Preferences for life-sustaining treatment in Korean adults: a cross-sectional study.

OBJECTIVES: Life-sustaining treatment is any treatment that serves to prolong life without reversing the underlying medical conditions, and includes cardiopulmonary resuscitation, mechanical ventilation, haemodialysis and left ventricular assist devices. This study aimed to investigate the thoughts on life-sustaining treatment of Koreans and to assess the factors associated with deciding to not receive life-sustaining treatment if they develop a terminal disease. DESIGN: Cross-sectional study. SETTING: Guro-gu centre for dementia from 1 May 2018 to 31 December 2019. PARTICIPANTS: In total, 150 individuals participated in this study. OUTCOME MEASURES: The questionnaire consisted of self-report items with some instructions, demographic characteristics, thoughts on life-sustaining treatment and psychosocial scales. The preferences of the participants were investigated on the assumption that they develop terminal cancer. The psychosocial scales included the Generalised Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Connor-Davidson Resilience Scale and Multidimensional Scale of Perceived Social Support (MSPSS). RESULTS: We classified our participants into two groups: individuals who wanted to receive life-sustaining treatment (IRLT) and individuals who wanted to not receive life-sustaining treatment (INLT). There were twice as many participants in the INLT group than there were in the IRLT. In making this decision, the INLT group focused more on physical and mental distress. Additionally, 32.7% of participants responded that terminal status was an optimal time for this decision, but more participants want to decide it earlier. The GAD-7 and PHQ-9 scores were significantly higher in the INLT group than in the IRLT group. However, the INLT group had significantly lower MSPSS family scores. CONCLUSION: Our findings can help assess issues regarding advance directives and life-sustaining treatment, and will be a reference for designing future studies on this issue.

Can we recommend mirtazapine and bupropion for patients at risk for bleeding?: A systematic review and meta-analysis.

BACKGROUND: Many studies have reported that selective serotonin reuptake inhibitors (SSRI) are associated with an increased risk of bleeding. Mirtazapine and bupropion, which commonly lack serotonin reuptake inhibition, have been recommended as alternatives for patients who are at risk for bleeding. However, the evidence for these recommendations is insufficient. METHODS: We conducted a systematic search, systematic review, and meta-analysis to investigate an evidence-based approach for the bleeding risks of mirtazapine and bupropion. From 1946 to May 2017, a total of 3981 studies were searched from PubMed, Embase, and the Cochrane Library. Among the studies, two independent reviewers selected studies per predefined eligibility criteria. RESULTS: A total of five meta-analyses were conducted. Patients taking mirtazapine were at a greater risk of gastrointestinal bleeding (OR = 1.17, 95% CI = 1.01-1.38) than those who did not take antidepressants. No differences were observed in the bleeding risk between mirtazapine and SSRI or between bupropion and SSRI. LIMITATIONS: The number of studies included in the meta-analysis was small. CONCLUSION: Our results suggest that it is premature to recommend mirtazapine and bupropion for patients who have a bleeding risk. More studies with larger sample sizes and longitudinal follow-ups are warranted.

The role of pro-inflammatory cytokines in the neuroinflammation and neurogenesis of schizophrenia.

Schizophrenia is a serious mental illness with chronic symptoms and significant impairment in psychosocial functioning. Although novel antipsychotics have been developed, the negative and cognitive symptoms of schizophrenia are still unresponsive to pharmacotherapy. The high level of social impairment and a chronic deteriorating course suggest that schizophrenia likely has neurodegenerative characteristics. Inflammatory markers such as pro-inflammatory cytokines are well-known etiological factors for psychiatric disorders, including schizophrenia. Inflammation in the central nervous system is closely related to neurodegeneration. In addition to pro-inflammatory cytokines, microglia also play an important role in the inflammatory process in the CNS. Uncontrolled activity of pro-inflammatory cytokines and microglia can induce schizophrenia in tandem with genetic vulnerability and glutamatergic neurotransmitters. Several studies have investigated the possible effects of antipsychotics on inflammation and neurogenesis. Additionally, anti-inflammatory adjuvant therapy has been under investigation as a treatment option for schizophrenia. Further studies should consider the confounding effects of systemic factors such as metabolic syndrome and smoking. In addition, the unique mechanisms by which pro-inflammatory cytokines are involved in the etiopathology of schizophrenia should be investigated. In this article, we aimed to review (1) major findings regarding neuroinflammation and pro-inflammatory cytokine alterations in schizophrenia, (2) interactions between neuroinflammation and neurogenesis as possible neural substrates for schizophrenia, and (3) novel pharmacological approaches.

Efficacy of adjunctive celecoxib treatment for patients with major depressive disorder: a meta-analysis.

BACKGROUND: Numerous studies have reported that inflammation is closely associated with depression, and adjunctive non-steroidal anti-inflammatory drug (NSAID) treatment has been suggested as a novel therapeutic approach for depression. METHODS: We searched electronic databases including Medline, Embase, and the Cochrane Central Register of Controlled Trials. We only included randomized controlled trials comparing adjunctive NSAIDs with placebos for treating depressive episodes. RESULTS: Of the 654 retrieved entries, we identified four relevant studies with a total of 150 patients (75 NSAID patients and 75 placebo patients) with depressive episodes. All four studies used celecoxib as the NSAID. The patients receiving adjunctive celecoxib had significantly higher mean changes in the Hamilton Rating Scale for Depression scores between baseline and endpoint measurements compared with those receiving placebo (weighted mean difference=3.26, 95% confidence interval; CI=1.81 to 4.71). The adjunctive celecoxib group also showed better remission (odds ratio; OR=6.58, 95% CI=2.55 to 17.00) and response rates (OR=6.49, 95% CI=2.89 to 14.55) than the placebo group. The all-cause drop-out rate was more favorable for the celecoxib group than for the placebo group (OR=0.45, 95% CI=0.18 to 1.13), although the statistical significance was not statistically significant (p=0.09). CONCLUSION: Adjunctive treatment with NSAIDs, particularly celecoxib, can be a promising strategy for patients with depressive disorder. Future studies with a larger sample size and longer study duration are needed to confirm the efficacy and tolerability of NSAIDs for depression.

TNF-alpha -308G>A polymorphism is associated with suicide attempts in major depressive disorder.

BACKGROUND: Despite the substantial role of the cytokine network in depression and suicide, few studies have investigated the role of genetic polymorphisms of pro- and anti-inflammatory cytokines in suicide in major depressive disorder (MDD). The aim of this study was to investigate whether tumor necrosis factor-alpha (TNF-alpha) -308G>A, interferon-gamma (IFN-gamma) +874A>T, and interleukin-10 (IL-10) -1082A>G are associated with increased risk for suicide attempts in MDD. METHODS: Among patients with MDD, 204 patients who had attempted suicide and 97 control patients who had not attempted suicide were recruited. A chi-square test was used to identify a possible risk genotype or allele type for suicide. A subsequent multivariate logistic regression analysis was conducted to investigate the influence of a risk genotype or allele type adjusted for other environmental factors. The lethality of the suicide attempt was also tested between genotype and allele types among suicidal patients with MDD. RESULTS: The GG genotype of the TNF-alpha -308G>A polymorphism was found to significantly increase risk for suicide attempt (adjusted OR=2.630, 95% CI=1.206 to 5.734). IFN-gamma +874A>T and IL-10 -1082A>G were not associated with risk for suicide. Lethality of the suicide attempt was not associated with any of the three cytokine genotypes or allele types. LIMITATIONS: Limitations include a relatively small sample size and a cross-sectional design. CONCLUSIONS: TNF-alpha -308G>A polymorphism is an independent risk factor for suicide attempts in MDD. Future studies should clarify the neural mechanisms by which the GG genotype of TNF-alpha -308G>A influences suicide in MDD.

Cytokine imbalance in the pathophysiology of major depressive disorder.

OBJECTIVE: A substantial body of evidence indicates that dysregulation of the immune system is associated with Major Depressive Disorder (MDD). Because most cytokines have pleiotropic effects, we measured various subsets of cytokines to examine the association between immune response and MDD. METHODS: Forty-eight hospitalized MDD patients and 63 normal controls were recruited. We measured in vitro monocytic (IL-6 and tumor necrosis factor (TNF)-alpha), Th1 (interferon (IFN)-gamma and interleukin (IL)-2), Th2 (IL-4), and Treg (transforming growth factor (TGF)-beta1) cytokine production as well as IL-2/IL-4 and IFN-gamma/IL-4 ratios for both groups. Depressive symptoms were assessed by Hamilton Depression Rating Scale. Patients were evaluated before and after 6 weeks of antidepressant treatment. RESULTS: At admission, IL-6, TNF-alpha, TGF-beta1 production, and IFN-gamma/IL-4 ratio were significantly higher, whereas IFN-gamma, IL-2, and IL-4 were significantly lower in MDD patients. After treatment, IL-6 and TGF-beta1 production were significantly lower than before treatment. CONCLUSION: We suggest that activation of monocytic proinflammatory cytokines, and inhibition of both Th1 and Th2 cytokines may be associated with immunological dysregulation in MDD. TGF-beta1 may be associated with the regulation of monocytic cytokines as well as Th1 and Th2 cytokines in MDD.