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The hyper-function of the striatal dopamine system has been suggested to underlie key pathophysiological mechanisms in schizophrenia. Moreover, patients have been observed to present a significant elevation of dopamine receptor availability compared to healthy controls. Although it is difficult to measure dopamine levels directly in humans, neurochemical imaging techniques such as single-photon emission computed tomography (SPECT) provide indirect indices of in vivo dopamine synthesis and release, and putative synaptic levels.
We focused on the role of dopamine postsynaptic regulation using [123I] iodobenzamide (IBZM) SPECT. We compared D2/3 receptor availability between 53 healthy controls and 21 medication-naive patients with recent-onset schizophrenia.
The mean specific striatal binding showed no significant difference between patients and controls (estimated difference = 0.001; 95% CI −0.11 to 0.11; F = 0.00, df = 1, 69; p = 0.99). There was a highly significant effect of age whereby IBZM binding declined with advancing age [estimated change per decade of age = −0.01(binding ratio); 95% CI −0.01 to −0.004; F = 11.5, df = 1, 69; p = 0.001]. No significant correlations were found between the mean specific striatal binding and psychopathological or cognitive rating scores.
Medication-naïve patients with recent-onset schizophrenia have similar D2/3 receptor availability to healthy controls. We suggest that, rather than focusing exclusively on postsynaptic receptors, future treatments should target the presynaptic control of dopamine synthesis and release.
Antipsychotics are widely used for treating patients with psychosis, and target threshold psychotic symptoms. Individuals at clinical high risk (CHR) for psychosis are characterized by subthreshold psychotic symptoms. It is currently unclear who might benefit from antipsychotic treatment. Our objective was to apply a risk calculator (RC) to identify people that would benefit from antipsychotics.
Drawing on 400 CHR individuals recruited between 2011 and 2016, 208 individuals who received antipsychotic treatment were included. Clinical and cognitive variables were entered into an individualized RC for psychosis; personal risk was estimated and 4 risk components (negative symptoms-RC-NS, general function-RC-GF, cognitive performance-RC-CP, and positive symptoms-RC-PS) were constructed. The sample was further stratified according to the risk level. Higher risk was defined based on the estimated risk score (20% or higher).
In total, 208 CHR individuals received daily antipsychotic treatment of an olanzapine-equivalent dose of 8.7 mg with a mean administration duration of 58.4 weeks. Of these, 39 (18.8%) developed psychosis within 2 years. A new index of factors ratio (FR), which was derived from the ratio of RC-PS plus RC-GF to RC-NS plus RC-CP, was generated. In the higher-risk group, as FR increased, the conversion rate decreased. A small group (15%) of CHR individuals at higher-risk and an FR >1 benefitted from the antipsychotic treatment.
Through applying a personal risk assessment, the administration of antipsychotics should be limited to CHR individuals with predominantly positive symptoms and related function decline. A strict antipsychotic prescription strategy should be introduced to reduce inappropriate use.
To evaluate age-related differences in the independent/combined association of added sugar intake from soda and body adiposity with hyperuricaemia in gender-stratified US adults.
Consumption of added sugar from soda was calculated from 24-h dietary interviews and categorised into none, regular and excessive consumption. Hyperuricaemia was defined as serum uric acid levels >417 mmol/l in men and >357 mmol/l in women. Multiple regression models with interaction terms and logistic models adjusted for covariates were conducted under survey-data modules.
National Health and Nutrition Examination Survey during 2007–2016.
15 338 adults without gout, failing kidneys, an estimated glomerular filtration rate < 30 or diabetes were selected.
The age-stratified prevalence rate of hyperuricaemia was 18·8–20·4 % in males and 6·8–17·3 % in females. Hyperuricaemia prevalence of approximately 50 % was observed in young and middle age males who consumed excessive added sugar from soda. Excessive added sugar intake was observed to be associated with 1·5- to 2·0-fold and 2·0- to 2·3-fold increased risk of the probability of hyperuricaemia in young and middle age males and middle age females, respectively. Study participants, regardless of age or gender, who were obese and consumed excessive added sugar from soda had the highest risk of having hyperuricaemia.
Our study revealed that the association between hyperuricaemia and consumption of excessive added sugar from soda may vary by age and gender. Obese adults who consumed excessive added sugar from soda had the highest risk of hyperuricaemia, a finding that was found across all age-specific groups for both genders.
Shortages of personal protective equipment during the coronavirus disease 2019 (COVID-19) pandemic have led to the extended use or reuse of single-use respirators and surgical masks by frontline healthcare workers. The evidence base underpinning such practices warrants examination.
To synthesize current guidance and systematic review evidence on extended use, reuse, or reprocessing of single-use surgical masks or filtering face-piece respirators.
We used the World Health Organization, the European Centre for Disease Prevention and Control, the US Centers for Disease Control and Prevention, and Public Health England websites to identify guidance. We used Medline, PubMed, Epistemonikos, Cochrane Database, and preprint servers for systematic reviews.
Two reviewers conducted screening and data extraction. The quality of included systematic reviews was appraised using AMSTAR-2. Findings were narratively synthesized.
In total, 6 guidance documents were identified. Levels of detail and consistency across documents varied. They included 4 high-quality systematic reviews: 3 focused on reprocessing (decontamination) of N95 respirators and 1 focused on reprocessing of surgical masks. Vaporized hydrogen peroxide and ultraviolet germicidal irradiation were highlighted as the most promising reprocessing methods, but evidence on the relative efficacy and safety of different methods was limited. We found no well-established methods for reprocessing respirators at scale.
Evidence on the impact of extended use and reuse of surgical masks and respirators is limited, and gaps and inconsistencies exist in current guidance. Where extended use or reuse is being practiced, healthcare organizations should ensure that policies and systems are in place to ensure these practices are carried out safely and in line with available guidance.
There is growing interest globally in using real-world data (RWD) and real-world evidence (RWE) for health technology assessment (HTA). Optimal collection, analysis, and use of RWD/RWE to inform HTA requires a conceptual framework to standardize processes and ensure consistency. However, such framework is currently lacking in Asia, a region that is likely to benefit from RWD/RWE for at least two reasons. First, there is often limited Asian representation in clinical trials unless specifically conducted in Asian populations, and RWD may help to fill the evidence gap. Second, in a few Asian health systems, reimbursement decisions are not made at market entry; thus, allowing RWD/RWE to be collected to give more certainty about the effectiveness of technologies in the local setting and inform their appropriate use. Furthermore, an alignment of RWD/RWE policies across Asia would equip decision makers with context-relevant evidence, and improve timely patient access to new technologies. Using data collected from eleven health systems in Asia, this paper provides a review of the current landscape of RWD/RWE in Asia to inform HTA and explores a way forward to align policies within the region. This paper concludes with a proposal to establish an international collaboration among academics and HTA agencies in the region: the REAL World Data In ASia for HEalth Technology Assessment in Reimbursement (REALISE) working group, which seeks to develop a non-binding guidance document on the use of RWD/RWE to inform HTA for decision making in Asia.
Non-medical opioid use (NMOU) is a growing crisis. Cancer patients at elevated risk of NMOU (+risk) are frequently underdiagnosed. The aim of this paper was to develop a nomogram to predict the probability of +risk among cancer patients receiving outpatient supportive care consultation at a comprehensive cancer center.
3,588 consecutive patients referred to a supportive care clinic were reviewed. All patients had a diagnosis of cancer and were on opioids for pain. All patients were assessed using the Edmonton Symptom Assessment Scale (ESAS), Screener and Opioid Assessment for Patients with Pain (SOAPP-14), and CAGE-AID (Cut Down-Annoyed-Guilty-Eye Opener) questionnaires. “+risk” was defined as an SOAPP-14 score of ≥7. A nomogram was devised based on the risk factors determined by the multivariate logistic regression model to estimate the probability of +risk.
731/3,588 consults were +risk. +risk was significantly associated with gender, race, marital status, smoking status, depression, anxiety, financial distress, MEDD (morphine equivalent daily dose), and CAGE-AID score. The C-index was 0.8. A nomogram was developed and can be accessed at https://is.gd/soappnomogram. For example, for a male Hispanic patient, married, never smoked, with ESAS scores for depression = 3, anxiety = 3, financial distress = 7, a CAGE score of 0, and an MEDD score of 20, the total score is 9 + 9+0 + 0+6 + 10 + 23 + 0+1 = 58. A nomogram score of 58 indicates the probability of +risk of 0.1.
Significance of results
We established a practical nomogram to assess the +risk. The application of a nomogram based on routinely collected clinical data can help clinicians establish patients with +risk and positively impact care planning.
OBJECTIVES/GOALS: We sought to examine: 1) variability in center acceptance patterns for heart allografts offered to the highest-priority candidates, 2) impact of this acceptance behavior on candidate survival, and 3) post-transplantation outcomes in candidates who accepted first rank offer vs. previously declined offer. METHODS/STUDY POPULATION: In this retrospective cohort study, the US national transplant registry was queried for all match runs of adult candidates listed for isolated heart transplantation between 2007-2017. We examined center acceptance rates for heart allografts offered to the highest-priority candidates and accounted for covariates in multivariable logistic regression. Competing risks analysis was performed to assess the relationship between center acceptance rate and waitlist mortality. Post-transplantation outcomes (patient survival and graft failure) between candidates who accepted their first-rank offers vs those who accepted previously declined offers were compared using Fine-Gray subdistribution hazards model. RESULTS/ANTICIPATED RESULTS: Among 19,703 unique organ offers, 6,302 (32%) were accepted for first-ranked candidates. After adjustment for donor, recipient, and geographic covariates, transplant centers varied markedly in acceptance rates (12%-62%) of offers made to first-ranked candidates. Lowest acceptance rate centers (<25%) associated with highest cumulative incidence of waitlist mortality. For every 10% increase in adjusted center acceptance rate, waitlist mortality risk decreased by 27% (SHR 0.73, 95% CI 0.67-0.80). No significant difference was observed in 5-year adjusted post-Tx survival and graft failure between hearts accepted at the first-rank vs lower-rank positions. DISCUSSION/SIGNIFICANCE OF IMPACT: Wide variability in heart acceptance rates exists among centers, with candidates listed at low acceptance rate centers more likely to die waiting. Similar post-Tx survival suggests previously declined allografts function as well as those accepted at first offer. Center-level decision is a modifiable behavior associated with waitlist mortality.
The extent of intertidal flats in the Yellow Sea region has declined significantly in the past few decades, resulting in severe population declines in several waterbird species. The Yellow Sea region holds the primary stopover sites for many shorebirds during their migration to and from northern breeding grounds. However, the functional roles of these sites in shorebirds’ stopover ecology remain poorly understood. Through field surveys between July and November 2015, we investigated the stopover and moult schedules of migratory shorebirds along the southern Jiangsu coast, eastern China during their southbound migration, with a focus on the ‘Critically Endangered’ Spoon-billed Sandpiper Calidris pygmaea and ‘Endangered’ Nordmann’s Greenshank Tringa guttifer. Long-term count data indicate that both species regularly occur in globally important number in southern Jiangsu coast, constituting 16.67–49.34% and 64.0–80.67% of their global population estimates respectively, and it is highly likely that most adults undergo their primary moult during this southbound migration stopover. Our results show that Spoon-billed Sandpiper and Nordmann’s Greenshank staged for an extended period of time (66 and 84 days, respectively) to complete their primary moult. On average, Spoon-billed Sandpipers and Nordmann’s Greenshanks started moulting primary feathers on 8 August ± 4.52 and 27 July ± 1.56 days respectively, and their moult durations were 72.58 ± 9.08 and 65.09 ± 2.40 days. In addition, some individuals of several other shorebird species including the ‘Endangered’ Great Knot Calidris tenuirostris, ‘Near Threatened’ Bar-tailed Godwit Limosa lapponica, ‘Near Threatened’ Eurasian Curlew Numenius arquata and Greater Sand Plover Charadrius leschenaultii also underwent primary moult. Our work highlights the importance of the southern Jiangsu region as the primary moulting ground for these species, reinforcing that conservation of shorebird habitat including both intertidal flats and supratidal roosting sites in this region is critical to safeguard the future of some highly threatened shorebird species.
Currently there is no consensus regarding how long anti-psychotics medication should be continued following a first/single psychotic episode. Clinically patients often request discontinuation after a period of remission. This is one of the first double-blind randomized-controlled studies designed to address the issue.
Patients with DSM-IV schizophrenia and related psychoses (excluding substance induced psychosis) who remitted well following a first/single-episode, and had remained well on maintenance medication for one year, were randomized to receive either maintenance therapy with quetiapine (400 mg/day), or placebo for 12 months. Relapse was defined by the presence of (i) an increase in at least one of the following PANSS psychotic symptom items to a threshold score (delusion, hallucinatory behaviour, conceptual disorganization, unusual thought content, suspiciousness); (ii) CGI Severity of Illness 3 or above; and (iii) CGI Improvement 5 or above.
178 patients were randomized. 144 patients completed the study (80.9%). The relapse rate was 33.7% (30/89) for the maintenance group and 66.3% (59/89) for the placebo group (log-rank test, chi-square=13.328, p<0.001). Relapse was not related to age or gender. Other significant predictors of relapse include medication status, pre-morbid schizotypal traits, verbal memory and soft neurological signs.
There is a substantial risk of relapse if medication is discontinued in remitted first-episode psychosis patients following one year of maintenance therapy. On the contrary 33.7% of patients discontinued medication and remained well.
Medication discontinuation in remitted single episode patients after a period of maintenance therapy is a major clinical decision and thus the identification of risk factors controlling for medication status is important.
Following a first/single episode with DSM-IV schizophrenia and related psychoses, remitted patients who had remained well on maintenance medication for at least one year were randomized to receive either maintenance therapy (with quetiapine 400 mg/day), or placebo for 12 months.
178 patients were randomized. Relapse rates were 33.7% (30/89) in maintenance group and 66.3% (59/89) in placebo group. Potential predictors were initially identified in univariate Cox regression models (p<0.1) and were subsequently entered into a multivariate Cox regression model for measuring the relapse risk. Significant predictors included patients on placebo (hazard ratio, 0.41; CI, 0.25 – 0.68; p=0.001); having more pre-morbid schizotypal traits (hazard ratio, 2.32; CI, 1.33 – 4.04; p=0.003); scoring lower in the logical memory test (hazard ratio, 0.94; CI, 0.9 – 0.99; p=0.028); and having more soft neurological signs (disinhibition) (hazard ratio, 1.33; CI, 1.02 – 1.74; p=0.039).
Relapse predictors may help to inform clinical decisions about discontinuation of maintenance therapy specifically for patients with a first/single episode psychosis following at least one year of maintenance therapy.
We are grateful to Dr TJ Yao at the Clinical Trials Center, University of Hong Kong, for statistical advice. The study was supported by investigator initiated trial award from AstraZeneca and the Research Grants Council Hong Kong (Project number: 765505).
It is known that Sexual Dysfunction (SD) is higher in patient with depression than in the general population. Though antidepressant seems to worsen the situation, there are also indications that the gender may play a role on it.
Evaluate the gender effect of sexual function among unmedicated MDD, MDD receiving antidepressant, and healthy controls.
The sample was formed by male and female Taiwanese outpatients in three age and sex matched groups, with sixty nine participants per group: unmedicated MDD, MDD receiving antidepressant, and healthy controls. the diagnoses of depressions were performed according DSM-IV and Taiwanese Depression Questionnaire. SD was evaluated with the Chinese version of the Changes in Sexual Functioning Questionnaire. Finally, the data was analyzed using SPSS software v17. Mixed designed ANOVA was used.
There are significant differences between males and females CSFQ results (sex main effect F = 82.44, p < 0.001) and between groups (group main effect F = 3.48, p = 0.034). Additionally, the 2-way interaction between sex and group was also significant (F = 3.40, p = 0.036). Simple main effect analysis shows differences among male participants, between healthy and medicated males (F = 11.41, p = 0.002), but not in female (F = 1.58, p = 0.21). However the statistics weren’t different between females groups, the medicated expresses better results (similar to healthy group) than the unmedicated one.
SD is different between genders in each of the groups. Antidepressant seems to increase SD in man, while improves sexual satisfaction/function among depressive woman. We speculate that psychological improvement after treatment may have different impact between genders on sexual satisfaction.
The mesolimbic dopaminergic system has been implicated in two kinds of reward processing, one in reinforcement learning (e.g prediction error) and another in incentive salience attribution (e.g. cue-reactivity). Both functions have been implicated in alcohol dependence with the former contributing to the persistence of chronic alcohol intake despite severe negative consequences and the latter playing a crucial role in cue-induced craving and relapse. The bicentric study “Learning in alcohol dependence (LeAD)” aims to bridge a gap between these processes by investigating reinforcement learning mechanisms and the influence that Pavlovian cues exert over behavior. We here demonstrate that alcohol dependent subjects show alterations in goal-directed, model-based reinforcement learning (Sebold et al., 2014) and demonstrate that prospective relapsing patients show reductions in the medial prefrontal cortex activation during goal-directed control. Moreover we show that in alcohol dependent patients compared to healthy controls, Pavlovian cues exert pronounced control over behavior (Garbusow et al., 2016). Again, prospective relapsing patients showed increased Nucleus accumbens activation during these cue-induced responses. These findings point to an important role of the mesolimbic dopaminergic system as a predictor of treatment outcome in alcohol dependence.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Experience of emotion is closely linked to valuation. Mood can be viewed as a bias to experience positive or negative emotions and abnormally biased subjective reward valuation and cognitions are core characteristics of major depression.
Thirty-four unmedicated subjects with major depressive disorder and controls estimated the probability that fractal stimuli were associated with reward, based on passive observations, so they could subsequently choose the higher of either their estimated fractal value or an explicitly presented reward probability. Using model-based functional magnetic resonance imaging, we estimated each subject's internal value estimation, with psychophysiological interaction analysis used to examine event-related connectivity, testing hypotheses of abnormal reward valuation and cingulate connectivity in depression.
Reward value encoding in the hippocampus and rostral anterior cingulate was abnormal in depression. In addition, abnormal decision-making in depression was associated with increased anterior mid-cingulate activity and a signal in this region encoded the difference between the values of the two options. This localised decision-making and its impairment to the anterior mid-cingulate cortex (aMCC) consistent with theories of cognitive control. Notably, subjects with depression had significantly decreased event-related connectivity between the aMCC and rostral cingulate regions during decision-making, implying impaired communication between the neural substrates of expected value estimation and decision-making in depression.
Our findings support the theory that abnormal neural reward valuation plays a central role in major depressive disorder (MDD). To the extent that emotion reflects valuation, abnormal valuation could explain abnormal emotional experience in MDD, reflect a core pathophysiological process and be a target of treatment.
Only 30% or fewer of individuals at clinical high risk (CHR) convert to full psychosis within 2 years. Efforts are thus underway to refine risk identification strategies to increase their predictive power. Our objective was to develop and validate the predictive accuracy and individualized risk components of a mobile app-based psychosis risk calculator (RC) in a CHR sample from the SHARP (ShangHai At Risk for Psychosis) program.
In total, 400 CHR individuals were identified by the Chinese version of the Structured Interview for Prodromal Syndromes. In the first phase of 300 CHR individuals, 196 subjects (65.3%) who completed neurocognitive assessments and had at least a 2-year follow-up assessment were included in the construction of an RC for psychosis. In the second phase of the SHARP sample of 100 subjects, 93 with data integrity were included to validate the performance of the SHARP-RC.
The SHARP-RC showed good discrimination of subsequent transition to psychosis with an AUC of 0.78 (p < 0.001). The individualized risk generated by the SHARP-RC provided a solid estimation of conversion in the independent validation sample, with an AUC of 0.80 (p = 0.003). A risk estimate of 20% or higher had excellent sensitivity (84%) and moderate specificity (63%) for the prediction of psychosis. The relative contribution of individual risk components can be simultaneously generated. The mobile app-based SHARP-RC was developed as a convenient tool for individualized psychosis risk appraisal.
The SHARP-RC provides a practical tool not only for assessing the probability that an individual at CHR will develop full psychosis, but also personal risk components that might be targeted in early intervention.
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.
This paper presents a comparative study on three types of slim coil structures used as a three-dimensional (3-D) receiver in a wireless power transfer system with a planar transmitter coil. The mutual coupling values and their variations between the receiver structures and the transmitter coil are compared under different distances and angular orientations with respect to the transmitter coil. The merits of performance are related to the consistency of the mutual coupling values under different orientations in a range of distances from the transmitter coil. The practical results show that slim 3-D receiver coil structures can be compatible with a planar transmitter coil with reasonably high-mutual coupling.
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.