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Corrected QT-interval (QTc) prolongation (QTP) is a rare but fatal adverse effect of antipsychotics. Clozapine is the only antipsychotic recommended for treatment of resistant schizophrenia; however, clozapine has been reported to cause QTP. We sought factors predictive of QTP in patients who had antipsychotic polypharmacy involving clozapine. We explored whether the clozapine blood concentration might predict QTP.We included 133 patients with schizophrenia spectrum disorder who had antipsychotic polypharmacy involving clozapine. We used the χ2 and nonparametric tests to compare clozapine therapeutic drug monitoring (TDM) values and QTc-prolonged person (QTPP) status. Multivariate regression and mediator models were used to identify risk factors for QTPP status and QTP.In total, 111 patients were prescribed clozapine. The QTPP rates were 31.3% (20) for men and 23.2% (16) for women. Compared with the non-QTPP group, the QTPP group exhibited significantly higher daily dose of all antipsychotics including clozapine, a higher clozapine dose, and elevated clozapine and norclozapine TDM values. Furthermore, such patients were prescribed a greater number of antipsychotics. Multivariate logistic regression revealed that only the clozapine TDM value could be predictive factor for QTPP status (P = 0.018). A clozapine TDM value above the therapeutic range (600 mg/dL) was associated with a high risk of QTPP status (adjusted odds ratio, 6.5; 95% confidence interval, 1.7-25.2; P = 0.006). The mediator model revealed that the clozapine TDM values completely mediated the association between the clozapine dose and the QTc interval.The clozapine blood concentration reliably predicts QTP in patients with clozapine use.

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.

Numerous patients around the globe are dying from coronavirus disease 2019 (COVID-19). While age is a known risk factor, risk analysis in the young generation is lacking. The present study aimed to evaluate the clinical features and mortality risk factors in younger patients (≤ 50 years) with a critical case of COVID-19 in comparison with those among older patients (50 years) in Korea.We analyzed the data of adult patients only in critical condition (requiring high flow nasal cannula oxygen therapy or higher respiratory support) hospitalized with PCR-confirmed COVID-19 at 11 hospitals in Korea from July 1, 2021 to November 30, 2021 when the delta variant was a dominant strain. Patients' electronic medical records were reviewed to identify clinical characteristics.During the study period, 448 patients were enrolled. One hundred and forty-two were aged 50 years or younger (the younger group), while 306 were above 50 years of age (the older group). The most common pre-existing conditions in the younger group were diabetes mellitus and hypertension, and 69.7% of the patients had a body mass index (BMI)25 kg/m². Of 142 younger patients, 31 of 142 patients (21.8%, 19 women) did not have these pre-existing conditions. The overall case fatality rate among severity cases was 21.0%, and it differed according to age: 5.6% (n = 8/142) in the younger group, 28.1% in the older group, and 38% in the ≥ 65 years group. Age (odds ratio [OR], 7.902; 95% confidence interval [CI], 2.754-18.181), mechanical ventilation therapy (OR, 17.233; 95% CI, 8.439-35.192), highest creatinine1.5 mg/dL (OR, 17.631; 95% CI, 8.321-37.357), and combined blood stream infection (OR, 7.092; 95% CI, 1.061-18.181) were identified as independent predictors of mortality in total patients. Similar patterns were observed in age-specific analyses, but most results were statistically insignificant in multivariate analysis due to the low number of deaths in the younger group. The full vaccination rate was very low among study population (13.6%), and only three patients were fully vaccinated, with none of the patients who died having been fully vaccinated in the younger group. Seven of eight patients who died had a pre-existing condition or were obese (BMI25 kg/m²), and the one remaining patient died from a secondary infection.About 22% of the patients in the young critical group did not have an underlying disease or obesity, but the rate of obesity (BMI25 kg/m²) was high, with a fatality rate of 5.6%. The full vaccination rate was extremely low compared to the general population of the same age group, showing that non-vaccination has a grave impact on the progression of COVID-19 to a critical condition. The findings of this study highlight the need for measures to prevent critical progression of COVID-19, such as vaccinations and targeting young adults especially having risk factors.

Background The genetic interactions in the circadian rhythm biological system are promising as a source of pathophysiology in mood disorder. We examined the role of the gene–gene interactions of clock genes in mood disorder. Methods We included 413 patients with mood disorder and 1294 controls. The clock genes investigated were BHLHB2, CLOCK, CSNK1E, NR1D1, PER2, PER3, and TIMELESS. Allele, genotype, and haplotype associations were tested. Gene–-gene interactions were analyzed using the non-parametric model-free multifactor-dimensionality reduction (MDR) method. Results TIMELESS rs4630333 and CSNK1E rs135745 were significantly associated with both major depressive disorder and bipolar disorder. The CLOCK haplotype was also strongly associated. The genetic roles of these SNPs were consistent from the allele and genotypic associations to the MDR interaction results. In MDR analysis, the combination of TIMELESS rs4630333 and CSNK1E rs135745 exhibited the most significant association with mood disorders in the two-locus model. BHLHB2 rs2137947 for major depressive disorder and CLOCK rs12649507 for bipolar disorder were the most significant third loci in the three-locus combination model. The four-locus SNP combination model showed the best balanced accuracy (BA), but its cross-validation consistency (CVC) was unsatisfactory. Limitations We included only 17 SNPs for seven circadian genes due to our limited resources; all subjects were ethnically Korean. Conclusions Our results suggest significant single-gene associations and gene–gene interactions of circadian genes with mood disorder. Gene–gene interactions play a crucial role in mood disorder, even when individual clock genes do not have significant roles.

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

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 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.

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.

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

A circadian rhythm disturbance is one of the essential components of the phenotype of bipolar disorder. It has been reported that casein kinase 1 epsilon (CSNK1E), a member of the clock gene family, is associated with psychiatric phenotypes.We performed a genetic association study to determine the genetic role of CSNK1E in bipolar disorder and circadian rhythm disturbances in the Korean population.The present study included 215 patients with bipolar disorder and 773 controls. Circadian characteristics were measured by the Korean version of the Composite Scale of Morningness (CS). Single-nucleotide polymorphisms (SNPs) of CSNK1E, rs1534891 and rs2075984, were genotyped. Chi-square analyses were performed to evaluate associations involving alleles and genotypes. Haplotype analysis was also performed, and the permutation p value was calculated. We also tested further associations involving these SNPs and scores on the CS.We found a positive association between SNP rs2075984 and bipolar disorder in both the allelic (p = .003) and genotypic (p = .006) distributions. No allelic or genotypic association between SNP rs1534891 and bipolar disorder was observed. A significant association of haplotype with bipolar disorder was found (p = .033). However, no association between the CS and the genotype of either SNP was found in the total sample.CSNK1E SNP rs2075984 seemed to play a significant role in the development of bipolar disorder in this Korean sample. This association does not seem to relate to the phase preference measured by the CS. Further studies on CSNK1E with larger samples and more SNPs are necessary.

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/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.

Mitochondrial dysfunction is implicated in the pathophysiology of major depressive disorder (MDD). This dysfunction can be indirectly assessed using the mitochondrial DNA (mtDNA) copy number. A total of 118 patients with MDD and 116 age- and sex-matched control subjects were recruited for this study, and mtDNA copy numbers were measured in peripheral blood cells. This study also examined the potential variables that might impact mtDNA copy number in MDD, including age and clinical features. Additionally, epigenetic control of mtDNA copy number was examined by assessing DNA methylation ratios in the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) promoter in nuclear DNA and the displacement loop (D-loop) region of mtDNA. The present results showed that patients with MDD had a higher mtDNA copy number and a decreased DNA methylation status in the PGC1α promoter. mtDNA copy numbers were negatively associated with an age, psychomotor agitation, and somatic symptoms in MDD. These results suggest that the alterations in mitochondrial function and epigenetic change of PGC1α may be relevant to the pathophysiology of MDD.

Circadian rhythm disturbance is highly prevalent in attention deficit hyperactivity disorder (ADHD). Recently, the association between the CLOCK gene and ADHD has been demonstrated in clinical samples, and the CLOCK gene's role was thought to be mediated by rhythm dysregulation. Meanwhile, ADHD has been suggested as the extreme end of a continuously distributed trait that can be found in the general population. Therefore, we examined two possibilities: (1) an ADHD-related continuous trait may be associated with the CLOCK gene, and (2) this association may be mediated by the degree of individuals' evening preference. To explore these possibilities, we performed a quantitative trait locus association study with a sample of 1,289 healthy adults. The Wender Utah Rating Scale (WURS) and the Composite Scale of Morningness (CSM) were utilized to measure the quantitative traits. Quantitative association analysis was performed using PLINK software. We found that rs1801260 (=T3111C) was associated with WURS scores in both allele-wise (p = 0.018) and haplotype-wise analyses (range of p values: 0.0155-0.0171) in male participants only. After controlling for the CSM total score as a covariate, the strength of the association did not change at all, suggesting that the association was not mediated by evening preference. Despite the very weak association signal, our results provide evidence that the CLOCK gene's association with ADHD in clinical samples may be generalizable to traits measured in the normal population. However, as our results failed to show a mediating role of evening preference, ongoing efforts are needed to identify the mechanisms by which the CLOCK gene determines ADHD-related traits.

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.

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.

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.

A significant overlap between childhood mood disorders and many aspects of attention deficit hyperactivity disorder (ADHD) has been established. High rates of co-occurrence, familial aggregation, and more severe clinical manifestations of the illnesses when they are comorbid suggest that common genetic and environmental factors may contribute to the development of both disorders. Research on the co-occurrence of childhood ADHD and mood disorders in childhood has been conducted. We retrospectively investigated childhood ADHD features in adults with mood disorders. Childhood ADHD features were measured with the Korean version of the Wender Utah Rating Scale (WURS). The sample consisted of 1305 subjects: 108 subjects were diagnosed with bipolar disorder type I, 41 with bipolar disorder type II, 101 with major depressive disorder, and 1055 served as normal controls. We compared total WURS scores as well as scores on 3 factors (impulsivity, inattention, and mood instability and anxiety) among the 4 different diagnostic groups. The 4 groups differed significantly from one another on all scores. The group with bipolar disorder type II obtained the highest total scores on the WURS. The impulsivity and inattention associated with childhood ADHD were more significantly related to bipolar disorder type II than with bipolar disorder type I. The mood instability and anxiety associated with childhood ADHD seem to be significantly related to major depressive disorder in adulthood. In conclusion, multifactorial childhood ADHD features were associated with mood disorders of adulthood.

Methylenetetrahydrofolate reductase (MTHFR), a critical enzyme in folate metabolism, plays an important role in DNA methylation. It has been suggested that abnormal DNA methylation contributes to the pathogenesis of schizophrenia and congenital anomalies. The previous findings regarding the genetic relationship between MTHFR and schizophrenia are controversial. This study investigated the association of the two functional polymorphisms of MTHFR, C677T and A1298C, with the risk for schizophrenia. Furthermore, we conducted an updated meta-analysis on the two polymorphisms. In addition, we investigated the relationship between the polymorphisms and minor physical anomaly (MPA), which may represent neurodevelopmental aberrations in 201 schizophrenia patients and 350 normal control subjects. There was no significant association between either of the two polymorphisms and the risk of schizophrenia (chi-square = 0.001, df = 1, P = 0.971 for C677T; chi-square = 1.319, df = 1, P = 0.251 for A1298C). However, in meta-analysis, the C677T polymorphism showed a significant association in the combined and Asian populations (OR = 1.13, P = 0.005; OR = 1.21, P = 0.011, respectively) but not in the Korean and Caucasian populations alone. Neither polymorphism was associated with MPAs measured by the Waldrop scale (chi-square = 2.513, df = 2, P = 0.285). In conclusion, the present findings suggest that in the Korean population, the MTHFR polymorphisms are unlikely to be associated with the risk for schizophrenia and neurodevelopmental abnormalities related to schizophrenia.

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.

Results of genome-wide association studies (GWASs) for bipolar disorder (BD) have indicated ANK3 as one of the most promising candidates for a susceptibility gene. In this study, we performed genetic association analysis of two single-nucleotide polymorphisms (SNPs) in ANK3 (rs1938526 and rs10994336), whose genome-wide significant associations were reported in a previous meta-analysis of GWASs, using genotyping data of Korean and Japanese case–control samples and a part of data from a GWAS in Han-Chinese from Taiwan. The total number of participants was 2,212 cases (352 from Korea, 860 from Japan, and 1,000 from Taiwan) and 2,244 controls (349 from Korea, 895 from Japan, and 1,000 from Taiwan). We could not detect any significant difference of allele frequency in individual analyses using each of the three populations. However, when we combined the three data sets and performed a meta-analysis, rs1938526 showed nominally significant association (P = 0.048, odds ratio = 1.09). The over-represented allele in BD was same as that reported in Caucasian GWASs. On the other hand, any significant association was not detected in rs10994336. This discrepancy between two SNPs may be explained by the different degree of linkage disequilibrium between Asian and Caucasian. These findings further supported the association between ANK3 and BD, and also suggested the genomic region around rs1938526 as a common risk locus across ethnicities. © 2011 Wiley-Liss, Inc.

Catheter-related infections (CRI) cause significant morbidity and mortality in cancer patients, particularly during episodes of chemotherapy-induced neutropenia. This study was performed to evaluate clinical features and outcomes of CRI in neutropenic cancer patients.We retrospectively analyzed clinical characteristics and outcome of febrile neutropenic cancer patients with CRI who visited the emergency department from January 1996 to June 2007.A total of 51 neutropenic cancer patients with CRI were identified and 53 organisms were isolated from culture specimens. The mean ± standard deviation patient age was 50 ± 15 y and the most common underlying disease was lymphoma (n = 27, 53%). Gram-positive organisms accounted for 77% of all isolated pathogens (41/53). Initial catheter salvage was attempted in 38 episodes of CRI, of which 20 were successful. In the current study the overall success rate of catheter salvage attempts was 52.6%. The failure rate of catheter salvage was significantly higher in CRI caused by Gram-negative pathogens than by Gram-positive pathogens.Although catheter salvage should be cautiously attempted for cancer patients with CRI, it might not be a treatment option for neutropenic cancer patients with CRI caused by Gram-negative bacteria.

Genes associated with circadian rhythms have been suggested to play an important role in the pathophysiology of bipolar disorder. A single nucleotide polymorphism (SNP) in the 3'-flanking region of CLOCK (3111T/C; rs1801260) has been reported to be associated with sleep disturbances and an increased recurrence rate in patients with bipolar disorder. We examined the association of CLOCK 3111T/C with bipolar disorder in 260 patients and 350 controls in a Korean population. CLOCK 3111T/C showed significant allelic and genotypic associations with bipolar disorder (P=0.012, P=0.033, respectively). Morningness/eveningness (M/E) was evaluated using the Composite Scale of Morningness (CSM) in 108 patients with bipolar disorder. In the subgroup analysis of the highest and lowest 25th percentile of M/E scores, significantly more C allele carriers were found among extreme evening types than among extreme morning types (P=0.041). After correcting for age, C allele carriers had lower M/E scores than those carrying the T/T genotype, but the association was not statistically significant. We also analyzed the association between age at onset (AAO) and CLOCK 3111T/C in the bipolar disorder group, and no association was found. Despite the relatively small sample sizes, these results support a possible role of the CLOCK 3111T/C SNP in bipolar disorder. Further studies with larger samples and more polymorphisms are necessary.

It has been suggested that bipolar disorder is associated with altered immune function. Monocyte chemoattractant protien-1 (MCP-1) is a chemokine that influences both neural and immune functions. We thus hypothesized that MCP-1 may be related to the development or pathophysiology of bipolar disorder. In this case–control study, we investigated the association between the A-2518G single nucleotide polymorphism (SNP) of the MCP-1 promoter and bipolar disorder. Patients with bipolar disorder ( n = 183; bipolar I = 145, bipolar II = 38) and healthy controls (350) were recruited for the study. No significant allelic or genotypic association was detected between the A-2518G polymorphism and any sample of bipolar disorder patients. When we pooled the healthy controls and the cases of bipolar I disorder from previous Korean studies and this study, we again found no significant association. No significant difference in either allele frequency or genotype distribution was observed between bipolar I and bipolar II disorders. There was no difference in the age at onset of bipolar disorder among the three genotype groups. Our data suggest that the A-2518G polymorphism of MCP-1 is not a major susceptibility factor for bipolar disorder in the Korean population. However, the physiological role of MCP-1 is highly suggestive of its being associated with bipolar disorder, and further analyses of other SNPs of MCP-1 remain to be performed.

Epidermal growth factor (EGF) is a well-known neurotrophic factor regulating the development of various neuronal cells, including dopaminergic neurons, and dysfunction of EGF signals has been demonstrated as a risk factor for schizophrenia. Recently, several researchers have investigated associations including age at onset (AAO) with EGF A61G functional polymorphism, but the results of these studies have been controversial. Thus, we investigated whether A61G plays a role in predisposition to schizophrenia and its effects on AAO. Our subjects included 190 patients with schizophrenia and 347 controls. We assessed three different points of AAO: age at first occurrence of positive psychotic symptoms, medication, and hospitalization as a patient with schizophrenia. We found no differences in allele and genotype frequencies between patients and controls or associations between A61G and AAOs across stratified points in the entire sample and in each gender. However, we found significant gender differences in patients with the AA genotype in all stratified points of AAOs. Subset analyses of G allele distribution between clinical subsets with an AAO cutoff of 20 years revealed that male patients with early onset schizophrenia were more likely to exhibit the common AA homozygote than male patients with adulthood onset schizophrenia. In conclusion, although we were unable to support an association between EGF A61G and schizophrenia, the AA genotype might play a disease-modifying role differentially according to gender.

Recent studies have suggested the involvement of Glycogen synthase kinase-3 beta (GSK-3 beta) in pathogenesis and treatment target of schizophrenia and bipolar disorder, which led to consider GSK-3 beta as one of the candidate genes for those disorders. However, the association analysis between GSK-3 beta and either schizophrenia or bipolar disorder is yet to be reported in Korean population. Along with 350 healthy individuals, a sample of 138 schizophrenia and 120 bipolar patients was analyzed for two common SNPs at position -1727 A/T and -50 C/T polymorphism localized in intron 1 of the gene. The results showed that allele, genotype and haplotype distributions for the two SNPs do not differ between the controls and neither schizophrenia nor bipolar disorder patients. We also analyzed the association between the controls and the combined samples of schizophrenia and bipolar disorder, but no association was found. In conclusion, these results suggest that the GSK-3 beta is not associated with the development of schizophrenia and bipolar disorder in Korean population.

Nontuberculous mycobacterial infection is rarely accompanied by pleural involvement. We report a very rare case of M. intracellulare pulmonary disease with pleural empyema. A 56-year-old man was admitted to our hospital because of fever, purulent sputum and pleuritic chest pain. A chest radiograph and CT revealed pneumonic consolidation in the left lower lobe and loculated hydropneumothorax. The sputum smear was positive for acid fast bacilli. The aspirated pleural fluid was grossly purulent and the smear of the pleural effusion was also positive for acid fast bacilli. M. intracellulare was identified by culture and PCR from sputum and pleural fluid specimens. The patient improved with percutaneous tube drainage of the purulent effusion and antibiotic treatment including clarithromycin, rifampicin, ethambutol and streptomycin.

Background Opportunistic infections are relatively rare in early human immunodeficiency virus infection, especially infection with Mycobacterium tuberculosis. Here, we report a patient who presented with acute human immunodeficiency virus and multidrug-resistant M. tuberculosis co-infections. Case presentation A 27-year-old homosexual male was admitted for fever, cough, and hepatitis. At the time of admission, the p24 antigen was detected in his serum, indicating that he had an acute human immunodeficiency virus infection. He was also diagnosed with disseminated tuberculosis spreading to the lung and skin. Anti-tuberculosis medication had been started earlier with one-week intervals of highly active antiretroviral therapy. Despite prolonged anti-tuberculosis treatment, the patient developed tuberculous meningitis on the 50th day of admission. Multidrug-resistant tuberculosis was cultured from his sputum and cerebrospinal fluid. The patient was successfully treated with second line anti-tuberculosis medication and antiretroviral treatment. Conclusion This is the first case of acute human immunodeficiency virus and multi drug-resistance tuberculosis co-infections. This case indicates that tuberculosis infection should be considered even in patients with acute human immunodeficiency virus infection. Electronic supplementary material The online version of this article (doi:10.1186/1471-2334-14-462) contains supplementary material, which is available to authorized users.

This study aimed to investigate the overall prescription pattern for patients with bipolar disorders in Korea and its relevance to the practice guidelines. Prescription records from all patients with bipolar I and II disorders who have been admitted or who started the outpatient treatment during the year of 2009 in 10 academic setting hospitals were reviewed. A total of 1447 patients with bipolar I and II disorders were included in this study. Longitudinal prescription patterns of inpatients and outpatients were analyzed by episode types and compared with the clinical practice guideline algorithms. In all phases, polypharmacy was chosen as an initial treatment strategy (>80%). The combination of mood stabilizer and atypical antipsychotics was the most favored. Antipsychotics were prescribed in more than 80% of subjects across all phases. The rate of antidepressant use ranged from 15% to 40%, and it was more frequently used in acute treatment and bipolar II subjects. The concordance rate of prescriptions for manic inpatients to the guidelines was higher and relatively more consistent (43.8%-48.7%) compared with that for depressive inpatients (18.6%-46.9%). Polypharmacy was the most common reason for nonconcordance. In Korean psychiatric academic setting, polypharmacy and atypical antipsychotics were prominently favored in the treatment of bipolar disorder, even with the lack of evidence of its superiority. More evidence is needed to establish suitable treatment strategies. In particular, the treatment strategy for acute bipolar depression awaits more consensuses.

Background & Aims Despite the high prevalence of antimicrobial-resistant Escherichia coli in hospital-acquired infections, the clinical epidemiology of fluoroquinolone (FQ) resistance in community-onset spontaneous bacterial peritonitis (SBP) in patients with cirrhosis is not well understood. This study was performed to evaluate clinical features and risk factors for community-onset SBP caused by FQ-resistant E. coli. Methods A case-control control study was performed using cases of community-onset SBP from June 2000 to August 2011 at Samsung Medical Center (Seoul, Korea). Patients with FQ-resistant E. coli were designated as case patients. A control group I (CG I) patient was defined as a person whose clinical sample yielded FQ-susceptible E. coli, and a control group II (CG II) patient was defined as a person with a negative culture result. Results A total of 82 subjects with community-onset SBP caused by E. coli were identified, of which 26 (31.7%) were FQ-resistant E. coli infection. Fifty-seven matched subjects were randomly selected for CG II. Compared with CG I, previous SBP episodes (OR, 4.91; 95% CI, 1.50–16.53; P = 0.010), prior use of FQ within 30 days (OR, 7.05; 95% CI, 1.17–42.38; P = 0.033), and third-generation cephalosporin resistance (OR, 17.68; 95% CI, 1.67–187.26; P = 0.017) were significantly associated with FQ-resistant E. coli. Compared with CG II, a previous SBP episode was significantly associated with FQ-resistant E. coli (OR, 4.20; 95% CI, 1.50–11.80; P = 0.006). Conclusion FQ-resistant E. coli is a significant cause of community-onset SBP, with relation to previous SBP episodes, recent FQ use and third-generation cephalosporin resistance.

Treatment of Enterobacter infection is complicated due to its intrinsic resistance to cephalosporins. Medical records of 192 adults with cancer who had Enterobacter bacteremia were analyzed retrospectively to evaluate the risk factors for and the treatment outcomes in extended-spectrum cephalosporin (ESC)-resistant Enterobacter bacteremia in adults with cancer. The main outcome measure was 30-day mortality. Of the 192 patients, 53 (27.6%) had bloodstream infections caused by ESC-resistant Enterobacter species. Recent use of a third-generation cephalosporin, older age, tumor progression at last evaluation, recent surgery, and nosocomial acquisition were associated with ESC-resistant Enterobacter bacteremia. The 30-day mortality rate was significantly higher in the resistant group. Multivariate analysis showed that respiratory tract infection, tumor progression, septic shock at presentation, Enterobacter aerogenes as the culprit pathogen, and diabetes mellitus were independent risk factors for mortality. ESC resistance was significantly associated with mortality in patients with E. aerogenes bacteremia, although not in the overall patient population.

Background/Aims: This study aimed to evaluate the efficacy of computed tomography (CT)-guided bone biopsy for the diagnosis of spinal infection and compared the clinical outcomes between tuberculous and pyogenic spinal infections. Methods: The retrospective cohort study included patients who received CT-guided bone biopsy at a tertiary hospital over the 13 years. Results: Among 100 patients, 67 had pyogenic spondylitis and 33 had tuberculous spondylitis. Pathogens were isolated from bone specimens obtained by CT-guided biopsy in 42 cases, with diagnostic yields of 61% (20/33) for tuberculous spondylitis and 33% (22/67) for pyogenic spondylitis. For 36 culture-proven pyogenic cases, Staphylococcus aureus was the most commonly isolated organism. Patients with pyogenic spondylitis more frequently presented with fever accompanied by an increase in inflammatory markers than did those with tuberculosis. Among all patients who underwent surgery, the incidence of late surgery performed one month after diagnosis was higher in patients with tuberculous infection (56.3%) than in those with pyogenic disease (23.3%, p = 0.026). Conclusions: Results obtained by CT-guided bone biopsy contributed to prompt diagnoses of spinal infections, especially those caused by tuberculosis. Despite administration of anti-tuberculous agents, patients with tuberculous spondylitis showed an increased tendency to undergo late surgery.

We describe the first reported case of endocarditis due to Neisseria skkuensis . The organism from the blood cultures taken on admission day was identified initially as unidentified Gram-negative cocci by Vitek2. Finally, it was identified as Neisseria skkuensis by 16 rRNA gene sequence analysis.

Increasing multidrug resistance (MDR) among extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae (ESBL-EK) is of a great concern, because the therapeutic options are severely limited. Thus, we performed a case-control study to evaluate risk factors for MDR among nosocomial bacteremia caused by ESBL-EK. All adult patients with ESBL-EK bacteremia from January 2009 through December 2010 were identified at our institution. MDR was defined as ESBL-EK that demonstrated in vitro resistance to trimethoprim-sulfamethoxazole (TMP-SMX), fluoroquinolone (FQ), and gentamicin. Case patients were those with an MDR ESBL-EK isolate, and control patients were those with a non-MDR ESBL-EK isolate. Among a total of 123 ESBL-EK isolates (74 [60.2%] E. coli and 49 [39.8%] K. pneumoniae) causing nosocomial bacteremia, 33 (26.8%) cases were due to MDR ESBL-EK. In a univariate analysis, the factors significantly associated with acquisition of MDR ESBL-EK were neutropenia, immunosuppressant use, urinary tract infection, and prior use of antibiotics, especially FQ (all p0.05). A multivariable analysis showed that a prior receipt of FQ (odds ratio [OR]=2.93; 95% confidence interval [CI]=1.07-8.01; p=0.036), percutaneous tube insertion (OR=4.04; 95% CI=1.56-10.75; p=0.005), and neutropenia (OR=4.22; 95% CI=1.56-11.45; p=0.005) were independent risk factors for MDR among ESBL-EK bacteremia in hospitalized patients. The CTX-M-15 enzyme was predominant in both the MDR ESBL-EK and non-MDR ESBL-EK groups (55% [11/20] vs. 55.6% [15/27]). Our data suggest that strategies designed to reduce MDR in ESBL-EK bacteremia should focus on limiting the use of FQ and minimizing invasive procedures such as tube insertion.

OBJECTIVES Community-genotype methicillin-resistant Staphylococcus aureus (MRSA) clones have emerged in the community worldwide and recently have been spreading into the hospitals. To identify predictors of sequence type 72-MRSA-SCCmec type IV (ST72-MRSA-IV) in patients with community-onset (CO) S. aureus infection, a case-control study was conducted among CO S. aureus infections, including healthcare-associated infections. METHODS Eighty-four patients with CO infections caused by ST72-MRSA-IV strains in Korea between 2007 and 2009 were selected as cases. Members of the control group were those with CO methicillin-susceptible S. aureus infections and they were matched by the admission date in a 1 : 1 ratio. RESULTS The most common type of infection was skin and soft tissue infection in both groups (48.8% versus 52.4%), followed by pneumonia. Female sex (OR 2.55, 95% CI 1.30-5.04), severe sepsis or septic shock (OR 3.05, 95% CI 1.09-8.55), prior hospitalization within the previous year (OR 2.18, 95% CI 1.10-4.32) and surgical site infection (SSI) (OR 4.63, 95% CI 1.38-15.59) were associated with ST72-MRSA-IV infections in multivariate analyses. CONCLUSIONS Female sex, SSI, severe sepsis or septic shock and prior hospitalization within the previous year were predictors of ST72-MRSA-IV among patients with CO S. aureus infection.

Failure of vancomycin in the treatment of meticillin-resistant Staphylococcus aureus (MRSA) bacteraemia has been reported despite full susceptibility of the organism to vancomycin. A retrospective observational cohort study including 137 patients with MRSA bacteraemia was performed at two centres in South Korea during 2009-2010. A total of 137 patients with MRSA bacteraemia receiving vancomycin therapy were enrolled during the study period. Isolates from 13 (9.5%) of the 137 patients had minimum inhibitory concentrations (MICs) ≥1 μg/mL. The 30-day cumulative survival was 53.8% for patients infected with isolates having a MIC≥1 μg/mL and 79.8% for patients infected with isolates having a MIC

The dual-specificity phosphatase 6 ( DUSP6 ) gene resides at chromosome location 12q22–23, which is one of the candidate loci for susceptibility to bipolar disorder and which encodes a phosphatase selective for extracellular signal-regulated kinase (ERK). Previously, we reported a positive association between the functional Leu114Val polymorphism (rs2279574) in DUSP6 and bipolar disorder. Given that the association between DUSP6 and the reported down-regulation of DUSP6 transcript in bipolar postmortem brains were sex-dimorphic, showing significance in women but not men, we performed two independent analyses in homogenous samples of male and female Korean patients with bipolar disorder or schizophrenia using samples enlarged from our previous report. Among the examined DUSP6 SNPs, five (rs769700, rs704076, rs770087, rs808820, and rs2279574) showed positive allelic associations, with the frequency of minor alleles (C, T, G, G, and G) in each SNP significantly increased in women with BD. Consequently, the “C-T-G-G-G” haplotype was significantly over-represented ( P = 0.016; OR = 3.242), whereas the “T-G-T-A-T” haplotype was significantly under-represented ( P = 0.014; OR = 0.697). We found no significant associations with DUSP6 SNPs in men with bipolar disorder or schizophrenia. We also investigated the functions of the functional SNPs' positive associations and found that Leu114Val (rs2279574; T/G) and Ser144Ala (rs770087; T/G) mutations in DUSP6 proteins reduced lithium-induced ERK1/2 phosphorylation in vitro, implicating the dominant active functions. Thus, DUSP6 may not only play important roles in the pathogenesis of bipolar disorder, particularly in women, but also affect the therapeutic response to lithium through modulating lithium's effects on intracellular signaling.

Summary Objectives This study was performed to identify risk factors in Pseudomonas aeruginosa bacteremia among Gram-negative bacterial infections in non-neutropenic patients with solid tumor. Methods A case–control study was performed to identify clinical predictors for P. aeruginosa bacteremia among non-neutropenic patients with Gram-negative bacteremia. Each case of P. aeruginosa bacteremia was matched to one or two controls with Escherichia coli , Klebsiella , Enterobacter or Citrobacter species in non-neutropenic patients with solid tumor. Results Seventy-eight patients with P. aeruginosa bacteremia were compared with 98 control patients who had other Gram-negative bacteremias. The most common types of cancer were biliary tract cancer (49/176, 27.8%) and hepatocellular carcinoma (38/176, 21.6%), followed by gastric and bladder cancer. Factors associated with development of P. aeruginosa bacteremia were the presence of lung cancer, percutaneous tubes, nosocomial exposure, an invasive procedure and previous antimicrobial therapy (all P P. aeruginosa bacteremia included the presence of lung cancer and previous antimicrobial therapy. In the subgroup analysis including 90 patients with community-onset bacteremia, the previous use of antimicrobial agents and presence of bladder cancer were independent factors significantly associated with P. aeruginosa bacteremia. Conclusions Underlying lung cancer and previous antimicrobial treatment were significantly associated with P. aeruginosa bacteremia in non-neutropenic patients with solid tumor. P. aeruginosa should be considered as a probable cause of Gram-negative bacteremia in this patient group.

V-akt murine thymoma viral oncogene homolog 1 (AKT1) has been suggested to be involved in the pathophysiology of schizophrenia. Recent, independent studies in Caucasian, Japanese, Iranian, and Chinese populations have reported that the AKT1 gene may be associated with schizophrenia, but these results have yet to be replicated in other populations. In the present study, we performed a case-control association study between AKT1 and schizophrenia in a Korean population. We genotyped six single nucleotide polymorphisms (SNP1 (rs3803300), SNP2 (rs1130214), SNP3 (rs3730358), SNP4 (rs1130233), SNP5 (rs2494732), SNP A (rs2498804)) of AKT1, selected from previous reports, in a sample of 283 subjects with schizophrenia and 350 controls. No significant difference in single marker polymorphisms or haplotype frequencies of the six SNPs in the AKT1 gene was observed between controls and subjects with schizophrenia. In addition, we carried out an updated meta-analysis of the six SNPs, and found no evidence for an association between the six SNPs and schizophrenia. Taken together, our results do not support the hypothesis that AKT1 is a susceptibility gene for schizophrenia.

The dysbindin gene (DTNBP1) has been associated with schizophrenia in several populations. Because the clinical characteristics of schizophrenia and bipolar disorder overlap in many respects and findings from genetic studies have suggested common genes between them, we conducted a case control association study of bipolar disorder in Korea to investigate the genetic association between DTNBP1 and bipolar disorder. In total, 163 patients with bipolar disorder and 350 controls were evaluated. We genotyped three single nucleotide polymorphisms of DTNBP1 (SNP A, P1763, and P1320) and analyzed the allele, genotype, and haplotype associations with bipolar disorder. We found significant genotypic associations with P1763 and P1320, but no association with SNP A in the bipolar I group. When we included bipolar II and schizoaffective disorder in the affected phenotype, the significance decreased. A positive association was observed between the SNP A-P1763 haplotype and the bipolar I phenotype. This haplotype association was lost when we either broadened our phenotype or included P1320 in a haplotype. The positive results of the present study lost significance after a Bonferroni correction for multiple testing. These findings are consistent with previous findings that showed a positive association of DTNBP1 with bipolar disorders. Moreover, our results suggest that DTNBP1 may contribute more to bipolar I disorder than bipolar II disorder or schizoaffective disorder. Further comprehensive studies will be required to clarify these association, however, it seems likely that DTNBP1 is a susceptibility gene for bipolar disorder.

The catechol-O-methyl transferase (COMT) gene has been a promising candidate in genetic research on schizophrenia because of its function in dopamine metabolism and its location on chromosome 22q11.2, which may be implicated in both schizophrenia and velocardiofacial syndrome (VCFS). To explore the possible genetic contribution of COMT to the development of schizophrenia, we focused on the subgroup of patients with schizophrenia characterized by minor physical anomalies as a phenotype and the 158 Val/Met polymorphism as a genotype. Since some physical anomalies are found in both schizophrenia and VCFS, schizophrenia patients with minor physical anomalies could represent the putative subgroup of schizophrenia linked to a disruption in neurodevelopment. Genotyping for the 158 Val/Met (472 G>A) polymorphism in the COMT gene was done for 239 patients with schizophrenia and 248 normal controls. Our analysis did not yield any significant between-group differences in terms of either allele or genotype frequency. We also could not find any association between the COMT gene and the schizophrenia subgroup with minor physical anomalies, although there was a significant difference in Waldrop total scores between the patients with schizophrenia and the normal controls. Analyses of subgroups based on other clinical variables also did not reveal significant differences. Overall, this study does not support the hypothesis that the 158 Val/Met polymorphism in the COMT gene is associated with schizophrenia in Koreans.

Inherited or acquired dysfunction of the dopamine system is believed to underlie the core symptoms of schizophrenia, and there are some evidences that dopamine transporter activity may be altered in schizophrenic patients. Therefore, dopamine transporter gene (DAT1) has been traditionally considered a probable candidate gene for the association study of schizophrenia. Until now, association studies of the dopamine transporter gene (DAT1) with schizophrenia have yielded largely negative results. However, these results cannot be regarded as conclusive in that they were all obtained from just a single marker, that is, 3′untranslated region variable number of tandem repeat (VNTR). We have therefore tried to find other single nucleotide polymorphisms (SNPs) in DAT1 gene and to use them as additional markers for the association study of schizophrenia. Searching for the SNPs had been done with 50 Korean schizophrenic patients. DNA sequences encompassing the whole exon and flanking exon–intron junctions were amplified and searched for the presence of SNPs. Total of five SNPs were found. Among these, three SNPs (1215A>G, 1398C>T, IVS11+14G>A) as well as the 3′ untranslated region VNTR were selected as the markers to be genotyped. The allelic and genotypic frequencies of these markers were determined in 252 schizophrenic patients and 271 controls and compared between them. The frequencies of algorithmically derived haplotypes were also compared. No evidence of association was found between any of these markers and schizophrenia. The result using haplotypes was also negative. However, when the patient subgroup with verified familial history and the subgroup with early age of onset were re-analyzed, weak trend of association between 1398C>T SNP marker with schizophrenia was found in both cases. In accordance with the previous literature, we could not find any evidence of association between DAT1 gene and schizophrenia. This result acquired more certainty because not only the VNTR but several SNPs present in DAT1 gene and newly constructed haplotypes were also used as additional markers. However, the finding of weak association between one of the SNP markers (1398C>T) and the specific subgroups of schizophrenia patients added further support to the importance of defining more homogenous subgroups in association studies.

Apolipoprotein E (ApoE) genotype has been found to affect the expression of a variety of neuropsychiatric disorders. We determined ApoE genotype frequencies and their relationship to clinical and pathological features in a diverse cohort of individuals with schizophrenia. There were no differences in ApoE genotype frequencies between schizophrenics and controls. However, the ApoE epsilon 4 genotype was associated with a younger age of onset of schizophrenia, and in an elderly subsample, individuals with the epsilon 4 allele more frequently exhibited co-existent dementia and had more neurofibrillary pathology (although none of the cases met criteria for Alzheimer's disease). This examination of ApoE in relation to clinical and neurobiological features of schizophrenia suggests that it modifies the phenotypic expression of the disease.

Panton-Valentine leukocidin (PVL)-positive USA300 clone has been the most successful community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) clone spreading in North America. In contrast, PVL-negative ST72-CA-MRSA has been predominant in Korea, and there has been no report of infections by the USA300 strain except only one case report of perianal infection. Here, we describe the first case of pneumonia caused by the USA300 strain following pandemic influenza A (H1N1) in Korea. A 50-year-old man was admitted with fever and cough and chest radiograph showed pneumonic consolidation at the right lower lung zone. He received a ventilator support because of respiratory failure. PCR for pandemic influenza A (H1N1) in nasopharyngeal swab was positive, and culture of sputum and endotracheal aspirate grew MRSA. Typing of the isolate revealed that it was PVL-positive, ST 8-MRSA-SCCmec type IV. The analysis of the PFGE patterns showed that this isolate was the same pulsotype as the USA300 strain.