One-Year Outcomes for Depression and Anxiety in SLE Patients.

Neuropsychiatric Systemic Lupus Erythematosus (NPSLE) is a severe form of SLE involving the nervous system, resulting in neurological and psychiatric symptoms. Although research has shown that SLE patients often suffer from cognitive impairments, depression, and anxiety, there are no specialized guidelines for psychiatric assessment and treatment. This study aimed to investigate the progression of neuropsychiatric symptoms in SLE patients, explicitly focusing on anxiety and depression, over a year. It also aimed to identify potential biomarkers linked to NPSLE and explore the connection between NPSLE and the overall progression of SLE. Our research involved a longitudinal study with 65 adults diagnosed with SLE. Participants underwent various physical, biochemical, and serological tests and were assessed using disease activity indexes like BILAG-2004 and SLEDAI-2K. Participants also underwent psychological assessments using the Hamilton Anxiety and Depression Rating Scales. The study did not find any significant impact of antidepressant therapy on the evolution of anxiety and depression among participants. However, medications like Methotrexate and Plaquenil showed a substantial reduction in these symptoms. Moreover, anxiolytic therapy seems to influence depression in SLE patients. The study also noted that anxiety levels tend to increase over time but are not directly associated with SLE activity. This study concludes that although specific SLE medications can affect the level of anxiety and depression, the overall effectiveness of neuropsychiatric therapy in managing these symptoms is limited. The findings suggest that further research into the tailored management of NPSLE symptoms and a deeper understanding of the disease's psychiatric aspects are needed.

Royal Jelly and Fermented Soy Extracts-A Holistic Approach to Menopausal Symptoms That Increase the Quality of Life in Pre- and Post-menopausal Women: An Observational Study.

BACKGROUND: The objective of this study was to determine the effects of royal jelly and fermented soy extracts on menopausal symptoms and on quality of life in pre- and post-menopausal women. MATERIALS AND METHOD: This prospective observational study was carried out in a Clinical Hospital of Brasov, Romania, during June 2020 and December 2021. Eighty pre- and post-menopausal women, aged between 45 and 60 years, were included in two groups. The first group (40 women) received a dietary supplement with fermented soy extract twice a day for eight weeks and the second group (40 women) received the same dietary supplement with fermented soy extracts and 1500 mg of royal jelly capsules for eight weeks. After the treatment, the MENQOL score, DASS-21 score, and the mean number and intensity of daily hot flushes were recorded and compared with baseline values. RESULTS: After eight weeks of treatment, the score of the MENQOL questionnaire and all its domains' scores decreased in comparison with the baseline in both groups (p < 0.001). Also, the DASS-21 score (p < 0.001), depression score (p < 0.001), anxiety score (p < 0.001), and stress score (p < 0.001) improved. The mean number and the intensity of hot flushes decreased in both groups (p < 0.001). Comparing these variables after the treatment in both groups, we observed that the women who received dietary supplements with fermented soy extracts and royal jelly capsules recorded better scores for MENQOL (vasomotor, physical, and psychosocial domains) and a more reduced mean number of daily hot flushes. CONCLUSIONS: This observational study suggests that both dietary fermented soy supplements and royal jelly capsules possess beneficial effects against menopausal symptoms, increase the quality of life in pre- and post-menopausal women, and that the effects might be significantly improved if those dietary supplements are administered in association.

Outcome of COVID-19 mRNA Vaccination in Patients Treated With Clozapine WHO Previously Went Through SARS-COV-2 Infection.

BACKGROUND: The outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic had multiple consequences for the health care system, especially for patients with mental illnesses. Schizophrenia patients particularly appear to have a higher risk of complications due to coronavirus-19 (COVID-19). Clozapine remains the gold standard for treatment-resistant schizophrenia (TRS). However, the COVID-19 pandemic had an important negative impact on clozapine treatment, mainly because of its administration protocol, which was very difficult to follow during the restrictions imposed in the pandemic, and its side effects in patients with COVID-19 infection. Vaccination is an effective method of avoiding SARS-CoV-2 infection or its severe complications, especially in susceptible populations. Data on adverse events after vaccination against COVID-19 are limited, both in the general population and in schizophrenia patients. STUDY QUESTION: The study aimed to investigate the safety of COVID-19 vaccination in patients treated with clozapine for hematological parameters. STUDY DESIGN: We conducted an analytical cross-sectional study between July 1, 2021, and June 30, 2022. We compared 2 groups of COVID-19 vaccinated patients who had previously experienced SARS-CoV-2 infection: The first group was treated with clozapine, whereas the second group was treated with other antipsychotics. MEASURES AND OUTCOMES: The primary objective was to identify granulocytopenia, leukocytopenia, and lymphocytopenia. The results were measured after the second dose of the Pfizer-BioNTech vaccine. RESULTS: This study included 100 patients. White blood cell count changes were limited to a few cases of mild granulocytopenia (8.16% in the clozapine group and 3.92% in the nonclozapine group, P = 0.37) with no cases of severe granulocytopenia or agranulocytosis. CONCLUSIONS: As far as leukocyte counts are concerned, mRNA COVID-19 vaccination seems to be safe in patients treated with clozapine who previously had SARS-CoV-2 infection. Leukocyte changes had no clinical implications.

Association between Inflammation and Thrombotic Pathway Link with Pathogenesis of Depression and Anxiety in SLE Patients.

As a complication of systemic lupus erythematosus (SLE), the neuropsychiatric form may manifest with neurological and psychiatric symptoms. Diagnosing neuropsychiatric SLE can be challenging due to the heterogeneity of this disease manifestation and the possibilities of investigation. This research aims to identify the possible associations between inflammation and thrombotic biomarkers alongside anxiety and/or depression manifestations in SLE patients. A group of 65 outpatients were investigated regarding the levels of depression, anxiety, disability, quality of life and other specific serum biomarkers linked with inflammation or coagulopathies. The results showed severe depression in eight participants, moderate depression in 22 (33.85%), and 26 (40%) subjects with mild depression. Anxiety was more prevalent within 64 participants (98.46%), while a degree of disability was reported by 52 participants (80%). Quality of life evaluated by EQ5D revealed a medium value of 1.57, and EQ5D VAS health medium value was 57.95 and was correlated with anxiety. A strong positive correlation between depression, anxiety and antibodies associated with anti-cardiolipin and anti beta2 glycoprotein I antibodies, lupus anticoagulant, ICAM-1, low C4 a and anti-ribosomal P antibodies were identified. These data results suggest that autoimmune/inflammatory and ischemic/thrombotic pathways could contribute to depression and anxiety as neuropsychiatric SLE manifestations.

Benzodiazepines and Mood Stabilizers in Schizophrenia Patients Treated with Oral versus Long-Acting Injectable Antipsychotics-An Observational Study.

Schizophrenia is a chronic, invalidating, and polymorphic disease, characterized by relapses and remission periods. The main treatment option in schizophrenia are antipsychotics, administered as an oral or as a long-acting injectable (LAI) formulation. Although international guidelines rarely recommend it, mood stabilizers (MS) and/or benzodiazepines (BZD) are frequently prescribed as adjunctive therapy in schizophrenia patients for various reasons. This is an observational, cross-sectional study including stabilized schizophrenia patients. A total of 315 patients were enrolled. Of these, 77 patients (24.44%) were stabilized on LAIs and 238 (75.56%) patients on oral antipsychotics (OAP). Eighty-four patients (26.66%) had concomitant treatment with MS and 119 patients (37.77%) had concomitant benzodiazepine treatment. No statistical significance was observed in MS or BZD use between LAIs and OAPs. In total, 136 patients (43.17%) were stabilized on antipsychotic monotherapy. Our study shows that the long-term use of benzodiazepines and mood stabilizers remains elevated among stabilized schizophrenia patients, regardless of the antipsychotic formulation (oral or LAI). Patients receiving second-generation LAI antipsychotics (SGA-LAI) seem to be more likely to be stabilized on monotherapy compared to those receiving oral antipsychotics. Further randomized controlled trials are necessary in order to clarify the benefits of the current drug polypharmacy trends.

Long-Acting Injectable Antipsychotics (LAIs) Prescribing Trends during the COVID-19 Pandemic in Romania.

Long acting injectable antipsychotics (LAIs) are considered the ideal treatment for schizophrenia, especially for young patients with high rates of non-adherence. In the current COVID-19 pandemic, it has been reported that the administration of LAIs decreased in some areas. The aim of this study was to evaluate the impact of COVID-19 pandemic on the initiation of LAIs. This is a retrospective mirror- image study covering a total period of 24 months: 12 months before and 12 months after the declaration of COVID-19 pandemic on March 11, 2020. During the study period, out of 218 patients admitted with schizophrenia, only 15 (1.3%) received LAIs at discharge. There was a 48.3% reduction in LAIs initiation compared to the pre-pandemic period (29 LAIs initiations in 2019 from 224 admissions). Despite the 27% reduction in the total number of admissions (1500 in 2019 vs. 1100 in 2020), the number of admissions with schizophrenia remained almost the same (224 in 2019 vs. 218 in 2020). COVID-19 pandemic brought an important challenge in the treatment of patients with schizophrenia, especially in the initiation of LAIs. This could have an important impact on the relapse rate in the next period.

WHODAS Assessment Feasibility and Mental Health Impact on Functional Disability in Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE), besides rheumatological dysfunction, manifests in neuropsychiatric disorders like depression and anxiety. Mental health illnesses in SLE patients have a high prevalence and a profound impact on quality of life, generating an increased disability and premature mortality. This study aimed to establish the degree of disability in patients with SLE and the impact of depression and anxiety on patients' functioning. Additionally, the study aimed to verify whether World Health Organization-Disability Assessment Schedule (WHODAS) 2.0 is suitable for the evaluation of patients with SLE associating depression and/or anxiety symptoms. Cross-sectional research was performed, including adult patients, diagnosed with SLE. To evaluate depression, anxiety, and functioning, approved questionnaires Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale, and, World Health Organization-Disability Assessment Schedule (WHODAS) were applied. Confirmatory factor analysis was performed on WHODAS subscales. Sixty-two patients were included in the research, with a mean of SLE diagnosis of 12.48 years; 53 patients (85%) had depression (p < 0.001). Anxiety was found in 38 patients (61.29%, p < 0.05). WHODAS assessment results depicted that 39 patients (62.90%, p < 0.05) manifested disability, from which 26 (66.66%, p < 0.05) presented moderate and severe disability. A strong correlation between the severity of anxiety and the degree of disability (r > 0.6, p < 0.001) was found. The WHODAS scale assessment proved to be a valuable tool for SLE patient's functioning assessment. This study suggests that depression and anxiety negatively impact WHODAS disability scores, decreasing the quality of life in SLE patients.

Neutropenia in Patients With Clozapine-Treated Schizophrenia: An Effect of Clozapine or a Consequence of SARS-CoV-2 Infection? A Systematic Review.

BACKGROUND: Clozapine is the only approved antipsychotic for treatment-resistant schizophrenia. Despite its therapeutic benefits, it is still widely underused, mainly because of its potential to cause agranulocytosis and neutropenia. Prescribing clozapine in COVID-19-positive patients became more challenging because of this potential side effect. This article is a review of literature on the risk of neutropenia associated with clozapine treatment in patients with COVID-19. AREAS OF UNCERTAINTY: In clozapine-treated COVID-19-positive patients, neutropenia was reported in some cases; is it a consequence of clozapine treatment or of SARS-Co2 infection? DATA SOURCES: Data were extracted from 2 databases: PubMed/MEDLINE and Google Scholar. We selected all original reports, from March 2020 until May 2022, on neutropenia associated with clozapine treatment in positive COVID-19 patients. Eleven studies were selected for the final analysis. THERAPEUTIC ADVANCES: Before the COVID-19 pandemic, neutropenia in clozapine-treated patients was reported in 3.8% of cases. During the pandemic, neutropenia rates seemed to be higher. As per the cause of neutropenia, studies reported contradictory results. We aim to clarify rates and causes of neutropenia in clozapine-treated COVID-19-positive patients. RESULTS: Three hundred eighty-eight articles were initially selected from the 2 databases. After excluding duplicates, unrelated articles, reviews, and guidelines, 11 studies were analyzed, all centered on clozapine treatment, COVID-19 infection, and associated neutropenia. CONCLUSIONS: Clozapine treatment in COVID-19-positive patients may be associated with a transient reduction of absolute neutrophils count, in some cases reaching neutropenia levels. Neutropenia rates reported in SARS-CoV-2-infected patients are higher than the prepandemic reports; therefore, we assume that the cause might be a result of the immunological interference between clozapine and SARS-CoV-2. Clozapine treatment needs to be continued whenever possible, with dose adjustments in relation to blood test results.

Clozapine and Neutropenia in Patients with Schizophrenia and SARS-CoV-2 Infection.

Background: Clozapine (CLZ) is used for treatment-resistant schizophrenia (TRS). Adverse reactions to clozapine include neutropenia. In March 2020, WHO declared the COVID-19 pandemic and after, psychiatrists raised concerns regarding continuation of clozapine, due to multiple restrictions. We aimed to provide a study on the association between neutropenia and clozapine in patients with schizophrenia and COVID-19. Aim: To assess the neutrophil count in patients with schizophrenia treated with clozapine and infected with COVID-19. Methods: The study patients with schizophrenia, according to DSM-5, admitted to the Clinical Hospital of Psychiatry and Neurology Brasov, Romania, between April 2020 and October 2021. The inclusion criteria included positive RT-PCR (real-time PCR) test for COVID-19 and treatment with clozapine. We assessed three values of ANC (absolute neutrophil count): before COVID-19 infection (last ANC obtained at mandatory check), during infection and 1 month after resolution (first negative PCR test). Results: Of the 105 cases, 95 did not have neutropenia. Fifty-nine patients were males (62.1%), mean age was 43.5 years (SD = 12.1) with an average of clozapine treatment of 52.4 months (SD = 11.9). At baseline, they had a small reduction in the ANC mean value (4.41 × 109/l; SD = 2.22) which did not constitute a statistically significant decline from the prior to COVID-19 mean value of 4.66 × 109/l (SD = 2.34; p = 0.45). Values were also normal in the first month after negative PCR testing (4.45 × 109/l; SD = 2.35; p = 0.91). A total of 10 patients (9.5%) had neutropenia. The age, dose of clozapine and duration of treatment were not statistically different compared to the group without neutropenia. Conclusion: Psychiatrists and other health professionals should keep in mind that neutrophil count may decrease during COVID-19 infection in patients taking clozapine and in some cases, neutropenia may even occur. We assumed that neutropenia could be caused by COVID-19 and clozapine interaction.

Switch from Olanzapine Long-Acting Injectable to its Oral Equivalent during COVID-19 Pandemic: a Real World Observational Study.

Schizophrenia is a psychiatric condition with chronic evolution, one of the most disabling diseases. The main cause for the disease's progression is considered to be the lack of compliance with the treatment. Long-acting injectable antipsychotics (LAIs) are an important treatment option for patients with schizophrenia. Olanzapine long-acting injection (OLZ-LAI) is a pamoate monohydrate salt of olanzapine that is administered by deep intramuscular gluteal injection. The aim of this paper is to report the effects of a sudden and unplanned switch from olanzapine long-acting injectable to oral olanzapine in remitted patients with schizophrenia due to restrictions caused by the COVID-19 pandemic. An observational study conducted in the Clinical Hospital of Psychiatry and Neurology of Brasov, Romania between April 2020 and March 2021. 27 patients with OLZ-LAI were entered into the study. Of 27 cases, 21 patients preferred to be switched to oral olanzapine (77.77%). Only 6 patients continued with the long-acting formulation. The main reason for the initiation of olanzapine pamoate in all the patients was non-adherence to oral medication (80.95%), and the mean age of starting LAI olanzapine was 36.42 years (SD ± 10.09). Within the following 12 months after switching from olanzapine LAI to OA, 15 patients (71.42%) relapsed, and 12 were admitted to the emergency psychiatric unit. The COVID-19 pandemic has brought multiple disservices to current medical practice. Sudden and unplanned switch from olanzapine long-acting formulation to oral olanzapine was followed by the high rate of relapse in remitted schizophrenia.

Rating Opportunity for Long-Acting Injectable Antipsychotic Initiation Index (ROLIN).

Background: Schizophrenia is a severe psychiatric condition with devastating consequences for the individual's functionality and leading to severe disability. Lack of insight and non-adherence to treatment remain the most important factors in the progression of the disease to chronicity. Despite their proven effectiveness in preventing relapses, reducing morbidity and mortality, long-acting injectable antipsychotics (LAIs) are still underused. One of the causes invoked is the lack of guidelines or protocols for initiating LAIs. Objective: The aim of this article is to present Rating Opportunity for Long-Acting Injectable Antipsychotic Initiation Index (ROLIN), a clinician-rated index that rates the important factors of the disorder across seven items: age, duration of illness, relapses, antipsychotic treatment response, family support, antipsychotic existing formulation and adherence. Method: A retrospective study in which all patients with schizophrenia discharged on oral antipsychotics without LAIs treatment lifetime were evaluated with ROLIN for opportunity for LAIs initiation. Results: Of 225 consecutive patients, 126 patients (56%) had a strong indication for initiating LAI (score between 25 and 35). Kolmogorov-Smirnov test was used for checking the normal distribution of values (95% CI for the mean = 9.5781 to 20.4219; 95% CI for the median = 6.5920 to 24.8161; SD = 9.7907; Coefficient of Skewness = 0.0743; Coefficient of Kurtosis = -1.1377). Conclusion: This paper proposed an instrument designed to improve treatment in schizophrenia using a simple conceptual model which integrates important predictors of good or poor outcomes.

Inflammatory Response in SARS-CoV-2 Infection of Patients with Schizophrenia and Long-Term Antipsychotic Treatment.

BACKGROUND: Schizophrenia patients are a population at particular risk of poor outcomes in COVID-19 infection. They have multiple comorbidities that have been identified as risk factors for severe COVID-19: diabetes, hypertension, chronic obstructive respiratory disease, and end-stage renal disease. AIM: The aim of this research was to evaluate the inflammatory response and in-hospital mortality in schizophrenia patients compared to a control group without mental illness. METHODS: A total of 101 consecutive individuals with schizophrenia tested positive for COVID-19 was compared with 101 individuals without schizophrenia admitted in the same hospital. The number of severe cases and the number of deaths caused by SARS-CoV-2 were evaluated between April 2020 and April 2021. RESULTS: There were no deaths in the group of patients with schizophrenia. Although the group had a higher number of cases with pulmonary and metabolic comorbidities, in the group with SCZ there were fewer severe cases compared to the control group. The values of some markers of inflammation (CRP and fibrinogen) were significantly lower in SCZ patients. The duration from infection to diagnosis and the start of symptomatic treatment was shorter for the group with SCZ (4.2±3.2 vs 5.3±4.6, p < 0.05). CONCLUSION: The main findings of the study were that vulnerable schizophrenia individuals on antipsychotic treatment showed a lower risk of SARS-CoV-2 severe infection and a likely better COVID-19 prognosis in a protective environment. Rapid access to specialists in case of need are factors that have determined the favorable evolution in a group considered high risk. It could be speculated that antipsychotics could play an important role in preventing SARS-CoV-2 severe manifestation and may exert protective effects against detrimental courses of COVID-19.

Clozapine Efficacy in a Case of Severe Treatment-Resistant Postpartum Psychosis.

BACKGROUND: The postpartum period is a difficult time for mother and family. Unfortunately, in some cases, two psychiatric complications may occur: postpartum psychoses (PPP) with a prevalence of 0.2% and a very low incidence of 0.25-0.50 per 1000 deliveries, and post-natal depressions with an incidence of 10 to 20% per 1000 deliveries. The onset of postpartum psychosis is in the first 4 weeks after childbirth with symptoms such as emotional lability, cognitive disorganization, delusional beliefs and hallucinations. It requires hospitalization due to the high risk of suicide and infanticide. The studies reveal that the treatment can include FGAs (first-generation antipsychotics), such as haloperidol, and SGAs (second-generation antipsychotics), such as olanzapine, quetiapine and risperidone. The literature is scarce in what resistant PPP is concerned and no such cases treated with clozapine have been reported, according to our knowledge. The present case report focuses on a female diagnosed with PPP who was treated with clozapine due to the lack of response to adequate dosage of 2 second-generation antipsychotics. CASE PRESENTATION: We present the case of a 30-year-old primiparous woman on her 3rd day after delivery, admitted in the psychiatric emergency unit for agitation, intrusive thoughts with a content frequently related to the infant, ideas of reference, disorganized speech, bizarre behavior, verbal stereotypes, insomnia and anxiety. Due to lack of response to adequate dosage of 2 second-generation antipsychotics, clozapine was initiated up to 250 mg/day. The symptoms remitted in the next 5 days and the patient was discharged. After discharge, at the patient's request, clozapine was replaced by olanzapine. Visit at 1 year revealed full remission of symptoms. CONCLUSION: Although data is extremely limited, clozapine has been shown to be effective and safe in a severe case of treatment-resistant PPP.

Rapid Titration of Clozapine in Schizophrenia and Bipolar Disorder.

Despite evidence accumulated over 30 years of clozapine efficacy in schizophrenia, its use is suboptimal. Long duration of standard titration and monitoring procedures are strong barriers in clozapine prescribing. The aim of the present paper is to discuss the challenges of rapid clozapine titration. The currently approved/recommended titration methods in US, Europe, and Australia are discussed. The rapid clozapine titration was introduced in our hospital in the early 2000's as "last resort" method for aggressive, belligerent or homicidal patients with schizophrenia and bipolar disorder. In our opinion, rapid clozapine titration might shorten the duration of patient and family suffering associated with uncontrolled psychotic symptoms, reduce the need and risks associated with polypharmacy, and reduce the costs of health care services of prolonged hospitalization. As there are no randomized controlled clinical trials to compare the efficacy and safety of standard versus rapid titration of clozapine in schizophrenia or bipolar disorder, future studies are needed.

Antipsychotics in Postpartum Psychosis.

BACKGROUND: Psychotic episodes in the postpartum period are life-threatening psychiatric emergencies, requiring urgent medical attention and admission to a psychiatric hospital. AREAS OF UNCERTAINTY: Although the postpartum psychosis (PPP) is the most severe psychiatric disorder associated with parturition, there is little information about what interventions are most effective. Because there are no specific guidelines for the treatment of PPP, the aim of the present review was to examine the available evidence regarding the treatment of PPP. DATA SOURCES: The PubMed database was searched based on the title and the abstract, using the key words "postpartum psychosis," "postpartum psychosis antipsychotics," "postpartum psychosis treatment," and "postpartum psychosis pharmacotherapy," for both interventional and observational, irrespective of language. RESULTS: A number of 14 publications met the study criteria, including case reports and case series. The antipsychotics (APs) use included both first generation APs, such as haloperidol and chlorpromazine, and second generation APs, mainly, olanzapine, quetiapine, and risperidone. The most frequently used AP was olanzapine. Olanzapine and quetiapine seem to be the most acceptable during breastfeeding. Proposed treatment algorithms for the successful management of PPP are discussed. CONCLUSIONS: The existing studies to date do not allow to draw a definitive conclusion regarding which treatment is the most effective or the most adequate. Existing evidence suggests that APs alone or in combination are responsible for sustained remission and that treated PPP has a higher pace of improvement of the mental status, with a rapid discharge from the hospital. Clinical studies to compare the efficacy and safety of different APs in the PPP are needed to provide guidance on treatment interventions.

A Systematic Review of Clinical Studies on the Effect of Psychoactive Cannabinoids in Psychiatric Conditions in Alzheimer Dementia.

BACKGROUND: The systematic reviews and meta-analyses performed until now did not provide the adequate picture of actual knowledge in the field of neuropsychiatric symptoms treatment using psychotropic cannabinoids in patients with Alzheimer disease (AD). THE STUDY QUESTION: Which is the level of evidence, from quantitative and qualitative point of view, concerning the efficacy and safety of the treatment with psychotropic cannabinoids of neuropsychiatric symptoms in AD? STUDY DESIGN: PubMed, EMBASE, Cochrane Database of Systematic Reviews, Google Scholar Data, and Clinicaltrials.gov were searched for randomized clinical trials with cannabinoids in Alzheimer dementia agitation and aggression. MEASURES AND OUTCOMES: The rationale, the objectives, and the methods used for searching the trials have been established according to PRISMA Criteria 2009. RESULTS: The total number of patients in the 9 publications evaluated in this study, which included data from 6 clinical trials, was 422 patients-treatments, where treatment was a psychoactive cannabinoid or placebo, some of them obtained by multiplying selected patients with the number of cannabinoid treatments in the crossover studies. There are multiple sources of bias in the analyzed studies; 2 elements have prevented conclusive results. One element was polypragmazia, a major role being played by the use of psychotropic drugs other than cannabinoids, in an effort to reduce agitation and aggressive behavior. The second one was the large number of concomitant symptoms, for example, pain (commonly causing anxiety and agitation). CONCLUSIONS: No clear conclusion can be drawn on the effectiveness of psychoactive cannabinoids in the treatment of psychiatric manifestations, in particular agitation and aggression, in AD. In the future, large randomized controlled trial with adequate designs, without crossover and for longer duration, adapted to cannabinoid pharmacokinetics, is required to establish the real efficacy and safety of these drugs in aggressive and/or agitated patients with AD.

C-Reactive Protein and T3: New Prognostic Factors in Acute Ischemic Stroke.

BACKGROUND: Several studies have shown that high level of plasma C-reactive protein (CRP) is associated with stroke outcomes and future vascular events, and a decrease in serum triiodothyronine (T3) was reported to be associated with stroke severity and poor prognosis. OBJECTIVE: The goal of this study is to evaluate CRP and T3 as independent predictors of poor functional and cognitive outcomes in patients with acute ischemic stroke at hospital discharge. METHODS: This study evaluated 120 patients who were admitted to the Clinical Hospital of Neurology and Psychiatry Brasov, between July 2016 and January 2017. The patients were evaluated for clinical stroke severity (National Institutes of Health Stroke Scale) and serum CRP and total T3 were evaluated on admission. Functional outcome and cognitive outcome were evaluated at discharge. RESULTS: The severity of NIHHS scores were associated with higher CRP levels (ß = .583, P = .000) and lower T3 concentration (ß = -.185, P = .043). Poor cognitive prognosis was associated with CRP levels (ß = .441, P = .000) but not with T3 concentrations (P = .142). Poor functional outcome was associated with higher CRP levels (ß = .457, P = .000), but not with T3 concentrations (P = .100). Using CRP and T3 as prognostic factors resulted in a probability of 53.5% to predict a poor functional outcome and of 80.42% to predict a poor cognitive outcome in stroke patients at discharge. CONCLUSIONS: The study showed that higher CRP and lower T3 levels were associated with stroke severity on admission. Functional outcome is likely secondary to stroke severity but functional outcome at discharge was associated with higher CRP levels and not with T3 concentration. Cognitive outcome was associated with higher CRP levels and not with T3 concentration.

Anticancer Activity of Toxins from Bee and Snake Venom-An Overview on Ovarian Cancer.

Cancer represents the disease of the millennium, a major problem in public health. The proliferation of tumor cells, angiogenesis, and the relationship between the cancer cells and the components of the extracellular matrix are important in the events of carcinogenesis, and these pathways are being used as targets for new anticancer treatments. Various venoms and their toxins have shown possible anticancer effects on human cancer cell lines, providing new perspectives in drug development. In this review, we observed the effects of natural toxins from bee and snake venom and the mechanisms through which they can inhibit the growth and proliferation of cancer cells. We also researched how several types of natural molecules from venom can sensitize ovarian cancer cells to conventional chemotherapy, with many toxins being helpful for developing new anticancer drugs. This approach could improve the efficiency of standard therapies and could allow the administration of decreased doses of chemotherapy. Natural toxins from bee and snake venom could become potential candidates for the future treatment of different types of cancer. It is important to continue these studies concerning therapeutic drugs from natural resource and, more importantly, to investigate their mechanism of action on cancer cells.

Clozapine for Treatment-Refractory Behavioral Disturbance in Dementia.

BACKGROUND: Behavioral and psychological symptoms in dementia significantly contribute to caregiver burden and impose patient hospitalization. The goal of treatment of admitted patients is the rapid remission of symptoms to allow their return to home as soon as possible. Intervention requires an intrusive approach with parenteral treatment and physical restraints, with a negative emotional impact on patients and their families. Despite the large utilization of antipsychotics for behavioral and psychological symptoms, there is no antipsychotic approved by the Food and Drug Administration for agitation in dementia. STUDY QUESTION: To evaluate efficacy and tolerability of clozapine in patients with treatment-resistant agitation associated with dementia. STUDY DESIGN: Cohort study with 337 patients, admitted between January 1, 2012 and December 31, 2016, with dementia according to The Diagnostic and Statistical Manual of Mental Disorders 4th ed. criteria. Clozapine was given in standard titration, starting with 6.25 or 12.5 mg. MEASURES AND OUTCOMES: Efficacy was measured by the need for physical restraints and time to discharge and tolerability by recording all side effects. Data collected included demographics, psychotropics used, physical restraints, length of stay, destination after discharge, and comorbidities. RESULTS: Of 337 cases, 315 (93.5%) patients received antipsychotics. There were 27 cases treated with clozapine. Before clozapine initiation, haloperidol was given in 16 cases (55.17%, mean = 7.43 mg/d, SD = ±4.01), and the treatment was stopped mainly because of extrapyramidal side effects. Other antipsychotics used were quetiapine (mean dose = 260 mg/d, SD = ±54.77), risperidone (mean dose = 3.3 mg/d, SD = ±0.57), and olanzapine (mean dose = 8.33 mg/d, SD = ±2.88). Mean dose of clozapine was 59.16 mg/d, (SD = ±40.48), ranging from 12.5 to 200 mg/d. There were a lower number of physical restraints after clozapine initiation than before (12 vs. 34, P < 0.05). CONCLUSIONS: Clozapine therapy seemed beneficial in treatment-resistant agitation in patients with dementia. The risk-benefit balance must be well weighed when clozapine is chosen. More studies are needed.