Detection of novel drug-adverse drug reaction signals in rheumatoid arthritis and ankylosing spondylitis: analysis of Korean real-world biologics registry data.

This study aimed to detect signals of adverse drug reactions (ADRs) associated with biological disease-modifying antirheumatic drugs (DMARDs) and targeted therapies in rheumatoid arthritis (RA) and ankylosing spondylitis (AS) patients. Utilizing the KOrean College of Rheumatology BIOlogics & Targeted Therapy Registry (KOBIO) data, we calculated relative risks, excluded previously reported drug-ADR pairs, and externally validated remaining pairs using US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and single centre's electronic health records (EHR) data. Analyzing data from 2279 RA and 1940 AS patients, we identified 35 significant drug-ADR pairs in RA and 26 in AS, previously unreported in drug labels. Among the novel drug-ADR pairs from KOBIO, 15 were also significant in the FAERS data. Additionally, 2 significant drug-laboratory abnormality pairs were found in RA using CDM MetaLAB analysis. Our findings contribute to the identification of 14 novel drug-ADR signals, expanding our understanding of potential adverse effects related to biological DMARDs and targeted therapies in RA and AS. These results emphasize the importance of ongoing pharmacovigilance for patient safety and optimal therapeutic interventions.

Comparison of contrast-enhanced ultrasonography and MRI results obtained by expert and novice radiologists indicating short-term response after transarterial chemoembolisation for hepatocellular carcinoma.

AIM: To evaluate inter-reader agreement between novice and expert radiologists in assessing contrast-enhanced ultrasonography (CEUS) and magnetic resonance imaging (MRI) images for detecting viable tumours with different sizes after conventional transarterial chemoembolisation (cTACE). MATERIALS AND METHODS: This prospective study included patients who had less than five hepatomas and who underwent cTACE. Hepatomas with one or two feeding arteries were selected as target lesions. CEUS and MRI were performed within 1 week after cTACE to evaluate viable tumours. RESULTS: The expert group had higher kappa values in evaluating all tumour sizes via CEUS compared with MRI. The novice group had similar kappa values. In patients with tumours measuring ≤3 cm, the expert group had higher kappa values in reading CEUS compared with MRI images; however, in the novice group, the kappa value was lower in evaluating CEUS compared with MRI images. In patients with tumours measuring >3 cm, the expert and novice groups had good to excellent kappa values. The confidence level of the two groups in reading MRI images was high; however, the novice group had a lower confidence level. CONCLUSION: CEUS is a convenient, cost-effective, and easy to apply imaging tool that can help interventionists perform early detection of viable hepatocellular carcinoma post-TACE. It has a higher inter-rater agreement in interpreting CEUS images compared with MRI images among expert radiologists even when they are extremely familiar with post-cTACE MRI images. In novice radiologists, there may be a learning curve to achieve good consistency in CEUS interpretation.

Identifying a sphenoid sinus fungus ball using a nomogram model.

BACKGROUND: Sphenoid sinus fungus ball (SSFB) is a rare entity and usually presents with non-specific symptoms. SSFB could potentially lead to serious orbital and intracranial complications. Computed tomography (CT) scan is usually the first imaging test of the diagnostic workup in patients with specific clinical symptoms. This study aimed to compare the clinical characteristics and CT features between SSFB and unilateral (non-fungus ball) chronic sphenoid rhinosinusitis (USRS) and help differentiate between these two most common inflammatory diseases of the sphenoid sinus. METHODS: By retrospective database review, 66 patients with a histopathologic diagnosis of isolated SSFB were recruited for analysis. Fifty-four patients who underwent endoscopic sinus surgery with clinical and histopathological diagnoses of USRS were enrolled as the control group. Clinical characteristics and CT features were evaluated. RESULTS: Headache, rhinorrhoea, nasal obstruction, postnasal dripping, and hyposmia were the most common symptoms in both groups. In the univariate analysis, older age, lower white blood cell counts, irregular surface, bony dehiscence, lateral wall sclerosis, and intralesional hyperdensity (IH) were significant predictors for SSFB. Older age, irregular surface, and IH remained statistically significant in the multivariate analysis. Based on the results of the regression analysis, a nomogram for predicting the probability of SSFB was plotted. CONCLUSIONS: We developed a nomogram model as a novel preoperative diagnostic tool for identifying SSFB according to the predictors both in clinical characteristics and on CT features. This could help the clinicians in predicting the probability of SSFB, to reduce ineffective or delayed treatment and occurrence of complications.

Sleep impairment in patients with empty nose syndrome.

BACKGROUND: Empty nose syndrome (ENS) is characterized by paradoxical nasal obstruction that usually occurs after turbinate surgery. Patients with ENS may also experience significant psychiatric symptoms and sleep dysfunction, which negatively affect the quality of life of affected subjects. This study aimed to evaluate sleep impairment and sleepiness in patients with ENS. METHODS: Patients with ENS and control participants were recruited prospectively. The Sino-Nasal Outcome Test-25 (SNOT-25), Empty Nose Syndrome 6-item Questionnaire (ENS6Q), Epworth Sleepiness Scale (EpSS), and modified sleep quality index (MSQI) were used to evaluate the participants before and after nasal surgery. RESULTS: Forty-eight patients with ENS and forty-eight age- and sex-matched control subjects were enrolled. The SNOT-25, ENS6Q, EpSS, and MSQI scores in the ENS group were all significantly higher than those in the control group before and after surgery. After surgery, ENS patients all exhibited significant improvements in SNOT-25, ENS6Q, EpSS, and MSQI scores. Regression analysis revealed that SNOT-25 score was a significant predictor of EpSS and MSQI in preoperative evaluations. ENS patients experiencing daytime sleepiness suffered from significantly more "dryness of nose" and "suffocation" than those not experiencing daytime sleepiness. CONCLUSIONS: Patients with ENS experienced significantly impaired sleep quality and sleepiness. Nasal reconstruction surgery improved the sleep quality of ENS patients. The severity of sleep dysfunction is associated with the severity of ENS symptoms. Recognizing individuals with significant sleep impairment and sleepiness and providing appropriate management are critical issues for ENS patients.

Olfaction after endoscopic surgery for sellar and parasellar disease: an updated systematic review and meta-analysis.

BACKGROUND: Whether endoscopic surgery for sellar/parasellar disease causes significant deficits in olfactory function remains unclear. We aimed to systematically review the olfactory outcomes in such settings based on the evidence up to date. METHODS: PubMed, EMBASE, and CENTRAL were searched through February 1, 2021. Included studies were limited to endoscopic surgery for sellar/parasellar disease with follow-up olfactory function measured by standardized olfactory testing methods or subjective assessment. The primary outcome was the change in olfactory function after surgery assessed by standardized olfactory testing methods. The secondary outcome was the change in subjective olfactory function. Random-effects model was used in obtaining combine effects. Study quality was assessed using the Newcastleâ€"Ottawa scale. Sensitivity analysis was carried out using the leave-one-out approach, and publication bias was assessed using Egger's test. RESULTS: The results show no significant difference in olfaction assessed by standardized olfactory testing methods at 1-3 months post-surgery (880 patients in 16 studies) or at 6-12 months post-surgery (1320 patients in 16 studies) compared to pre-surgery, whereas a significantly lower subjective olfaction at 3 months was observed. In addition, the lack of significant change in olfaction as assessed by standardized olfactory testing methods was observed regardless of whether patients were treated with or without the nasoseptal flap (NSF) harvesting. Heterogeneity and publication bias were observed, whereas sensitivity analysis showed the meta-analysis results are robust. CONCLUSION: The findings of this updated systematic review and meta-analysis support the conclusion that endoscopic surgery for sellar and parasellar pathology may pose no greater risk of olfactory dysfunction. In addition, the current evidence does not support there is an increased risk of diminished olfaction among patients treated with NSF during surgery.

Photocurrent-driven transient symmetry breaking in the Weyl semimetal TaAs.

Symmetry plays a central role in conventional and topological phases of matter, making the ability to optically drive symmetry changes a critical step in developing future technologies that rely on such control. Topological materials, like topological semimetals, are particularly sensitive to a breaking or restoring of time-reversal and crystalline symmetries, which affect both bulk and surface electronic states. While previous studies have focused on controlling symmetry via coupling to the crystal lattice, we demonstrate here an all-electronic mechanism based on photocurrent generation. Using second harmonic generation spectroscopy as a sensitive probe of symmetry changes, we observe an ultrafast breaking of time-reversal and spatial symmetries following femtosecond optical excitation in the prototypical type-I Weyl semimetal TaAs. Our results show that optically driven photocurrents can be tailored to explicitly break electronic symmetry in a generic fashion, opening up the possibility of driving phase transitions between symmetry-protected states on ultrafast timescales.

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.

Pedagogically fast model to evaluate and optimize passively Q-switched Nd-doped solid-state lasers.

The coupled rate equations with the spatial overlap effect for four-level passively Q-switched lasers are fully considered. A transcendental equation is derived for the residual fraction of the inversion density after the finish of the Q-switched pulse. Comprehensive calculations for the transcendental equation were executed to attain an analytical function for precisely fitting the residual fraction of the inversion density. With the fitting function, a pedagogical model with the correction for high output coupling is developed to straightforwardly analyze the output pulse energy and peak power. Detailed experiments are carried out to validate the model.

Powerful Q-switched Raman laser at 589 nm with a repetition rate between 200 and 500 kHz.

We demonstrate a highly powerful acousto-optically Q-switched Nd:YVO4 yellow laser at 589 nm by using a Np-cut KGW crystal and a phase-matching lithium triborate crystal to performance the intracavity stimulated Raman scattering and second-harmonic generation, respectively. We experimentally verify that the design of the separate cavity is superior to the conventional design of the shared cavity. By using the separate cavity, the optical-to-optical efficiency can be generally higher than 32% for the repetition rate within 200-500 kHz. The maximum output power at 589 nm can be up to 15.1 W at an incident pump power of 40 W and a repetition rate of 400 kHz.

Variables associated with stability after Le Fort I osteotomy for skeletal class III malocclusion.

The purpose of this study was to assess skeletal stability and predictors of relapse in patients undergoing an isolated Le Fort I osteotomy. A retrospective cohort study of 92 subjects undergoing Le Fort I osteotomy for Class III malocclusion was implemented. Predictor variables were demographic and perioperative factors. The primary outcome variable was postoperative skeletal position with relapse defined as >2mm sagittal and/or vertical change at A-point on serial lateral cephalograms at immediate postoperative, 1 year, and latest follow-up time points. Mean advancement at A-point was 6.28±2.63mm and mean lengthening was 0.92±1.76mm. Eight subjects (8.70%) had relapse (>2mm) in the sagittal plane, and two subjects (2.17%) in the vertical plane. No subjects required reoperation for relapse as overbite and overjet remained in an acceptable range due to dental compensation. In regression analysis, magnitude of maxillary advancement was an independent predictor of relapse in the sagittal plane (P=0.008). There were no significant predictors of relapse in the vertical plane. This study suggests that isolated Le Fort I osteotomy for correction of skeletal Class III malocclusion is a stable procedure and that greater advancement is an independent risk factor for sagittal relapse.

Highly efficient solid-state Raman yellow-orange lasers created by enhancing the cavity reflectivity.

A new, to the best of our knowledge, output coupler (OC) with enhancement of the cavity reflectivity is proposed to remarkably elevate the output powers and efficiencies of diode-pumped Nd:GdVO4/KGW Raman yellow-orange lasers. The cavity reflectivity is effectively increased by using the double-sided dichroic coating on the OC. In comparison with the conventional single-sided coating, the conversion efficiency can be boosted from 15% to 26.3% in the experiment of a yellow laser at 578.8 nm, and the maximum output power can be increased from 5.7 to 10.5 W in the quasi-continuous-wave mode with 50% duty cycle and frequency of 500 Hz. Furthermore, in the operation of an orange laser at 588 nm, the maximum output power can be improved from 5.6 to 7.0 W by replacing the conventional OC with the new one.

Comparison of influenza hospitalization outcomes among adults, older adults, and octogenarians: a US national population-based study.

OBJECTIVES: This study sought to more fully elucidate the age-related trends in influenza mortality with a secondary goal of uncovering implications for treatment and prevention. METHODS: In this retrospective cohort analysis of data from the Nationwide Readmission Database, patients with influenza as a primary or secondary discharge diagnosis were separated into three age groups: 55 638 adults aged 20-64 years, 36 862 adults aged 65-79 years and 41 806 octogenarians aged ≥80 years. Propensity score (PS) weighting was performed to isolate age from other baseline differences. Crude and PS-weighted hazard ratios (HR) were calculated from the in-hospital all-cause 30-day mortality rate. Admission threshold bias was minimized by comparison of influenza with bacterial pneumonia mortality. RESULTS: Adults aged 20-64 years experienced higher in-hospital 30-day mortality compared with older adults aged 65-79 years (HR 0.66; 95% CI 0.55-0.79). Octogenarians had the highest mortality rate, but this was statistically insignificant compared with the adult cohort (HR 1.09; 95% CI 0.94-1.27). This trend was not explained by admission threshold bias: the 30-day mortality rate due to in-hospital bacterial pneumonia increased consistently with age (older adult HR 1.45; 95% CI 1.32-1.59; octogenarian HR 1.99; 95% CI 1.82-2.18). CONCLUSIONS: Adults aged 20-64 years and octogenarians were more likely to experience all-cause 30-day mortality during influenza hospitalization compared with older adults aged 65-79 years. These data emphasize the importance of prevention and suggest the need for more tailored treatment interventions based on risk stratification that includes age.

Comparison of efficacy and safety of empagliflozin vs linagliptin added to premixed insulin in patients with uncontrolled type 2 diabetes: A randomized, open-label study.

AIMS: Sodium-glucose cotransporter-2 (SGLT2) inhibitors and dipeptidyl peptidase (DPP)-4 inhibitors added to insulin regimens in patients with type 2 diabetes mellitus (T2DM) can improve glycaemic control. This study compared the efficacy and safety of empagliflozin and linagliptin added to premixed insulin therapy in patients with poorly controlled T2DM. METHODS: In this 24-week, open-label, parallel-design randomized controlled trial, patients with poorly controlled T2DM despite a premixed insulin regimen were randomized to receive 5mg of linagliptin (n=53) or 25mg of empagliflozin (n=53) for 24 weeks. RESULTS: At week 24, changes in glycated haemoglobin (HbA1c) from baseline were -0.06±0.17% and -1.01±0.16% in the linagliptin and empagliflozin groups, respectively, and the mean treatment HbA1c difference was -0.88% (95% CI: -1.33, -0.43). At week 24, the empagliflozin group showed significant reductions, compared with the linagliptin group, in fasting plasma glucose (P<0.001), body weight (P<0.001), systolic blood pressure (P=0.003) and total daily insulin dose (P=0.042). Hypoglycaemia was reported to be slightly, and not significantly, higher in the empagliflozin group vs linagliptin group (30.2% vs 22.6%, respectively; P=0.51). Similar percentages of patients (1.9%) had urinary tract infections in the two groups. CONCLUSION: In Asian patients with inadequately controlled T2DM while taking premixed insulin, the addition of empagliflozin for 24 weeks provided better glycaemic control and greater reductions in body weight and systolic blood pressure than the addition of linagliptin. Clinical Trial Registration #: NCT03458715.

High-power diode-pumped Nd:GdVO4/KGW Raman laser at 578 nm.

A diode-pumped neodymium-doped gadolinium vanadate (Nd:GdVO4) laser is developed as a compact efficient yellow light at 578 nm by means of intracavity stimulated Raman scattering (SRS) in a potassium gadolinium tungstate (KGW) crystal and the second-harmonic generation in a lithium triborate crystal. The SRS process with a shift of 768cm-1 is achieved by setting the polarization of the fundamental wave along the Ng axis of the KGW crystal. The self-Raman effect arising from the Nd:GdVO4 crystal is systematically explored by employing two kinds of coating specification for the output coupler. With a specific coating on the output coupler to suppress the self-Raman effect, the maximum output power at 578 nm can reach 3.1 W at a pump power of 32 W. Moreover, two different lengths for the Nd:GdVO4 crystal are individually used to verify the influence of the self-Raman effect on the lasing efficiency.

Efficient solid-state Raman yellow laser at 579.5 nm.

A highly efficient diode-pumped Nd:YVO4/KGW Raman yellow laser is developed to produce a 6.8 W yellow light at 579.5 nm accompanied by a 3.2 W Stokes wave at 1159 nm under an incident pump power of 30 W. The intracavity stimulated Raman scattering with the shift of 768cm-1 is generated by setting the polarization of the fundamental wave along the Ng direction of an Np-cut KGW crystal. The Nd:YVO4 gain medium is coated as a cavity mirror to reduce the cavity losses for the fundamental wave. More importantly, the KGW crystal is specially coated to prevent the Stokes wave from propagating through the gain medium to minimize the cavity losses for the Stokes wave.

Predicting Performances on Processing and Memorizing East Asian Faces from Brain Activities in Face-Selective Regions: A Neurocomputational Approach.

For more than two decades, a network of face-selective brain regions has been identified as the core system for face processing, including occipital face area (OFA), fusiform face area (FFA), and posterior region of superior temporal sulcus (pSTS). Moreover, recent studies have suggested that the ventral route of face processing and memory should end at the anterior temporal lobes (i.e., vATLs), which may play an important role bridging face perception and face memory. It is not entirely clear, however, the extent to which neural activities in these face-selective regions can effectively predict behavioral performance on tasks that are frequently used to investigate face processing and face memory test that requires recognition beyond variation in pose and lighting, especially when non-Caucasian East Asian faces are involved. To address these questions, we first identified during a functional scan the core face network by asking participants to perform a one-back task, while viewing either static images or dynamic videos. Dynamic localizers were effective in identifying regions of interest (ROIs) in the core face-processing system. We then correlated the brain activities of core ROIs with performances on face-processing tasks (component, configural, and composite) and face memory test (Taiwanese Face Memory Test, TFMT) and found evidence for limited predictability. We next adopted an multi-voxel pattern analysis (MVPA) approach to further explore the predictability of face-selective brain regions on TFMT performance and found evidence suggesting that a basic visual processing area such as calcarine and an area for structural face processing such as OFA may play an even greater role in memorizing faces. Implications regarding how differences in processing demands between behavioral and neuroimaging tasks and cultural specificity in face-processing and memory strategies among participants may have contributed to the findings reported here are discussed.

Exploiting a monolithic passively Q-switched Nd:YAG laser to mimic a single neuron cell under periodic stimulation.

A monolithic passively Q-switched Nd:YAG laser under periodic pulse pumping is originally exploited to emulate the response of a single neuron cell stimulated by periodic pulse inputs. Experimental results reveal that the output characteristics of the monolithic passively Q-switched laser can analogously manifest not only the firing patterns but also the frequency-locked plateaus of the single neuron cell. Moreover, the sine circle map is innovatively used to generate the output pulse sequences that can exactly correspond to experimental firing patterns. The present exploration indicates that a monolithic passively Q-switched solid-state laser is highly feasible to be developed as a compact artificial neuron cell.

Timing jitter reduction of passively Q-switched solid-state lasers by coupling resonance between pumping and firing rates.

The coupling resonance between pumping and firing rates is originally proposed to achieve the timing jitter reduction of a Nd:YVO4 laser passively Q-switched with a saturable absorber. When the pumping rate is higher than the spontaneous emission rate, it is experimentally confirmed that the pulse firing rate can be fractionally locked with the pumping rate by controlling the pump power. The locking characteristics of the firing rate display a variety of complex plateaus that can be excellently manifested with the sine-circle map. From numerical analyses, the coupling strength can be verified to be effectively enhanced by reducing the duty cycle of the pumping rate.

Battling COVID-19: critical care and peri-operative healthcare resource management strategies in a tertiary academic medical centre in Singapore.

In December 2019, a cluster of atypical pneumonia cases were reported in Wuhan, China, and a novel coronavirus elucidated as the aetiologic agent. Although most initial cases occurred in China, the disease, termed coronavirus disease 2019, has become a pandemic and continues to spread rapidly with human-to-human transmission in many countries. This is the third novel coronavirus outbreak in the last two decades and presents an ensuing healthcare resource burden that threatens to overwhelm available healthcare resources. A study of the initial Chinese response has shown that there is a significant positive association between coronavirus disease 2019 mortality and healthcare resource burden. Based on the Chinese experience, some 19% of coronavirus disease 2019 cases develop severe or critical disease. This results in a need for adequate preparation and mobilisation of critical care resources to anticipate and adapt to a surge in coronavirus disease 2019 case-load in order to mitigate morbidity and mortality. In this article, we discuss some of the peri-operative and critical care resource planning considerations and management strategies employed in a tertiary academic medical centre in Singapore in response to the coronavirus disease 2019 outbreak.

Patients' Reports of Traumatic Experience and Posttraumatic Stress in Psychiatric Settings.

OBJECTIVE: To determine the prevalence of traumatic experience (TE) among patients in psychiatric settings in Hong Kong and the associations between TE and levels of distress and anxiety and depressive symptoms. METHODS: 129 patients who have received inpatient psychiatric services were recruited. Their lifetime TE was assessed using the Life Event Checklist (LEC), and TE in psychiatric settings using the Psychiatric Experiences Questionnaire (PEQ). Their level of distress symptoms was assessed using the Impact of Event Scale-Revised (IES-R), and the level of anxiety and depressive symptoms using the Hospital Anxiety and Depression Scale (HADS). RESULTS: The prevalence of direct and indirect TE was 84.5%, as was the prevalence of TE in psychiatric settings. Common TE in psychiatric settings included witnessing another patient being taken down (61.2%), being put in restraints of any kind (41.1%), and witnessing another patient being physically assaulted by another patient (36.4%). TE in psychiatric settings associated with high prevalence of severe or extreme distress 1 week after the event included being forced to take medication against their will (52.2%), being threatened with physical violence (52.2%), and experiencing a physical assault (50.0%). Lifetime TE (the total number of LEC items reported) was associated with severity of distress and anxiety and depressive symptoms, whereas TE in psychiatric settings (the total number of PEQ items reported) was associated with severity of distress only. The total number of LEC items reported is the only predictor of levels of distress and anxiety and depressive symptoms. CONCLUSIONS: Lifetime TE and TE in psychiatric settings are common among patients with SMI. Trauma-informed care is suggested for mental health services.