Real-world effectiveness of long-acting injections for reducing recurrent hospitalizations in patients with schizophrenia.

BACKGROUND: The comparative effectiveness of antipsychotic long-acting injections (LAIs) and oral medication is not clear due to various methodological problems. METHODS: To compare the effectiveness of LAIs and oral antipsychotics in preventing readmission in patients with schizophrenia, we performed a within-subject analysis of data collected from 75,274 patients hospitalized with schizophrenia over a 10-year period (2008-2017). Readmission rates were compared according to medication status (non-medication, oral medication alone, and LAI medication). Each admission episodes were compared according to medication status before admission. RESULTS: Total 132,028 episodes of admission were analyzed. During 255,664 person-years of total observation, 101,589 outcome events occurred. Comparing LAI to only oral medication, IRR was 0.71 (0.64-0.78, P < 0.001). IRR of LAI to only oral medication of first index admission was 0.74 (0.65-0.86). As hospitalization was repeated, IRR of second, third, and fourth or more index admission decreased 0.65 (0.53-0.79), 0.56 (0.43-0.76), and 0.42 (0.31-0.56), respectively. CONCLUSIONS: LAI treatment reduced the readmission rate by 29% compared with oral medication in real-world settings. Moreover, LAIs reduced the readmission rate by 58% in patients with repeated admissions. The more readmissions, the greater the effect of LAIs in reducing the risk of re-hospitalization compared with oral antipsychotics.

Incidence of Severe Chronic Neutropenia in South Korea and Related Clinical Manifestations: A National Health Insurance Database Study.

Background and objectives: Severe chronic neutropenia (SCN) is a condition in which absolute neutrophil counts remain at a low level (under 500/µL) over months or years. Because of the rare onset of SCN, its epidemiology, prognosis, and clinical manifestations have not yet been fully understood. In particular, large-cohort studies in Asian countries are still insufficient. Therefore, in this study, national health insurance data was used to investigate the epidemiologic features and prognosis of SCN in South Korea. MATERIALS AND METHODS: The data from the Health Insurance Review and Assessment database recorded between 1 January 2011 and 31 December 2015 were explored. SCN was defined based on the ICD-10 code, registry of benefit extension policy, and inclusion criteria of the study. After identifying patients with SCN, annual incidence and their co-morbidities were analyzed. RESULTS: Among the initially identified patients with severe neutropenia (N = 2145), a total of 367 patients had SCN and were enrolled. The annual incidence rate of SCN ranged from 0.12 to 0.17 per 100,000 person-year (PY) during the study period. The highest incidence was observed in pediatric patients aged between 0 to 9 years (N = 156), followed by women in their fifties (N = 43). The total incidence rate was 0.17 in females and 0.12 in males (Relative risk (RR): 1.43, 95%, CI: 1.16-1.76). The most common accompanying condition was mild respiratory infection, but about 3.2% of patients progressed to hematologic malignancy after an average of 2.4 years. CONCLUSIONS: This nationwide population-based epidemiological study showed that incidence of SCN is higher in pediatrics and middle-aged women. As progression to hematologic malignancy was significantly higher in the age of in 45-49 year olds, careful follow-up is necessary in this group. However, since this study lacks the molecular information, these finding need to be interpreted with great caution.

Effort-Based Reinforcement Processing and Functional Connectivity Underlying Amotivation in Medicated Patients with Depression and Schizophrenia.

Amotivation is a common phenotype of major depressive disorder and schizophrenia, which are clinically distinct disorders. Effective treatment targets and strategies can be discovered by examining the dopaminergic reward network function underlying amotivation between these disorders. We conducted an fMRI study in healthy human participants and medicated patients with depression and schizophrenia using an effort-based reinforcement task. We examined regional activations related to reward type (positive and negative reinforcement), effort level, and their composite value, as well as resting-state functional connectivities within the meso-striatal-prefrontal pathway. We found that integrated reward and effort values of low effort-positive reinforcement and high effort-negative reinforcement were behaviorally anticipated and represented in the putamen and medial orbitofrontal cortex activities. Patients with schizophrenia and depression did not show anticipation-related and work-related reaction time reductions, respectively. Greater amotivation severity correlated with smaller work-related putamen activity changes according to reward type in schizophrenia and effort level in depression. Patients with schizophrenia showed feedback-related putamen hyperactivity of low effort compared with healthy controls and depressed patients. The strength of medial orbitofrontal-striatal functional connectivity predicted work-related reaction time reduction of high effort negative reinforcement in healthy controls and amotivation severity in both patients with schizophrenia and those with depression. Patients with depression showed deficient medial orbitofrontal-striatal functional connectivity compared with healthy controls and patients with schizophrenia. These results indicate that amotivation in depression and schizophrenia involves different pathophysiology in the prefrontal-striatal circuitry.SIGNIFICANCE STATEMENT Amotivation is present in both depression and schizophrenia. However, treatment involves the use of drugs that enhance serotonin activity in depression and inhibit serotonin and dopamine activity in schizophrenia. Understanding how motivation processed in the mesocorticolimbic and nigostriatal pathways is affected in depression and schizophrenia is important in discovering treatment targets and strategies for amotivation. To our knowledge, this is the first study to compare patients with depression and schizophrenia in a common functional construct. By using an effort-based reinforcement task and examining resting-state functional connectivity in the dopaminergic network, we propose that difference in striato-orbitofrontal dysfunction in effort-based reinforcement between depression and schizophrenia may be related to differences in the extent of functional dysconnectivity in the dopaminergic pathway.

Association of fracture risk with benzodiazepine among adults in South Korea.

This study examined the association between fracture and benzodiazepine (BZD) prescription in Korean adults using case-crossover (CCO) and self-controlled case-series (SCCS) designs, which have the advantage to control confounding bias, such as individual characteristics. Patients with fracture were defined as patients who visited the emergency room and orthopedics department with the ICD-10 diagnosis code for fracture. Fractures due to motor vehicle accidents and stroke were excluded. Whereas the CCO design presented odds ratio (OR) using a conditional logistic regression model, SCCS design showed incidence rate ratio (IRR) using a conditional Poisson regression model. The concomitant drugs that can affect the fracture were adjusted. Sensitivity analysis and subgroup analysis by age (elderly vs. nonelderly), action mechanism (short-acting vs. long-acting), and prescription duration (short-term user vs. long-term user) were conducted. The adjusted OR (AOR) for control period I (prior to 90 days from case) was 1.39 (95% CI=1.25-1.54) for all BZD prescriptions. The adjusted ORs for other control periods showed similar trends. The adjusted IRRs (AIRR) during the first 4 weeks, 4-8 weeks, 8-12 weeks, and 12-16 weeks from new BZD use were 1.46 (95% CI=1.28-1.66), 1.23 (95% CI=1.01-1.49), 1.09 (95% CI=0.86-1.37), and 1.38 (95% CI=1.07-1.77), respectively. Regardless of age group, action mechanism, or prescription duration, fracture risk was higher during case period than control. The risk for fracture was higher in both elderly and non-elderly people with BZD prescription than in those without BZD prescription. Careful monitoring for people who start BZD treatment and further research in the non-elderly is required.

Association study of DKK2 polymorphisms with alcohol dependence and alcohol-related harm.

BACKGROUND: Alcohol dependence (AD) is a common disorder with both environmental and genetic factors. Previous studies have shown that the genomic region from chromosome 4q22-q32 is closely associated with AD. Furthermore, a study with Irish subjects revealed that the polymorphisms of Dickkopf WNT signaling pathway inhibitor (DKK2), located at 4q25, showed a significant association with AD. METHODS: We conducted a replication study of the association between DKK2 polymorphisms and AD with 459 alcoholics and 444 normal controls, all of Korean descendent. To rank the AD of the subjects, Alcohol Use Disorders Identification Test (AUDIT) was utilized. Using the TaqMan assay, 21 single-nucleotide polymorphisms (SNPs) of DKK2 were genotyped. RESULTS: Our analysis showed that rs17037102 (Q146R) was significantly associated with overall AUDIT score (p = 0.003, p(corr)  = 0.05 in dominant model). Further analysis showed that the SNP was significantly associated with alcohol-related harm (p = 0.001, p(corr)  = 0.02 in co-dominant model). Several other SNPs, including the 3 SNPs which were associated with AD in European population, showed marginal associations that were erased when corrections for multiple testing was applied. Furthermore, rs17037102 was in linkage disequilibrium with the nonexonic DKK2 SNPs which showed associations with AD in the previous study with Irish population, which suggests that rs17037102 may be the causal SNP. CONCLUSIONS: We found 1 DKK2 SNP to be significantly associated with alcohol-related harm in alcoholic subjects. The SNP might be the causal SNP which led its linked SNPs to show associations in previous studies.

In-depth investigation for prescribing trends of benzodiazepines in South Korea.

This study aimed to investigate national prescription trends of benzodiazepines (BZD) for adults between 2007 and 2011 using Health Insurance Review and Assessment Service (HIRA) database in South Korea. Data analysis was performed by claim unit or patient unit. For the analysis of patient unit, each claim was merged by the same patient. Defined daily dose (DDD) was used to analyze the data in terms of dose and periods of BZD prescription. We identified a total of 22,361,449 adult patients who had BZD prescription at least once in 1,989,263 claims during 5 years. The average national BZD prescription prevalence for 1 year was 23.7%, 7.9%, 4.7%, and 3.2% of >= 1 day supply, >= 30 days supply, >= 90 days supply, and >= 180 days supply, respectively. The trends for 5 years were very similar. Among study population, 87.7% visited only non-psychiatric departments and the most frequent indication was gastrointestinal related diseases. BZD consumption expressed as DDDs per 1,000 inhabitants per day was 109.2. BZD consumption tended to be ~ 4 x higher in elderly than that of non-elderly (268.6 vs. 60.0 in male and 367.7 vs. 90.9 in female). Our study indicated the possibilities for inappropriate prescription of BZD, and the limitation policy on continuous prescription over 30 days supply did not seem to be effective. The effective interventions including an educational program for appropriate prescription of BZD should be considered.

Implications of helplessness in depression: diagnosing mild cognitive impairment and analyzing its effects on cognitive decline in older adults.

Background: This study focuses on how elements of depression correlate with mild cognitive impairment (MCI) in older adults and the diagnostic efficacy of combining these components with the Mini-Mental State Examination (MMSE). The study also investigated the connection between individual depression components and overall cognitive function, as measured by the total score (TS) of the consortium to establish a registry for Alzheimer's disease (AD) assessment battery. Methods: The study included 196 nondemented adults aged 65 to 90 years at a university hospital and community. Comprehensive clinical assessments including the 30-item Geriatric Depression Scale (GDS) to measure components of depressive symptoms, TS, and blood nutritional biomarkers. Results: Our stepwise logistic regression analysis highlighted the 'helplessness item' (odds ratio = 4.531, 95% CI = 2.218 to 9.258, p < 0.001) as a significant predictor for MCI diagnosis. Further, models incorporating 'helplessness item + MMSE' demonstrated markedly enhanced accuracy in diagnosing MCI, surpassing the performance of the MMSE used independently. Notably, the group characterized by helplessness showed a significant reduction in TS (B = -5.300, SE = 1.899, ß = -0.162, p = 0.006), with this trend being particularly pronounced in individuals exhibiting lower levels of physical activity. Interestingly, this correlation did not manifest in participants with higher physical activity levels. Conclusion: Our findings suggest that helplessness is highly effective in diagnosing MCI and is linked to a decrease in cognitive function. Therefore, when addressing MCI and AD-related cognitive decline, clinicians should consider helplessness.

High-Volume Hospital Had Lower Mortality of Severe Intracerebral Hemorrhage Patients.

Objective: Intracerebral hemorrhage (ICH) accompanies higher mortality rates than other type of stroke. This study aimed to investigate the association between hospital volume and mortality for cases of ICH. Methods: We used nationwide data from 2013 to 2018 to compare high-volume hospitals (≥32 admissions/year) and low-volume hospitals (<32 admissions/year). We tracked patients' survival at 3-month, 1-year, 2-year, and 4-year endpoints. The survival of ICH patients was analyzed at 3-month, 1-year, 2-year, and 4-year endpoints using Kaplan-Meier survival analysis. Multivariable logistic regression analysis and Cox regression analysis were performed to determine predictive factors of poor outcomes at discharge and death. Results: Among 9,086 ICH patients who admitted to hospital during 18-month period, 6,756 (74.4%) and 2,330 (25.6%) patients were admitted to high-volume and low-volume hospitals. The mortality of total ICH patients was 18.25%, 23.87%, 27.88%, and 35.74% at the 3-month, 1-year, 2-year, and 4-year, respectively. In multivariate logistic analysis, high-volume hospitals had lower poor functional outcome at discharge than low-volume hospitals (odds ratio, 0.80; 95% confidence interval, 0.72-0.91; p < 0.001). In the Cox analysis, high-volume hospitals had significantly lower 3-month, 1-year, 2-year, and 4-year mortality than low-volume hospitals (p < 0.05). Conclusion: The poor outcome at discharge, short- and long-term mortality in ICH patients differed according to hospital volume. High-volume hospitals showed lower rates of mortality for ICH patients, particularly those with severe clinical status.

Extended genetic effects of ADH cluster genes on the risk of alcohol dependence: from GWAS to replication.

Alcohol dependence (AD) is a multifactorial and polygenic disorder involving complex gene-to-gene and gene-to-environment interactions. Several genome-wide association studies have reported numerous risk factors for AD, but replication results following these studies have been controversial. To identify new candidate genes, the present study used GWAS and replication studies in a Korean cohort with AD. Genome-wide association analysis revealed that two chromosome regions on Chr. 4q22-q23 (ADH gene cluster, including ADH5, ADH4, ADH6, ADH1A, ADH1B, and ADH7) and Chr. 12q24 (ALDH2) showed multiple association signals for the risk of AD. To investigate detailed genetic effects of these ADH genes on AD, a follow-up study of the ADH gene cluster on 4q22-q23 was performed. A total of 90 SNPs, including ADH1B rs1229984 (H47R), were genotyped in an additional 975 Korean subjects. In case-control analysis, ADH1B rs1229984 (H47R) showed the most significant association with the risk of AD (p = 2.63 × 10(-21), OR = 2.35). Moreover, subsequent conditional analyses revealed that all positive associations of other ADH genes in the cluster disappeared, which suggested that ADH1B rs1229984 (H47R) might be the sole functional genetic marker across the ADH gene cluster. Our findings could provide additional information on the ADH gene cluster regarding the risk of AD, as well as a new and important insight into the genetic factors associated with AD.

The 5-item Alcohol Use Disorders Identification Test (AUDIT-5): an effective brief screening test for problem drinking, alcohol use disorders and alcohol dependence.

AIMS: To identify an optimal brief version of the Alcohol Use Disorders Identification Test (AUDIT) and to evaluate its effectiveness as a screening test for problem drinking (PD), alcohol use disorders (AUD) and alcohol dependence (AD). METHODS: A multicenter trial was conducted from March, 2010, to January, 2012, in 101 normal comparison, 203 risky drinking, 92 alcohol abuse and 101 AD men aged below 65 years of age in a Korean population. For the purposes of screening, risky drinking, alcohol abuse and AD were grouped: all the three grouped as PD and the latter two grouped as AUD. Logistic regression analysis was used to determine the items among the 10-item AUDIT that provided information predictive of PD, AUD and AD. Receiver operating characteristic (ROC) curve analysis was performed to investigate the discrimination ability of the brief versions of AUDIT, 10-item AUDIT and Cut-down, Annoyed, Guilt, Eye-opener as a screen for PD, AUD and AD. Areas under the ROC curve were compared between tests according to the method suggested by Hanley and McNeil. RESULTS: The 5-item AUDIT (AUDIT-5: AUDIT items 2, 4, 5, 9 and 10) was obtained by stepwise multiple regression analyses for each screening. AUDIT-5 exhibited an AUD screening accuracy significantly superior to that of the 10-item AUDIT, but other brief versions of AUDIT and CAGE did not. Furthermore, AUDIT-5 had a high PD and AD screening accuracy equivalent to that of the 10-item AUDIT. CONCLUSION: These results strongly support the usefulness of AUDIT-5 for screening of PD, AUD and AD in clinical settings in Korean male populations.

The current situation of treatment systems for alcoholism in Korea.

Alcoholism is becoming one of the most serious issues in Korea. The purpose of this review article was to understand the present status of the treatment system for alcoholism in Korea compared to the United States and to suggest its developmental direction in Korea. Current modalities of alcoholism treatment in Korea including withdrawal treatment, pharmacotherapy, and psychosocial treatment are available according to Korean evidence-based treatment guidelines. Benzodiazepines and supportive care including vitamin and nutritional support are mainly used to treat alcohol withdrawal in Korea. Naltrexone and acamprosate are the drugs of first choice to treat chronic alcoholism. Psychosocial treatment methods such as individual psychotherapy, group psychotherapy, family therapy, cognitive behavior therapy, cue exposure therapy, 12-step facilitation therapy, self-help group therapy, and community-based treatment have been carried out to treat chronic alcoholism in Korea. However, current alcohol treatment system in Korea is not integrative compared to that in the United States. To establish the treatment system, it is important to set up an independent governmental administration on alcohol abuse, to secure experts on alcoholism, and to conduct outpatient alcoholism treatment programs and facilities in an open system including some form of continuing care.

Association between physical activity and episodic memory and the moderating effects of the apolipoprotein E ε4 allele and age.

Background: An abundance of evidence indicates that physical activity may protect against Alzheimer's disease (AD) and related cognitive decline. However, little is known about the association between physical activity and AD-related cognitive decline according to age and the apolipoprotein E (APOE) ε4 allele (APOE4) as major risk factors. Therefore, we examined whether age and APOE4 status modulate the effects of physical activity on episodic memory as AD-related cognition in non-demented older adults. Methods: We enrolled 196 adults aged between 65 and 90 years, with no dementia. All participants underwent comprehensive clinical assessments including physical activity evaluation and APOE genotyping. The AD-related cognitive domain was assessed by the episodic memory, as the earliest cognitive change in AD, and non-memory cognition for comparative purposes. Overall cognition was assessed by the total score (TS) of the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery. Results: We found significant physical activity × age and physical activity × APOE4 interaction effects on episodic memory. Subgroup analyses indicated that an association between physical activity and increased episodic memory was apparent only in subjects aged > 70 years, and in APOE4-positive subjects. Conclusion: Our findings suggest that physical activity has beneficial effects on episodic memory, as an AD-related cognitive domain, in individuals aged > 70 years and in APOE4-positive individuals. Physicians should take age and APOE4 status account into when recommending physical activity to prevent AD-related cognitive decline.

The association between adverse childhood experiences and self-harm among South Korean children and adolescents: a cross-sectional study.

PURPOSE: Adolescent self-harm is a public health problem. Research suggests a link between adverse childhood experiences (ACEs) and self-destructive behaviors. Few studies, however, have examined the effects of ACEs on self-harm among Asian adolescents. This study explored the association between lifetime ACEs and a history of self-harm among Korean children and adolescents in elementary, middle, and high schools. METHODS: A cross-sectional, retrospective medical record review was conducted on a dataset of a national psychiatrist advisory service for school counselors who participated in the Wee Doctor Service from January 1 to December 31, 2020. The data were analyzed using multiple logistic regression to predict self-harm. RESULTS: Student cases (n=171) were referred to psychiatrists by school counselors for remote consultation. Multiple logistic regression analyses revealed that the odds of self-harm were higher among high school students (adjusted odds ratio [aOR]=4.97; 95% confidence interval [CI]=1.94-12.76), those with two or more ACEs (aOR=3.27; 95% CI=1.43-7.47), and those with depression (aOR=3.06; 95% CI=1.32-7.10). CONCLUSION: The study's findings provide compelling evidence that exposure to ACEs can increase vulnerability to self-harm among Korean students. Students with a history of ACEs and depression, as well as high school students, require increased attention during counseling. School counselors can benefit from incorporating screening assessment tools that include questions related to ACEs and depression. Establishing a systematic referral system to connect students with experts can enhance the likelihood of identifying self-harm tendencies and offering the essential support to prevent self-harm.

The Prevalence and Clinical Characteristics of Borderline Personality Disorder in South Korea Using National Health Insurance Service Customized Database.

PURPOSE: The purpose of the present study was to identify the prevalence and clinical characteristics of borderline personality disorder (BPD) in South Korea using the Korean National Health Insurance database (DB). MATERIALS AND METHODS: We used the National Health Insurance Service (NHIS)'s research DB (NHIS-2021-1-790) from January 1, 2010 to December 31, 2019, to make customized DB including sociodemographic information and absence or presence of BPD and other psychiatric disorders. The prevalence and the age of onset of BPD was estimated. To compare medical service utilization between the BPD group and the control group, a 1:1:1 propensity score matching was employed, and the regression analysis was conducted. RESULTS: The prevalence of BPD per 10000 people was 0.96 in 2010 and 1.06 in 2019. The prevalence ratio of males to females was 1:1.38 in 2010 and 1:1.65 in 2019, showing that BPD was more prevalent in females. The patients' overall average age of onset was 33.19±14.6 years, with the highest prevalence shown in 8503 people in their 20s. By administrative district, the highest prevalence of BPD per 10000 people was shown in Seoul with 8.71 and the lowest in Jeollanam-do with 2.35. The BPD patients showed a pattern of extensive use of general and mental healthcare services. CONCLUSION: This study identified the prevalence of BPD on a national DB set in South Korea. Although the prevalence of BPD in South Korea was relatively low compared to other countries, there was a steady increase in the number of BPD patients over a decade, which may be possibly due to an increased awareness of mental health and campaigns among healthcare providers and users in the country.

High-intensity walking in midlife is associated with improved memory in physically capable older adults.

BACKGROUND: Little is known about the associations of midlife- and late life-initiated walking with Alzheimer's disease (AD)-related cognitive decline in humans. We aimed to investigate whether high-intensity, prolonged, midlife-initiated walking is associated with changes in AD-related cognitive decline in physically capable older adults. METHODS: We studied 188 physically capable participants aged 65-90 years without dementia who underwent comprehensive clinical assessment, including of their walking modality (i.e., intensity, duration, midlife- or late life-onset), memory- or non-memory and total cognitive performance, and blood or nutritional biomarkers. RESULTS: The walking group showed better episodic memory (B = 2.852, SE = 1.214, ß = 0.144, p = 0.020), but not non-memory cognition, than the non-walking group. High-intensity walking starting in midlife was significantly associated with better episodic memory (B = 9.360, SE = 3.314, ß = 0.446, p = 0.005) compared to the non-walking group. In contrast, there were no differences in cognition according to walking duration, regardless of the onset time. The walking group also showed a similar association with overall cognition. CONCLUSIONS: Among physically capable older adults without dementia, walking, particularly at high intensity and starting in midlife, is associated with improved episodic memory, an AD-related cognitive domain. Further attention should be paid to the role of walking in terms of AD prevention.

Manganese level and cognitive decline in older adults with the APOE e4 allele: a preliminary study.

This study examined the relationship between serum manganese level and cognition, and the moderating effect of apolipoprotein E ε4 (APOE4) on this relationship. A total of 164 non-demented participants underwent clinical assessments including serum manganese level and cognition [episodic memory score (EMS), non-memory score (NMS) for executive function/attention/language/ visuospatial skill, and total score (TS)]. Serum manganese × APOE4 interaction had a significant effect on EMS and TS. Serum manganese level was inversely associated with EMS and TS in APOE4-positive but not APOE4-negative participants. APOE4 should be considered a key component in Alzheimer's disease studies that included manganese imbalance as a risk factor.

Ginseng intake and Alzheimer disease-specific cognition in older adults according to apolipoprotein ε4 allele status.

Background: The probable association among ginseng intake, Alzheimer's disease (AD)-specific cognition, and apolipoprotein ε4 (APOE4) remains poorly investigated. Hence, we examined the association between ginseng intake and AD-specific cognition in older adults under the moderating effect of APOE4 status. Methods: This study enrolled 160 adults aged 65-90 years without dementia. All participants underwent comprehensive dietary and clinical assessments including ginseng intake, AD-related cognition (i.e., delayed episodic memory, as the earliest cognitive change in AD), and non-memory cognition for comparative purposes. Results: Ginseng intake was associated with higher delayed episodic memory, but not non-memory cognition, compared to no ginseng intake. The interaction between ginseng intake and APOE4 status had a significant effect on delayed episodic memory. Subgroup analyses showed that ginseng intake was associated with higher delayed episodic memory in the APOE4-negative but not the APOE4-positive subgroup. The benefits of ginseng intake on delayed episodic memory were prominent in the high duration (≥5 years) and midlife onset (<65 years) groups. Conclusion: Our study of older adults with no dementia suggests that ginseng intake (with high duration and midlife onset) had a beneficial effect on AD-specific cognitive decline, i.e., the delayed episodic memory. In addition, APOE4 status moderates the association between ginseng intake status and AD-specific cognitive decline.

Spicy food intake predicts Alzheimer-related cognitive decline in older adults with low physical activity.

A plausible association exists among spicy food consumption, physical activity, and Alzheimer's disease (AD) or cognitive decline, but it remains poorly investigated. We aimed to examined the association between spicy food and AD-related memory decline or global cognitive decline in older adults under the moderating effect of physical activity. Total 196 non-demented older adults were included. Participants underwent comprehensive dietary and clinical assessments including spicy food intake, AD-related memory, global cognition, and physical activity. The strength of spicy food was stratified into three categories: 'not spicy' (reference), 'low spiciness', and 'high spiciness'. Multiple linear regression analyses were performed to examine the relationships between spicy level and cognition. The spicy level was the independent variable in each analysis; it was entered as a stratified categorical variable using the three categories. We found a significant association between a high level of spiciness in food and decreased memory ([Formula: see text] - 0.167, p < 0.001) or global cognition ([Formula: see text] - 0.122, p = 0.027), but not non-memory cognition. To explore the moderating effects of age, sex, apolipoprotein E ε4 allele-positivity, vascular risk score, body mass index, and physical activity on the associations between spicy level and memory or global cognition, the same regression analyses were repeated including two-way interaction terms between the spicy level and each of the six variables as an additional independent variable. An interactive effect was detected between a high level of spiciness in food and physical activity on the memory ([Formula: see text] 0.209, p = 0.029) or global cognition ([Formula: see text] 0.336, p = 0.001). Subgroup analyses showed that the association between a high level of spiciness in food and a lower memory ([Formula: see text] - 0.254, p < 0.001) and global score ([Formula: see text] - 0.222, p = 0.002) was present only in older adults with low physical activity, but not in older adults with high physical activity. Our findings suggest that spicy food intake is predictive of AD-related cognitive decline, i.e., episodic memory; this relationship is worsened by physically inactive lifestyle.

Neuregulin induces CTGF expression in hypertrophic scarring fibroblasts.

Hypertrophic scarring (HTS) is a common fibroproliferative disorder that typically follows thermal and other injuries involving the deep dermis. These pathogenic mechanisms are regulated by connective tissue growth factor (CTGF) and transforming growth factor-ß. We found that neuregulin-1 (NRG1), as well as NRG receptors, HER-2, and HER-3 were upregulated in HTS fibroblasts (HTSF), compared with normal fibroblasts. Furthermore, NRG1 stimulation increased the expression of CTGF in HTSF. In the presence of inhibitors of PI3K, Src, Smad, or reactive oxygen species, the effect of NRG1 on CTGF expression decreased significantly. In particular, the combination of LY294002 or PP2 with SB431542 blocked NRG1-mediated CTGF expression in HTSF. Finally, we demonstrated that siRNA for CTGF, AG825, LY294002, and PP2, either alone or in co-treatment, effectively reduced extracellular matrix expression. Taken together, our results suggest that NRG1 is involved in fibrotic scar pathogenesis via PI3K- or Src-mediated CTGF expression.

The effectiveness of continuing group psychotherapy for outpatients with alcohol dependence: 77-month outcomes.

BACKGROUND: Group psychotherapy (PT) is one of the most common interventions used to treat alcohol dependence (AD), and it is assumed to be effective. Despite its common clinical use, long-term trials that have been conducted to examine the efficacy of group PT in the treatment of outpatients with AD are limited and often lack appropriate comparisons. On that basis, a long-term comparative trial was performed with the main objective of evaluating the effectiveness of continuing group PT for outpatients with AD. METHODS: Quasi-experimental trial was conducted from January 2004 to May 2010 in 177 AD subjects who had completed an inpatient 10-week alcohol treatment program. Abstinence rates of the combined group (experimental group: outpatient individual PT plus group PT, N = 94) and the standard outpatient individual PT-only group (comparison group, N = 83) were statistically compared using Kaplan-Meier survival analysis. Predictive factors of abstinence rate for alcohol were assessed using Cox regression analysis. RESULTS: Abstinence rates of the combined PT group were significantly high relative to those of the outpatient individual PT-only group. Significant predictive factors for the alcohol abstinence rate were outpatient group PT and age. Even after controlling for confounding factors, outpatient group PT was a significant predictive factor for the alcohol abstinence rate. CONCLUSIONS: Our findings indicate that for AD patients who had completed an inpatient 10-week alcohol treatment, outpatient group PT appears to be an effective form of continuing care or aftercare within the context of an outpatient service delivery system.