Synthesis, antiplasmodial activity and in silico molecular docking study of pinocembrin and its analogs.

BACKGROUND: Malaria remains the major health problem responsible for many mortality and morbidity in developing countries. Because of the development of resistance by Plasmodium species, searching effective antimalarial agents becomes increasingly important. Pinocembrin is a flavanone previously isolated as the most active antiplasmodial compound from the leaves of Dodonaea angustifolia. For a better understanding of the antiplasmodial activity, the synthesis of pinocembrin and a great number of analogs was undertaken. METHODS: Chalcones 5a-r were synthesized via Claisen-Schmidt condensation using 2,4-dibenzyloxy-6-hydroxyacetophenone and aromatic aldehydes as substrates under basic conditions. Cyclization of compounds 5a-r to the corresponding dibenzylated pinocembrin analogs 6a-r was achieved using NaOAc in EtOH under reflux. Catalytic hydrogenation using 10% Pd/C as catalyst in an H-Cube Pro was used for debenzylation to deliver 7a-l. The structures of the synthesized compounds were characterized using various physical and spectroscopic methods, including mp, UV, IR, NMR, MS and HRMS. The synthesized dibenzylated flavanones 6a-d, 6i and 7a were evaluated for their in vivo antiplasmodial activities against Plasmodium berghei infected mice. Molecular docking simulation and drug likeness properties of compounds 7a-l were assessed using AutoDock Vina and SwissADME, respectively. RESULTS: A series of chalcones 5a-r has been synthesized in yields ranging from 46 to 98%. Treatment of the chalcones 5a-r with NaOAc refluxing in EtOH afforded the dibenzylated pinocembrin analogs 6a-r with yields up to 54%. Deprotection of the dibenzylated pinocembrin analogs delivered the products 7a-l in yields ranging from 78 to 94%. The dibenzylated analogs of pinocembrin displayed percent inhibition of parastaemia in the range between 17.4 and 87.2% at 30 mg/kg body weight. The parastaemia inhibition of 87.2 and 55.6% was obtained on treatment of the infected mice with pinocembrin (7a) and 4'-chloro-5,7-dibenzylpinocembrin (6e), respectively. The mean survival times of those infected mice treated with these two compounds were beyond 14 days indicating that the samples suppressed P. berghei and reduced the overall pathogenic effect of the parasite. The molecular docking analysis of the chloro derivatives of pinocembrin revealed that compounds 7a-l show docking affinities ranging from - 8.1 to - 8.4 kcal/mol while it was -7.2 kcal/mol for chloroquine. CONCLUSION: Pinocembrin (7a) and 4'-chloro-5,7-dibenzyloxyflavanone (6e) displayed good antiplasmodial activity. The in silico docking simulation against P. falciparum dihydrofolate reductase-thymidylate synthase revealed that pinocembrin (7a) and its chloro analogs 7a-l showed better binding affinity compared with chloroquine that was used as a standard drug. This is in agreement with the drug-like properties of compounds 7a-l which fulfill Lipinski's rule of five with zero violations. Therefore, pinocembrin and its chloro analogs could serve as lead compounds for further antiplasmodial drug development.

Misdiagnosis, detection rate, and associated factors of severe psychiatric disorders in specialized psychiatry centers in Ethiopia.

BACKGROUND: There are limited studies on the prevalence of misdiagnosis as well as detection rates of severe psychiatric disorders in specialized and non-specialized healthcare settings. To the best of our knowledge, this is the first study to determine the prevalence of misdiagnosis and detection rates of severe psychiatric disorders including schizophrenia, schizoaffective, bipolar, and depressive disorders in a specialized psychiatric setting. METHOD: In this cross-sectional study, a random sample of 309 patients with severe psychiatric disorders was selected by systematic sampling technique. Severe psychiatric disorders were assessed using the Structured Clinical Interview for DSM-IV (SCID). The potential determinates of misdiagnosis were explored using univariable and multivariable logistic regression models, adjusting for the potential confounding factors. RESULT: This study revealed that more than a third of patients with severe psychiatric disorders were misdiagnosed (39.16%). The commonly misdiagnosed disorder was found to be a schizoaffective disorder (75%) followed by major depressive disorder (54.72%), schizophrenia (23.71%), and bipolar disorder (17.78%). Among the patients detected with the interview by SCID criteria, the highest level of the correct diagnosis was recorded in the medical record for schizophrenia (76.29%) followed by bipolar (72.22%), depressive (42.40%), and schizoaffective (25%) disorders with detection rate (sensitivity) of 0.76 (95% CI 0.69-0.84), 0.42 (95% CI 0.32-0.53), 0.72 (95% CI 0.60-0.84), and 0.25 (95% CI 0.09-0.41), respectively for schizophrenia, depressive, bipolar, and schizoaffective disorders. Patients with bipolar disorder were more likely to be misdiagnosed as having schizophrenia (60%), whereas schizophrenic patients were more likely to be misdiagnosed as having bipolar disorder (56.25%) and patients with depressive disorders were more likely to be misdiagnosed as having schizophrenia (54.72%). Having a diagnosis of schizoaffective and depressive disorders, as well as suicidal ideation, was found to be significant predictors of misdiagnosis. CONCLUSION: This study showed that roughly four out of ten patients with severe psychiatric disorders had been misdiagnosed in a specialized psychiatric setting in Ethiopia. The highest rate of misdiagnosis was observed for schizoaffective disorder (3 out of 4), followed by major depressive disorder (1 out of 2), schizophrenia (1 out of 4), and bipolar disorders (1 in 5). The detection rates were highest for schizophrenia, followed by bipolar, depressive, and schizoaffective disorders. Having a diagnosis of schizoaffective and depressive disorders as well as suicidal ideation was found to be significant predictors of misdiagnosis.

Prevalence and correlates of diagnosed and undiagnosed epilepsy and migraine headache among people with severe psychiatric disorders in Ethiopia.

BACKGROUND: There is a paucity of research on the prevalence of diagnosed as well as undiagnosed neurological disorders with episodic manifestations such as epilepsy and migraine headaches in people with severe psychiatric disorders (SPD). To the best of our knowledge, this is the first study analyzing and comparing the prevalence of diagnosed and undiagnosed chronic neurological disorders with episodic manifestations including epilepsy and migraine headache in people with SPD. METHOD: This quantitative cross-sectional survey was undertaken among 309 patients with SPD selected by a systematic random sampling technique. The Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) was used to confirm SPD among the participants. The International Classification of Headache Disorders (ICHD-3) and International League Against Epilepsy (ILAE) were used to define migraine headache and epilepsy, respectively]. Risk factors for chronic neurologic disorders were explored by using logistic regression models. RESULT: In this study, the prevalence of overall neurological disorders, epilepsy, and migraine headache among people with SPD were found to be 5.2% (95%CI 3.2-8.3), 1.6% (95%CI 0.7-3.9), and 3.9% (95%CI 2.2-6.7), respectively. We found that a considerably higher proportion of people with SPD had undiagnosed overall neurological disorder (87.5%; 14/16), epilepsy (60%; 3/5), as well as migraine headaches (100%; 12/12). On the other hand, in this study, 12.5%, 40%, and 0% of patients with overall neurologic disorder, epilepsy, and migraine headaches respectively were diagnosed by the professionals. Higher disability score (WHODAS score) was associated with increased odds of having neurological disorders compared with the lower WHODAS score [OR = 1.30 (95% CI 1.02-1.66)]. CONCLUSION: Whilst the prevalence estimates of neurological disorders with episodic manifestations including epilepsy and migraine headache was high among people with SPD, the vast majority of them remained undiagnosed. The diagnosis rates of those disorders were significantly low, perhaps surprisingly zero for migraine headache. High WHODAS score was associated with increased odds of having neurological disorders. Routine screening and management of epilepsy and migraine headache are imperative among people with SPD.

Food insecurity and the risk of depression in people living with HIV/AIDS: a systematic review and meta-analysis.

BACKGROUND: The link between food insecurity and depression in people living with HIV/AIDS (PLWHA) has been explored in numerous studies; however, the existing evidence is inconclusive due to inconsistent results. Therefore, the objective of this systematic review and meta-analysis is to examine the relationship between food insecurity and depression in PLWHA. METHODS: We systematically searched PubMed, EMBASE, and Scopus to identify relevant studies. A random-effect model was used for conducting the meta-analysis. We assessed the risk of publication bias by funnel plot and Egger's regression asymmetry test. RESULTS: In this review, seven studies were included in the final analysis. Our meta-analysis revealed that food insecurity significantly increased the risk of depression in PLWHA [RR 2.28 (95% CI 1.56-3.32)]. This association remained significant after adjusting for the confounding effects of drug use [RR 1.63 (95% CI 1.27-2.10)], social support [RR 2.21 (95% CI 1.18-4.16)] as well as ART drugs [RR 1.96 (95% CI 1.17-3.28)]. Our subgroup and sensitivity confirmed the robustness of the main analysis. CONCLUSION: This systematic review and meta-analysis suggest a significant association between food insecurity and increased risk of depression PLWHA. Therefore, early screening and management of food insecurity in PLWHA seem to be necessary.

A Systematic Review and Meta-Analysis of the Prevalence of Post-Traumatic Stress Disorder among Homeless People.

Post-traumatic stress disorder (PTSD) is common among homeless people and is associated with an increased risk of mortality from suicide, medical causes, and drug-related problems. However, there are no previous systematic review and meta-analysis studies that reported the consolidated magnitude of PTSD among homeless people. A literature search was conducted on PubMed, Embase, and Scopus to discover pertinent studies that determined the prevalence of PTSD among the homeless. Articles were evaluated by titles, abstracts, and full-text. Comprehensive meta-analysis software was used to conduct the meta-analysis. Subgroup and sensitivity analysis were performed and Cochran's Q- and the I2 test were used to assess heterogeneity. The evidence of publication bias was evaluated by using Egger's test and visual inspection of the symmetry in funnel plots. From the total, 19 studies with 20,364 participants across seven countries were included in the final analysis. Our meta-analysis revealed that the pooled prevalence of PTSD among homeless people was 27.38% (95% CI; 21.95-33.57). In our subgroup analysis, we found that the prevalence of PTSD was considerably high as measured by the screening instrument (35.93%) than the diagnostic instrument (23.57% %). The prevalence of PTSD among homeless showed a significant variation by the location of the studies, the instruments used to measure PTSD as well as the quality of the included studies. This review showed that the pooled prevalence estimate of PTSD among homeless peoples was remarkably high (27.38%). Early screening and treatment of PTSD among homeless peoples are warranted to alleviate suffering.

Undiagnosed HIV, hepatitis B, and hepatitis C infections in people with severe psychiatric disorders in Ethiopia.

BACKGROUND: Worldwide, there is limited epidemiologic evidence on the seroprevalence of undiagnosed chronic viral infections including HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) infections among patients with severe psychiatric disorders. To our knowledge, this is the first study to explore and compare undiagnosed seroprevalence rates of HIV, HBV, and HCV infections among patients with severe psychiatric disorders. METHOD: In this study, we included a random sample of 309 patients with severe psychiatric disorders selected by systematic sampling technique. We used a structured clinical interview for DSM-IV (SCID) to confirm the diagnosis of severe psychiatric disorders among the participants. Binary and multivariable logistic regression models, adjusting for the potential confounding factors was used to explore the potential determinants of chronic viral infections. RESULT: The prevalence estimates of HIV infection among patients with severe psychiatric disorders in this study (3.24%) was roughly 3 times the estimated population prevalence of HIV infection in Ethiopia (1.1%). This study showed that the prevalence rates of HBV and HCV infections among patients with severe psychiatric disorders were 4.85 and 1.29%, respectively. Our results also showed that among patients with chronic viral infections, HIV, HBV and HCV, 76.92, 60, 80, and 75% respectively were undiagnosed. Regarding associated factors, the presence of chronic viral infection was found to be significantly associated with the age of the participants (ranging between 30 and 40 years) after adjusting for the possible confounding factors [AOR = 3.95 (95%CI.18-13.17)]. CONCLUSION: Even though the prevalence estimates of HIV (3.24%), HBV (4.85%), and HCV (1.29%) infections were high among patients with severe psychiatric disorders, the majority of them remained undiagnosed. HBV was found to be the commonly undiagnosed infection (4 out of 5) followed by HCV (3 out of 4) and HIV (6 out of 10). The present study provided evidence of a significant association between the age of the participant (between 30 and 40 years) and chronic viral infections in patients with severe psychiatric disorders. Increasing the awareness of psychiatry professionals and early screening, as well as interventions of chronic viral infections among patients with severe psychiatric disorders are imperative.

Perceptions of the causes of schizophrenia and associated factors by the Holy Trinity Theological College students in Ethiopia.

INTRODUCTION: There is a cultural variability around the perception of what causes the syndrome of schizophrenia. As far as the cause of schizophrenia by the general public concerned, people living in western countries focus mainly on biological and social risk factors such as genetic vulnerability, disease of the brain, infection or stressful social conditions or personal weakness, but the predominant views held by people living in non-western countries focus mainly on supernatural and religious factors. Awareness and beliefs about the causes of mental illnesses influence the preferred treatments. The aim of this study was to determine the perceptions regarding the etiology of schizophrenia and the associated factors by theology students. METHODS: An institution-based cross-sectional study was conducted among Holy Trinity Theological College students from May to June 2016. Self-administered Short Explanatory Model Interview was used to assess the perception of what causes the syndrome of schizophrenia. Data entry was performed by Epi-info version 3.5.3 and the Statistical Program for Social Science (SPSS version 20) was used for data clearance, and analyses. RESULTS: A total of 409 students were involved in the survey. The mean age of the participants was 33.3 years (standard deviation ± 8.3) and almost all 94.4% of them were males. The majority (81.7%) of the participant recognized schizophrenia as a mental illness. Only 16.9% of the participants attributed supernatural phenomenon as a cause of schizophrenia and most of them 76.5% (313) thought of psychosocial problems as the cause of schizophrenia. About 40.1% of the participant endorsed biological factors as a cause of schizophrenia. About two-thirds (68.2%) of the participant thought schizophrenia as severe but not fatal illness and about 22.2% of them thought both severe and fatal illness. As far as the course concerned majority (88.5%) of the participants thought schizophrenia as a chronic illness and about 11.5% thought acute illness. Regarding the treatment, almost all (99.8%) of reported schizophrenia is treatable. Moreover, concerning the consequences of the illness about 18.8% reported the death as a consequence and about 66.7, 34.7 and 7.8% reported madness, family disintegration and losing a job, respectively. Urban residency and holding other degree were significantly associated with biological factors as a cause of schizophrenia (p < 0.05). Whereas getting information from mass media and health professional, marital status (married) and urban residence were significantly associated with psychosocial factors as the cause of schizophrenia. Furthermore, rural residency was significantly associated with the supernatural phenomenon as the cause of schizophrenia. CONCLUSION: In the current study, the majority of the participant recognized schizophrenia as a mental illness and a treatable syndrome. A vast majority of the participant thought of psychosocial problems as the cause of schizophrenia about two-thirds of the participant thought schizophrenia as a severe but not fatal illness. As far as the course concerned majority (88.5%) of the participants thought schizophrenia as a chronic illness. Concerning the consequences of the illness, about 18.8% reported the death as a consequence and about 66.7, 34.7, and 7.8% reported madness, family disintegration and losing a job, respectively. Residency, marital status, and source of information were significantly associated with perceived causes of schizophrenia. Linking mental health service with spiritual care to address community mental health care needs and for early detection as well as referral linkage of mentally ill patients is warranted.

A systematic review and meta-analysis of epidemiology of depression in people living with HIV in east Africa.

BACKGROUND: Depression is the most prevalent psychiatric disorder among people living with HIV (PLWHIV) and is associated with poor quality of life, additional comorbidities, disability, unemployment, poorer therapeutic outcomes and risky behaviors. The present systematic review and meta-analysis aims to systematically summarize empirical evidence and to formulate recommendations for future research. METHODS: We searched PubMed, EMBASE, SCOPUS, and relevant literature for possible studies to include. A qualitative and quantitative analysis was undertaken for this systematic review. Subgroup and sensitivity analysis were performed. Cochran's Q- and the I2 test were used to assess heterogeneity. The presence of publication bias was evaluated by using Egger's test and visual inspection of the symmetry in funnel plots. RESULTS: Of 283 titles initially identified, 81 abstracts were eligible for review. Of these, 46 articles qualified for full text review and 19 were retained. In our meta-analysis the pooled prevalence of depression in PLWHIV was 38% (95% CI 29.30-47.54). The pooled prevalence estimates of depression was 49.79% in Ethiopia and 30.88% in Uganda. In addition, the prevalence of depression was 12.40% and 46% as measured by diagnostic and screening instrument respectively. Our qualitative synthesis showed that factors such as having opportunistic infection, perceived stigma, negative life event, WHO clinical staging of disease, hospitalization in the past one month, stressful life events, food insecurity, self-efficacy, missed frequency of clinic visit, frequency of follow-up, older age, low income, urban residence and being government employee were strongly and significantly associated with depression in PLWHIV in east Africa. CONCLUSION: The pooled prevalence estimates of prevalence of depression in PLWHIV was 38%. The prevalence estimates of depression in PLWHIV in Ethiopia was significantly higher than Uganda. In addition the prevalence of depression was significantly higher in studies conducted by screening than diagnostic instrument. Routine screening and integrated management of depression into the existing HIV care services is warranted. Validation and use of standard instrument to assess depression in PLWHIV is needed. Moreover, longitudinal and community based studies focusing on incidence and determinates of depression in PLWHIV are recommended.

Mental, neurologic, and substance use (MNS) disorders among street homeless people in Ethiopia.

BACKGROUND: About 25-60% of the homeless population is reported to have some form of mental disorder. To our knowledge, there are no studies aimed at the screening, diagnosis, treatment, care, rehabilitation, and support of homeless people with mental, neurologic, and substance use (MNS) disorders in general in Ethiopia. This is the first study of its kind in Africa which was aimed at screening, diagnosis, care, treatment, rehabilitation, and support of homeless individuals with possible MNS disorder. METHODS: Community-based survey was conducted from January to March 2015. Homeless people who had overt and observable psychopathology and positive for screening instruments (SRQ20, ASSIST, and PSQ) were involved in the survey and further assessed for possible diagnosis by structured clinical interview for DSM-IV diagnoses and international diagnostic criteria for seizure disorders for possible involvement in care, treatment, rehabilitation services, support, and training. The Statistical Program for Social Science (SPSS version 20) was used for data entry, clearance, and analyses. RESULTS: A total of 456 homeless people were involved in the survey. Majority of the participants were male (n = 402; 88.16%). Most of the homeless participants had migrated into Addis Ababa from elsewhere in Ethiopia and Eritrea (62.50%). Mental, neurologic, and substance use disorders resulted to be common problems in the study participants (92.11%; n = 420). Most of the participants with mental, neurologic, and substance use disorders (85.29%; n = 354) had psychotic disorders. Most of those with psychosis had schizophrenia (77.40%; n = 274). Almost all of the participants had a history of substance use (93.20%; n = 425) and about one in ten individuals had substance use disorders (10.54%; n = 48). Most of the participants with substance use disorder had comorbid other mental and neurologic disorders (83.33%; n = 40). CONCLUSION AND RECOMMENDATION: Mental, neurologic, and substance use disorders are common (92.11%) among street homeless people in Ethiopia. The development of centers for care, treatment, rehabilitation, and support of homeless people with mental, neurologic, and substance use disorders is warranted. In addition, it is necessary to improve the accessibility of mental health services and promote better integration between mental and primary health care services, as a means to offer a better general care and to possibly prevent homelessness among mentally ill.

Correction to: Mental health training for primary health care workers and implication for success of integration of mental health into primary care: evaluation of effect on knowledge, attitude and practices (KAP).

[This corrects the article DOI: 10.1186/s13033-017-0169-8.].

Mental health training for primary health care workers and implication for success of integration of mental health into primary care: evaluation of effect on knowledge, attitude and practices (KAP).

BACKGROUND: Mental disorders are always remained a neglected public health problems in low and middle-income countries (LMICs), most people with mental disorders never receive effective care and there is a large treatment gap. In order to solve the problem integration of mental health into primary health care is recommended and in Ethiopia implementation of the scale of mental health services at primary health care level was started in 2014. For the success of the integration of mental health into primary health care, primary care health professionals are the key personnel who are responsible for the management of mental, neurologic and substance use disorders. However, proper training and education of primary care health professionals is mandatory for an optimal performance and success of integration. This interventional study was conducted to assess the effectiveness of mental health training course for scale up of mental health services at primary health care level in Ethiopia. METHODS: This quasi-experimental pre- and post-study design was conducted in Ethiopia from October to December 2016 using quantitative data collection methods. A total of 94 primary health care professionals were included in the study. The intervention was conducted by psychiatry professionals using standardized World Health Organization (WHO) Mental Health Gap Action Programme (mhGAP) guide prepared for scaling up of mental health care through integration into primary health care (PHC) and general medical services. Pre- and post intervention assessment was done for knowledge, attitude and practice (KAP); and statistically analyzed. A paired sample t test with p values was performed to test the differences between the pre- and post-test. In additions mean and standard deviation of the responses were calculated. Overall the response rate was 100% at the end of the intervention. RESULTS: The study resulted in a significant improvement in knowledge, attitude and practice (KAP) of PHC workers about all the four mental, neurologic and substance use disorders during the post intervention survey (p < 0.05). Post intervention the knowledge of health professionals increased by 53.19% for psychosis, 42.56% for depression, 19.25% for epilepsy and 54.22% for alcohol use disorders. Similarly, post intervention attitude increased by 55.32% for psychosis, 40.42% for depression, 36.17% for epilepsy and 43.6% for alcohol use disorders. In addition, post intervention case identification rate increased by 62.78% for psychosis, 55.46% for depression, 21.35% for epilepsy and 41.49% for alcohol use disorders with significant p value (p < 0.05). CONCLUSIONS: The study results suggest that mental health training could be an effective intervention for improving knowledge, attitudes, and practices among primary health care professionals regarding mental, neurologic and substance use disorders. Training is a prerequisite and vital to enhance the knowledge, attitude, and practice of primary care professionals which plays a significant role for the easy success of integrated care and treatment of mental, neurologic and substance use disorders into the existing general health care services.