Detection of significant liver fibrosis in Chinese psoriasis patients receiving methotrexate: a comparison between transient elastography and liver histology.

INTRODUCTION: Methotrexate (MTX) is effective for treating psoriasis and psoriatic arthritis, but its potential hepatoxicity remains a concern. Liver biopsy, the gold standard for detecting MTX-induced liver injury, is invasive and carries considerable risk. Transient elastography (TE) offers a non-invasive alternative for detecting advanced liver fibrosis. This study investigated the performance of TE in detecting MTX-induced liver fibrosis among Chinese psoriasis patients, compared with liver biopsy. METHODS: This study included adult patients with clinical psoriasis. Liver stiffness measurement using TE was performed in patients receiving MTX. Exclusion criteria were known liver cirrhosis, positive viral hepatitis carrier status, or conditions influencing TE performance. Liver biopsy was performed when liver stiffness was ≥7.1 kilopascals (kPa) or when the total cumulative dose (TCD) of MTX was ≥3.5 g. RESULTS: A total of 228 patients were screened; among 34 patients who met the inclusion criteria, nine (26.5%) had significant liver fibrosis (Roenigk grade ≥3a). The area under the receiver operating characteristic curve was 0.76 (95% confidence interval=0.59-0.93; P=0.021), indicating that TE had satisfactory performance in detecting liver fibrosis. A cut-off value of 7.1 kPa of liver stiffness yielded 100% sensitivity and 68% specificity. Liver fibrosis was not correlated with the TCD of MTX or the duration of MTX use; it was significantly correlated with obesity and diabetes status (body mass index ≥30 kg/m2, waist circumference ≥138 cm, and glycated haemoglobin level ≥7.8%). CONCLUSION: Transient elastography is reliable and superior to the TCD for detecting liver fibrosis in Chinese psoriasis patients receiving MTX. Liver biopsy should be reserved for high-risk patients or patients with liver stiffness ≥11.7 kPa on TE.

Cutaneous manifestations, viral load, and prognosis among hospitalised patients with COVID-19: a cohort study.

INTRODUCTION: Various cutaneous manifestations have been reported as symptoms of coronavirus disease 2019 (COVID-19), which may facilitate early clinical diagnosis and management. This study explored the incidence of cutaneous manifestations among hospitalised patients with COVID-19 and investigated its relationships with viral load, co-morbidities, and outcomes. METHODS: This retrospective study included adult patients admitted to a tertiary hospital for COVID-19 from July to September 2020. Clinical information, co-morbidities, viral load (cycle threshold [Ct] value), and outcomes were analysed. RESULTS: In total, 219 patients with confirmed COVID-19 were included. Twenty patients presented with new onset of rash. The incidence of new rash was 9.1% (95% confidence interval=6.25%-14.4%). The most common manifestations were maculopapular exanthem (n=6, 42.9%, median Ct value: 24.8), followed by livedo reticularis (n=4, 28.6%, median Ct value: 21.3), varicella-like lesions (n=2, 14.3%, median Ct value: 19.3), urticaria (n=1, 7.1%, median Ct value: 14.4), and acral chilblain and petechiae (n=1, 7.1%, median Ct value: 33.1). The median Ct values for patients with and without rash were 22.9 and 24.1, respectively (P=0.58). There were no significant differences in mortality or hospital stay between patients with and without rash. Patients with rash were more likely to display fever on admission (P<0.01). Regardless of cutaneous manifestations, patients with older age, hypertension, and chronic kidney disease stage ≥3 had significantly higher viral load and mortality (P<0.05). CONCLUSION: This study revealed no associations between cutaneous manifestation and viral load or clinical outcomes. Older patients with multiple co-morbidities have risks of high viral load and mortality; they should be closely monitored.

Fate of thiamethoxam from treated seeds in mesocosms and response of aquatic invertebrate communities.

Thiamethoxam is a neonicotinoid insecticide widely applied in the Canadian Prairies. It has been detected in surface waters of agro-ecosystems, including wetlands, but the potential effects on non-target invertebrate communities in these wetlands have not been well characterized. In an effort to understand better the fate of thiamethoxam in wetlands and the response of invertebrates (zooplankton and emergent insects), model systems were used to mimic wetland flooding into planted fields. Outdoor mesocosms were treated with a single application of thiamethoxam-treated canola seeds at three treatment levels based on a recommended seeding rate (i.e., 6 kg/ha; 1×, 10×, and 100× seeding rate) and monitored over ten weeks. The mean half-life of thiamethoxam in the water column was 6.2 d. There was no ecologically meaningful impact on zooplankton abundances or community structure among treatments. Statistically significant differences were observed in aquatic insect abundance between control mesocosms and the two greatest thiamethoxam treatments (10× and 100× seeding rate). The observed results indicate exposure to thiamethoxam at environmentally relevant concentrations likely does not represent a significant ecological risk to abundance and community structure of wetland zooplankton and emergent insects.

Safety and effectiveness of switching to Abacavir/Lamivudine plus rilpivirine for maintenance therapy in virologically suppressed HIV-1 individuals in Singapore (SEALS).

BACKGROUND: The efficacy and tolerability of an antiretroviral regimen are important considerations for selection of HIV-1 infection maintenance therapy. Abacavir/lamivudine plus rilpivirine (ABC/3TC + RPV) has been shown in international studies to be effective and well-tolerated in virologically suppressed individuals. This study evaluated the effectiveness and safety of switching to ABC/3TC + RPV as maintenance therapy in virologically suppressed HIV-1 infected individuals in Singapore. METHODS: In this retrospective, single-centre study, we included individuals who were prescribed ABC/3TC + RPV, had HIV-1 viral load (VL) < 50 copies/ml immediately pre-switch, and had no documented history of resistance mutations or virologic failure to any of the components. The follow-up period was 48 ± 12 weeks. The primary outcome was the proportion of individuals who maintained virologic suppression of HIV-1 VL < 50 copies/ml at the end of follow-up period based on on-treatment analysis. The secondary outcomes were the resistance profiles associated with virologic failure, changes in immunologic and metabolic parameters, and the safety profile of ABC/3TC + RPV. RESULTS: A total of 222 individuals were included in the study. The primary outcome was achieved in 197 individuals [88.8%, 95% confidence interval: 83.7-92.4%]. There were 21 individuals (9.5%) who discontinued treatment for non-virologic reasons. The remaining 4 individuals experienced virologic failure, of whom, 3 of these individuals had developed emergent antiretroviral resistance and had HIV-1 VL > 500 copies/ml at the end of the 48 ± 12 weeks follow-up period. The remaining individual experienced sustained low level viremia and subsequently achieved viral suppression without undergoing resistance testing. A total of 49 adverse events were observed in 31 out of 222 individuals (14.0%), which led to 13 individuals discontinuing therapy. Neuropsychiatric adverse events were most commonly observed (53.1%). A statistically significant increase in CD4 was observed (p < 0.01), with a median absolute change of 31 cells/uL (interquartile range: - 31.50 to 140.75). No significant changes in lipid profiles were detected. CONCLUSION: ABC/3TC + RPV is a safe and effective switch option for maintenance therapy in virologically suppressed HIV-1 individuals with in Singapore.

Inter-relationships among psychopathology, premorbid adjustment, cognition and psychosocial functioning in first-episode psychosis: a network analysis approach.

BACKGROUND: 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. METHOD: 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. RESULTS: 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. CONCLUSION: 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.

Febrile neutropenia and its associated hospitalization in breast cancer patients on docetaxel-containing regimen: A retrospective cohort study on duration of prophylactic GCSF administration.

PURPOSE: To compare febrile neutropenia (FN) incidence and hospitalization among breast cancer patients on docetaxel with no granulocyte colony-stimulating factors (GCSF) primary prophylaxis (PP), 4/5-day PP, or 7-day PP. METHODS: We identified 3916 breast cancer patients using docetaxel-cyclophosphamide (TC), doxorubicin-cyclophosphamide then docetaxel (AC-T), fluorouracil-epirubicin-cyclophosphamide then docetaxel (FEC-T), docetaxel-carboplatin-trastuzumab (TJH), or docetaxel-doxorubicin-cyclophosphamide (TAC) from a hospital pharmacy dispensing database in Hong Kong between 2014 and 2016. Patients were offered GCSF within 5 days since administering docetaxel. Outcomes included FN incidence, time to first hospitalization, hospitalization rate, and duration. RESULTS: In TC regimen, FN incidence (with odds ratio, OR) of patients with no PP, 4/5-day PP, and 7-day PP was 21.69%, 7.95% (OR 0.31, p < 0.001), and 5.33% (OR 0.20, p < 0.001), respectively. In TJH regimen, FN incidence of patients with no PP, 4/5-day PP, and 7-day PP was 38.26%, 8.33% (OR 0.15, p < 0.001), and 8.57% (OR 0.15, p < 0.001), respectively. FN incidence of patients on AC-T regimen with no PP and 4/5-day PP was 20.93% and 6.84%, respectively (OR 0.28, p = 0.005); with FEC-T regimen, the incidence was 9.91% and 4.77%, respectively (OR 0.46, p = 0.035). Only 3.27% FN cases were not hospitalized. Mean (±standard deviation, SD) time to first hospitalization was 8.21 ± 2.44 days. Mean (±SD) duration of hospitalization for patients with no PP, 4/5-day PP, and 7-day PP was 4.66 ± 2.60, 4.37 ± 2.85, and 5.12 ± 2.97 days, respectively. CONCLUSION: GCSF prophylaxis in breast cancer patients on docetaxel could reduce FN incidence and hospitalization. 4/5-day PP demonstrated similar efficacy to 7-day PP with superior saving benefits on healthcare expenditure.

Socioecological differences in factors associated with inconsistent condom use with female sex workers and casual partners: an observational study of heterosexual men attending an anonymous HIV testing clinic in Singapore.

Sexual practices among heterosexual men may differ between female sex workers (FSWs) and casual partners. We surveyed 203 heterosexual men and investigated the attributes associated with inconsistent condom use among them. Lower educational attainment was positively associated with inconsistent condom use with FSWs (adjusted prevalence ratio (aPR) 2.63; P = 0.018) and casual partners (aPR 1.55; P = 0.022), whereas early age of sexual debut (aPR 3.00; P = 0.012) and alcohol use during sex (aPR 7.95; P < 0.001) were positively associated with inconsistent condom use with FSWs. Socioecological factors may explain such differences.

Depression and anxiety among university students in Hong Kong.

INTRODUCTION: Entry into tertiary education is a critical juncture where adolescents proceed to adulthood. This study aimed to determine the prevalence of depression and anxiety, and factors associated with such symptoms, among university undergraduate students in Hong Kong. METHODS: A cross-sectional questionnaire study was employed. A total of 1200 undergraduate students from eight University Grants Committee-funded universities were invited to complete three sets of questionnaires, including the 9-item patient health questionnaire for screening of depressive symptoms, the 7-item generalised anxiety disorder scale for screening of anxiety symptoms, and a socio-demographic questionnaire. RESULTS: Among the valid responses (n=1119) analysed, 767 (68.5%) respondents indicated mild to severe depressive symptoms, which were associated with mild to severe anxiety symptoms. Several lifestyle and psychosocial variables, including regular exercise, self-confidence, satisfaction with academic performance, and optimism towards the future were inversely related with mild to severe depressive symptoms. A total of 599 (54.4%) respondents indicated mild to severe anxiety symptoms, which were associated with level of academic difficulty. Satisfaction with friendship, sleep quality, and self-confidence were inversely associated with mild to severe anxiety symptoms. CONCLUSION: More than 50% of respondents expressed some degree of depressive and anxiety symptoms (68.5% and 54.4%, respectively). Approximately 9% of respondents exhibited moderately severe to severe depressive symptoms; 5.8% exhibited severe anxiety symptoms. Respondents reporting regular exercise, higher self-confidence, and better satisfaction with both friendship and academic performance had fewer depressive and anxiety symptoms.

Immune reconstitution inflammatory syndrome in HIV infection: taking the bad with the good.

In this review, we will describe the immunopathogies of immune reconstitution inflammatory syndrome, IRIS. IRIS occurs in a small subset of HIV patient, initiating combination antiretroviral therapy (ART), where immune reconstitution becomes dysregulated, resulting in an overly robust antigen-specific inflammatory reaction. We will discuss IRIS in terms of the associated coinfections: mycobacteria, cryptococci, and viruses.

Administrative data is as good as medical chart review for comorbidity ascertainment in patients with infections in Singapore.

The Charlson comorbidity index (CCI) is widely used for control of confounding from comorbidities in epidemiological studies. International Classification of Diseases (ICD)-coded diagnoses from administrative hospital databases is potentially an efficient way of deriving CCI. However, no studies have evaluated its validity in infectious disease research. We aim to compare CCI derived from administrative data and medical record review in predicting mortality in patients with infections. We conducted a cross-sectional study on 199 inpatients. Correlation analyses were used to compare comorbidity scores from ICD-coded administrative databases and medical record review. Multivariable regression models were constructed and compared for discriminatory power for 30-day in-hospital mortality. Overall agreement was fair [weighted kappa 0·33, 95% confidence interval (CI) 0·23-0·43]. Kappa coefficient ranged from 0·17 (95% CI 0·01-0·36) for myocardial infarction to 0·85 (95% CI 0·59-1·00) for connective tissue disease. Administrative data-derived CCI was predictive of CCI ⩾5 from medical record review, controlling for age, gender, resident status, ward class, clinical speciality, illness severity, and infection source (C = 0·773). Using the multivariable model comprising age, gender, resident status, ward class, clinical speciality, illness severity, and infection source to predict 30-day in-hospital mortality, administrative data-derived CCI (C = 0·729) provided a similar C statistic as medical record review (C = 0·717, P = 0·8548). In conclusion, administrative data-derived CCI can be used for assessing comorbidities and confounding control in infectious disease research.

Pathobiology of radiation myelopathy and strategies to mitigate injury.

STUDY DESIGN: This is a narrative review of the literature. OBJECTIVES: The objectives of this study were to review the current concepts underlying the pathobiology of radiation-induced spinal cord injury; to discuss potential biologic strategies to mitigate spinal cord injury following radiation; and to provide an update on the clinical guidelines to prevent injury in the era of image-guided stereotactic body radiotherapy (SBRT). SETTING: This study was conducted in Toronto, Canada. METHODS: A MEDLINE search was performed using the following terms: radiation injury; radiation myelopathy; CNS radiation injury; brain necrosis, radiation; demyelination, radiation; blood-brain barrier, radiation; white matter necrosis; and SBRT. RESULTS AND CONCLUSION: The biologic response of the spinal cord after radiation is a continuously evolving process. Death of vascular endothelial cells and disruption of the blood-spinal cord barrier leads to a complex injury response, resulting in demyelination and tissue necrosis. At present, there is no evidence that the pathobiology of cord injury after SBRT is different from that after standard fractionation. Although permanent myelopathy has become a rare complication following conventional fractionated radiation treatment, cases of radiation myelopathy have re-emerged with the increasing role of spine stereotactic body radiation therapy and reirradiation. Experimental biologic strategies targeting the injury response pathways hold promise in mitigating this dreaded late effect of radiation treatment.

Autophagic Adaptations to Long-term Habitual Exercise in Cardiac Muscle.

Autophagy has been shown to be responsive to physical exercise. However, the effects of prolonged habitual exercise on autophagy in cardiac muscle remain unknown. The present study aimed to examine whether long-term habitual exercise alters the basal autophagic signalling in cardiac muscle. Female Sprague-Dawley rats aged 2 months were randomly assigned to control and exercise groups. Animals in exercise group were kept in cages with free access exercise wheels to perform habitual exercise for 5 months. Animals in the control group were placed in cages without exercise wheels. Ventricular muscle tissues were harvested for analysis after 5 months. Phosphorylation statuses of upstream autophagic regulatory proteins and protein expressions of downstream autophagic facts remained unchanged in the cardiac muscle of exercise animals when compared to control animals. Intriguingly, the protein abundance of microtubule-associated protein-1 light chain -3 II (LC3-II), heat shock protein 72 (HSP72) and peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α) were significantly increased in cardiac muscle of exercise rats relative to control rats. 5 months of habitual exercise causes the adaptive increase in LC3-II reserve without altering autophagic flux, which probably contributes to the elevation of cellular autophagic capacity and efficiency of cardiac muscle.

Sound production in the tiger-tail seahorse Hippocampus comes: Insights into the sound producing mechanisms.

Acoustic signals of the tiger-tail seahorse (Hippocampus comes) during feeding were studied using wavelet transform analysis. The seahorse "click" appears to be a compounded sound, comprising three acoustic components that likely come from two sound producing mechanisms. The click sound begins with a low-frequency precursor signal, followed by a sudden high-frequency spike that decays quickly, and a final, low-frequency sinusoidal component. The first two components can, respectively, be traced to the sliding movement and forceful knock between the supraorbital bone and coronet bone of the cranium, while the third one (purr) although appearing to be initiated here is produced elsewhere. The seahorse also produces a growling sound when under duress. Growling is accompanied by the highest recorded vibration at the cheek indicating another sound producing mechanism here. The purr has the same low frequency as the growl; both are likely produced by the same structural mechanism. However, growl and purr are triggered and produced under different conditions, suggesting that such "vocalization" may have significance in communication between seahorses.

Preliminary evidence of the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) on swallowing functions in post-stroke individuals with chronic dysphagia.

BACKGROUND: There is growing evidence of potential benefits of repetitive transcranial magnetic stimulation (rTMS) in the rehabilitation of dysphagia. However, the site and frequency of stimulation for optimal effects are not clear. AIMS: The aim of this pilot study is to investigate the short-term effects of high-frequency 5 Hz rTMS applied to the tongue region of the motor cortex on swallowing functions and the quality of life of post-stroke individuals with dysphagia. METHODS & PROCEDURES: Two male and two female participants were assigned randomly to active and sham groups. The participants in the active group received 10 sessions of active rTMS for 2 weeks, whereas the sham participants received 10 sessions of sham rTMS for 2 weeks. Each participant received a total of 3000 pulses of 5 Hz active or sham rTMS per day for 10 days. Outcome measures were taken at baseline, 1 week and 1 month post-rTMS. OUTCOMES & RESULTS: Participants who received active rTMS had improved swallowing functions and swallowing-related quality of life at 1 week and 1 month post-stimulation. CONCLUSIONS & IMPLICATIONS: The study showed that excitatory rTMS applied over the tongue motor cortex is a feasible approach in individuals with chronic post-stroke dysphagia. Further investigation with larger sample population is warranted to support the benefit of this stimulation protocol.

Validation of the emergency surgery score (ESS) in a UK patient population and comparison with NELA scoring: a retrospective multicentre cohort study.

INTRODUCTION: Accurate risk scoring in emergency general surgery (EGS) is vital for consent and resource allocation. The emergency surgery score (ESS) has been validated as a reliable preoperative predictor of postoperative outcomes in EGS but has been studied only in the US population. Our primary aim was to perform an external validation study of the ESS in a UK population. Our secondary aim was to compare the accuracy of ESS and National Emergency Laparotomy Audit (NELA) scores. METHODS: We conducted an observational cohort study of adult patients undergoing emergency laparotomy over three years in two UK centres. ESS was calculated retrospectively. NELA scores and all other variables were obtained from the prospectively collected Emergency Laparotomy and Laparoscopic Scottish Audit (ELLSA) database. The primary and secondary outcomes were 30-day mortality and postoperative intensive care unit (ICU) admission, respectively. RESULTS: A total of 609 patients were included. Median age was 65 years, 52.7% were female, the overall mortality was 9.9% and 23.8% were admitted to ICU. Both ESS and NELA were equally accurate in predicting 30-day mortality (c-statistic=0.78 (95% confidence interval (CI), 0.71-0.85) for ESS and c-statistic=0.83 (95% CI, 0.77-0.88) for NELA, p=0.196) and predicting postoperative ICU admission (c-statistic=0.76 (95% CI, 0.71-0.81) for ESS and 0.80 (95% CI, 0.76-0.85) for NELA, p=0.092). CONCLUSIONS: In the UK population, ESS and NELA both predict 30-day mortality and ICU admission with no statistically significant difference but with higher c-statistics for NELA score. Both scores have certain advantages, with ESS being validated for a wider range of outcomes.

Factor analysis of the Chinese version of the Autism Spectrum Quotient 10 and its association with schizotypal traits in adolescents and young adults in Hong Kong.

BACKGROUND: There is evidence suggesting that autistic traits are associated with schizotypal traits. This study examined the factor structure of the Autism Spectrum Quotient 10 (AQ-10) and its associations with schizotypal traits (measured by the Schizotypal Personality Questionnaire-Brief [SPQ-B]) in a cohort of Chinese adolescents and young adults. METHODS: Invitation letters, stratified by locations and housing types, were randomly sent to individuals aged 15 to 24 years for participation. Assessments were made using face-to-face or online interviews. Autistic traits were assessed using the Chinese version of the AQ-10. Schizotypal personality traits were assessed using the Chinese version of the 22-item SPQ-B. RESULTS: In total, 395 male and 536 female participants (mean age, 19.93 years) were recruited between July 2020 and May 2021. Exploratory factor analysis of the AQ-10 yielded three factors (theory of mind, task switching, and attention deficits) explaining 55.11% of the total variance. Autistic traits were positively correlated with schizotypal traits of disorganised features (r = 0.21, p < 0.001), interpersonal relationship deficits (r = 0.19, p < 0.001), and cognitive-perceptual deficits (r = 0.11, p = 0.001). CONCLUSION: In Chinese adolescents and young adults, autistic traits, especially task switching and attention deficits (compared with theory of mind) are more closely correlated with schizotypal personality traits. Disentangling the overlapping and diametrical structure of autistic traits and schizotypal traits may help understand their aetiologies, assessment, and interventions.

Robust unfolding of MeV x-ray spectra from filter stack spectrometer data.

We present an inversion method capable of robustly unfolding MeV x-ray spectra from filter stack spectrometer (FSS) data without requiring an a priori specification of a spectral shape or arbitrary termination of the algorithm. Our inversion method is based upon the perturbative minimization (PM) algorithm, which has previously been shown to be capable of unfolding x-ray transmission data, albeit for a limited regime in which the x-ray mass attenuation coefficient of the filter material increases monotonically with x-ray energy. Our inversion method improves upon the PM algorithm through regular smoothing of the candidate spectrum and by adding stochasticity to the search. With these additions, the inversion method does not require a physics model for an initial guess, fitting, or user-selected termination of the search. Instead, the only assumption made by the inversion method is that the x-ray spectrum should be near a smooth curve. Testing with synthetic data shows that the inversion method can successfully recover the primary large-scale features of MeV x-ray spectra, including the number of x-rays in energy bins of several-MeV widths to within 10%. Fine-scale features, however, are more difficult to recover accurately. Examples of unfolding experimental FSS data obtained at the Texas Petawatt Laser Facility and the OMEGA EP laser facility are also presented.