Develop and Validate a Prognostic Index With Laboratory Tests to Predict Mortality in Middle-Aged and Older Adults Using Machine Learning Models: A Prospective Cohort Study.

BACKGROUND: Prognostic indices can enhance personalized predictions of health burdens. However, a simple, practical, and reproducible tool is lacking for clinical use. This study aimed to develop a machine learning-based prognostic index for predicting all-cause mortality in community-dwelling older individuals. METHODS: We utilized the Healthy Aging Longitudinal Study in Taiwan (HALST) cohort, encompassing data from 5 663 participants. Over the 5-year follow-up, 447 deaths were confirmed. A machine learning-based routine blood examination prognostic index (MARBE-PI) was developed using common laboratory tests based on machine learning techniques. Participants were grouped into multiple risk categories by stratum-specific likelihood ratio analysis based on their MARBE-PI scores. The MARBE-PI was subsequently externally validated with an independent population-based cohort from Japan. RESULTS: Beyond age, sex, education level, and BMI, 6 laboratory tests (low-density lipoprotein, albumin, aspartate aminotransferase, lymphocyte count, high-sensitivity C-reactive protein, and creatinine) emerged as pivotal predictors via stepwise logistic regression (LR) for 5-year mortality. The area under curves of MARBE-PI constructed by LR were 0.799 (95% confidence interval [95% CI]: 0.778-0.819) and 0.756 (95% CI: 0.694-0.814) for the internal and external validation data sets, and were 0.801 (95% CI: 0.790-0.811) and 0.809 (95% CI: 0.774-0.845) for the extended 10-year mortality in both data sets, respectively. Risk categories stratified by MARBE-PI showed a consistent dose-response association with mortality. The MARBE-PI also performed comparably with indices constructed with clinical health deficits and/or laboratory results. CONCLUSIONS: The MARBE-PI is considered the most applicable measure for risk stratification in busy clinical settings. It holds potential to pinpoint older individuals at elevated mortality risk, thereby aiding clinical decision-making.

Lower HbA1C of glycemic control is associated with higher risk of depressive symptoms in elderly with type 2 diabetes mellitus-A Nationwide Community-based study.

OBJECTIVE: We investigated the correlation between glycemic control status and depressive symptoms in type 2 diabetes elderly. METHODS: A total of 1527 participants with type 2 diabetes aged 55 years and older from the Healthy Aging Longitudinal Study in Taiwan study were included in this cross-sectional study. The Center for Epidemiologic Studies Depression Scale (CESD) (20 items) score of ≥16 was indicative of depressive symptoms. The participants were divided into HbA1c ≥ 6.5% and < 6.5% representing the glycemic control. Multiple logistic regression (MLR) and Generalized linear model (GLM) were used. RESULTS: The MLR analysis showed that the low HbA1c group had significant two-fold increased odds of depressive symptoms compared to the high HbA1c group (OR 1.89, 95% CI 1.17-3.05). The risk of depressive symptoms was lower among males (OR 0.49, 95% CI 0.30-0.80) and those with higher BMI (OR 0.93, 95% CI 0.86-1.00); whereas the risk was higher among those who lived alone (OR 2.37, 95% CI 1.31-4.27) and with ADL disability (OR 3.01, 95% CI 1.85-4.89). The GLM showed that the dimension of depressive affect reached statistical significance with lower HbA1c. CONCLUSION: This nationwide community-based study shows that depressive symptoms are associated with lower HbA1C, reminding us that more attention should be paid to the presence of depressive symptoms in those with lower HbA1C. Further research is needed to clarify the causal relationship.

Functional Outcomes in a Randomized Controlled Trial of Animal-Assisted Therapy on Middle-Aged and Older Adults with Schizophrenia.

Deficits in cognition, physical, and social functions in adults with schizophrenia may become salient with aging. While animal-assisted therapy (AAT) can benefit physical function in older adults and improve symptoms of psychotic disorders, the effect of AAT on middle-aged patients with schizophrenia is unclear. The current randomized controlled trial aimed to explore the efficacy of AAT for middle-aged patients with schizophrenia. Forty participants were randomly assigned to either the AAT or control group. The AAT group participated in one-hour sessions with dog-assisted group activities once a week for 12 weeks. The controls participated in dose-matched, non-animal-related recreational activities. Both groups remained on their usual psychotropic medication during the trial. Evaluations included the Chair Stand Test (CST), Timed Up-and-Go (TUG) test, Montreal Cognitive Assessment (MoCA), 5-Meter walk test (5MWT), and Assessment of Communication and Interaction Skills (ACIS). The increases in CST repetitions and ACIS scores were larger in the AAT group than in the controls. The two groups did not differ significantly in MoCA scores, TUG performance, or the 5MWT. The AAT group showed a greater increase in lower extremity strength and social skills, but no improvement in cognitive function, agility, or mobility. Further research with more sensitive evaluations and longer follow-up is needed.

Comparative effectiveness of antidepressants on geriatric depression: Real-world evidence from a population-based study.

BACKGROUND: There is little real-world evidence about effectiveness of different antidepressants on geriatric depression. METHODS: We used population-based claims data in Taiwan between 1997 and 2013 to include older patients (≥ 60 years of age) who were diagnosed with depression and started to use antidepressants. All patients were followed up until discontinuation of antidepressant use or the end of the study period. Treatment outcomes were set as the risk of switching to another antidepressant, receiving augmentation therapy, and psychiatric hospitalization. We used cox proportional hazards regression models to calculate hazard ratios with 95% confidence intervals (CIs) and adjust for several confounding factors (aHRs). RESULTS: During the study period, a total of 207,946 elderly patients with depression received one of the following 11 antidepressants: sertraline, fluoxetine, paroxetine, escitalopram, citalopram, fluvoxamine, venlafaxine, duloxetine, moclobemide, mirtazapine, and bupropion. Compared to the patients treated with sertraline, those treated with fluvoxamine / venlafaxine had significantly but modestly higher risks of switching (aHR [95% CI]: 1.16 [1.11-1.21] / 1.10 [1.06-1.14]), augmentation (1.06 [1.02-1.10] / 1.08 [1.05-1.12]), and hospitalization (1.28 [1.03-1.58] / 1.37 [1.16-1.62]). Otherwise, the remaining 9 antidepressants yielded no consistent result in the three outcomes. LIMITATIONS: This study is a multi-arm and active controlled trial, lacking a placebo group. CONCLUSION: As treating geriatric depression, no individual antidepressant posed consistently better effectiveness in the outcomes of switching antidepressant, receiving augmentation, and psychiatric hospitalization than any other one, whereas clinicians should be cautious when prescribing fluvoxamine and venlafaxine.

Stigma, depression, and anxiety among patients with head and neck cancer.

PURPOSE: Patients with head and neck cancer (HNC) are vulnerable to psychiatric comorbidities, particularly anxiety and depression, and also suffer from cancer stigma. This study aimed to comprehensively compare HNC patients' stigma, depression, and anxiety, and elucidate the underlying relationships among them. METHODS: This cross-sectional study recruited inpatients with HNC from a medical center. Measurements included a psychiatric diagnostic interview, the Shame and Stigma Scale (SSS), the Hamilton Anxiety Rating Scale (HAM-A), the Hamilton Depression Rating Scale (HAM-D), the Explanatory Model Interview Catalogue (EMIC), and stressors of HNC patients. Structural equation modeling was used to establish models of potential mechanisms. RESULTS: Those patients having stressors of worry about health (t = 5.21, p < 0.001), worry about job (t = 2.73, p = 0.007), worry about family (t = 2.25, p = 0.026), or worry about economic problems (t = 2.09, p = 0.038) showed significantly higher SSS score than those having no such stressor. The SSS total score was significantly correlated with HAM-A (r = 0.509, p < 0.001), HAM-D (r = 0.521, p < 0.001), and EMIC (r = 0.532, p < 0.001) scores. Structural equation modeling was used to propose the possible effect of stigma on anxiety (ß = 0.51, p < 0.001), and then the possible effect of anxiety on depression (ß = 0.90, p < 0.001). CONCLUSION: Stigma is significantly correlated with anxiety and depression and might in HNC patients. Proper identification of comorbidities and a reduction of stigma should be advised in mental health efforts among patients with HNC.

Develop and Apply Electrocardiography-Based Risk Score to Identify Community-Based Elderly Individuals at High-Risk of Mortality.

With an aging world population, risk stratification of community-based, elderly population is required for primary prevention. This study proposes a combined score developed using electrocardiographic (ECG) parameters and determines its long-term prognostic value for predicting risk of cardiovascular mortality. A cohort-study, conducted from December 2008 to April 2019, enrolled 5,380 subjects in Taiwan, who were examined, using three-serial-12-lead ECGs, and their health/demographic information were recorded. To understand the predictive effects of ECG parameters on overall-survival, Cox hazard regression analysis were performed. The mean age at enrollment was 69.04 ± 8.14 years, and 47.4% were males. ECG abnormalities, LVH [hazard ratio (HR) = 1.39, 95% confidence intervals (CI) = (1.16-1.67), P = 0.0003], QTc [HR = 1.31, CI = (1.07-1.61), P = 0.007] and PR interval [HR = 1.40, CI = (1.01-1.95), P = 0.04], were significantly associated with primary outcome all-cause death. Furthermore, LVH [HR = 2.37, CI = (1.48-3.79), P = 0.0003] was significantly associated with cardiovascular death, while PR interval [HR = 2.63, CI = (1.24- 5.57), P = 0.01] with unexplained death. ECG abnormality (EA) score was defined based on the number of abnormal ECG parameters for each patient, which was used to divide all patients into sub-groups. Competing risk survival analysis using EA score were performed by using the Gray's test, which reported that high-risk EA groups showed significantly higher cumulative incidence for all three outcomes. Prognostic models using the EA score as predictor were developed and a 10-fold cross validation design was adopted to conduct calibration and discrimination analysis, to establish the efficacy of the proposed models. Overall, ECG model could successfully predict people, susceptible to all three death outcomes (P < 0.05), with high efficacy. Statistically significant (P < 0.001) improvement of the c-indices further demonstrated the robustness of the prediction model with ECG parameters, as opposed to a traditional model with no EA predictor. The EA score is highly associated with increased risk of mortality in elderly population and may be successfully used in clinical practice.

Animal-Assisted Therapy in Middle-Aged and Older Patients With Schizophrenia: A Randomized Controlled Trial.

Objective: Animal-assisted therapy (AAT) has the potential to improve the symptomology, negative emotions, and level of well-being in older adults, as well as patients with mental illness. However, there remains limited evidence supporting the treatment efficacy of AAT in middle-aged and older adults with schizophrenia. Therefore, this study implemented a randomized controlled trial to assess the efficacy of a 12-week AAT psychological intervention with dogs for middle-aged and older patients with chronic schizophrenia in a clinical setting. Method: Patients, age ≥ 40 years, with chronic schizophrenia were allocated randomly to either the AAT group or control group. Patients in the AAT group received an additional hour -long AAT session every week for 12 weeks. Patients in the control group received the usual treatment plus an hour long non-animal related intervention. All patients were assessed based on primary outcome measures before and after the 12-week intervention, including the Positive and Negative Syndrome Scale (PANSS), Depression Anxiety Stress Scales Assessment (DASS), and Chinese Happiness Inventory (CHI). Results: Patients who received AAT had greater improvements in the PANSS and DASS-stress subscale scores than the control group (p < 0.05). The effect was small (success ratio different, SRD = 0.25) for the PANSS and the DASS-stress subscale (SRD = 0.15). There were no significant differences in the change scores of the CHI between the AAT and control groups (p = 0.461). Conclusions: AAT seemed to be effective in reducing psychiatric symptoms and stress levels of middle-aged and older patients with schizophrenia. AAT could be considered as a useful adjunctive therapy to the usual treatment programs.

Quantitative urinary tract infection diagnosis of leukocyte esterase with a microfluidic paper-based device.

Leukocyte esterase (LE) is a useful marker that can be used in establishing a diagnosis of urinary tract infections (UTIs). The development of a UTI diagnostic method with quantitative determinations of biomarkers across all age groups is becoming more important. In this report, microfluidic resistance sensors based on silver ink (Ag ink) and silver ink mixed with ZnO nanoparticles (Ag-ZnO ink) were synthesized and coated on cellulose paper, namely LE-Ag-µPADs and LE-Ag-ZnO-µPADs, respectively, for the sensitive detection of LE. The microfluidic design increases the precision of data and further allows for quantitative determination and early detection of LE in human urine. The quantification of LE relies on the change in the resistance readout coating with Ag ink as well as Ag-ZnO ink in the detection zone. A mixture of 3-(N-tosyl-l-alaninyloxy)-5-phenylpyrrole (PE) and 1-diazo-2-naphthol-4-sulfonic acid (DAS) was deposited in the sample zone to selectively recognize LE, and the resulting nonconductive products, i.e., azo compounds, further reacted with the Ag ink and Ag-ZnO ink to increase resistance. The quantitative detectable LE concentrations between 2 to 32 (×5.2 U mL-1), i.e. ≈12 to 108 µg L-1, cover the commercial dipstick range of trace, +1 and +2. The minimum detectable concentration of LE in urine was 1 (×5.2 U mL-1). The lower concentrations of LE detectable by LE-Ag-µPADs (1-8 × 5.2 U mL-1) are below the value achieved with the ELISA LE kit. Urine samples from inpatients with indwelling urinary catheters were used, and the LE levels measured by the present device were highly correlated with those determined by a commercial urine analyser.

Differential relationship of uric acid to mortality and clinical biomarkers of aging according to grip strength in older adults: a cohort study.

Uric acid is both a pro-oxidant and antioxidant. We investigated serum uric acid's association with mortality and aging biomarkers in older adults with varying levels of grip strength. A total of 5329 community-dwelling adults aged ≥55 years underwent assessments of serum uric acid levels, grip strength, and biomarkers of diverse physiological systems. The primary outcome was all-cause mortality. We observed a significant (P < .001) interaction between uric acid levels and grip strength on all-cause mortality risk. Among participants with low grip strength, a nonlinear association (P for nonlinearity = .006) was observed between serum uric acid levels and mortality risk after multivariate adjustment. Compared with participants with neither extreme uric acid levels nor low grip strength, those with a combination of high serum uric acid and low grip strength exhibited greater risks of mortality (adjusted hazard ratio [aHR], 1.52; 95% confidence interval [CI], 1.15-2.02) and deviations in biomarkers of specific systems, so did those with a combination of low serum uric acid and low grip strength (aHR, 1.52; 95% CI, 1.13-2.05). In conclusion, there was a J-shaped association between serum uric acid and the risk of all-cause mortality in older adults. This was primarily true for those with low grip strength.

Prognostic value and prevalence of complete right bundle branch block in an elderly population: a community-based 10-year prospective study.

Complete right bundle branch block (CRBBB) occurs in 0.2% to 1.3% of the general population, but its prognostic significance in the geriatric population is unknown. We prospectively investigated the prevalence and prognostic value of CRBBB in individuals aged ≥65 years in a community-based population in Taiwan. A total of 5,830 community-dwelling individuals were prospectively recruited from 7 regions across Taiwan starting in December 2008 through March 2013. Those aged ≥65 years were included in the analysis (N=3,383). All subjects underwent a home visit and standardized medical exams and were followed up annually until the end of April 2019; cause of death was documented by citizen death records. The mean age of the study cohort was 73.5±5.9 years (65-104), and 47.21% were men. Among these individuals, 171 (5.05%) had CRBBB; the prevalence was higher in men (7.08%) than in women (3.25%). Subjects with CRBBB were older than those without CRBBB (75.4±6.5 vs. 73.4±5.9), and the frequency of CRBBB increased with age. Survival analysis revealed that all-cause mortality and cardiac mortality were similar in individuals with and without CRBBB during a mean follow-up of 92.6±23.6 months. CRBBB is not associated with increased risk of mortality in the geriatric population.

Methylphenidate and the risk of burn injury among children with attention-deficit/hyperactivity disorder.

AIMS: Attention-deficit/hyperactivity disorder (ADHD) is associated with a higher risk of burn injury than in the normal population. Nevertheless, the influence of methylphenidate (MPH) on the risk of burn injury remains unclear. This retrospective cohort study analysed the effect of MPH on the risk of burn injury in children with ADHD. METHOD: Data were from Taiwan's National Health Insurance Research Database (NHIRD). The sample comprised individuals younger than 18 years with a diagnosis of ADHD (n = 90 634) in Taiwan's NHIRD between January 1996 and December 2013. We examined the cumulative effect of MPH on burn injury risk using Cox proportional hazards models. We conducted a sensitivity analysis for immortal time bias using a time-dependent Cox model and within-patient comparisons using the self-controlled case series model. RESULTS: Children with ADHD taking MPH had a reduced risk of burn injury, with a cumulative duration of treatment dose-related effect, compared with those not taking MPH. Compared with children with ADHD not taking MPH, the adjusted hazard ratio for burn injury was 0.70 in children taking MPH for <90 days (95% confidence interval (CI) 0.64-0.77) and 0.43 in children taking MPH for ≥90 days (95% CI 0.40-0.47), with a 50.8% preventable fraction. The negative association of MPH was replicated in age-stratified analysis using time-dependent Cox regression and self-controlled case series models. CONCLUSION: This study showed that MPH treatment was associated with a lower risk of burn injury in a cumulative duration of treatment dose-related effect manner.

The 10-Year Prognosis and Prevalence of Brugada-Type Electrocardiograms in Elderly Women: A Longitudinal Nationwide Community-Based Prospective Study.

BACKGROUND: Brugada syndrome is a disorder associated with sudden cardiac death and characterized by an abnormal electrocardiogram (ECG). Previous studies were predominantly conducted in men, and the data on long-term prognosis are limited. Information about women, especially elderly women, is lacking. OBJECTIVE: The aim of this study was to investigate the long-term prognosis of the Brugada ECG pattern in elderly women. METHOD: We investigated the 10-year prognosis of the Brugada ECG pattern in elderly women in a nationwide community-based population in Taiwan. Community-dwelling women older than 55 years were prospectively recruited from December 2008 to March 2013 by a stratified random sampling method. All enrolled individuals were followed up annually until April 2019, and the cause of death was documented by citizen death records. RESULTS: Among 2597 women, 60 (2.31%) had a Brugada-type ECG, and this prevalence was higher than the mean global prevalence of 0.23%. One woman had a type 1 ECG (0.04%), whereas 15 (0.58%) and 44 (1.70%) women had type 2 and type 3 ECG patterns, respectively. Cox survival analysis revealed that all-cause mortality and cardiac mortality were similar in the individuals with and without a Brugada-type ECG during a mean follow-up of 96.1 ± 20.5 months. CONCLUSIONS: Our findings suggest that Brugada ECG patterns are not infrequent in elderly women but are not associated with increased risk of mortality in long-term follow-up; these findings may help reduce unnecessary anxiety for physicians, nurses, allied health caregivers, and patients.

Association Between Attention Deficit Hyperactivity Disorder and Risk of Burn Injury: A Propensity-Matched Cohort Study.

PURPOSE: Literature suggests that attention deficit hyperactivity disorder (ADHD) is associated with a high risk of unintentional injury. However, few studies have focused on whether risk of burn injury is relatively high among patients with ADHD. The aim of this study was to investigate whether ADHD affects the risk of burn injury. MATERIALS AND METHODS: Individuals aged <18 years with a current diagnosis of ADHD (N = 52,705) and age-, sex-, and other comorbidity-matched controls were selected from Taiwan's National Health Insurance Research Database for the period of January 1996 to December 2013. Burn injury was identified in both groups, and risk was evaluated using Cox proportional hazards models. We also explored the effects of age and sex on the association. RESULTS: We determined that patients with ADHD had an increased probability of burn injury compared with the control group (ADHD vs controls, 4.6% vs 2.6%; adjusted hazard ratio [aHR] = 1.78; 95% confidence interval [CI] = 1.66-1.90). The effect of ADHD on burn injury was more prominent among those aged <6 years (aHR = 1.96; 95% CI = 1.75-2.20) relative to those aged ≥6 years (aHR = 1.69; 95% CI = 1.56-1.83). Both sexes had similar risk profiles. CONCLUSION: The study findings contribute to the increasing body of evidence that ADHD is associated with proneness to burn injury, particularly in children aged <6 years.

Role of electrocardiographic early repolarization pattern in long-term outcomes of a community-based middle-aged and geriatric ambulatory population: a prospective cohort study.

In some studies, electrocardiographic early repolarization pattern (ERP) has been associated with an increased risk of death from cardiac causes. However, little is known about the prognostic significance of ERP in the middle-aged and geriatric general populations. We investigated the prevalence and long-term prognostic significance of early repolarization pattern (ERP) on electrocardiograms (ECGs) in the Healthy Aging Longitudinal Study (HALST) cohort of 4615 middle-aged and geriatric community-dwelling Han Chinese adults from Taiwan. The study subjects were followed-up for 95±22 months. A positive ERP of ≥0.1 mV was observed in 889 (19.3%) of the subjects. Kaplan-Meier survival curve analysis showed that ERP was not associated with all-cause and cardiovascular mortality (log-rank test, P=0.13 and 0.84, respectively). Cox regression analysis after adjusting for covariables revealed that age, blood pressure, smoking, diabetes, stroke, chronic kidney disease, and corrected QT interval (QTc) were associated with increased risk of all-cause mortality (P<0.05). Age, and stroke were risk factors associated with increased risk of cardiovascular mortality (P<0.05). However, ERP alone was not associated with all-cause or cardiovascular mortality. These findings show that ERP is common in the middle-aged and geriatric Han-Chinese individuals from the HALST cohort and is not associated with all-cause or cardiovascular mortality.

Quantitative determination of leukocyte esterase with a paper-based device.

The commercially-available colorimetric urine dipstic for the early detection of urinary tract infection (UTI) has several limitations. The quantitative determination of urinary leukocyte esterase (LE) for predicting UTI remains uncertain. This study presents a paper-based analytical device to detect LE (LE-PAD) as a point-of-care quantitative test for UTI. The LE-PAD is composed of a coating of mixed 3-(N-tosyl-L-alaninyloxy)-5-phenylpyrrole (PE) and 1-diazo-2-naphthol-4-sulfonic acid (DAS) deposited onto a silver conducting film (Ag film). The LE/urine reacts with the PE and DAS, and the resulting products in turn react with the silver coating, causing a change in resistivity. The quantitative calibration curve was established in this study and has been used to analyse urine samples from inpatients with urinary catheters (n = 21). The results revealed that the level of LE determined by LE-PADs was predictive of UTI diagnosis with an area under the receiver operating characteristic curve of 0.875 (95% confidence interval, 0.704-1.000). Using an appropriate cut-off value, the sensitivity and specificity of UTI diagnosis by LE-PAD were 87.5% and 92.3%, while the LE-positivities of urine dipstics were 62.5% and 76.9%, respectively. For UTI diagnosis, the LE-PAD demonstrated positive and negative likelihood ratios of 11.38 and 0.14, suggesting that the novel LE-PAD is a reliable test.

Validation of the Chinese Version of the Shame and Stigma Scale in Patients with Head and Neck Cancer.

PURPOSE: Head and neck cancer (HNC) patients suffer from perceived shame and stigma due to the illness diagnosis, as well as disfigurement following surgery. To measure HNC patients' perception of shame and stigma, the Shame and Stigma Scale (SSS) was developed and preliminarily validated. In this study, we aimed to translate, adapt, and validate the SSS in Chinese. METHODS: This study consisted of a cross-sectional design with consecutive sampling and consisted of two stages: (1) translation of the SSS into Chinese by two bilingual professionals and (2) examination of the Chinese version of the SSS (C-SSS) for internal consistency, inter-rater reliability, test-retest reliability, construct validity, and concurrent validity. In total, 159 inpatients with HNC (mean age: 56.8 years, 95% males) were enrolled at a medical center in Southern Taiwan. RESULTS: The Principal Component Analysis of the C-SSS revealed a five-factor structure: 4 of the 5 factors were replicated in the original SSS, including Shame with Appearance, Regret, Social/Speech Concern, and Sense of Stigma; only factor 4, Self-discrimination, was newly identified in the current study. C-SSS showed acceptable internal validity (Cronbach's α =0.85), test-retest reliability, inter-rater reliability, and fair concurrent validity with the Taiwanese Depression Questionnaire (TDQ), Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), and Explanatory Model Interview Catalogue (EMIC). CONCLUSION: The findings of this study indicate that C-SSS is a reliable and valid instrument for evaluating HNC patients' perception of shame and stigma in the Taiwanese population.

NLRP12 Regulates Anti-viral RIG-I Activation via Interaction with TRIM25.

Establishing the balance between positive and negative innate immune mechanisms is crucial for maintaining homeostasis. Here we uncover the regulatory crosstalk between two previously unlinked innate immune receptor families: RIG-I, an anti-viral cytosolic receptor activated type I interferon production, and NLR (nucleotide-binding domain, leucine repeat domain-containing protein). We show that NLRP12 dampens RIG-I-mediated immune signaling against RNA viruses by controlling RIG-I's association with its adaptor MAVS. The nucleotide-binding domain of NLRP12 interacts with the ubiquitin ligase TRIM25 to prevent TRIM25-mediated, Lys63-linked ubiquitination and activation of RIG-I. NLRP12 also enhances RNF125-mediated, Lys48-linked degradative ubiquitination of RIG-I. Vesicular stomatitis virus (VSV) infection downregulates NLRP12 expression to allow RIG-I activation. Myeloid-cell-specific Nlrp12-deficient mice display a heightened interferon and TNF response and are more resistant to VSV infection. These results indicate that NLRP12 functions as a checkpoint for anti-viral RIG-I activation.

The effect of peer influence on the use of CT by emergency physicians for patients with headaches.

BACKGROUND: It is challenging for emergency physicians (EPs) to distinguish between patients with life-threatening and benign headaches. We examined the effect of peer influence on computed tomography use by EPs for patients with headache and evaluated the peer influence effect in EPs with different levels of risk tolerance. METHODS: We conducted a before- and after-retrospective case review, and administered the Risk-Taking subscale of the Jackson Personality Index to attending physicians. Each EP computed tomography (CT) use rate, patient number, and CT use, were e-mailed every two months to enhance EP team norm and establish a trend in behavior. RESULTS: Of the 665 (before intervention) and 669 (after intervention) patients with headache, 206 (31%) and 171 (25.6%) underwent brain CT scans, respectively. Decreased use of CT examination was found in the post-intervention group (OR = 0.758, 95% CI: 0.593-0.967), especially for most risk-tolerant physicians (OR = 0.530, 95% CI: 0.311-0.889). There was prolonged ED length of stay (LOS) in the pre-intervention group (OR = 51.52, 95% CI: 26.998-76.050). CONCLUSIONS: We observed that peer influence is an effective way to improve CT use rate and emergency department LOS for patients with isolated headache, especially for most risk-tolerant physicians. These findings could enhance the development of appropriate guidelines to assist ED physicians' CT use.

Excited catatonia in a patient with fatal pulmonary embolism and a successful treatment strategy.

BACKGROUND: Patients with psychiatric disorders in critical condition are difficult to treat. In this study, we report on a patient with underlying schizoaffective disorder who developed catatonia, cardiac arrest, and pulmonary embolism, as well as a successful treatment strategy. CASE PRESENTATION: The inpatient is a 41-year-old morbidly obese male with schizoaffective disorder whose clozapine dosage was titrated from 100 mg to 175 mg due to auditory hallucination and agitation. The patient abruptly developed acute cardiopulmonary symptoms associated with an elevated troponin-I level. He was transferred to a cardiac intensive care unit, where he remained for 3 days. He was also found to have excited catatonic symptoms, and the lorazepam-diazepam protocol was initiated to quickly relieve the catatonia. Once the coronary angiogram was read as normal, the patient was transferred back to the psychiatric ward. However, the patient then suffered from in-hospital cardiac arrest. He was resuscitated and again transferred to the medical intensive care unit. Computed tomography confirmed the diagnosis of a pulmonary embolism. The patient was treated with Rivaroxaban 30 mg/d for the first 21 days, followed by 20 mg daily for 3 months. To control his severe and refractory psychotic symptoms, the patient was re-prescribed clozapine. During the 15-month follow-up period, the patient demonstrated a fair response and tolerability to clozapine 150 mg without symptoms relapse and no thromboembolic event. CONCLUSION: This report can serve to remind psychiatrists and physicians to be aware of fatal conditions in patients with psychiatric diseases and physical illnesses.