rTMS effects on urges and severity of tobacco use disorder operate independently of a retrieval-extinction component and involve frontal-striatal pathways.

BACKGROUND: Although smoking remains a leading cause of preventable disease, the treatment options for smoking are limited. The present study evaluated the neural features underlying effects of repetitive transcranial magnetic stimulation (rTMS) for reducing smoking cravings. In addition, the efficacy of a simulated retrieval-extinction procedure to augment rTMS efficacy was examined. METHODS: Sixty-one individuals with tobacco use disorder (TUD) were randomized into three groups: classic rTMS, retrieval rTMS (viewed smoking videos before rTMS), and sham rTMS. rTMS was performed on the left dorsolateral prefrontal cortex (DLPFC) over 5 days using a standard figure-8 coil. Smoking cravings and brain responses to smoking cues were measured before and after rTMS treatment. Changes in functional connectivity (FC) among different brain regions were calculated. RESULTS: rTMS reduced smoking urges in TUD. Both active-rTMS groups demonstrated greater activations of the DLPFC, caudate, and bilateral insula relative to the sham group. Increased FC was observed between executive and reward network brain regions, and decreased FC was observed within reward network regions. Compared with standard rTMS, retrieval-extinction rTMS demonstrated similar outcomes and was associated with less activation of the medial frontal gyrus. CONCLUSIONS: rTMS increased activations in brain regions implicated in executive control and reward processing. Strengthened prefrontal-striatal pathway suggests that rTMS enhanced top-down control over smoking cravings. The retrieval-extinction process, although associated with some different and multiple similar neural correlates as the standard rTMS, did not enhance cessation outcomes.

Control of an outbreak of COVID-19 at a tertiary hospital in Taiwan.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has circulated in Taiwan since late 2019. Healthcare facilities are vulnerable to COVID-19 outbreaks due to clusters of symptomatic patients and susceptible hosts. Prompt control of outbreaks is crucial. In May 2021, an index case of COVID-19 was detected at Far Eastern Memorial Hospital (FEMH) in New Taipei City, Taiwan, 3 days after hospital admission, spreading to 26 patients and staff. Herein we evaluate control of this COVID-1 outbreak. METHODS: To control the outbreak, the index case ward was closed, and large-scale COVID-19 testing (RT PCR) was performed for all inpatients, caregivers and healthcare workers (HCWs). All exposed persons were quarantined. Thorough investigation was conducted to analyze the transmission route. RESULTS: The outbreak comprised 12 patients, 12 caregivers, and 3 HCWs. Seven patients expired and the remaining cases recovered. Overall, 456 patients/caregivers and 169 HCWs were quarantined. Analysis showed that longer exposure time was the main cause of HCW infection; all three infected HCWs were primary-care nurses related to the index case. To diminish hidden cases, all hospitalized patients/caregivers received PCR examinations and all results were negative. Thereafter, all patients/caregivers routinely received PCR examination on admission. Hospital-wide PCR screening for HCW detected 4 positive HCWs unrelated to this outbreak, and a second-round of screening detected 2 more cases, with no additional cases during the following 6 months. CONCLUSION: Prompt infection control measures and large-scale PCR screening can control a COVID-19 outbreak within 2 weeks. Exposure time is the major risk factor for HCW infection.

Screening for Cryptococcal Antigenemia and Burden of Cryptococcosis at the Time of HIV Diagnosis: A Retrospective Multicenter Study.

INTRODUCTION: Screening for cryptococcal antigen (CrAg) is recommended for people living with HIV (PLWH) who present with low CD4 lymphocyte counts. Real-world experience is important to identify gaps between the guidelines and clinical practice. We investigated the trends of CrAg testing and prevalence of cryptococcal antigenemia among PLWH at the time of HIV diagnosis and the related mortality in Taiwan from 2009 to 2018. METHODS: Medical records of newly diagnosed PLWH seeking care at six medical centers around Taiwan between 2009 and 2018 were reviewed. The annual trends of PLWH who had CrAg testing and cryptococcal antigenemia were examined by Cochran-Armitage test. Among PLWH with CD4 < 200 cells/µl, timing of CrAg testing was analyzed for association with 12-month all-cause mortality in Kaplan-Meier plots and in a Cox proportional hazards model after adjustments. RESULTS: Among 5372 included PLWH, 1150 (21.4%) presented with baseline CD4 < 100 cells/µl, and this proportion had decreased during the study period [from 108 (29.3%) in 2009 to 93 (22.3%) in 2018 (P = 0.039)]. The overall prevalence of cryptococcal antigenemia was 7.8% among PLWH with CD4 < 100 cells/µl, which remained stable during the 10-year study period (P = 0.356) and was 2.6% among PLWH with CD4 100-199 cells/µl. The uptake of CrAg testing had increased from 65.7% in 2009 to 78.0% in 2018 (P = 0.002) among PLWH with CD4 < 100 cells/µl. Late CrAg testing, defined by 14 days or later after HIV diagnosis, was associated with increased risk of 12-month mortality compared to early CrAg testing (adjusted hazard ratio 2.028, 95% CI 1.109-3.708). CONCLUSIONS: Burden of cryptococcosis remained high among PLWH with low CD4 lymphocyte counts in Taiwan. Uptake of CrAg screening among late HIV presenters was still suboptimal and delayed. Late CrAg testing was associated with a higher mortality.

Linezolid as salvage therapy for central nervous system infections due to methicillin-resistant Staphylococcus aureus at two medical centers in Taiwan.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA)-associated central nervous system infections are potentially devastating. Linezolid has good penetration into cerebrospinal fluid and brain tissue. In clinical practice, linezolid may be used to treat central nervous system infections caused by MRSA resulting from glycopeptide intolerance or treatment failure. However, the clinical experience of linezolid in treating MRSA related central nervous system infections is scarce. METHODS: From 2006 to 2016, patients aged ≥20 years who had central nervous system infections caused by MRSA treated with linezolid for more than 24 hours were retrospectively included from two medical centers. The demographic details, treatment response, side effects, and relapse of infection were reviewed. RESULTS: Sixty-six patients with proven CNS infection caused by MRSA were treated with linezolid. The mean age was 53.3 years. The diagnoses in this cohort consisted of brain abscesses (n = 19, 28.8%), spinal epidural abscess (n = 18, 27.3%), meningitis only (n = 12, 18.2%), meningitis with brain epidural abscess (n = 9, 13.6%), and spine device-related infection (n = 5, 7.6%). The main reasons to prescribe linezolid were glycopeptide treatment failure (51.5%) and glycopeptide allergy (48.5%). Ninety-one percent of patients were treated with linezolid for more than 14 days. The in-hospital mortality rate was 13.6%. The relapse rate after treatment was 16.7%. Drug-related adverse events (mainly cytopenia) were observed in 27.3% of patients, but none of the adverse events was fatal. CONCLUSIONS: In our retrospective study, linezolid demonstrated promising effect as a salvage therapy for central nervous system infection caused by MRSA, whether due to drug allergy or glycopeptide treatment failure.

Klebsiella pneumoniae bacteremia revisited: Comparison between 2007 and 2017 prospective cohorts at a medical center in Taiwan.

BACKGROUND: Community onset K. pneumoniae bacteremia (KPB) is a major problem in Taiwan for decades. We aimed to revisit the role of virulent genotype K1/K2 and possible predisposing factors, compared to our published 2007 cohort. METHODS: All adult patients with monomicrobial KPB during 2017 at a medical center in Taiwan were prospectively enrolled. We genotyped the major K types of K. pneumoniae strains, and analyzed the role of prior use of antibiotic or proton pump inhibitor (PPI). RESULTS: A total of 213 cases were enrolled. Compared to our previous 2007 study (n = 231), there was a higher percentage of patients with community onset bacteremia (75% vs. 60%, p = 0.003). The overall mortality rate was lower in 2017 (23% vs. 32%, p = 0.02), while the rates of antimicrobial resistance (all classes) were higher in 2017. There were 40 cases of liver abscesses in 2017 (19%), with an overall mortality rate of 7.5%. The prevalence of K1 was similar (16% in 2017 vs. 19% in 2007), but the prevalence of K2 decreased significantly (7% in 2017 vs. 17% in 2007, p = 0.001). After excluding 39 cases without data of recent medication use, 48 of 174 (28%) of patients had received a PPI within 90 days. Patients with recent PPI use had more complicated underlying illnesses, higher antimicrobial resistance, and higher in-hospital mortality, but was negatively associated with liver abscess (4% vs. 24%, p = 0.002). Of patients with community-acquired bacteremia, 51% used antibiotics within 90 days. After excluding 37 patients received antibiotics within 14 days before the detection of bacteremia, patient with antibiotic use within 15-90 days had higher Pittsburgh bacteremia scores (4.5 vs. 2.7, p = 0.04), creatinine levels, and frequency of recent surgery, but was not associated with liver abscess (21% vs. 31%, p = 0.33). DISCUSSION: In summary, after a decade, community onset KPB is still prevalent (1.3 case per 1000 emergency department visit). K1 remains to be the dominant genotype. The association of prior ampicillin/amoxicillin or PPIs use for liver abscess is not confirmed.

Ongoing transmission of Entamoeba histolytica among newly diagnosed people living with HIV in Taiwan, 2009-2018.

Recent outbreaks of enterically transmitted infections, including acute hepatitis A and shigellosis, have raised the concerns of increasing Entamoeba histolytica infection (EHI) among people living with HIV (PLWH) in Taiwan. This study investigated the prevalence of EHI, its temporal trends, and associated factors among newly diagnosed PLWH in Taiwan. Medical records of newly diagnosed PLWH at six medical centers in Taiwan between 2009 and 2018 were reviewed. The annual prevalence of invasive amoebiasis and seroprevalence of E. histolytica were determined and examined by the Cochran-Armitage test. The clinical characteristics associated with invasive amoebiasis and seropositivity for E. histolytica were analyzed in multivariable regression models. Among 5362 patients seeking HIV care at six medical centers in Taiwan during the 10-year study period, 119 (2.2%) had invasive amoebiasis at the time or within six months of their HIV diagnosis. Among 3499 who had indirect hemagglutination antibody (IHA) determined, 284 (8.1%) had positive IHA (≥1:32) and 205 (5.9%) had high-titre IHA (≥1:128). The prevalence of invasive amoebiasis increased from 1.3% in 2012 to 3.3% in 2018 (p = 0.024). Invasive amoebiasis was independently associated with a greater age, men who have sex with men, rapid plasma reagin titre ≥1:4, and concurrent shigellosis and giardiasis. Increasing prevalence of invasive amoebiasis among newly diagnosed PLWH in Taiwan calls for strategies to prevent ongoing transmission in this population. Routine screening of EHI for early diagnosis and treatment is recommended, especially among men who have sex with men and those who present with other sexually or enterically transmitted infections.

Increased risks of tic disorders in children with epilepsy: A nation-wide population-based case-control study in Taiwan.

Both epilepsy and tic disorders may share common mechanisms with the involvement of abnormal cortical-basal ganglion circuit connection and dopaminergic dysfunction. However, the association between epilepsy and tic disorders has never been studied. This study investigated the risks of developing tic disorders among children with epilepsy using databases of a universal health insurance system in Taiwan. The data analyzed in this study were retrieved from the National Health Insurance Research Database in Taiwan. The study cohort included children with epilepsy between 2001 and 2007 (n=2629) and a three-fold age- and gender-matched controls (n=7887). All subjects were followed up for 3 years from the date of cohort entry to identify their admissions due to tic disorders (ICD-9-CM codes 307.2, 307.20-307.23). Cox hazard regression analysis was performed to estimate the effect of epilepsy on the occurrence of tics. The epilepsy cohort had a higher prevalence of tics (1.7% vs. 0.2%), and a 8.70-fold increased risk of developing a tic disorder compared with the controls (adjusted hazard ratio (AHR) 8.70, 95% confidence interval (CI) 4.26-16.37, p<0.001). Male patients were observed to have a higher risk of developing a tic disorder (AHR 1.90, 95% CI=1.04-3.46, p<0.001) compared to female individuals. Patients with multiple antiepileptic drugs treatment also exhibited higher crude OR for developing tic disorders. This nationwide population-based cohort study, for the first time, demonstrated that there is a significantly increased risk for tic disorders among children with epilepsy. We also found males, attention deficit disorder and the use of multiple AEDs to be independent risk factors of tic disorders. Closely evaluating possible tic disorders would be crucial for improving the outcome and life quality in children with epilepsy.

Increased risk of epilepsy in children with Tourette syndrome: A population-based case-control study.

The association between epilepsy and Tourette syndrome has rarely been investigated. In this retrospective cohort study, we analyzed a dataset of 1,000,000 randomly sampled individuals from the Taiwan National Health Insurance Research Database to determine the risk of epilepsy in children with Tourette syndrome. The study cohort consisted of 1062 patients with Tourette syndrome aged ≤ 18 years, and the control group consisted of three times the number of age- and sex-matched patients without Tourette syndrome, who were insurants, from the same database during the same period. The Tourette syndrome group had an 18.38-fold increased risk of epilepsy than the control group [hazard ratio=18.38, 95% confidence interval (CI)=8.26-40.92; P<0.001]. Even after adjusting for the comorbidities, the risk of epilepsy in the Tourette syndrome group with comorbidities remained high (hazard ratio=16.27, 95% CI=6.26-18.46; P<0.001), indicating that the increased risk was not associated with comorbidities. This population-based retrospective cohort study provides the first and strong evidence that Tourette syndrome is associated with a higher risk of epilepsy. A close follow-up of children with Tourette syndrome for the development of epilepsy is warranted.

SCMPSP: Prediction and characterization of photosynthetic proteins based on a scoring card method.

BACKGROUND: Photosynthetic proteins (PSPs) greatly differ in their structure and function as they are involved in numerous subprocesses that take place inside an organelle called a chloroplast. Few studies predict PSPs from sequences due to their high variety of sequences and structues. This work aims to predict and characterize PSPs by establishing the datasets of PSP and non-PSP sequences and developing prediction methods. RESULTS: A novel bioinformatics method of predicting and characterizing PSPs based on scoring card method (SCMPSP) was used. First, a dataset consisting of 649 PSPs was established by using a Gene Ontology term GO:0015979 and 649 non-PSPs from the SwissProt database with sequence identity <= 25%.- Several prediction methods are presented based on support vector machine (SVM), decision tree J48, Bayes, BLAST, and SCM. The SVM method using dipeptide features-performed well and yielded - a test accuracy of 72.31%. The SCMPSP method uses the estimated propensity scores of 400 dipeptides - as PSPs and has a test accuracy of 71.54%, which is comparable to that of the SVM method. The derived propensity scores of 20 amino acids were further used to identify informative physicochemical properties for characterizing PSPs. The analytical results reveal the following four characteristics of PSPs: 1) PSPs favour hydrophobic side chain amino acids; 2) PSPs are composed of the amino acids prone to form helices in membrane environments; 3) PSPs have low interaction with water; and 4) PSPs prefer to be composed of the amino acids of electron-reactive side chains. CONCLUSIONS: The SCMPSP method not only estimates the propensity of a sequence to be PSPs, it also discovers characteristics that further improve understanding of PSPs. The SCMPSP source code and the datasets used in this study are available at http://iclab.life.nctu.edu.tw/SCMPSP/.

Is schizophrenia associated with an increased risk of chronic kidney disease? A nationwide matched-cohort study.

OBJECTIVE: The impact of schizophrenia on vital diseases, such as chronic kidney disease (CKD), has not as yet been verified. This study aims to establish whether there is an association between schizophrenia and CKD. DESIGN: A nationwide matched cohort study. SETTING: Taiwan's National Health Insurance Research Database. PARTICIPANTS: A total of 2338 patients with schizophrenia, and 7014 controls without schizophrenia (1:3), matched cohort for sex, age group, geography, urbanisation and monthly income, between 1 January 2003 and 31 December 2007, based on the International Classifications of Disease Ninth Edition (ICD-9), Clinical Modification codes. PRIMARY AND SECONDARY OUTCOME MEASURES: After making adjustments for confounding risk factors, a Cox proportional hazards model was used to compare the risk of developing CKD during a 3-year follow-up period from the index date. RESULTS: Of the 2338-subject case cohort, 163 (6.97%) developed a CKD, as did 365 (5.20%) of the 7014 control participants. Cox proportional hazards regression analysis revealed that patients with schizophrenia were more likely to develop CKD (HR=1.36, 95% CI 1.13 to 1.63; p<0.001). After adjusting for gender, age group, hypertension, diabetes mellitus, hyperlipidaemia, heart disease and non-steroid anti-inflammatory drugs (NSAIDs) usage, the HR for patients with schizophrenia was 1.25 (95% CI 1.04 to 1.50; p<0.05). Neither typical nor atypical antipsychotics was associated an increased risk of CKD in patients with schizophrenia. CONCLUSIONS: The findings from this population-based retrospective cohort study suggest that schizophrenia is associated with a 25% increase in the risk of developing CKD within only a 3-year follow-up period.