative to controls, and that decreased sensitivity to reward-benefit but not effort-cost was correlated with diminished motivation. Reward-discounting and sensitivity indices were generally unrelated to other symptom dimensions, antipsychotic dose and cognitive deficits.
This study provides the first evidence of cognitive effort-based decision-making impairment in FEP, and indicates that decreased effort expenditure is associated with amotivation. Our findings further suggest that abnormal effort allocation and amotivation might primarily be related to blunted reward valuation. Prospective research is required to clarify the utility of effort-based measures in predicting amotivation and functional outcome in FEP.
We studied trends in the incidence of health care-associated infections (HAIs) in LTCFs between 2009 and 2015 and determined the effect of participation in our network. Elder-care physicians reported weekly the number of cases of influenza-like illness, gastroenteritis, (probable) pneumonia, urinary tract infections (UTIs) and all-cause mortality. Trends in the incidence of infection and mortality in relation to LTCF characteristics were calculated using multilevel univariate and multivariate logistic regression. Thirty LTCF participated for 3 years or more, 16 for 2 years and the remaining 12 LTCF for 1 year. During the study period, the median number of beds decreased from 158 to 139, whereas the percentage of residents with private bedrooms increased from 14% to 87%. UTIs were the most frequently reported infections, followed by (probable) pneumonia and gastroenteritis. Adjusted for calendar year and season, we observed a statistically significant decrease in the incidence of influenza-like illness (odds ratio (OR) = 0.8, P < 0.01) and (probable) pneumonia (OR = 0.8, P < 0.01) for each extra year an LTCF participated. Although there are other likely contributors, such as more private rooms and enhanced infection control measures, the decreasing trend of HAI in LTCFs participating in surveillance implies that surveillance is a valuable addition to current strategies to optimise infection control.
Better understanding of interplay among symptoms, cognition and functioning in first-episode psychosis (FEP) is crucial to promoting functional recovery. Network analysis is a promising data-driven approach to elucidating complex interactions among psychopathological variables in psychosis, but has not been applied in FEP.
This study employed network analysis to examine inter-relationships among a wide array of variables encompassing psychopathology, premorbid and onset characteristics, cognition, subjective quality-of-life and psychosocial functioning in 323 adult FEP patients in Hong Kong. Graphical Least Absolute Shrinkage and Selection Operator (LASSO) combined with extended Bayesian information criterion (BIC) model selection was used for network construction. Importance of individual nodes in a generated network was quantified by centrality analyses.
Our results showed that amotivation played the most central role and had the strongest associations with other variables in the network, as indexed by node strength. Amotivation and diminished expression displayed differential relationships with other nodes, supporting the validity of two-factor negative symptom structure. Psychosocial functioning was most strongly connected with amotivation and was weakly linked to several other variables. Within cognitive domain, digit span demonstrated the highest centrality and was connected with most of the other cognitive variables. Exploratory analysis revealed no significant gender differences in network structure and global strength.
Our results suggest the pivotal role of amotivation in psychopathology network of FEP and indicate its critical association with psychosocial functioning. Further research is required to verify the clinical significance of diminished motivation on functional outcome in the early course of psychotic illness.
The aim of the study was to investigate any association between extrauterine growth restriction (EUGR) and intestinal flora of <30-week-old preterm infants. A total of 59 preterm infants were assigned to EUGR (n=23) and non-EUGR (n=36) groups. Intestinal bacteria were compared by using high-throughput sequencing of bacterial rRNA. The total abundance of bacteria in 344 genera (7568 v. 13,760; P<0.0001) and 456 species (10,032 v. 18,240; P<0.0001) was significantly decreased in the EUGR group compared with the non-EUGR group. After application of a multivariate logistic model and adjusting for potential confounding factors, as well as false-discovery rate corrections, we found four bacterial genera with higher and one bacterial genus with lower abundance in the EUGR group compared with the control group. In addition, the EUGR group showed significantly increased abundances of six species (Streptococcus parasanguinis, Bacterium RB5FF6, two Klebsiella species and Microbacterium), but decreased frequencies of three species (one Acinetobacter species, Endosymbiont_of_Sphenophorus_lev and one Enterobacter_species) compared with the non-EUGR group. Taken together, there were significant changes in the intestinal microflora of preterm infants with EUGR compared to preterm infants without EUGR.
Better understanding of the complex interplay among key determinants of functional outcome is crucial to promoting recovery in psychotic disorders. However, this is understudied in the early course of illness. We aimed to examine the relationships among negative symptoms, neurocognition, general self-efficacy and global functioning in first-episode psychosis (FEP) patients using structural equation modeling (SEM).
Three hundred and twenty-one Chinese patients aged 26–55 years presenting with FEP to an early intervention program in Hong Kong were recruited. Assessments encompassing symptom profiles, functioning, perceived general self-efficacy and a battery of neurocognitive tests were conducted. Negative symptom measurement was subdivided into amotivation and diminished expression (DE) domain scores based on the ratings in the Scale for the Assessment of Negative Symptoms.
An initial SEM model showed no significant association between functioning and DE which was removed from further analysis. A final trimmed model yielded very good model fit (χ2 = 15.48, p = 0.63; comparative fit index = 1.00; root mean square error of approximation <0.001) and demonstrated that amotivation, neurocognition and general self-efficacy had a direct effect on global functioning. Amotivation was also found to mediate a significant indirect effect of neurocognition and general self-efficacy on functioning. Neurocognition was not significantly related to general self-efficacy.
Our results indicate a critical intermediary role of amotivation in linking neurocognitive impairment to functioning in FEP. General self-efficacy may represent a promising treatment target for improvement of motivational deficits and functional outcome in the early illness stage.
Relapse is distressingly common after the first episode of psychosis, yet it is poorly understood and difficult to predict. Investigating changes in cognitive function preceding relapse may provide new insights into the underlying mechanism of relapse in psychosis. We hypothesized that relapse in fully remitted first-episode psychosis patients was preceded by working memory deterioration.
Visual memory and verbal working memory were monitored prospectively in a 1-year randomized controlled trial of remitted first-episode psychosis patients assigned to medication continuation (quetiapine 400 mg/day) or discontinuation (placebo). Relapse (recurrence of positive symptoms of psychosis), visual (Visual Patterns Test) and verbal (Letter–Number span test) working memory and stressful life events were assessed monthly.
Remitted first-episode patients (n = 102) participated in the study. Relapsers (n = 53) and non-relapsers (n = 49) had similar baseline demographic and clinical profiles. Logistic regression analyses indicated relapse was associated with visual working memory deterioration 2 months before relapse [odds ratio (OR) 3.07, 95% confidence interval (CI) 1.19–7.92, P = 0.02], more stressful life events 1 month before relapse (OR 2.11, 95% CI 1.20–3.72, P = 0.01) and medication discontinuation (OR 5.52, 95% CI 2.08–14.62, P = 0.001).
Visual working memory deterioration beginning 2 months before relapse in remitted first-episode psychosis patients (not baseline predictor) may reflect early brain dysfunction that heralds a psychotic relapse. The deterioration was found to be unrelated to a worsening of psychotic symptoms preceding relapse. Testable predictors offer insight into the brain processes underlying relapse in psychosis.
Delusional disorder (DD) is thought to be distinct from schizophrenia (SZ). However, few systematic investigations have been conducted on DD because of the difficulty in ascertaining a representative sample size. Existing knowledge has been mostly generated from inpatient cohorts, which may be biased towards a more severe sample.
We compared the demographic, clinical and cognitive differences between 71 patients with first-episode DD and 71 age-matched patients with first-episode SZ. Participants were consecutively recruited from a population-based territory-wide study of early psychosis in Hong Kong targeting first-episode psychosis. Basic demographic information, premorbid functioning, duration of untreated psychosis, pathways to care, symptomatology, social, occupational, and cognitive functioning were comprehensively assessed using standardized measurements.
Patients with DD had less premorbid schizoid and schizotypal traits compared to patients with SZ. More patients with DD were married compared to patients with SZ. However, at first episode, there were no significant differences between the two groups in regards to the duration of untreated psychosis, pathways to care, symptom severity, neurocognitive performance, treatment, and functioning.
Our findings challenge previous thinking that patients with DD had better functioning than patients with SZ. This study not only provides an updated perspective into conceptualizing the clinical differences between DD and SZ, but also expands the descriptive account of the two disorders to include the neurocognitive dimension.
Despite evidence on the short-term benefits of early intervention (EI) service for psychosis, long-term outcome studies are limited by inconsistent results. This study examined the 10-year outcomes of patients with first-episode psychosis who received 2-year territory-wide EI service compared to those who received standard care (SC) in Hong Kong using an historical control design.
Consecutive patients who received the EI service between 1 July 2001 and 30 June 2002, and with diagnosis of schizophrenia-spectrum disorders, were identified and matched with patients who received SC first presented to the public psychiatric service from 1 July 2000 to 30 June 2001. In total, 148 matched pairs of patients were identified. Cross-sectional information on symptomatology and functioning was obtained through semi-structured interview; longitudinal information on hospitalization, functioning, suicide attempts, mortality and relapse over 10 years was obtained from clinical database. There were 70.3% (N = 104) of SC and 74.3% (N = 110) of EI patients interviewed.
Results suggested that EI patients had reduced suicide rate (χ2(1) = 4.35, p = 0.037), fewer number [odds ratio (OR) 1.56, χ2 = 15.64, p < 0.0001] and shorter duration of hospitalization (OR 1.29, χ2 = 4.06, p = 0.04), longer employment periods (OR −0.28, χ2 = 14.64, p < 0.0001) and fewer suicide attempts (χ2 = 11.47, df = 1, p = 0.001) over 10 years. At 10 years, no difference was found in psychotic symptoms, symptomatic remission and functional recovery.
The short-term benefits of the EI service on number of hospitalizations and employment was sustained after service termination, but the differences narrowed down. This suggests the need to evaluate the optimal duration of the EI service.
Cognitive impairment is a core feature of schizophrenia. Its relationship with duration of untreated psychosis (DUP), a potentially malleable prognostic factor, has been less studied, with inconsistent findings being observed in the literature. Previous research investigating such a relationship was mostly cross-sectional and none of those prospective studies had a follow-up duration beyond 2 years.
A total of 93 Hong Kong Chinese aged 18 to 55 years presenting with first-episode schizophrenia-spectrum disorder were studied. DUP and pre-morbid adjustment were measured using a structured interview incorporating multiple sources of information. Psychopathological evaluation was administered at intake, after clinical stabilization of the first psychotic episode, and at 12, 24 and 36 months. Cognitive functions were measured at clinical stabilization, and at 12, 24 and 36 months.
DUP exerted differential effects on various cognitive domains, with memory deficits being the most related to DUP even when potential confounders including pre-morbid adjustment and sex were adjusted. Prolonged DUP was associated with more severe impairment in visual memory at clinical stabilization and verbal memory at 24 and 36 months. Further, patients with a long DUP were found to have worse outcomes on negative symptoms at 36 months. The effects of DUP on verbal memory remained significant even when negative symptoms were taken into consideration.
Our findings provided further supportive evidence that delayed treatment to first-episode psychosis is associated with poorer cognitive and clinical outcomes. In addition, DUP may specifically affect memory function and its adverse impact on verbal memory may only become evident at a later stage of the recovery process.
We present a short Chandra observation that confirms a previous unidentified extended X-ray source, G308.3-1.4, as a new supernova remnant (SNR) in the Milky Way. Apart from identifying its SNR nature, a bright X-ray point source has also been discovered at the geometrical center. Its X-ray spectral properties are similar to those of a particular class of neutron star known as central compact objects (CCOs). On the other hand, the optical properties of this counterpart suggests it to be a late-type star. Together with the interesting ~ 1.4 hours X-ray periodicity found by Chandra, this system can possibly provide the first direct evidence of a compact binary survived in a supernova explosion.
We investigated cerebral structural connectivity and its relationship to symptoms in never-medicated individuals with first-onset schizophrenia using diffusion tensor imaging (DTI).
We recruited subjects with first episode DSM-IV schizophrenia who had never been exposed to antipsychotic medication (n=34) and age-matched healthy volunteers (n=32). All subjects received DTI and structural magnetic resonance imaging scans. Patients' symptoms were assessed on the Positive and Negative Syndrome Scale. Voxel-based analysis was performed to investigate brain regions where fractional anisotropy (FA) values significantly correlated with symptom scores.
In patients with first-episode schizophrenia, positive symptoms correlated positively with FA scores in white matter associated with the right frontal lobe, left anterior cingulate gyrus, left superior temporal gyrus, right middle temporal gyrus, right middle cingulate gyrus, and left cuneus. Importantly, FA in each of these regions was lower in patients than controls, but patients with more positive symptoms had FA values closer to controls. We found no significant correlations between FA and negative symptoms.
The newly-diagnosed, neuroleptic-naive patients had lower FA scores in the brain compared with controls. There was positive correlation between FA scores and positive symptoms scores in frontotemporal tracts, including left fronto-occipital fasciculus and left inferior longitudinal fasciculus. This implies that white matter dysintegrity is already present in the pre-treatment phase and that FA is likely to decrease after clinical treatment or symptom remission.
Precise wafer-to-wafer alignment accuracy is crucial to interconnecting circuits on different wafers in three dimensional integrated circuits. We discuss the use of fabricated structures on wafer surfaces to mechanically achieve higher alignment accuracy than can be achieved with our existing (baseline) alignment protocol. The keyed alignment structures rely on structures with tapered side-walls that can slide into each after two wafers are “pre-aligned” using our baseline alignment protocol. Results indicate that alignment accuracy is about a quarter micron, well below the one micron alignment accuracy obtained in our baseline alignment procedure using commercial state-of-the-art wafer alignment equipment. In addition to improving alignment, the alignment structures also hinder undesirable bonding-induced misalignment. The keyed alignment structures are also promising for nano-imprint lithography.