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In an investigation of six anti-SARS-CoV-2 antibody kits with different target antigen and methodology, each kit showed comparable performance. As false-positive reactions occurred independently with different kits, specificity increased to 100% when pairs of kits were used. With three-kit combination, both sensitivity (99.1%) and specificity (100%) increased.

Objective: It has been difficult to establish specific subtypes of obstructive sleep apnea (OSA) due to the heterogeneous nature of the disor- der. Previous studies have attempted to exact clinical subgroups or phenotypes of the disorder. However, the psychiatric impact of OSA has been often overlooked, and thus, this study used cluster analysis to examine subgroups of OSA incorporating mood states.Methods: This study is comprised of 346 adult OSA patients (apnea-hypopnea index, AHI≥5) who underwent polysomnography at Nowon Eulji Medical Center from January 2003 to November 2012. Their data also included validated self-report questionnaires that evaluate daytime sleepi- ness, sleep quality, morningness-eveningness, and mood states: Epworth Sleepiness Scale, Korean version of the Pittsburgh Sleep Quality In- dex (PSQI-K), Horne and Östberg Questionnaire, and Korean edition of Profile of Mood States (K-POMS), respectively. A K-means cluster analy- sis was performed to determine the optimal number of clusters and characteristics.Results: We identified three clusters: cluster 1, moderately symptomatic OSA with the least disturbed mood (n=166); cluster 2, severely symptomatic OSA not so disturbed mood (n=90); cluster 3, moderately symptomatic with highest disturbed mood (n=90). Cluster 1 had the lowest AHI and the lowest K-POMS total scores. Cluster 2, despite having the most severe OSA parameters, did not show mood disturbances. Cluster 3 had the highest K-POMS total scores and PSQI-K scores.Conclusion: Certain individuals with OSA are more likely to suffer from disturbed mood states without serious OSA indices. Psychiat- ric manifestations should also be considered when determining the severity of the disorder.

Objective Telomere shortening has been seen in major psychiatric disorders, including major depressive disorder. However, only a few small studies have examined this in bipolar disorder (BD). We compared the telomere length in patients with BD1 or BD2 with that in matched healthy controls. Methods We included 215 patients with BD (128 BD1, 87 BD2) and 204 age- and sex-matched healthy controls. Relative telomere length was determined by quantitative polymerase chain reaction. The patients and controls were compared separately for age groups, sex, and BD subgroups (BD1 and BD2). Results We found significant telomere shortening in patients with BD1 (p < 0.001), but not in patients with BD2. In male patients with BD1, the 30−39 year age group had significant shortening of telomere length than controls (p = 0.01). Female patients with BD1 in the 19−29-year age group had significantly shortened telomeres compared to the controls (p < 0.01). Conclusion Our results suggest a significant reduction in telomere length in BD1. Telomere shortening would be a potential biomarker for BD.

Major depressive disorder (MDD) is the most common mood disorder, and causes various mental, physical and cognitive symptoms. Clinicians diagnose MDD using multiple interviews and overall impression during the interviews, which makes MDD diagnosis highly subjective. To overcome this, we investigated novel protein biomarker for MDD. Serum from each subject were analyzed using nano liquid chromatography-triple time-of-flight mass spectrometry. We identified two proteins, zinc-alpha-2-glycoprotein (ZA2G) and keratin type II cytoskeletal 1 (K2C1), as final biomarkers. These biomarkers were downregulated during depression (p 0.05, AUC of ROC0.7). ZA2G is related to tryptophan metabolism, which is a main serotonin synthesis pathway. K2C1 is involved in the kinin-kallikrein system, which produces bradykinin, an anti-inflammatory mediator in the brain. Our results suggest that the two protein candidates are related to inflammation and that MDD is highly associated with inflammation. Finally, since all subjects in the two groups were taking antidepressants, our results suggest that the identified biomarkers could determine the presence or absence of illness and could be used to monitor therapeutic effects.

Neutralizing antibodies targeted at the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein have been developed and now under evaluation in clinical trials. The US Food and Drug Administration currently issued emergency use authorizations for neutralizing monoclonal antibodies in non-hospitalized patients with mild to moderate coronavirus disease 2019 (COVID-19) who are at high risk for progressing to severe disease and/or hospitalization. In terms of this situation, there is an urgent need to investigate the clinical aspects and to develop strategies to deploy them effectively in clinical practice. Here we provide guidance for the use of anti-SARS-CoV-2 monoclonal antibodies for the treatment of COVID-19 based on the latest evidence.

Because major depressive disorder (MDD) and bipolar disorder (BD) manifest with similar symptoms, misdiagnosis is a persistent issue, necessitating their differentiation through objective methods. This study was aimed to differentiate between these disorders using a targeted proteomic approach. Multiple reaction monitoring-mass spectrometry (MRM-MS) analysis was performed to quantify protein targets regarding the two disorders in plasma samples of 270 individuals (90 MDD, 90 BD, and 90 healthy controls (HCs)). In the training set (72 MDD and 72 BD), a generalizable model comprising nine proteins was developed. The model was evaluated in the test set (18 MDD and 18 BD). The model demonstrated a good performance (area under the curve (AUC) >0.8) in discriminating MDD from BD in the training (AUC = 0.84) and test sets (AUC = 0.81) and in distinguishing MDD from BD without current hypomanic/manic/mixed symptoms (90 MDD and 75 BD) (AUC = 0.83). Subsequently, the model demonstrated excellent performance for drug-free MDD versus BD (11 MDD and 10 BD) (AUC = 0.96) and good performance for MDD versus HC (AUC = 0.87) and BD versus HC (AUC = 0.86). Furthermore, the nine proteins were associated with neuro, oxidative/nitrosative stress, and immunity/inflammation-related biological functions. This proof-of-concept study introduces a potential model for distinguishing between the two disorders.

Purpose To compare the clinical efficacy between peramivir and oseltamivir in hospitalized patients with influenza. Patients and methods Retrospective cohort study examined data from 542 adult patients with laboratory-confirmed seasonal influenza hospitalized in five teaching hospitals and one secondary hospital between August 2017 and May 2018. The main outcome was the defervescence rate within 3 days from the first administration of peramivir or oseltamivir. The secondary outcomes were mortality and duration of hospitalization/intensive care unit (ICU) stay. Results Of the 542 enrolled patients, 251 were administered the standard dose of peramivir (300 mg, single dose), 42 were administered peramivir at doses exceeding 300 mg, and 249 were administered oseltamivir (75 mg, twice daily for 5 days). There were more ICU and pneumonia cases and older patients in the peramivir group, especially the high-dose group. The Charlson comorbidity index (CCI) scores were similar among the three groups. There were no significant differences in defervescence rates within 3 days between the three groups. The mortality and duration of hospital and ICU stays also did not differ significantly. The factors associated with 30-day mortality were ICU admission, high CCI score, and pneumonia. Conclusion Treatment of influenza with either peramivir or oseltamivir in hospitalized adults resulted in generally similar clinical outcomes. Peramivir treatment showed good clinical response in influenza patients with pneumonia or admitted to the ICU.

Background/Aims Methicillin-resistant Staphylococcus aureus (MRSA) is highly prevalent in hospitals, and has recently emerged in the community. The impact of methicillin-resistance on mortality and medical costs for patients with S. aureus bacteremia (SAB) requires reevaluation. Methods We searched studies with SAB or endocarditis using electronic databases including Ovid-Medline, Embase-Medline, and Cochrane Library, as well as five local databases for published studies during the period January 2000 to September 2011. Results A total of 2,841 studies were identified, 62 of which involved 17,563 adult subjects and were selected as eligible. A significant increase in overall mortality associated with MRSA, compared to that with methicillin-susceptible S. aureus (MSSA), was evidenced by an odds ratio (OR) of 1.95 (95% confidence interval [CI], 1.73 to 2.21; p < 0.01). In 13 endocarditis studies, MRSA increased the risk of mortality, with an OR of 2.65 (95% CI, 1.46 to 4.80). When three studies, which compared mortality rates between CA-MRSA and CA-MSSA, were combined, the risk of methicillin-resistance increased 3.23-fold compared to MSSA (95% CI, 1.25 to 8.34). The length of hospital stay in the MRSA group was 10 days longer than that in the MSSA group (95% CI, 3.36 to 16.70). Of six studies that reported medical costs, two were included in the analysis, which estimated medical costs to be $9,954.58 (95% CI, 8,951.99 to 10,957.17). Conclusions MRSA is still associated with increased mortality, longer hospital stays and medical costs, compared with MSSA in SAB in studies published since the year 2000.

Rationale: Until now, no cohort studies have evaluated the relationship between high-risk human papillomavirus (HPV) infection and new-onset cardiovascular diseases (CVD). Objective: We investigated an association between high-risk HPV infection and the development of CVD. Methods and Results: We conducted a cohort study of 63 411 women aged 30 or older without CVD at baseline who underwent a high-risk HPV test and were followed annually or biennially from 2011 to 2016. CVD was ascertained through the linkage to the Health Insurance and Review Agency database. A Cox-proportional hazards regression model was used to estimate adjusted hazard ratios (HRs) with 95% CIs of incident CVD. The prevalence of high-risk HPV infection was 7.6%. During 261 598.9 person-years of follow-up, 1122 cases of new-onset CVD were identified (incidence rate of 4.3 per 10 3 person-years). High-risk HPV infection was significantly associated with incident CVD. After adjustment for possible confounders, and high sensitivity C-reactive protein, a significant association between high-risk HPV infection and incident CVD was still observed, with a corresponding HR (95% CI) of 1.25 (1.03–1.52). This association was stronger among individuals with obesity and those with metabolic syndrome. Multivariable-adjusted HR (95% CI) for incident CVD comparing high-risk HPV-positive- to high-risk HPV-negative participants was 1.10 (0.87–1.39) in the nonobese, whereas corresponding HR (95% CI) was 1.73 (1.19–2.51) in those with obesity ( P for interaction by obesity=0.02). Similarly, multivariable-adjusted HR (95% CI) for incident CVD comparing high-risk HPV-positive- to high-risk HPV-negative participants was 1.09 (0.87–1.36) in those without metabolic syndrome and 1.99 (1.28–3.08) in those with MetS ( P for interaction=0.05). Conclusion: In this large cohort, high-risk HPV infection was significantly associated with an increased risk of developing CVD, especially in obese individuals and those with MetS, indicating that high-risk HPV might affect CVD risk with possible effect modification by obesity and MetS.

Major depressive disorder (MDD) is a common disorder involving depressive mood and decreased motivation. Due to its high heterogeneity, novel biomarkers are required to diagnose MDD. In this study, a proteomic method was used to identify a new MDD biomarker. Using sequential window acquisition of all theoretical mass spectra acquisitions and multiple reaction monitoring analysis via mass spectrometry, relative and absolute quantification of proteins in the sera was performed. The results of the relative quantitation by sequential window acquisition for all theoretical mass spectra data showed that seven proteins were significantly differently expressed between MDD patients and other patients with remission status. However, absolute quantification by multiple reaction monitoring analysis identified prothrombin as the only significantly upregulated protein in the depressive state compared to remission (p &lt, 0.05) and was, thus, subsequently selected as an MDD biomarker. The area under the curve for prothrombin was 0.66. Additionally, increased prothrombin/thrombin induced hyper-activation of platelets via activating protease-activated receptors, a feature associated with MDD, specifically, activated platelets secrete various molecules related to MDD, including brain-derived neurotropic factors and serotonin. Therefore, prothrombin is a potential screening, prognostic, and diagnostic marker for MDD.

Introduction Cigarette smoking is a leading cause of death worldwide and is associated with various diseases. However, studies addressing its impact on infection-related deaths are limited. This study examined the relationship between smoking and infection-related mortality. Aims and Methods A cohort of 583 034 South Korean adults who underwent annual or biennial health examinations were followed up for infection-related deaths using national records. Cox proportional hazards regression assessed hazard ratios (HRs) and 95% confidence intervals (CIs) for infection-related mortality. Results The median follow-up was 9.1 years (maximum 18 years), and 335 infection-related deaths were identified. Current smoking, but not former smoking, was positively associated with an increased risk of infection-related mortality. After adjusting for possible confounders, the multivariable-adjusted HRs (95% CIs) for infection-related mortality comparing former and current smokers with never smokers were 0.94 (0.68–1.30) and 1.45 (1.05–2.02), respectively; and those for infection-related mortality by number of pack-years comparing 10–19.9 and ≥20 pack-years to Conclusions Current smoking status, intensity, and pack-years were associated with an increased risk of infection-related death, with the highest risk of infection-related mortality found consistently in individuals with ≥20 pack-years. Implications In this large-scale cohort study of relatively young and middle-aged South Korean adults, current smoking, smoking intensity, and pack-years were associated with an increased risk of death due to infections; in particular, a significantly increased risk of infection-related mortality was consistently found in individuals with ≥20 pack-years. When appropriate, infection-related mortality should be included in smoking-attributable mortality burdens, and effective smoking control measures should be considered to improve infection-related mortality.

Clinical applicability of rapid diagnostic test kit for SARS-CoV-2 antibodies was evaluated. The kit detected antibodies from day 9-56 of illness. IgG bands were observed up to 1: 1000 dilutions. The kit could detect 90.5% of IgG and 61.9% of IgM antibodies of mild febrile patients without pneumonia.

Background Remdesivir is widely used for the treatment of coronavirus disease 2019 (COVID-19), but controversies regarding its efficacy still remain. Methods A retrospective cohort study was conducted to evaluate the effect of remdesivir on clinical and virologic outcomes of severe COVID-19 patients from June to July 2020. Primary clinical endpoints included clinical recovery, additional mechanical ventilator (MV) support, and duration of oxygen or MV support. Viral load reduction by hospital day (HD) 15 was evaluated by calculating changes in cycle threshold (Ct) values. Results A total of 86 severe COVID-19 patients were evaluated including 48 remdesivir-treated patients. Baseline characteristics were not significantly different between the two groups. Remdesivir was administered an average of 7.42 days from symptom onset. The proportions of clinical recovery of the remdesivir and supportive care group at HD 14 (56.3% and 39.5%) and HD 28 (87.5% and 78.9%) were not statistically different. The proportion of patients requiring MV support by HD 28 was significantly lower in the remdesivir group than in the supportive care group (22.9% vs. 44.7%, P = 0.032), and MV duration was significantly shorter in the remdesivir group (average, 1.97 vs. 5.37 days; P = 0.017). Analysis of upper respiratory tract specimens demonstrated that increases of Ct value from HD 1–5 to 11–15 were significantly greater in the remdesivir group than the supportive care group (average, 10.19 vs. 5.36; P = 0.007), and the slope of the Ct value increase was also significantly steeper in the remdesivir group (average, 5.10 vs. 2.68; P = 0.007). Conclusion The remdesivir group showed clinical and virologic benefit in terms of MV requirement and viral load reduction, supporting remdesivir treatment for severe COVID-19., Graphical Abstract

Objectives: To investigate antibody production in asymptomatic and mild COVID-19 patients. Methods: Sera from asymptomatic to severe COVID-19 patients were collected. Microneutralization (MN), fluorescence immunoassay (FIA), and enzyme-linked immunosorbent assay (ELISA) were performed. Results: A total of 70 laboratory-confirmed COVID-19 patients were evaluated, including 15 asymptomatic/anosmia, 49 mild symptomatic, and 6 pneumonia patients. The production of the neutralizing antibody was observed in 100% of pneumonia, 93.9% of mild symptomatic, and 80.0% of asymptomatic/anosmia groups. All the patients in the pneumonia group showed high MN titer (&ge, 1:80), while 36.7% of mild symptomatic and 20.0% of asymptomatic/anosmia groups showed high titer (p &lt, 0.001). Anti-SARS-CoV-2 antibodies could be more sensitively detected by FIA IgG (98.8%) and ELISA (97.6%) in overall. For the FIA IgG test, all patients in the pneumonia group exhibited a high COI value (&ge, 15.0), while 89.8% of mild symptomatic and 73.3% of asymptomatic/anosmia groups showed a high value (p = 0.049). For the ELISA test, all patients in the pneumonia group showed a high optical density (OD) ratio (&ge, 3.0), while 65.3% of mild symptomatic and 53.3% of asymptomatic/anosmia groups showed a high ratio (p = 0.006). Conclusions: Most asymptomatic and mild COVID-19 patients produced the neutralizing antibody, although the titers were lower than pneumonia patients. ELISA and FIA sensitively detected anti-SARS-CoV-2 antibodies.

Background & Aims Although coronavirus disease 2019 (COVID-19) is characterized by fever and respiratory symptoms, some patients have no or mild symptoms. Severe acute respiratory syndrome-coronavirus (SARS-CoV-2) has been detected in feces of patients. We investigated gastrointestinal symptoms and shedding of virus into feces of patients with asymptomatic or mild COVID-19. Methods We collected data from 46 patients (median age, 26 y; 46% men) with asymptomatic or mild COVID-19 (without fever and pneumonia) and prolonged respiratory shedding of SARS-CoV-2, quarantined from April 4, 2020, through April 24, 2020, in Korea. Respiratory specimens included upper respiratory specimens (nasopharyngeal and oropharyngeal swabs) and lower respiratory specimens (sputum), and were collected twice per week. The median interval between COVID-19 diagnosis to the start of fecal sample collection was 37 days (range, 29–41 d); 213 stool specimens were collected from 46 patients. We used real-time reverse-transcription polymerase chain reaction to detect SARS-CoV-2 in the respiratory and fecal specimens. Results Gastrointestinal manifestations were observed in 16 of the 46 patients (35%); diarrhea was the most common (15%), followed by abdominal pain (11%), dyspepsia (11%), and nausea (2%). Virus RNA was detected in feces from 2 patients without gastrointestinal symptoms (4%). Mean cycle threshold values from the time of quarantine to the time of fecal collection tended to be lower in patients with virus detected in fecal samples than in patients without virus in fecal samples (29.91 vs 33.67 in the first week, 29.47 vs 35.71 in the fifth week, respectively). Shedding of virus into feces persisted until day 50 after diagnosis; fecal samples began to test negative before or at approximately the time that respiratory specimens also began to test negative. Conclusions In an analysis of fecal and respiratory specimens from patients with COVID-19 in quarantine in Korea, we found that the gastrointestinal tract could be a route of transmission of SARS-CoV-2 even in patients with asymptomatic or mild disease, with no gastrointestinal symptoms. The viral load of the respiratory specimens appears be related to shedding of the virus into feces in this group of patients.

Taeniasis is a cosmopolitan helminthic disease caused by Taenia species, which included Taenia solium, Taenia saginata, and Taenia asiatica. These parasites typically infect the small intestine, but cases of aberrant migration have been reported. We treated a 70-year-old man who presented with vomiting and colicky abdominal pain. On physical examination, Murphy’s sign was positive, and laboratory findings indicated severe inflammation. Computed tomography and magnetic resonance cholangiopancreatography revealed typical features of cholecystitis. An 82-cm-long, slender and degenerated, parasite-like organism was aspirated through a percutaneous transhepatic gallbladder drainage tube. After extensive washing of the organism, we detected yellowish-brown colored, spherical 37.9 × 33.8-µm-sized taenid eggs with thick transverse striations. Hematoxylin–eosin-stained worm sections also contained Taeniidae eggs. Polymerase chain reaction amplification of DNA extracted from the worm with species-specific cytochrome c1 (cox1) primer sets detected a T. solium–specific fragment. Because of sustained high fever combined with inflammatory signs, the patient underwent laparoscopic cholecystectomy and inflamed gallbladder removal. A histopathologic specimen demonstrated chronic reactive cholecystitis. The patient’s fever and leukocytosis rapidly resolved after surgery. We experienced an uncommon case of biliary taeniasis representing cholecystitis caused by adult worm of T. solium.

Background Despite recent advances in the treatment of drug reaction with eosinophilia and systemic symptoms (DRESS), the mainstay of treatment involves discontinuing the culprit drugs and administering topical or systemic corticosteroid. Objective The clinical use of a tumor necrosis factor (TNF)-alpha inhibitor was rarely explored in treatment of DRESS. Methods We present a case of corticosteroid-induced DRESS that was successfully treated with a TNF-alpha inhibitor without sequalae. Results This is the first case report that showed the clinical use of a TNF alpha inhibitor in treating corticosteroids- induced DRESS and immediate hypersensitivity reactions. The HLA-B*5801 was identified as a possible genetic factor associated with a corticosteroid-induced DRESS. Conclusions A TNF-alpha inhibitor could be a primary option in treating DRESS, especially in patients with hypersensitivity reaction to corticosteroids.

Background There is some evidence that resilience is related to mental illness. Patients with a mood disorder have a tendency to show eveningness, and they tend to be less resilient. However, no study has investigated the association between resilience and morningness-eveningness in patients with a mood disorder. The aim of this study was to explore whether morningness-eveningness is related to resilience in patients with a mood disorder. Methods We recruited 224 patients with major depressive disorder (MDD), 77 with bipolar disorder (BD), and 958 control participants. Morningness-eveningness and resilience were evaluated using the Composite Scale of Morningness (CS) and the Connor-Davidson Resilience Scale (CD-RISC), respectively. Results The CD-RISC scores were significantly lower in patients with MDD, followed by those with BD, than those of the control group. The CD-RISC score was positively correlated with the CS score in patients with MDD and BD. Multiple linear regression analyses revealed that the CS score was significantly associated with the CD-RISC score after controlling for the possible influence of age, gender, length of education, economic status, onset age, and suicide attempt history in the MDD group. However, the association did not reach statistical significance in patients with BD. Conclusions Higher resilience was positively correlated with morningness in patients with MDD or BD. In multiple regression analysis, a significant linear relationship was observed between resilience and morningness only in patients with MDD. The biological mechanism underlying the relationship between morningness-eveningness and resilience should be explored.

Hepatitis B virus (HBV) infection has been associated with a decreased prevalence of dyslipidaemia in cross-sectional studies, but cohort studies are limited. We investigated the longitudinal effects of chronic HBV infection on the development of dyslipidaemia. We performed a cohort study of 62 287 non-cirrhotic adult men and women free of dyslipidaemia who underwent serologic testing for hepatitis B surface antigen (HBsAg) and were followed annually or biennially for an average of 4.46 years. A parametric proportional hazard model was used to estimate the adjusted hazard ratio with 95% confidence interval (CI) for incident dyslipidaemia according to HBsAg seropositivity status. We identified 12 331 incident cases of hypercholesterolaemia during 278 004.4 person-years of follow-up (incident rate 44.4 per 1000 person-years). In models adjusted for age, sex, body mass index, year of screening exam, smoking status, alcohol intake, regular exercise and education level, the adjusted hazard ratios (95% CIs) for incident hypercholesterolaemia, high LDL cholesterolaemia; hypertriglyceridaemia, high non-HDL cholesterolaemia and low HDL cholesterolaemia comparing HBsAg-positive to HBsAg-negative participants was 0.71 (0.64-0.79), 0.83 (0.78-0.89), 0.61 (0.54-0.70), 0.69 (0.63-0.75) and 1.10 (0.98-1.24), respectively. An inverse association between HBsAg positivity and incident high apolipoprotein B were also identified, with a corresponding a hazard ratio of 0.63 (0.55-0.72). In a large cohort of apparently healthy Korean adults, HBsAg seropositivity was associated with lower risk of development of dyslipidaemia, suggesting a role of HBV infection in lipid metabolism.

To evaluate the impacts of fluconazole minimum inhibitory concentration (MIC) according to primary antifungal agents on Candida glabrata bloodstream infection (BSI), a multicenter retrospective cohort study was conducted in Korea, concerning the time period from January 2010 to February 2016. A total of 197 adult patients with C. glabrata BSI were included in the study, and neutropenia (P = 0.026), APACHE II score (P = 0.004), and fluconazole resistance (HR 3.960, 95% CI 1.395-11.246, P = 0.010) were associated with 30-day mortality in multivariate analysis. In subgroup analysis, fluconazole MIC = 32 μg/mL in the azole-treated group (HR 6.691, 95% CI 1.569-28.542, P = 0.010) and fluconazole MIC ≥ 64 μg/mL in the non-azole-treated group (HR 3.337, 95% CI 1.183-9.411, P = 0.023) showed the highest hazard ratio (HR) for 30-day mortality. Increased fluconazole MIC was associated with poor outcome both in azole- and non-azole-treated patients with C. glabrata BSI.

Objectives The widespread administration of carbapenems to patients with ESBL-producing Enterobacteriaceae bacteraemia (ESBL-B) has accelerated the emergence of carbapenem-resistant Enterobacteriaceae. This study aimed to systematically review recently published data to evaluate the clinical effectiveness of carbapenems, compared with other antibiotics, in the treatment of ESBL-B. Methods We searched the Ovid-Medline, Ovid-Embase, Cochrane Library and five Korean local databases until January 2016. We selected studies that reported overall mortality in patients with ESBL-B who had been treated with carbapenems and alternatives. Overall mortality was assessed as the primary outcome and sepsis-related mortality and adverse events were analysed as secondary outcomes. Results Thirty-five publications fulfilled the inclusion criteria. Regarding empirical therapy, there were no significant differences between the groups that received carbapenems and those that received non-carbapenems in relation to overall mortality. Regarding definitive therapy, overall mortality was lower for patients administered carbapenems compared with those administered non-carbapenems [risk ratio (RR) 0.78, 95% CI 0.61-0.98], non-β-lactam/β-lactamase inhibitor combinations (non-BL/BLI) (RR 0.71, 95% CI 0.56-0.90) and cephalosporins (RR 0.56, 95% CI 0.42-0.74). There were no differences between the carbapenems and the other antibiotics, namely BL/BLIs, quinolones and aminoglycosides. Conclusions This meta-analysis showed that BL/BLIs may be promising alternative antibiotics for definitive therapy in patients with ESBL-B. However, the lack of robust data derived from randomized controlled trials limits the conclusions and inferences from the pooled data.

Gut dysbiosis is regarded as a pathogenetic factor of nonalcoholic fatty liver disease (NAFLD), but its role in NAFLD persistence is unknown. We investigated the influence of the gut microbiota on persistent NAFLD. This cohort study included 766 subjects with 16S ribosomal RNA (rRNA) gene sequencing data from fecal samples at baseline who underwent repeated health check-up examinations. Fatty liver was determined using ultrasound at baseline and follow-up. Participants were categorized into four groups: none (control), developed, regressed, or persistent NAFLD. The persistent NAFLD group had lower richness compared with the control group. Significant differences were also found in both non-phylogenic and phylogenic beta diversity measures according to NAFLD persistence. Pairwise comparisons indicated that taxa abundance mainly differed between the control and persistent NAFLD groups. A relative high abundance of Fusobacteria and low abundance of genera Oscillospira and Ruminococcus of the family Ruminococcaceae and genus Coprococcus of the family Lachnospiraceae were found in the persistent NAFLD group. Based on the functional predictions, pathways related to primary and secondary bile acid biosynthesis were highly detected in the persistent NAFLD group compared with the control group. These findings support that the composition of the gut microbiome associated with dysregulation of bile acid biosynthetic pathways may contribute to the persistence of NAFLD. This is the first cohort study to demonstrate the influence of microbiota on persistent NAFLD. Our findings may help identify potential targets for therapeutic intervention in NAFLD.

To evaluate clinical features and prognostic factors of non-albicans candidemia, we conducted a retrospective multicenter cohort study at 7 university hospitals in Korea from January 2010 to February 2016. A total of 721 patients with non-albicans candidemia were included in the analysis. C. tropicalis was most commonly identified (36.5%), followed by C. glabrata (27.2%), C. parapsilosis (25.7%), and C. krusei (2.4%). Clinical presentation of C. tropicalis candidemia was most severe with highest median C-reactive protein level (10.1 mg/dL) and Acute Physiology and Chronic Health Evaluation II score (14, both P ≪ 0.05). C. tropicalis showed the highest 14- and 30-day mortality (28.9% and 44.1%). In multivariate analysis, C. tropicalis infection was significantly related with 14- (P = 0.005) and 30-day mortality (P = 0.033). In conclusion, C. tropicalis infection presented most severely and showed worst clinical outcome among non-albicans candidemia.

Patients with COVID-19 have been reported to experience gastrointestinal symptoms as well as respiratory symptoms, but the effects of COVID-19 on the gut microbiota are poorly understood. We explored gut microbiome profiles associated with the respiratory infection of SARS-CoV-2 during the recovery phase in patients with asymptomatic or mild COVID-19. A longitudinal analysis was performed using the same patients to determine whether the gut microbiota changed after recovery from COVID-19. We applied 16S rRNA amplicon sequencing to analyze two paired fecal samples from 12 patients with asymptomatic or mild COVID-19. Fecal samples were selected at two time points: during SARS-CoV-2 infection (infected state) and after negative conversion of the viral RNA (recovered state). We also compared the microbiome data with those from 36 healthy controls. Microbial evenness of the recovered state was significantly increased compared with the infected state. SARS-CoV-2 infection induced the depletion of Bacteroidetes, while an abundance was observed with a tendency to rapidly reverse in the recovered state. The Firmicutes/Bacteroidetes ratio in the infected state was markedly higher than that in the recovered state. Gut dysbiosis was observed after infection even in patients with asymptomatic or mild COVID-19, while the composition of the gut microbiota was recovered after negative conversion of SARS-CoV-2 RNA. Modifying intestinal microbes in response to COVID-19 might be a useful therapeutic alternative.

The presence of an association between chronic hepatitis B virus (HBV) infection and fatty liver is controversial. We examined the association between HBV infection and the development of nonalcoholic fatty liver disease (NAFLD). We conducted a cohort study of 83,339 participants without NAFLD at baseline who underwent serologic testing for hepatitis B surface antigen (HBsAg) between 2002 and 2006 and were followed annually or biennially until December 2014. NAFLD was defined as the presence of ultrasonographic fatty liver in the absence of excessive alcohol use or other identifiable causes. We used a parametric Cox model to estimate adjusted hazard ratios with 95% confidence intervals of incident NAFLD. During 484,736.1 person-years of follow-up, 20,200 incident NAFLD cases were identified. In models adjusted for age, sex, year of visit, smoking status, alcohol intake, regular exercise, education level, and body mass index, the adjusted hazard ratio (95% confidence interval) for incident NAFLD comparing HBsAg-positive to HBsAg-negative participants was 0.83 (0.73-0.94). After introducing HBV infection and confounders (including homeostasis model assessment of insulin resistance and metabolic factors) as time-dependent exposures, the association between HBV infection and decreased risk of incident NAFLD was attenuated but persisted. These associations were consistently observed across clinically relevant, prespecified subgroups. Conclusion: In this large cohort of apparently healthy Korean adults, HBsAg seropositivity was associated with lower risk of developing NAFLD, indicating a possible effect of HBV infection on the pathogenesis of NAFLD development. (Hepatology 2017;65:828-835).

Summary The association between HBV infection and incident thrombocytopenia among subjects without cirrhosis or splenomegaly is unknown. Therefore, we sought to elucidate the association between HBV infection and the development of thrombocytopenia in a large cohort of apparently healthy men and women. A cohort study was performed in 122 200 participants without liver cirrhosis or splenomegaly who underwent comprehensive health examinations and were followed until December 2014. HBV infection was defined by the presence of hepatitis B surface antigen (HBsAg) at baseline. Thrombocytopenia was defined as a platelet count

The aim of this study was to evaluate the impact of insulin resistance on the persistence of a protective level of anti-HBs (hepatitis B surface antigen) in a nondiabetic general population. A cohort study was designed comprising of 38 473 Korean men and women with anti-HBs at concentrations ≥10 mIU/mL, who underwent a health examination. Insulin resistance was assessed with a homoeostasis model assessment of insulin resistance (HOMA-IR). A decline in anti-HBs to

Despite the global effort to mitigate the spread, coronavirus disease 2019 (COVID-19) has become a pandemic that took more than 2 million lives. There are numerous ongoing clinical studies aiming to find treatment options and many are being published daily. Some effective treatment options, albeit of variable efficacy, have been discovered. Therefore, it is necessary to develop an evidence-based methodology, to continuously check for new evidence, and to update recommendations accordingly. Here we provide guidelines on pharmaceutical treatment for COVID-19 based on the latest evidence.

The changes in the gut microbiota of healthy hepatitis B virus (HBV) carriers, including asymptomatic and non-cirrhotic subjects, have been rarely scrutinized. From 1463 faecal samples in health examinees, in total 112 subjects, including 36 hepatitis B surface antigen (HBsAg)-positive and 76 control subjects, were included. Twenty-eight of 36 HBsAg-positive individuals (78%) showed normal alanine aminotransferase (ALT) levels (normal ALT group), whereas eight subjects exhibited elevated ALT levels (22%, high ALT group). By using 16S rRNA gene sequencing, the distance between normal and high ALT groups among HBsAg-positive subjects showed a significant separation after the pairwise comparison of weighted UniFrac distance (permutational analysis of variance q-value = 0.039), when compared with the distances to the control group. In comparison with the control group, the normal ALT group had Anaerostipes as a significant taxon that showed a positive association (Coefficient (Coef.) = 0.028, q = 0.039). Desulfovibrio (Coef. = 0.54, q = 0.014) and Megasphaera (Coef. = 1.41, q = 0.030) showed positive correlations, and Acidaminococcus (Coef. = &minus, 1.31, q = 4.15 &times, 10&minus, 75) exhibited a negative correlation with high ALT level. Gut microbial composition was different according to HBV-induced serum ALT levels, indicative of a potential link between gut and liver metabolism.

OBJECTIVE: The features of childhood attention deficit hyperactivity disorder (ADHD) are significantly associated with adult mood disorders. Some genetic factors may be common to both ADHD and mood disorders underlie the association between these two phenotypes. The present study aimed to determine whether a genetic role may be played by the serotonin transporter-linked polymorphic region (5-HTTLPR) in the childhood ADHD features of adult patients with mood disorders. METHODS: The present study included 232 patients with major depressive disorder (MDD), 154 patients with bipolar disorder (BPD), and 1,288 normal controls. Childhood ADHD features were assessed with the Korean version of the Wender Utah Rating Scale (WURS-K). The total score and the scores of three factors (impulsivity, inattention, and mood instability) from the WURS-K were analyzed to determine whether they were associated with the 5-HTTLPR genotype. RESULTS: In the BPD type II group, the 5-HTTLPR genotype was significantly associated with the total score (p=0.029) and the impulsivity factor (p=0.004) on the WURS-K. However, the inattention and mood instability factors were not associated with the 5-HTTLPR genotype. BPD type I, MDD and normal control groups did not exhibit any significant associations between the WURS-K scores and the 5-HTTLPR genotype. CONCLUSION: The findings suggest that the 5-HTTLPR genotype may play a role in the impulsivity component of childhood ADHD in patients with BPD type II. Because of a small sample size and a single candidate gene, further studies investigating other candidate genes using a larger sample are warranted to determine any common genetic links. Language: en

Objective We examined the relationship between chronotype and sleep disturbance, and assessed various factors that might be associated with sleep disturbance in Korean firefighters. Methods Self-administered questionnaires assessing chronotype, depression, alcohol use, posttraumatic stress disorder (PTSD), stress response and sleep quality were examined in 515 firefighters. Results Evening type firefighters more reported depression, alcohol use, PTSD, stress response and sleep disturbance. Also evening chronotype was the most significant risk factor for poor sleep quality (odds ratio [OR], 4.812; 95% confidence interval [CI], 2.448-9.459), even after controlling for all other variables (OR, 3.996; 95% CI, 1.806-8.841). Conclusion Chronotype was the factor most strongly associated with sleep disturbance, and therefore should be considered an important variable in sleep quality, particularly in occupations involving stressful activities, such as firefighting.

Background The dopamine transporter gene (DAT1) is an established genetic risk factor for attention deficit hyperactivity disorder (ADHD). Therefore, we hypothesized that DAT1 may also influence the manifestation of ADHD-related traits in the normal population. Methods A quantitative association study was carried out on 1289 healthy adults. ADHD-related traits were measured using the 25-item Wender Utah Rating Scale (WURS-25). This scale is a self-administered instrument intended to retrospectively measure features of childhood ADHD. Previous studies typically identified three component factors: (i) impulsivity, (ii) inattention, and (iii) mood instability. Our group found that these factors were associated with various diagnoses, such as bipolar disorder and major depression. Six polymorphic markers within the DAT1 gene (rs27072, rs11133767, rs429699, rs27048, rs2937639), including the 3'-untranslated region variable number of tandem repeats, were used as genetic markers. Results The WURS-25 total score was not associated with any of the markers that we examined. However, the mood instability trait was associated significantly with rs2937639 in male participants (P=0.008); this result was supported by several haplotype-wise findings among the surrounding markers (P=0.00001-0.004). Conclusion Our study results suggest that DAT1 polymorphisms may modulate mood instability traits in the normal population. Considering that mood instability tends to persist through the entire course of ADHD and is highly prevalent in many diseases that are comorbid with ADHD, this trait may be a core endophenotype that defines the role of the DAT1 gene in various psychiatric conditions.

Background Argyria is a rare irreversible cutaneous pigmentation disorder caused by prolonged exposure to silver. Herein, we report a case of generalized argyria that developed after chronic ingestion of soluble silver-nano particles and presented with muscle weakness. Case presentation A 74-year-old woman visited our emergency room, complaining of fever and mental deterioration. She was diagnosed with acute pyelonephritis and recovered after antibiotic therapy. At presentation, diffuse slate gray-bluish pigmented patches were noticed on her face and nails. Two months prior to visiting our hospital, she was diagnosed with inflammatory myopathy and given steroid therapy at another hospital. We performed a nerve conduction study that revealed polyneuropathy. In skin biopsies from pigmented areas of the forehead and nose, the histopathologic results showed brown-black granules in basement membranes of sweat gland epithelia, which are diagnostic findings of argyria. We reviewed pathology slides obtained from the left thigh muscles and found markedly degenerated myofibers with disorganization of myofibrils without inflammatory reactions, consistent with unspecified myopathy, rather than inflammatory myopathy. The patient was diagnosed with generalized argyria with polyneuropathy and myopathy and transferred to a rehabilitation institution after being tapered off of steroids. Conclusions Clinicians should be aware of clinical manifestations of argyria and consider it in differential diagnosis when they examine patients who present with skin pigmentation and muscle weakness.

Aspergillus tracheobronchitis (AT), an unusual form of invasive pulmonary aspergillosis (IPA), is characterized by pseudomembrane formation, ulcer or obstruction that is predominantly confined to tracheobronchial tree. Hematologic malignancies, neutropenia, solid organ transplantation, chronic corticosteroid therapy and acquired immunodeficiency syndrome (AIDS) are known to be major predisposing conditions. However, since the introduction of highly active antiretroviral therapy, there is only one reported case of AT in AIDS patient. After pandemic of influenza A/H1N1 2009, there are several reports of IPA in patient with influenza and most of them received corticosteroid or immunosuppressive therapy before the development of IPA. We present a 45 year-old AIDS patient with influenza A infection who developed pseudomembranous AT without corticosteroid use or immunosuppressive therapy.

Background/Aims Methicillin-resistant Staphylococcus aureus bacteremia (MRSAB) is a major bloodstream infection with a high mortality rate. Identification of factors associated with early mortality in MRSAB patients would be useful for predicting prognosis and developing new therapeutic options. Methods A prospective cohort of MRSAB patients was examined between August 2008 and June 2011. Early and late mortality was defined as death within 2 and 28 days of blood culture, respectively. The clinical and microbiological characteristics in the early and late mortality and survival groups were compared. Risk factors associated with severe sepsis or septic shock were also investigated. Results A total of 385 adult MRSAB patients whose S. aureus isolates were available were enrolled; of these patients, 25 patients (6.5%) and 50 (13%) died early and late, respectively. Compared with both the late-mortality group and the survival group, severe sepsis or septic shock was a statistically significant independent risk factor associated with early mortality. Rapidly or ultimately fatal McCabe and Jackson classification (adjusted odds ratio [aOR], 1.94; 95% confidence interval [CI], 1.25 to 3.02) and pneumonia (aOR, 2.04; 95% CI, 1.03 to 4.02) were independently associated with severe sepsis or septic shock. A vancomycin minimum inhibitory concentration (MIC) ≥ 1.5 μg/mL was associated with a reduced incidence of severe sepsis or septic shock (aOR, 0.53; 95% CI, 0.34 to 0.84). Conclusions Severity of illness seems to be the most important risk factor associated with early mortality in MRSAB. Although vancomycin MIC was not independently associated with early mortality, reduced vancomycin susceptibility appears to be linked to reduced disease severity.

Background: In 2015, an outbreak of Middle East Respiratory Syndrome coronavirus (MERS-CoV) infection occurred in South Korea involving 186 patients, 39 of whom were healthcare workers (HCWs) exposed to the infection An effective post-exposure prophylaxis (PEP) strategy may limit the spread of infection;however, there is no consensus regarding PEP for MERS-CoV infection In this study, we assessed (1) the efficacy of oral ribavirin and lopinavir/ritonavir as PEP for HCWs exposed to patients with severe MERS-CoV pre-isolation pneumonia, and (2) safety of the PEP regimen Methods: We retrospectively enrolled 43 HCWs with high-risk exposure to MERS-CoV from 5 hospitals affected during this outbreak in South Korea The rate of MERS-CoV infection was compared between 22 workers at 1 hospital who received PEP consisting of oral ribavirin and lopinavir/ritonavir after exposure to patients with severe MERS-CoV pre-isolation pneumonia and 21 workers at other hospitals who did not receive PEP Results: Six workers (14%) developed MERS-CoV infection;all of these subjects belonged to the non-PEP group The attack rate was lower in the PEP group compared with the non-PEP group (0% vs 28 6%;Odds ratio = 0 405, 95% confidence interval = 0 274–0 599;P = 0 009) The most commonly reported side effects of PEP therapy were nausea and diarrhea, but there were no severe adverse effects associated with PEP therapy Conclusion: PEP with a combination of oral ribavirin and lopinavir/ritonavir appears to be effective and generally safe for preventing MERS-CoV infection after high-risk exposure in healthcare workers Disclosures: All authors: No reported disclosures FAU - Park, So Yeon

Background No cohort studies have evaluated the effect of hepatitis B virus (HBV) infection on the risk of herpes zoster. We investigated the association of HBV infection with the development of herpes zoster. Methods We performed a cohort study of 224,691 non-cirrhotic adult men and women free of herpes zoster at baseline who underwent serologic testing for hepatitis B surface antigen (HBsAg) and were followed annually or biennially for a median of 4.2 years. Incident cases of herpes zoster were ascertained using the Korean Health Insurance and Review Agency (HIRA) database. A Cox proportional hazard model was used to estimate the adjusted hazard ratio (aHR) with 95% confidence interval (CI) for incident herpes zoster according to HBsAg seropositivity status. Results During 830,073.4 person-years of follow-up, 11,061 cases of incident herpes zoster were identified. HBsAg seropositivity was inversely associated with the development of herpes zoster. After adjustment for possible confounders, the multivariable-adjusted hazard ratios (95% CI) for herpes zoster comparing HBsAg-positive to HBsAg-negative participants was 0.83 (0.75–0.93). Conclusion In a large cohort of Korean adults, HBsAg seropositivity was associated with lower risk of herpes zoster, suggesting that HBV seems to inhibit the reactivation of varicella-zoster virus. Disclosures All authors: No reported disclosures.

The current study compared the long-term effectiveness, safety, and tolerability of paliperidone extended-release (ER) among patients with schizophrenia who had switched from risperidone (risperidone group) or other antipsychotic medications (non-risperidone group) due to lack of efficacy, intolerability, or non-adherence.This open-label, prospective, multicenter, 48 week study utilized the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression-Severity scale (CGI-S), the Personal and Social Performance scale (PSP), and the Subjective Well-being under Neuroleptics scale (SWN) to assess patients with schizophrenia. Additionally, extrapyramidal symptoms (EPS) and subjective side effects were evaluated with validated scales.Clinicaltrials.gov identifier: NCT00864045.The completion rate for this study was 51.6% (95/184), and 169 patients finished with ≥1 post-baseline assessment (81 patients in the risperidone group, 88 in the non-risperidone group). The mean (SD) PANSS total score decreased significantly from 78.3 (18.8) to 65.5 (19.7) in the risperidone group and from 79.1 (19.8) to 65.4 (20.8) in the other group (all p 0.001). Similar to PANSS, the severity rating for overall scores of the CGI-S and the PSP scores improved significantly from baseline (all p 0.001). The magnitude of improvement in all effectiveness measures at 48 weeks did not differ between the two groups. EPS and subjective side effects improved significantly for all patients. Akathisia (18.5%) and increased weight (14.1%) were the main adverse events. Elevated prolactin levels were identified in female subjects in the non-risperidone group.Switching from previously unsuccessful antipsychotic treatments to paliperidone ER can be a useful option to achieve long-term improvement in symptoms and functioning for patients with schizophrenia. The clinical effectiveness appeared to be similar in patients who previously received risperidone and those treated with other antipsychotic medications. The open-label design and lack of a placebo group were limitations.

Background Staphylococcus aureus bacteremia (SAB) is the Staphylococcal infections in blood, one of the most common and fatal bacterial infectious diseases worldwide in adults as well as children or neonates. Recently, some studies have yielded inconsistent findings about the association between methicillin-resistance and mortality in patients with SAB. We performed a meta-analysis to assess the impact of methicillin-resistance on mortality in children or neonates with S. aureus bacteremia. Materials and methods We searched using electronic databases such as Ovid-Medline, EMBASE-Medline, and Cochrane Library, as well as five local databases for published studies during the period of 1 January 2000 to 15 September 2011. Two reviewers independently selected articles in accordance with predetermined criteria and extracted prespecified data based on standardized forms. All cohort studies, which compared in-hospital mortality or SAB-related mortality in children and neonates with methicillin-resistant S. aureus (MRSA) infection to those with methicillin-susceptible S. aureus (MSSA), were included. We conducted meta-analysis using the fixed-effect model to obtain pooled estimates of effect. Results Of 2,841 screened studies, seven cohort studies were finally selected for analysis. In children or neonates, MRSA bacteremia was associated with a higher mortality compared with MSSA bacteremia (pooled odds ratio [OR] 2.33, P = 0.0008, 95% confidence interval [CI] 1.42 to 3.82, I(2) = 0%). Four studies reported SAB-related mortality, the pooled OR of these studies was 2.03 (P = 0.29, 95% CI 0.55 to 7.53, I(2) = 0%). A significant increase in mortality associated with methicillin resistance was found in the subgroup analyses of the studies with only neonates (OR: 2.66, 95% CI: 1.46 to 4.85, P = 0.001), prospectively design ones (OR: 3.20, 95% CI: 1.66 to 6.15, P = 0.0005,), the larger studies (OR: 2.89, 95% CI: 1.62 to 5.16, P = 0.0003) and the higher quality studies (OR: 2.76, 95% CI: 1.50 to 5.06, P = 0.001). Conclusions MRSA bacteremia is associated with increased mortality compared with MSSA bacteremia in children or neonates. Due to limited studies for mortality in children or neonates with SAB, further research is needed to evaluate the impact of methicillin resistance on mortality in those populations.

Summary Background There are no available studies on the duration and risk factors of vancomycin-resistant enterococci (VRE) carriage after hospital discharge. In this study we investigated the duration of colonization with VRE and the risk factors for prolonged carriage in the outpatient clinic after discharge from the hospital. Methods The study took place from January 2008 to September 2009. Patients were included if they were identified as persistent VRE carriers by follow-up rectal swab or stool cultures in the outpatient setting, after discharge from the hospital without clearance of VRE. The probability of culture positivity and clearance was analyzed from the discharge date. Cox regression was performed to determine the risk factors for prolonged carriage. VRE clearance was defined as VRE-negative rectal (or stool) cultures on at least three consecutive occasions a minimum of 1 week apart. Results One hundred twenty-seven patients were included in this study. Follow-up cultures were conducted for a median of 8.86 weeks (range 1–90 weeks) after hospital discharge. The median duration of culture positivity of VRE was 5.57 weeks (range 0–50.14 weeks). Ninety-six out of 127 patients (75.6%) showed the first negative culture result at a median time of 4.86 weeks (range 0–66 weeks) after discharge. Among these patients, 15 were lost to follow-up after the first negative culture and eight were lost after the second negative culture. Sixty-eight patients (53.5%) were confirmed to have clearance of VRE during follow-up in the outpatient clinic. The median time to clearance after discharge was 8.86 weeks (range 2–90 weeks). In the cleared cases, the median time to the first negative VRE culture result was 4.71 weeks (range 0–66 weeks). Ninety percent of patients showed the first negative culture result at 25 weeks and VRE clearance at 30 weeks after discharge. Surgery or antibiotic use during admission ( p =0.048 and p =0.001, respectively), dialysis ( p =0.046), and discharge to a nursing home or other health care institution ( p =0.025) were independently associated with prolonged colonization with VRE. Conclusions The median duration of VRE colonization was 5.57 weeks after hospital discharge. In the cases with clearance during follow-up, the median time to clearance after discharge was 8.86 weeks. Risk factors for prolonged carriage were surgery, antibiotic use during admission, dialysis, and discharge to a nursing home or other health care institution. Therefore, patients with these risk factors should be managed more carefully to prevent transmission of VRE in the outpatient clinic.

Bipolar disorder (BD) and attention deficit hyperactivity disorder (ADHD) exhibit remarkably high rates of comorbidity, as well as patterns of familial co-segregation. Epidemiological data suggests that these disorders either share a common genetic architecture or that ADHD features in BD may represent an etiologically distinct subtype. We previously used the Wender Utah Rating Scale (WURS) to assess ADHD features in BD families and identified three heritable factors relating to impulsivity, mood instability, and inattention. Linkage analysis revealed a LOD score of 1.33 for the inattention factor on 5p15.3 near the dopamine transporter gene (DAT1), which has been associated with both BD and ADHD. Pharmacological evidence also suggests a role for DAT in both disorders. We have now evaluated the association of ten DAT1 variants for the WURS total score and factors in an overlapping sample of 87 BD families. Significant associations for three SNPs were observed across the WURS measures, notably for a SNP in intron 8 with the WURS total score (P = 0.007) and for variants in introns 9 and 13 with mood instability (P = 0.009 and 0.004, respectively). Analysis of an independent sample of 52 BD cases and 46 healthy controls further supported association of the intron 8 variant with mood instability (P = 0.005), and a combined analysis confirmed the associations of this SNP with WURS total score. Impulsivity and mood instability (P = 0.002, 0.007, and 8 × 10−4, respectively). These data suggest that variants within DAT1 may predispose to a subtype of BD characterized by early prodromal features that include attentional deficits. © 2012 Wiley Periodicals, Inc.

Candida species are the leading causes of invasive fungal infection among hospitalized patients and are responsible for major economic burdens. The goals of this study were to estimate the costs directly associated with the treatment of candidemia and factors associated with increased costs, as well as the impact of first-line antifungal agents on the outcomes and costs. A retrospective study was conducted in a sample of 199 patients from four university-affiliated tertiary care hospitals in Korea over 1 year. Only costs attributable to the treatment of candidemia were estimated by reviewing resource utilization during treatment. Risk factors for increased costs, treatment outcome, and hospital length of stay (LOS) were analyzed. Approximately 65% of the patients were treated with fluconazole, and 28% were treated with conventional amphotericin B. The overall treatment success rate was 52.8%, and the 30-day mortality rate was 47.9%. Hematologic malignancy, need for mechanical ventilation, and treatment failure of first-line antifungal agents were independent risk factors for mortality. The mean total cost for the treatment of candidemia was $4,743 per patient. Intensive care unit stay at candidemia onset and antifungal switch to second-line agents were independent risk factors for increased costs. The LOS was also significantly longer in patients who switched antifungal agents to second-line drugs. Antifungal switch to second-line agents for any reasons was the only modifiable risk factor of increased costs and LOS. Choosing an appropriate first-line antifungal agent is crucial for better outcomes and reduced hospital costs of candidemia.

Despite the high prevalence of antimicrobial resistance among Pseudomonas aeruginosa bacteremia, the clinical consequence of resistance remains unclear. The purpose of this study was to identify predictors of mortality and evaluate the clinical impact of antimicrobial resistance on outcome in P. aeruginosa bacteremia. A retrospective cohort study including patients with P. aeruginosa bacteremia was performed. The risk factors for antimicrobial resistances were evaluated, and the impact of the respective resistances on mortality was assessed. Of 202 P. aeruginosa bacteremia cases, the resistance rates to ceftazidime, piperacillin, imipenem, fluoroquinolone, and aminoglycoside were 36.6%, 22.3%, 22.8%, 23.8%, and 17.8%, respectively. A prior use of fluoroquinolones and an indwelling urinary catheter were common risk factors for all types of antimicrobial resistance. The overall 30-day mortality rate was 25.2% (51/202), and the risk factors for mortality were corticosteroid use, nosocomial acquisition, polymicrobial infection, an increasing Charlson's weighted co-morbidity index, and intensive care unit care (p

Clinical and microbiological characteristics of healthcare-associated acute pyelonephritis (HCA-APN) have not been described in detail yet. We sought to delineate the differences between community-associated (CA)- and HCA-APN with specific interest in antibiotic resistance of causative microorganisms.We conducted a retrospective cohort study during a 1-y period at a large referral center. Patients who visited the emergency department with symptoms and signs of APN were included in the study population.Among 319 cases with community-onset APN, 201 cases (63%) were classified as HCA-APN. Patients with HCA-APN had higher SOFA (sequential organ failure assessment) scores, longer length of hospital stay and a lower rate of complete response to antimicrobial therapy. Patients with complicated APN also had characteristics similar to those seen in HCA-APN. However, 14-day mortality rates were not different between CA-APN vs HCA-APN and between uncomplicated APN vs complicated APN. With regard to microbiological characteristics, Escherichia coli were less common in HCA-APN than in CA-APN (62.7% vs 93.2%, p0.001). Among E. coli isolates, quinolone resistance and extended-spectrum beta-lactamase (ESBL) production were more common in HCA-APN than in CA-APN (38.9% vs 12.7%, p0.001; 15.9% vs 0.8%, p0.001, respectively).HCA-APN, and complicated APN, represents a distinct subset of urinary tract infections with more antibiotic-resistant pathogens and worse outcomes, which physicians should consider to provide optimal treatment.