scholarly journals Mitochondrial modulators in the treatment of bipolar depression: a systematic review and meta-analysis

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Liang Liang ◽  
Junyu Chen ◽  
Ling Xiao ◽  
Qing Wang ◽  
Gaohua Wang
Keyword(s):  
Depressive Symptoms ◽  
Subgroup Analysis ◽  
Rating Scale ◽  
Bipolar Depression ◽  
Meta Analysis ◽  
Depression Scale ◽  
Small Sample ◽  
Antidepressant Effect ◽  
Young Mania ◽  
Scale Scores

AbstractMitochondrial dysfunction has been implicated in the risk, pathophysiology, and progression of mood disorders, especially bipolar disorder (BD). Thus, the objective of this meta-analysis was to determine the overall antidepressant effect of mitochondrial modulators in the treatment of bipolar depression. Outcomes included improvement in depression scale scores, Young Mania Rating Scale (YMRS) and Clinical Global Impression-Severity Scale (CGI-S) score. Data from randomized controlled trials (RCTs) assessing the antidepressant effect of diverse mitochondrial modulators were pooled to determine standard mean differences (SMDs) compared with placebo.13 RCTs were identified for qualitative review. The overall effect size of mitochondrial modulators on depressive symptoms was −0.48 (95% CI: −0.83 to −0.14, p = 0.007, I2 = 75%), indicative of a statistically significant moderate antidepressant effect. In the subgroup analysis, NAC improved depressive symptoms compared with placebo (−0.88, 95% CI: −1.48 to −0.27, I2 = 81%). In addition, there was no statistical difference between mitochondrial modulators and placebo in YMRS. Although mitochondrial modulators were superior to placebo in CGI-S score (−0.44, 95% CI: −0.83 to −0.06, I2 = 71%), only EPA was superior to placebo in subgroup analysis. Overall, a moderate antidepressant effect was observed for mitochondrial modulators compared with placebo in the treatment of bipolar depression. The small number of studies, diversity of agents, and small sample sizes limited interpretation of the current analysis.

Adaptation and validation of the Korean Version of the Bipolar Depression Rating Scale (K-BDRS)

2016 ◽  
Vol 33 (S1) ◽  
pp. s236-s237
Author(s):  
W.M. Bahk ◽  
M.D. Kim ◽  
Y.E. Jung ◽  
Y.S. Woo ◽  
J. Lee ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Depressive Symptoms ◽  
Psychometric Properties ◽  
Rating Scale ◽  
Bipolar Depression ◽  
Depression Scale ◽  
Reliability And Validity ◽  
Hamilton Depression Scale ◽  
Young Mania ◽  
Korean Version

ObjectivesThe Bipolar Depression Rating Scale (BDRS) is a scale for assessment of the clinical characteristics of bipolar depression. The primary aims of this study were to describe the development of the Korean version of the BDRS (K-BDRS) and to establish more firmly its psychometric properties in terms of reliability and validity.MethodsThe study included 141 patients (62 male and 79 female) who had been diagnosed with bipolar disorder, were currently experiencing symptoms of depression, and were interviewed using the K-BDRS. Other measures included the Montgomery and Asberg Depression Scale (MADRS), the 17-item Hamilton Depression Scale (HAMD), and the Young Mania Rating Scale (YMRS). Additionally, the internal consistency, concurrent validity, inter-rater reliability, and test-retest reliability of the K-BDRS were evaluated.ResultsThe Cronbach's α-coefficient for the K-BDRS was 0.866, the K-BDRS exhibited strong correlations with the HAMD (r = 0.788) and MADRS (r = 0.877), and the mixed symptoms score of the K-BDRS was significantly correlated with the YMRS (r = 0.611). An exploratory factor analysis revealed three factors that corresponded to psychological depressive symptoms, somatic depressive symptoms, and mixed symptoms.ConclusionsThe present findings suggest that the K-BDRS has good psychometric properties and is a valid and reliable tool for assessing depressive symptoms in patients with bipolar disorder.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Personality Trait Predictive Utility and Stability in Transcranial Magnetic Stimulation (rTMS) for Major Depression: Dissociation of Neuroticism and Self-Criticism

2019 ◽  
Vol 65 (4) ◽  
pp. 264-272 ◽  
Author(s):  
Daniel C. Kopala-Sibley ◽  
Gabrielle B. Chartier ◽  
Shiv Bhanot ◽  
Jaeden Cole ◽  
Peter Y. Chan ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Transcranial Magnetic Stimulation ◽  
Major Depression ◽  
Magnetic Stimulation ◽  
Rating Scale ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Meta Analysis ◽  
Small Sample ◽  
Antidepressant Response ◽  
Critical Patients

Background: Cost-efficient and non-invasive predictors of antidepressant response to repetitive transcranial magnetic stimulation (rTMS) are required. The personality vulnerabilities—neuroticism and self-criticism—are associated with antidepressant outcomes in other modalities; however, self-criticism has not been examined in response to rTMS, and the literature on neuroticism and rTMS is inconsistent. Methods: This naturalistic, 4-week study involved daily dorsolateral prefrontal cortex (DLFPC) rTMS for major depression (15 unipolar, 2 bipolar). Participants completed the Big Five Inventory (neuroticism) and the Depressive Experiences Questionnaire (self-criticism) at baseline and at the end of treatment. Changes in depressive symptoms, as rated by the clinician, were quantified using the 21-item Hamilton Depression Rating Scale. Given the inconsistencies in data regarding the stability of neuroticism in patients receiving rTMS, we performed a systematic review and quantitative meta-analysis of trials examining rTMS and neuroticism. Results: rTMS significantly improved depressive symptoms, and this was predicted by higher levels of self-criticism but not neuroticism. Self-criticism was stable over the 4 weeks of rTMS; however, neuroticism decreased, and this was not related to decreases in depressive symptoms. Our quantitative meta-analysis of 4 rTMS trials in major depression ( n = 52 patients) revealed decreases in neuroticism, with a moderate effect size. Limitations: Our results are limited by a small sample size, and the absence of a sham-rTMS group. Our meta-analysis included only 4 trials. Conclusion: Highly self-critical patients appear to benefit more from rTMS than less self-critical patients. Neuroticism, a conceptually similar but distinct personality domain, does not appear to predict antidepressant response, yet this vulnerability factor for depression decreases after rTMS.

scholarly journals Reduced Plasma Dopamine-β-Hydroxylase Activity Is Associated With the Severity of Bipolar Disorder: A Pilot Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Zuoli Sun ◽  
Qijing Bo ◽  
Zhen Mao ◽  
Feng Li ◽  
Fan He ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Rating Scale ◽  
Bipolar Depression ◽  
Depression Scale ◽  
Hamilton Depression Scale ◽  
Cognitive Assessments ◽  
Young Mania ◽  
Neuropsychological Status ◽  
Patient Health ◽  
Depressive Episodes

Dopamine-β-hydroxylase (DβH) is an enzyme converting dopamine to norepinephrine, a key neurotransmitter in mood disorders, such as major depressive disorder (MDD) and bipolar disorder (BD). Due to overlapping symptomology of unipolar and bipolar depression, the present study attempted to explorer if the plasma DβH activity could discriminate the depressive episodes of BD from MDD. The aim of this study was to compare the plasma DβH activity among MDD patients (n = 104), BD patients (n = 101), and healthy controls (n = 160). Clinical characteristics and cognitive function were assessed using the Young Mania Rating Scale (YMRS), Hamilton Depression Scale (HAM-D), Hamilton Anxiety Scale (HAM-A), Patient Health Questionnaire-9 (PHQ-9), and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Our data showed a lower plasma DβH activity in patients with BD, not MDD, than that in controls. For the BD patients, the plasma DβH activities were negatively correlated with HAM-D scores and HAM-A scores. However, there was no significant correlation between plasma DβH activity and severity of depressive symptoms in MDD patients. No significant correlation between DβH activities and cognitive assessments neither in BD nor in MDD patients. The present study provides evidence that BD is associated with decreased circulating DβH activity.

scholarly journals Prevalence of depression and depressive symptoms among outpatients: a systematic review and meta-analysis

BMJ Open ◽  
2017 ◽  
Vol 7 (8) ◽  
pp. e017173 ◽  
Author(s):  
Jinghui Wang ◽  
Xiaohang Wu ◽  
Weiyi Lai ◽  
Erping Long ◽  
Xiayin Zhang ◽  
...  
Keyword(s):  
Systematic Review ◽  
Depressive Symptoms ◽  
Meta Analysis ◽  
Significant Proportion ◽  
Depression Scale ◽  
Developed Countries ◽  
Self Report ◽  
Cochrane Library ◽  
Significant Heterogeneity ◽  
Prevalence Of Depression

ObjectivesDepression and depressive symptoms are common mental disorders that have a considerable effect on patients’ health-related quality of life and satisfaction with medical care, but the prevalence of these conditions varies substantially between published studies. The aim of this study is to conduct a systematic review and meta-analysis to provide a precise estimate of the prevalence of depression or depressive symptoms among outpatients in different clinical specialties.DesignSystematic review and meta-analysis.Data sources and eligibility criteriaThe PubMed and PsycINFO, EMBASE and Cochrane Library databases were searched to identify observational studies that contained information on the prevalence of depression and depressive symptoms in outpatients. All studies included were published before January 2016. Data characteristics were extracted independently by two investigators. The point prevalence of depression or depressive symptoms was measured using validated self-report questionnaires or structured interviews. Assessments were pooled using a random-effects model. Differences in study-level characteristics were estimated by meta-regression analysis. Heterogeneity was assessed using standard χ2tests and the I2statistic. The study protocol has been registered with PROSPERO under number CRD42017054738.ResultsEighty-three cross-sectional studies involving 41 344 individuals were included in this study. The overall pooled prevalence of depression or depressive symptoms was 27.0% (10 943/41 344 individuals; 95% CI 24.0% to 29.0%), with significant heterogeneity between studies (p<0.0001, τ2=0.3742, I2=96.7%). Notably, a significantly higher prevalence of depression and depressive symptoms was observed in outpatients than in the healthy controls (OR 3.16, 95% CI 2.66 to 3.76, I2=72.0%, χ2=25.33). The highest depression/depressive symptom prevalence estimates occurred in studies of outpatients from otolaryngology clinics (53.0%), followed by dermatology clinics (39.0%) and neurology clinics (35.0%). Subgroup analyses showed that the prevalence of depression and depressive symptoms in different specialties varied from 17.0% to 53.0%. The prevalence of depression and depressive symptoms was higher among outpatients in developing countries than in outpatients from developed countries. Moreover, the prevalence of depression and depressive symptoms in outpatients slightly decreased from 1996 to 2010. Regarding screening instruments, the Beck Depression Inventory led to a higher estimate of the prevalence of depression and depressive symptoms (1316/4702, 36.0%, 95% CI 29.0% to 44.0%, I2=94.8%) than the Hospital Anxiety and Depression Scale (1003/2025, 22.0%, 95% CI 12.0% to 35.0%, I2=96.6%).ConclusionOur study provides evidence that a significant proportion of outpatients experience depression or depressive symptoms, highlighting the importance of developing effective management strategies for the early identification and treatment of these conditions among outpatients in clinical practice. The substantial heterogeneity between studies was not fully explained by the variables examined.

scholarly journals The Relationship Between Reported Pain and Depressive Symptoms Among Adolescents

2018 ◽  
Vol 36 (2) ◽  
pp. 87-93 ◽  
Author(s):  
Sofie Borgman ◽  
Ida Ericsson ◽  
Eva K. Clausson ◽  
Pernilla Garmy
Keyword(s):  
Abdominal Pain ◽  
Back Pain ◽  
Depressive Symptoms ◽  
Depression Scale ◽  
Epidemiological Studies ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Scale Scores ◽  
Prevalence Of Pain ◽  
The Relationship

Pain and depressive symptoms are common reasons for adolescents to contact the school nurse. The aim was to describe the prevalence of pain (headache, abdominal pain, and back pain) and depressive symptoms among adolescents and to examine whether there is an association between pain and depressive symptoms. This cross-sectional survey included students ( N = 639) in Sweden (median age: 16 years). Over half of the female participants (56%) and one third of male participants (33%) had weekly headaches, abdominal pain, or back pain. Almost every second girl (48%) and one in four boys (25%) had depressive symptoms (as measured by the Center for Epidemiological Studies Depression Scale, scores ≥ 16). There was a significant association between having pain (headache, abdominal pain, or back pain) and having depressive symptoms. It is of great importance for school nurses to adequately identify and treat the cause of pain and other factors contributing to depression.

Exploring Clinical Characteristics of Bipolar Depression: Internal Structure of the Bipolar Depression Rating Scale

2009 ◽  
Vol 43 (9) ◽  
pp. 830-837 ◽  
Author(s):  
Jae Seung Chang ◽  
Yong Min Ahn ◽  
Han Young Yu ◽  
Hye Jean Park ◽  
Kyu Young Lee ◽  
...  
Keyword(s):  
Internal Structure ◽  
Rating Scales ◽  
Rating Scale ◽  
Bipolar Depression ◽  
Cluster Structure ◽  
Hierarchical Cluster ◽  
Symptom Cluster ◽  
Extrapyramidal Symptoms ◽  
Young Mania ◽  
Drug Induced

Objective: Due to its pleomorphic phenomenology, the clinical features of bipolar depression are difficult to assess. The objective of the present study was therefore to explore the internal structure of the Bipolar Depression Rating Scale (BDRS) in terms of the phenomenological characteristics of bipolar depression. Methods: Sixty patients with DSM-IV bipolar depression completed the BDRS, depression and excitement subscales of the Positive and Negative Syndrome Scale (PANSS-D and PANSS-E), 17-item Hamilton Depression Rating Scale, Montgomery–Äsberg Depression Rating Scale, Young Mania Rating Scale (YMRS), and the Drug-Induced Extrapyramidal Symptoms Scale. The internal structure of the BDRS was explored through hierarchical cluster analysis (HCA) using Ward's method and multidimensional scaling (MDS). Results: From 20-item BDRS data, the HCA yielded two symptom clusters. The first cluster included 12 items of conventional depressive symptoms. The second cluster included eight items of mixed symptoms. The MDS identified a depressive–mixed dimension. The depressive symptom cluster showed a more cohesive and conglomerate cluster structure on the MDS map compared to the mixed symptom cluster. After controlling for the effects of treatment-emergent extrapyramidal symptoms, strong positive correlations were observed between the BDRS and other depression rating scales, and the BDRS also weakly correlated with the YMRS and the PANSS-E. Conclusions: The internal structure of BDRS appears to be sensitive to complex features of bipolar depression. Hence, the BDRS may have an advantage in evaluating clinical changes in patients with bipolar depression within the therapeutic process.

Recovery and its correlates among patients with bipolar disorder: A study from a tertiary care centre in North India

2016 ◽  
Vol 62 (8) ◽  
pp. 726-736 ◽  
Author(s):  
Sandeep Grover ◽  
Nandita Hazari ◽  
Jitender Aneja ◽  
Subho Chakrabarti ◽  
Sunil Sharma ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Mental Illness ◽  
Depressive Symptoms ◽  
Rating Scale ◽  
Tertiary Care ◽  
North India ◽  
Personal Recovery ◽  
Tertiary Care Centre ◽  
Young Mania ◽  
Level Of Functioning

Background and Aim: The goal of treatment in mental illness has evolved from a symptom-based approach to a personal recovery–based approach. The aim of this study was to evaluate the predictors of personal recovery among patients with bipolar disorder. Methodology: A total of 185 patients with bipolar disorder, currently in remission, were evaluated on Recovery Assessment Scale (RAS), Internalized Stigma of Mental Illness Scale (ISMIS), Brief Religious coping scale (RCOPE), Duke University Religiosity Index (DUREL), Religiousness Measures Scale, Hamilton depression rating scale (HDRS), Young Mania rating scale (YMRS) and Global Assessment of Functioning (GAF) scale. Results: The mean age of the sample was 40.5 (standard deviation (SD), 11.26) years. Majority of the participants were male, married, working, Hindu by religion and belonged to extended/joint families of urban background. In the regression analysis, RAS scores were predicted significantly by discrimination experience, stereotype endorsement and alienation domains of ISMIS, level of functioning as assessed by GAF, residual depressive symptoms as assessed by HDRS and occupational status. The level of variance explained for total RAS score and various RAS domains ranged from 36.2% to 46.9%. Conclusion: This study suggests that personal recovery among patients with bipolar disorder is affected by stigma, level of functioning, residual depressive symptoms and employment status of patients with bipolar disorder.

scholarly journals Effectiveness of Attachment-Based Family Therapy compared to Treatment as Usual for Depressed Adolescents in Community Mental Health Clinics

2021 ◽  
Author(s):  
Luxsiya Waraan ◽  
Erling W. Rognli ◽  
Nikolai Olavi Czajkowski ◽  
Marianne Aalberg ◽  
Lars Mehlum
Keyword(s):  
Mental Health ◽  
Depressive Symptoms ◽  
Family Therapy ◽  
Depression Scale ◽  
Small Sample ◽  
Post Treatment ◽  
Treatment Manual ◽  
Future Research ◽  
Hamilton Depression Scale ◽  
Treatment As Usual

Abstract Background: Major Depressive Disorder (MDD) is a disabling mood disorder, profoundly affecting a large number of adolescent’s quality of life. To date, no obvious treatment of choice for MDD in adolescents is available and progress in the treatment of depressed adolescents will have important public health implications. Attachment-Based Family Therapy (ABFT), as the only empirically supported family therapy model designed to treat adolescent depression, aims to repair interpersonal ruptures and rebuild an emotionally protective parent-child relationship. Objective: To study the effectiveness of ABFT compared with treatment as usual (TAU) delivered within child- and adolescent mental health services (CAMHS) to adolescents with MDD.Method: Sixty adolescents (86.7% girls), aged 13-18 years (M = 14.9, SD = 1.35), with MDD referred to two CAMHS were randomized to 16 weeks of ABFT or TAU. ABFT consisted of weekly therapy sessions (family/individual or both) according to the treatment manual. TAU was not monitored. Primary outcomes were assessed by blinded evaluators at baseline and post-treatment with the Hamilton Depression Scale (HAMD). Self-reported (Beck Depression Inventory-II, BDI-II) depressive symptoms were assessed at baseline, and after 4, 6, 8, 10,12, 14, and 16 weeks. Analyses were performed according to intent-to-treat principles. Results: At post-treatment, clinician-rated remission rates on the HAMD (5 % in ABFT and 3.33% in TAU, p =1, OR=1.54, Fisher’s exact test) and self-reported symptoms of depression on the BDI-II did not differ significantly between groups (X2[2, N = 60] =0.06 , p = 0.97). In both treatment groups participants reported significantly reduced depressive symptoms, but the majority (63.3 %) of adolescents were still in the clinical range after 16 weeks of treatment. Conclusion: ABFT was not superior to TAU. Remission and response rates were low in both groups, suggesting none of the treatments were effective in treating MDD in adolescents. Findings must be viewed in the context of the study’s small sample size, missing data, and implementation challenges. Continued efforts to improve treatment for MDD in outpatient clinics are warranted . Future research should examine moderators of and mechanisms for individual differences to treatment response, as well as the feasibility and cost-effectiveness of implementing treatment models which may require extensive training and expertise to yield clinically meaningful improvements in non-research settings. Trial Registration: Clinicaltrials.gov identifier: NCT01830088 https://clinicaltrials.gov/ct2/show/NCT01830088?term=Villab%C3%B8&draw=2&rank=1 Date of registration: April 12, 2013

scholarly journals Post-Stroke Psychiatric and Cognitive Symptoms in West Asia, South Asia and Africa: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 10 (16) ◽  
pp. 3655
Author(s):  
Sangeetha Mahadevan ◽  
Moon Fai Chan ◽  
Marzieh Moghadas ◽  
Maithili Shetty ◽  
David T. Burke ◽  
...  
Keyword(s):  
Systematic Review ◽  
South Asia ◽  
Rating Scale ◽  
Meta Analysis ◽  
Grey Literature ◽  
Depression Scale ◽  
Stroke Survivors ◽  
Cognitive Symptoms ◽  
Post Stroke ◽  
Pooled Prevalence

Recent research has shown that the prevalence of stroke incidents and the number of survivors in developing countries surpass those from developed countries. This study aimed to enumerate the prevalence of post-stroke psychiatric and cognitive symptoms among stroke survivors from West and South Asia and Africa through a systematic review and meta-analysis. Data from each country was systematically acquired from five major databases (PsycINFO, Web of Science, Scopus, PubMed/Medline, and Google Scholar (for any missing articles and grey literature)). Meta-analytic techniques were then used to estimate the prevalence of various post-stoke psychiatric and cognitive symptoms. A total of 36 articles were accrued from 11 countries, of which 25 were evaluated as part of the meta-analysis. The pooled prevalence of post-stroke depression as per the Hospital Anxiety and Depression Scale (HADS), Hamilton Depression Rating Scale, Patient Health Questionnaire, Schedules for Clinical Assessment in Neuropsychiatry (SCAN), Geriatric Depression Scale, and the Montgomery–Asberg Depression Rating Scale ranged from 28.00 to 50.24%. Pooled prevalence of post-stroke anxiety based on the HADS and SCAN was 44.19% and 10.96%, respectively. The pooled prevalence of post-stroke cognitive impairment as per the Mini-Mental Status Examination was 16.76%. This present review has suggested that both psychiatric and cognitive symptoms are common among stroke survivors. Concerted efforts are needed to institute robust studies using culturally sensitive measures to contemplate mechanisms that address the unmet needs of this vulnerable population.

scholarly journals Prevalence and Influencing Factors of Anxiety and Depression Symptoms Amongst Surgical Nurses During COVID-19 Pandemic: A Large-Scale Cross-Sectional Study

2020 ◽  
Author(s):  
Chun-Xia Ren ◽  
De-Cun Zhou ◽  
Yin-Guang Fan ◽  
Bao-Zhu Li ◽  
Wan-Fei Zhang ◽  
...  
Keyword(s):  
Social Support ◽  
Depressive Symptoms ◽  
Influencing Factors ◽  
Rating Scale ◽  
Depression Scale ◽  
Anxiety And Depression ◽  
Depression Symptoms ◽  
Cross Sectional ◽  
Self Rating ◽  
Surgical Nurses

Abstract BackgroundThe outbreak of novel 2019 coronavirus disease (COVID-19) has imposed an enormous physical and psychological pressure on people across the world. This study focused on evaluating the prevalence and influencing factors of anxiety and depression symptoms in surgical nurses during the epidemic in China. MethodA cross-sectional, multicenter quantitative study was conducted in Anhui province (China) from March 3, 2020 to March 19, 2020, with a questionnaire package which consisted of general information questionnaire，Zung's self-rating anxiety scale (SAS), Zung's self-rating Depression Scale (SDS) and social support rating scale (SSRS). A total of 3600 surgical nurses participated in the survey by Wechat and QQ. Data were analysed using multiple linear regression models. ResultsA total of 3492 surgical nurses from 12tertiary hospitals and 12 secondary hospitals in one province of mainland China completed the survey. The prevalence rates of anxiety symptoms and depressive symptoms were 24.83% and 22.39%, respectively. The average level of anxiety and depression of surgical nurses were higher than that of the Chinese norm (P< 0.05).Levels of social support for surgical nurses were significantly negatively associated with the degree of anxiety (r = -0.630, P < 0.001) and depression (r = -0.578, P < 0.001). Fertility status (β = 1.469, P = 0.003), hospital (β = -0.611, P < 0.001), participation in care for COVID-19 patients (β = 2.229, P < 0.001), likelihood of being infected with COVID-19 (β = 1.146, P < 0.001), social support (β = -0.623, P < 0.001) were significantly influencing surgical nurses’ anxiety degree. Similarly, these characteristics were significantly associated with the odds of experiencing depression symptoms in surgical nurses. Divorce and widowed surgical nurses (β = -2.654, P < 0.001) were significantly more likely to experience depressive symptoms than single nurses. ConclusionIn this survey, we found that the surgical nurses had high anxiety and depression symptoms during the COVID-19 outbreak in China. The findings suggest that targeted psychological interventions to promote the mental health of surgical nurses with psychological problems need to be immediately implemented.

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