Addressing methodological concerns in omega-3 trial for bipolar disorder relapse prevention.

Our response addresses concerns raised about our pilot trial on omega-3 for bipolar disorder. We clarify randomization procedures, highlight the benefits of eicosapentaenoic-predominant formulations for a specific bipolar patients subgroup, and justify the use of Kaplan-Meier analysis despite limitations. We acknowledge analytical challenges due to strict inclusion criteria and encourage future research on specific bipolar subtypes and larger-scale trials for robust validation.

Omega-3 polyunsaturated fatty acids in the prevention of relapse in patients with stable bipolar disorder: A 6-month pilot randomized controlled trial.

This study investigated the efficacy and safety of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in relapse prevention of bipolar disorder (BD), addressing the shortcomings of current medications. Thirty-one stable BD patients were randomized to receive n-3 PUFAs or placebo for 6 months and intergroup differences in the incidence of the recurrence of bipolar depression were assessed. Differences in depression severity, manic symptoms, and routine biochemical parameters were also assessed. Interestingly, n-3 PUFAs demonstrated a favorable preventive effect on bipolar depression recurrence (p=0.005; Log-Rank) and reduced depression severity compared to placebo, and were well-tolerated, suggesting their potential as a safe prophylactic therapy for BD.

Effects of Omega-3 Polyunsaturated Fatty Acids Intake on Vasomotor Symptoms, Sleep Quality and Depression in Postmenopausal Women: A Systematic Review.

The menopausal transition is often accompanied with distressing manifestations, such as vasomotor symptoms, sleep disruptions, and depressive syndrome. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have emerged as a potential intervention to alleviate these symptoms. This review aimed to comprehensively assess the impact of n-3 PUFAs supplementation on vasomotor symptoms, sleep quality, and depression among postmenopausal women. We conducted a systematic literature search of randomized controlled trials across the Cochrane Library, Web of Science, PubMed, CINAHL, EMBASE, and SCOPUS databases from inception to August 2023. Among the initial pool of 163 identified studies, nine studies met the inclusion criteria and were incorporated into this systematic review. Notably, four studies detected potential benefits of n-3 PUFAs in improving hot flashes and night sweats. On the contrary, sleep quality outcomes displayed heterogeneity across the studies. Incorporating diverse scales, such as the Hamilton Depression Rating Scale-21, the Patient Health Questionnaire depression scale, and Generalized Anxiety Disorder-7 for depression outcomes, we found inconclusive evidence of n-3 PUFA's impact on depression. Overall, the combined analysis of these studies did not provide substantial evidence to support the efficacy of n-3 PUFAs in improving vasomotor symptoms, sleep quality, and depression. Further well-designed randomized clinical trials with larger participant groups are crucial to validate and generalize these results. Review Registration: PROSPERO registration no: CRD42023421922.

Varicose veins are associated with an increased risk of mitral valve regurgitation: a nationwide population-based cohort study.

BACKGROUND: Varicose veins (VV) and mitral valve regurgitation (MR) are both common diseases. The aim was to investigate whether VV are associated with an increased risk of MR. METHODS: We conducted a nationwide cohort study to assess the association between VV and risk of developing MR. Drawn from the Taiwan National Health Insurance Research Database (NHIRD), the records of 56,898 patients with VV (the VV cohort) and 56,898 propensity score-matched patients without VV (the non-VV cohort) in the years 2007 to 2015 were identified. Follow-up duration was calculated from the date of entry in the cohort until the occurrence of a first MR diagnosis, death, or the end of the observation period (December 31, 2015), whichever occurred first. Hazard ratios (HRs) and accompanying 95% confidence intervals (CIs) derived from the Cox proportional hazards model were used to estimate the association between VV and MR risks. RESULTS: After multivariable adjustment, VV was associated with an increased risk of MR (adjusted HR, 1.63; 95% CI: 1.52-1.74). Notably, significant associations between VV and MR risk were evident in both genders and in all age groups. A trend of significant increase of MR risk was also observed with increasing frequency of annual clinical visits for VV. Within the VV cohort, the subgroup of MR presence had higher incidences of atrial fibrillation, heart failure, valve-related surgeries, and mortality (P<0.001). CONCLUSIONS: This population-based cohort study revealed that VV was associated with an increased risk of MR in a Taiwanese population. Vigilance of MR existence should be emphasized in patients of VV due to its potentially poor long-term outcomes.

Change of employment status in patients with depression - A longitudinal study using national claims data.

Depression increases an individual's risk of work disability, sick leave, unemployment, and early retirement. This population-based study identified 3673 depressive patients utilizing national claim data from Taiwan and aimed to investigate changes in employment status among depressive patients, compared to matched controls, with the longest observation of up to 12 years. This study found depressive patients had an adjusted hazard ratio of 1.24 for changing to non-income earners compared to controls. Moreover, younger age, lower payroll bracket, urbanity, and geographical area were associated with increased risk among patients with depression. Despite these increased risks, most depressive patients remained employed.

Genomic-Analysis-Oriented Drug Repurposing in the Search for Novel Antidepressants.

From inadequate prior antidepressants that targeted monoamine neurotransmitter systems emerged the discovery of alternative drugs for depression. For instance, drugs targeted interleukin 6 receptor (IL6R) in inflammatory system. Genomic analysis-based drug repurposing using single nucleotide polymorphism (SNP) inclined a promising method for several diseases. However, none of the diseases was depression. Thus, we aimed to identify drug repurposing candidates for depression treatment by adopting a genomic-analysis-based approach. The 5885 SNPs obtained from the machine learning approach were annotated using HaploReg v4.1. Five sets of functional annotations were applied to determine the depression risk genes. The STRING database was used to expand the target genes and identify drug candidates from the DrugBank database. We validated the findings using the ClinicalTrial.gov and PubMed databases. Seven genes were observed to be strongly associated with depression (functional annotation score = 4). Interestingly, IL6R was auspicious as a target gene according to the validation outcome. We identified 20 drugs that were undergoing preclinical studies or clinical trials for depression. In addition, we identified sarilumab and satralizumab as drugs that exhibit strong potential for use in the treatment of depression. Our findings indicate that a genomic-analysis-based approach can facilitate the discovery of drugs that can be repurposed for treating depression.

Aristolochic acid and the risk of cancers in patients with type 2 diabetes: Nationwide population-based cohort study.

BACKGROUND: Both aristolochic acid (AA) exposure and diabetic can increase risk of certain cancers,whetherAAexposureincreases cancer risk in diabetic patientsisunknown. The purpose of this study was to investigate the association between the use of Chinese herbal products containing AA and the risk of cancer in diabetic patients. METHODS: A cohort study was conducted using the National Health Insurance Research Database in Taiwan. Patients older than 18 years who were diagnosed with diabetes between 1997 and 2010 were enrolled in our cohort. The use of Chinese herbal products containing AA was recorded from the beginning of 1997 until the ban of herbs containing AA in November 2003. Patients were individually tracked to identify cancer incidence between 1997 and 2013. Only patients who visited traditional Chinese medicine clinics between 1997 and 1 year before the end of follow-up were included in the cohort to ensure comparability. Cox proportional hazards regression was used to calculate the hazard ratio for the association between the use of Chinese herbal products containing AA and the occurrence of cancer. RESULTS: Among the 430 377 male and 431 956 female patients with diabetes enrolled in our cohort, 37 554 and 31 535 cancer diagnoses were recorded during the study period, respectively. The use of AA-containing herbal products was associated with a significantly higher risk of liver, colorectum, kidney, bladder, prostate, pelvis, and ureter cancer in a dose-dependent manner. An increased risk of extrahepatic bile duct cancer in women was also associated with AA exposure at doses of more than 500 mg. CONCLUSIONS: Association between AA exposure and the risk of some cancers were found in this study. AA exposure might increase risk of kidney,bladder,pelvis, ureter,liver,colorectum,andprostatecancer in all patientsandextrahepatic bile duct cancerin women.

Clinical Validation of Cardiac Arrest Hospital Prognosis (CAHP) Score and MIRACLE2 Score to Predict Neurologic Outcomes after Out-of-Hospital Cardiac Arrest.

Background. Out-of-hospital cardiac arrest (OHCA) remains a challenge for emergency physicians, given the poor prognosis. In 2020, MIRACLE2, a new and easier to apply score, was established to predict the neurological outcome of OHCA. Objective. The aim of this study is to compare the discrimination of MIRACLE2 score with cardiac arrest hospital prognosis (CAHP) score for OHCA neurologic outcomes. Methods. This retrospective cohort study was conducted between January 2015 and December 2019. Adult patients (>17 years) with cardiac arrest who were brought to the hospital by an emergency medical service crew were included. Deaths due to trauma, burn, drowning, resuscitation not initiated due to pre-ordered "do not resuscitate" orders, and patients who did not achieve return of spontaneous circulation were excluded. Receiver operating characteristic curve analysis with Youden Index was performed to calculate optimal cut-off values for both scores. Results. Overall, 200 adult OHCA cases were analyzed. The threshold of the MIRACLE2 score for favorable neurologic outcomes was 5.5, with an area under the curve (AUC) value of 0.70 (0.61−0.80, p < 0.001); the threshold of the CAHP score was 223.4, with an AUC of 0.77 (0.68−0.86, p < 0.001). On setting the MIRACLE2 score cut-off value, we documented 64.7% sensitivity (95% confidence interval [CI], 56.9−71.9%), 66.7.0% specificity (95% CI, 48.2−82.0%), 90.8% positive predictive value (PPV; 95% CI, 85.6−94.2%), and 27.2% negative predictive value (NPV; 95% CI, 21.4−33.9%). On establishing a CAHP cut-off value, we observed 68.2% sensitivity (95% CI, 60.2−75.5%), 80.6% specificity (95% CI, 62.5−92.6%), 94.6% PPV (95% CI, 88.6%−98.0%), and 33.8% NPV (95% CI, 23.2−45.7%) for unfavorable neurologic outcomes. Conclusions. The CAHP score demonstrated better discrimination than the MIRACLE2 score, affording superior sensitivity, specificity, PPV, and NPV; however, the CAHP score remains relatively difficult to apply. Further studies are warranted to establish scores with better discrimination and ease of application.

Kawasaki disease in childhood and psychiatric disorders: A population-based case-control prospective study in Taiwan.

BACKGROUND: Kawasaki disease (KD) is a common childhood acute inflammatory disease and potentially triggers a chronic inflammation. Although some researches have investigated neurodevelopmental consequences following KD, the findings have been inconsistent. This is the first population-based study targeted on KD and common psychiatric disorders. OBJECTIVES: We aimed to investigate the association between KD and psychiatric disorders and hypothesized that standard anti-inflammatory treatment by intravenous immunoglobulin (IVIG) may protect against development of psychiatric disorders. METHOD: We retrieved data from Taiwan's National Health Insurance Research database (NHIRD). Patients (n = 282,513) with psychiatric disorders (the case group) during 1997-2013 were included, and the control group was matched with age, sex, income and urbanization (1:1). We calculated the prevalence of KD in both groups and estimated odd ratios (ORs) and 95% confidence intervals (CIs) in the subgroup analyses for KD in conditions of age, severity, and common psychiatric comorbidity. RESULTS: Numbers of patients with KD were 460 in the cases and 380 in the controls (p = .006), and the crude OR of KD was 1.21 times greater (95% CI = 1.06-1.39, p = .006) in the case than the control groups. KD patients without IVIG treatment (n = 126) were higher in the cases than those in the controls (n = 54), with the OR of 2.33 (95% CI = 1.70-3.21, p < .0001). Subgroup analyses showed that KD survivors were at significant risk for autism spectrum disorders (ASD) (OR = 2.15, 95% CI = 1.27-3.65; p = .005) and attention deficit and hyperactivity disorders (ADHD) (OR = 1.19, 95% CI = 1.02-1.39; p = 0.03), and a trend of increased risk for anxiety disorders (OR = 1.36, 95%CI = 0.99-1.86; p = 0.05). CONCLUSIONS: Patients with KD were more likely to have comorbid psychiatric disorders, including ASD and ADHD. Moreover, anti-inflammatory treatment with IVIG may have potential prophylactic effects against the development of psychiatric disorders.

Statins and the risks of decompensated liver cirrhosis and hepatocellular carcinoma determined in patients with alcohol use disorder.

BACKGROUND: Alcohol-related liver disease (ALD) is the most common cause of liver disease. No medication can improve ALD and abstinence from alcohol is the sole effective strategy. Statin use has been demonstrated to have protective effects against liver cirrhosis and hepatocellular carcinoma (HCC) in patients with virus-related liver diseases. Whether statin use has a similar association among patients with alcohol use disorder (AUD) that can lead to ALD, is unknown. METHOD: We conducted a population-based cohort study using Taiwan's National Health Insurance Research Database from 1997 to 2013 to compare risks of decompensated liver cirrhosis and hepatocellular carcinoma (HCC) between the statin exposed and unexposed groups in the patients with AUD. The incidence rates of decompensated liver cirrhosis and HCC were calculated between patients exposed and unexposed to statins with 1:4 propensity score matching. Cox proportional hazard regressions were performed to evaluate hazard ratios (HRs). RESULTS: The incidence rates of decompensated liver cirrhosis and HCC in the statin-exposed group differed from those in the unexposed group (decompensated cirrhosis: 269.9 vs. 628.9 cases per 100,000 person-years; HCC: 116.7 vs. 318.3 cases per 100,000 person-years). The HRs for decompensated liver cirrhosis and HCC were 0.43 (95% CI, 0.37-0.51) and 0.40 (95% CI, 0.31-0.51), respectively, after adjustment. CONCLUSIONS: Statin use was associated with reduced risk of decompensated liver cirrhosis and HCC among AUD patients in a cumulative dose effect manner. Statins might have some potential effects on mitigating ALD progression beside abstinence from alcohol. Further research is needed.

Antidepressants and the risk of myocardial infarction among patients with diabetes: A population-based cohort study.

OBJECTIVE: To investigate the impact of antidepressants (ATDs) on the risk of myocardial infarction (MI) among patients with diabetes mellitus (DM). METHODS: This was a retrospective population-based cohort study that used data obtained from the National Health Insurance Research Database in Taiwan. The study cohort included diabetic patients who were older than 50 years from 1997 to 2010. We then randomly assigned individuals to the matched cohort at a 1:1 ratio according to their demographic data. Both study and matched cohorts were followed up to compare the risk of MI between patients with and without ATD use from 2000 until the end of 2013. Multivariate Cox proportional hazards models were used to evaluate the relationship between ATD treatment and the occurrence of MI. RESULTS: After adjustment for confounders, patients with ATD use of more than 180 days had a lower risk of MI than those without ATD use in the matched cohort (adjusted hazard ratio [HR] = 0.68, 95% confidence interval [CI], 0.66-0.71). The adjusted HRs of MI were 0.77 (95% CI, 0.73-0.81) and 0.56 (95% CI, 052.-0.60) in patients with DM and ATD use of 180 > cDDD ≥ 28 and cDDD ≥ 180, respectively. When the duration of ATD treatment was 180 days or longer, MI risk was significantly reduced (after adjustment) for all classes of ATD except bupropion. CONCLUSIONS: Most ATDs, but not bupropion, were associated with significantly reduced risk of MI among the DM population.

Examination of neuroinflammatory cytokine interleukin-1 beta expression in the medial prefrontal cortex, amygdala, and hippocampus for the paradoxical effects of reward and aversion induced by morphine.

A growing body of evidence has shown that abused drugs could simultaneously induce the paradoxical effect-reward and aversion. Moreover, the medial prefrontal cortex (mPFC), amygdala, and hippocampus were involved in this paradoxical effect by abused drugs. However, no research examined whether neuroinflammatory changes in the mPFC [including cingulate cortex area 1 (Cg1); prelimbic cortex (PrL); infralimbic cortex (IL)], basolateral amygdala, and hippocampus [e.g., CA1, CA2, CA3, and dentate gyrus (DG)] after morphine-induced reward in conditioned place preference (CPP) and aversion in conditioned taste aversion (CTA). The results showed that after morphine administration, the consumption of a 0.1% saccharin solution decreased; the mean time spent in the morphine-paired side compartment of the CPP box increased, indicating that morphine simultaneously induced the paradoxical effects of reward and aversion. The PrL and IL of the mPFC, the BLA of the amygdala, the CA1, CA2, CA3, and DG of the hippocampus but not the Cg1 presented hyperactive IL-1ß expression in response to morphine's aversion and reward. The mPFC, amygdala, and hippocampus may appear neuroinflammation activity following morphine-induced paradoxical effect-reward in CPP and aversion in CTA. The present data may provide a better understanding of the relationship between neuroinflammation and morphine addiction.

Psychometric properties of the Internalized Stigma of Mental Illness (ISMI) Scale in Indonesia.

Objective: The Internalized Stigma of Mental Illness (ISMI) scale is widely used to examine internalized stigma among people with mental illness. However, an Indonesian version does not yet exist. We developed an Indonesian translation of the ISMI scale and assessed its psychometric properties. Method: We included 280 inpatients with mental illness diagnoses in 2 hospitals and a rehabilitation center. We followed the guidelines proposed by Sousa and Rojjanasrirat (2011) to translate the questionnaire. The reliability was evaluated by measuring the internal consistency (Cronbach's alpha) and test-retest reliability. Test validity was measured through exploratory factor analysis (EFA) to examine the structure of the scale and confirmatory factor analysis (CFA) to determine the model fits. Results: The EFA yielded 5 factors with Cronbach's alpha coefficients of .96 for the total scale and .95, .95, .93, .94, and .82 for the 5 subscales. The test-retest reliability indicated excellent results, demonstrated by the interclass correlation coefficient ranging between .76 and .92 for all ISMI scale items. The Kaiser-Meyer-Olkin test statistic was 0.95, and Bartlett's test of sphericity value was significant. Conclusions and Implications for Practice: The CFA indicated that the ISMI scale has an acceptable model fit. The Indonesian version of the ISMI scale demonstrated good psychometric properties for measuring internalized stigma of psychiatric patients in Indonesia. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Genome-wide association study of early-onset bipolar I disorder in the Han Taiwanese population.

The search for susceptibility genes underlying the heterogeneous bipolar disorder has been inconclusive, often with irreproducible results. There is a hope that narrowing the phenotypes will increase the power of genetic analysis. Early-onset bipolar disorder is thought to be a genetically homogeneous subtype with greater symptom severity. We conducted a genome-wide association study (GWAS) for this subtype in bipolar I (BPI) disorder. Study participants included 1779 patients of Han Chinese descent with BPI disorder recruited by the Taiwan Bipolar Consortium. We conducted phenotype assessment using the Chinese version of the Schedules for Clinical Assessment in Neuropsychiatry and prepared a life chart with graphic depiction of lifetime clinical course for each of the BPI patient recruited. The assessment of onset age was based on this life chart with early onset defined as ≤20 years of age. We performed GWAS in a discovery group of 516 early-onset and 790 non-early-onset BPI patients, followed by a replication study in an independent group of 153 early-onset and 320 non-early-onset BPI patients and a meta-analysis with these two groups. The SNP rs11127876, located in the intron of CADM2, showed association with early-onset BPI in the discovery cohort (P = 7.04 × 10-8) and in the test of replication (P = 0.0354). After meta-analysis, this SNP was demonstrated to be a new genetic locus in CADM2 gene associated with early-onset BPI disorder (P = 5.19 × 10-8).