Contrast-enhanced US to Improve Diagnostic Performance of O-RADS US Risk Stratification System for Malignancy.

Background The Ovarian-Adnexal Reporting and Data System (O-RADS) has limited specificity for malignancy. Contrast-enhanced US can help distinguish malignant from benign lesions, but its added value to O-RADS has not yet been assessed. Purpose To establish a diagnostic model combining O-RADS and contrast-enhanced US and to validate whether O-RADS plus contrast-enhanced US has a better diagnostic performance than O-RADS alone. Materials and Methods This prospective study included participants from May 2018 to March 2021 who underwent contrast-enhanced US before surgery and had lesions categorized as O-RADS 3, 4, or 5 by US, with a histopathologic reference standard. From April 2021 to July 2022, participants with pathologically confirmed ovarian-adnexal lesions were recruited for the validation group. In the pilot group, the initial enhancement time and enhancement intensity in comparison with the uterine myometrium, contrast agent distribution pattern, and dynamic changes in enhancement of lesions were assessed. Contrast-enhanced US features were used to calculate contrast-enhanced US scores for benign (score ≤2) and malignant (score ≥4) lesions. Lesions were then re-rated according to O-RADS category plus contrast-enhanced US scores. Receiver operating characteristic curves were constructed and compared using the DeLong method. The combined system was validated in an independent group. Results The pilot group included 76 women (mean age, 44 years ± 13 [SD]), and the validation group included 46 women (mean age, 42 years ± 14). Differences in initial enhancement time (P < .001), enhancement intensity (P < .001), and dynamic changes in enhancement (P < .001) between benign and malignant lesions were observed in the pilot group. Contrast-enhanced US scores were calculated using these features. The O-RADS risk stratification was upgraded one level for contrast-enhanced US scores of 4 or more and downgraded one level for contrast-enhanced US scores of 2 or less. In the validation group, the diagnostic performance of O-RADS plus contrast-enhanced US score was higher (area under the receiver operating characteristic curve [AUC] = 0.93) than O-RADS (AUC = 0.71, P < .001). Conclusion Contrast-enhanced US improved the diagnostic performance for malignancy of the O-RADS categories 3-5. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Grant in this issue.

Prevalence and correlates of suicidal ideation among older adults attending primary care clinics in Wuhan, China: A multicenter cross-sectional study.

Background: Primary care represents an ideal setting for screening for and managing suicidal older adults but the clinical epidemiology of suicidal ideation in Chinese older primary care patients remains unclear. This study investigated the prevalence and correlates of suicidal ideation in older Chinese adults receiving primary care. Methods: This multicenter cross-sectional survey included a total of 769 older adults (≥65 years) from seven urban and six rural primary care clinics in Wuhan, China. The presence of depressive symptoms and suicidal ideation was assessed with the Geriatric Depression Scale and a single-item question "In the past 12 months, did you think about ending your life?," respectively. Results: The 12-month prevalence of suicidal ideation in older primary care patients was 16.6%. Significant correlates of suicidal ideation were poor economic status (vs. good, OR = 2.80, P = 0.008), heart disease (OR = 2.48, P = 0.005), chronic gastric ulcer (OR = 3.55, P = 0.012), arthritis (OR = 2.10, P = 0.042), and depressive symptoms (OR = 11.29, P < 0.001). Conclusions: Suicidal ideation is common among older adults attending Chinese primary care clinics. It is necessary to integrate psychological crisis intervention into primary care to prevent late-life suicide.

Exosome-mediated aptamer S58 reduces fibrosis in a rat glaucoma filtration surgery model.

AIM: To confirm whether exosome-mediated delivery of aptamer S58 (Exo-S58) has a better antifibrotic effect than naked S58 in human conjunctival fibroblasts (HConFs) and a rat glaucoma filtration surgery (GFS) model. METHODS: To enhance the effective reaction time of aptamer S58 in vivo, we loaded aptamer S58 into exosomes derived from HEK293T cells by PEI transfection to determine the effect of Exo-S58 in HConFs and a rat GFS model. RESULTS: Exo-S58 can significantly reduce cell proliferation, migration and fibrosis in TGF-ß2-induced HConFs. In an in vivo experiment, Exo-S58 treatment prolonged filtering bleb retention and reduced fibrosis compared with naked S58 treatment in GFS rats. CONCLUSION: The exosomes are safe and valid carriers to deliver aptamers. Furthermore, Exo-S58 exhibited superior antifibrotic effect than naked S58 both in HConFs cells and rat GFS models.

Anticancer activity of ruthenium(II) plumbagin complexes with polypyridyl as ancillary ligands via inhibiting energy metabolism and GADD45A-mediated cell cycle arrest.

To study the antitumor activity and action mechanism of Ru(II) polypyridyl plumbagin (PLN) complexes, four complexes [Ru(PLN)(DMSO)2]Cl (Ru1), [Ru(bpy)2(PLN)](PF6) (bpy is bipyridine) (Ru2), [Ru(phen)2(PLN)](PF6) (phen is 1,10-phenanthroline) (Ru3), and [Ru(DIP)2(PLN)](PF6) (DIP is 4,7-diphenyl-1,10-phenanthroline) (Ru4) were obtained and fully characterized. Lipophilicity, cellular uptake and cytotoxicity of these Ru(II) complexes are in the order of: Ru1

COVID-19 Vaccine Uptake, Acceptance, and Hesitancy Among Persons With Mental Disorders During the Second Stage of China's Nationwide Vaccine Rollout.

Persons with mental disorders (PwMDs) are a priority group for COVID-19 vaccination, but empirical data on PwMDs' vaccine uptake and attitudes toward COVID-19 vaccines are lacking. This study examined the uptake, acceptance, and hesitancy associated with COVID-19 vaccines among Chinese PwMDs during China's nationwide vaccine rollout. In total, 906 adult PwMDs were consecutively recruited from a large psychiatric hospital in Wuhan, China, and administered a self-report questionnaire, which comprised standardized questions regarding sociodemographics, COVID-19 vaccination status, attitudes toward COVID-19 vaccines, and psychopathology. Vaccine-recipients were additionally asked to report adverse events that occurred following vaccination. PwMDs had a much lower rate of vaccination than Wuhan residents (10.8 vs. 40.0%). The rates of vaccine acceptance and hesitancy were 58.1 and 31.1%, respectively. Factors associated with vaccine uptake included having other mental disorders [odds ratio (OR) = 3.63], believing that ≥50% of vaccine-recipients would be immune to COVID-19 (OR = 3.27), being not worried about the side effects (OR = 2.59), and being an outpatient (OR = 2.24). Factors associated with vaccine acceptance included perceiving a good preventive effect of vaccines (OR = 12.92), believing that vaccines are safe (OR = 4.08), believing that ≥50% of vaccine-recipients would be immune to COVID-19 (OR = 2.20), and good insight into the mental illness (OR = 1.71). Adverse events occurred in 21.4% of vaccine-recipients and exacerbated pre-existing psychiatric symptoms in 2.0% of vaccine-recipients. Nevertheless, 95.2% of vaccine-recipients rated adverse events as acceptable. Compared to the 58.1% vaccine acceptance rate and the 40.0% vaccination rate in the general population, the 10.8% vaccine coverage rate suggested a large unmet need for COVID-19 vaccination in Chinese PwMDs. Strategies to increase vaccination coverage among PwMDs may include provision of reliable sources of information on vaccines, health education to foster positive attitudes toward vaccines, a practical guideline to facilitate clinical decision-making for vaccination, and the involvement of psychiatrists in vaccine consultation and post-vaccination follow-up services.

Recent Advances in Asialoglycoprotein Receptor and Glycyrrhetinic Acid Receptor-Mediated and/or pH-Responsive Hepatocellular Carcinoma- Targeted Drug Delivery.

BACKGROUND: Hepatocellular carcinoma (HCC) seriously affects human health, especially, it easily develops multi-drug resistance (MDR) which results in treatment failure. There is an urgent need to develop highly effective and low-toxicity therapeutic agents to treat HCC and to overcome its MDR. Targeted drug delivery systems (DDS) for cancer therapy, including nanoparticles, lipids, micelles and liposomes, have been studied for decades. Recently, more attention has been paid to multifunctional DDS containing various ligands such as polymer moieties, targeting moieties, and acid-labile linkages. The polymer moieties such as poly(ethylene glycol) (PEG), chitosan (CTS), hyaluronic acid, pullulan, poly(ethylene oxide) (PEO), poly(propylene oxide) (PPO) protect DDS from degradation. Asialoglycoprotein receptor (ASGPR) and glycyrrhetinic acid receptor (GAR) are most often used as the targeting moieties, which are overexpressed on hepatocytes. Acid-labile linkage, catering for the pH difference between tumor cells and normal tissue, has been utilized to release drugs at tumor tissue. OBJECTIVES: This review provides a summary of the recent progress in ASGPR and GAR-mediated and/or pH-responsive HCC-targeted drug delivery. CONCLUSION: The multifunctional DDS may prolong systemic circulation, continuously release drugs, increase the accumulation of drugs at the targeted site, enhance the anticancer effect, and reduce side effects both in vitro and in vivo. But it is rarely used to investigate MDR of HCC; therefore, it needs to be further studied before going into clinical trials.

Synthesis, structural characterization and antitumor activity of six rare earth metal complexes with 8-hydroxyquinoline derivatives.

The rare earth metal Gd(III), Yb(III), Lu(III), Eu(III), Tb(III) and Ho(III) complexes 1-6 with 2-((2-(pyridin-2-yl)hydrazono)methyl)quinolin-8-ol (H-L) as ligands were synthesized. The in vitro cytotoxicity assay indicated that the cytotoxicity of 1 was equivalent to cisplatin and higher than that of H-L and other complexes towards T24 tumor cells. The mechanism study indicated that 1 caused significant up-regulation of the proteins p27, p21 and p53 in T24 cells and cell cycle arrest in G2 phase. In addition, 1 induced effective T24 cells apoptosis via mitochondrial dysfunction pathway, which was indicated by changes in mitochondrial membrane potential (Δψ), reactive oxygen species (ROS), intracellular Ca2+ and the mitochondria-related proteins (including cytochrome C (Cyt C), B-cell lymphoma-2 (Bcl-2), Bcl-2-associated x (Bax) and apoptotic protease activating factor-1 (Apaf-1)). Moreover, 1 could activate caspase-3/8/9 in T24 cells. Therefore, complex 1 is a promising and potent anticancer drug candidate.

Prevalence of prenatal and postpartum depression in fathers: A comprehensive meta-analysis of observational surveys.

BACKGROUND: Increasing attention has been paid to maternal prenatal and postpartum depressive symptoms (depression thereafter), but little is known about the prevalence of paternal prenatal and postpartum depression. To fill this gap, the current study meta-analyzed the worldwide prevalence of prenatal and postpartum depression in fathers. METHODS: Studies that reported paternal depression occurring between the first trimester and the first postpartum year were identified by searching both international (PubMed, PsycINFO, Web of Science and EMBASE) and Chinese (WanFang and CNKI) databases between their inception date and July 1, 2018. A random-effects model was used to calculate pooled estimates and 95% confidence intervals. RESULTS: Forty-seven studies with 20,728 subjects were included in the meta-analysis. The prevalence of prenatal depression in fathers was 9.76% in all three trimesters, 13.59% in the first, 11.31% in the second and 10.12% in the third trimester. The prevalence of postpartum depression was 8.75% within a whole year, 8.98% within one-month, 7.82% between one- and three months, 9.23% between three months and six months and 8.40% between six months to twelve months after child-birth. The prevalence of paternal postpartum depression was moderated by year of publication, study area, age of fathers of ≥18 years, quality assessment score and mean age (all P<0.05). CONCLUSIONS: This meta-analysis found that the prevalence of prenatal and postpartum depression in fathers was relatively common. Regular screening, effective prevention and appropriate treatment need to be implemented in this population.

MicroRNA-527 inhibits TGF-ß/SMAD induced epithelial-mesenchymal transition via downregulating SULF2 expression in non-small-cell lung cancer.

OBJECTIVE: To explore the potential mechanism which miR-527 targeting the heparan sulfate 6-O-endosulfatase (SULF2) regulates TGF-ß/SMAD signaling pathway induced epithelial-mesenchymal transition (EMT) in non-small-cell lung cancer (NSCLC). METHODS: 38 pairs of lung tumor biopsies and corresponding paracancerous biopsies were obtained from NSCLC patients with surgical resection, normal human bronchial epithelial BEAS-2B cells and five NSCLS cell lines were applied for our study. miR-527 and SULF2 expression were determined by qRT-PCR and immunohistochemistry. MiR-527 and SULF2 biological link were predicted by Targetscan.org and tested by dual luciferase. Cells proliferation and apoptosis were respectively detected by EDU staining and flow cytometry. Cells migration was examined by transwell and scratch-wound assay. Expression of proteins related to EMT and TGF-ß/SMAD signaling pathway, such as E-cadherin, N-cadherin, p-Samd3 and p-Smad2, was detected by western blot. RESULTS: miR-527 expression was decreased in lung tumor tissues and NSCLS cell lines, conversely, SULF2 expression was significantly increased. In addition, we found that miR-527 targeted 3'-untranslated regions (3'-UTR) of SULF2 and mediated its expression. Overexpression of miR-527 evidently suppressed NSCLC proliferation, invasion and EMT via TGF-ß/SMAD signaling pathway. Moreover, the silence of SULF2 exhibited a similar effect. CONCLUSION: miR-527 targeting SULF2 down-regulated SULF2 expression, concurrently, suppressed NSCLC epithelial-mesenchymal transition and invasion via inhibiting TGF-ß/SMAD signaling pathway.

Adjunctive minocycline for major mental disorders: A systematic review.

OBJECTIVES: This meta-analysis of randomized controlled trials (RCTs) examined the efficacy and safety of minocycline for three major mental disorders: schizophrenia, bipolar disorder and major depressive disorder (MDD). METHODS: A systematic literature search of major electronic databases was conducted. Meta-analysis of clinical efficacy as defined by the respective studies, all-cause discontinuation, adverse drug reactions (ADRs) with standardized mean difference (SMD) and risk ratios (RRs) and their 95% confidence intervals (CI) was conducted using random-effects model. Quality assessment was performed with the Jadad scale and Cochrane risk of bias. RESULTS: Sixteen RCTs (n=1357) on minocycline (50-300 mg/day) for schizophrenia (13 RCTs, n=1196), bipolar depression (1 RCT, n=49), and MDD (2 RCTs, n=112) were analyzed separately by diagnosis. Twelve RCTs mentioned randomized allocation specifically; the weighted Jadad scores were 4.0. Adjunctive minocycline outperformed placebo in improving total psychopathology [SMD: -0.45 (95%CI: -0.73, -0.16), p=0.002; I2=77%], positive [SMD: -0.15 (95%CI: -0.28, -0.02), p=0.02; I2=0%], negative [SMD: -0.62 (95%CI: -0.95, -0.28), p=0.0003; I2=85%] and general psychopathology scores [SMD: -0.28 (95%CI: -0.53, -0.03), p=0.03; I2=59%] in schizophrenia. Minocycline showed no significant effect on depressive and manic symptoms in both bipolar depression and MDD. Minocycline caused significantly less headache (p=0.02, number-needed-to-harm=14, 95%CI=5-14) than placebo in schizophrenia. All-cause discontinuation and other ADRs were similar between minocycline and placebo in each diagnostic category. CONCLUSION: In this meta-analysis, adjunctive minocycline appeared to be efficacious and safe for schizophrenia. However, the efficacy of adjunctive minocycline for bipolar depression or MDD could not be demonstrated. REVIEW REGISTRATION: PROSPERO: CRD42018102483.

Eukaryotic initiation factor 5A2 and human digestive system neoplasms.

Eukaryotic initiation factor 5A2 (eIF5A2), as one of the two isoforms in the family, is reported to be a novel oncogenic protein that is involved in multiple aspects of many types of human cancer. Overexpression or gene amplification of EIF5A2 has been demonstrated in many cancers. Accumulated evidence shows that eIF5A2 initiates tumor formation, enhances cancer cell growth, increases cancer cell metastasis, and promotes treatment resistance through multiple means, including inducing epithelial-mesenchymal transition, cytoskeletal rearrangement, angiogenesis, and metabolic reprogramming. Expression of eIF5A2 in cancer correlates with poor survival, advanced disease stage, as well as metastasis, suggesting that eIF5A2 function is crucial for tumor development and maintenance but not for normal tissue homeostasis. All these studies suggest that eIF5A2 is a useful biomarker in the prediction of cancer prognosis and serves as an anticancer molecular target. This review focuses on the expression, subcellular localization, post-translational modifications, and regulatory networks of eIF5A2, as well as its biochemical functions and evolving clinical applications in cancer, especially in human digestive system neoplasms.

Adjunctive memantine for major mental disorders: A systematic review and meta-analysis of randomized double-blind controlled trials.

OBJECTIVE: As a non-competitive N-methyl-d-aspartate receptor antagonist, memantine has been used to treat major mental disorders including schizophrenia, bipolar disorder, and major depressive disorder (MDD). This meta-analysis systematically investigated the effectiveness and tolerability of adjunctive memantine for patients with schizophrenia, bipolar disorder, and MDD. METHODS: Only randomized controlled trials (RCTs) were identified and included in the study. Data of the three disorders were separately synthesized using the RevMan 5.3 software. RESULTS: Fifteen RCTs (n = 988) examining memantine (5-20 mg/day) as an adjunct treatment for schizophrenia (9 trials with 512 patients), bipolar disorder (3 trials with 319 patients), and MDD (3 trials with 157 patients) were analyzed. Memantine outperformed the comparator regarding total psychopathology with a standardized mean difference (SMD) of -0.56 [95% confidence interval (CI): -1.01, -0.11; I2 = 76%, P = 0.01] and negative symptoms with an SMD of -0.71 (95% CI: -1.09, -0.33; I2 = 74%, P = 0.0003) in schizophrenia, but no significant effects were found with regard to positive symptoms and general psychopathology in schizophrenia, or depressive and manic symptoms in bipolar disorder or depressive symptoms in MDD. Memantine outperformed the comparator in improving cognitive performance in schizophrenia with an SMD of 1.07 (95% CI: 0.53, 1.61; P < 0.0001, I2 = 29%). No group differences were found in the rates of adverse drug reactions and discontinuation due to any reason in the three major mental disorders. CONCLUSIONS: Memantine as an adjunct treatment appears to have significant efficacy in improving negative symptoms in schizophrenia. The efficacy and safety of adjunctive memantine for bipolar disorder or MDD needs to be further examined. REVIEW REGISTRATION: PROSPERO: 42018099045.

Prevalence of suicide attempts in individuals with schizophrenia: a meta-analysis of observational studies.

AIMS: Suicide attempt is an important indicator of suicide and potential future mortality. However, the prevalence of suicide attempts has been inconsistent across studies. This meta-analysis aimed to examine the prevalence of suicide attempts in individuals with schizophrenia and associated correlates. METHODS: Relevant publications in Embase, PsycINFO, PubMed, Web of science and Cochrane were systematically searched. Data on the prevalence of suicide attempts in individuals with schizophrenia were pooled using a random-effects model. RESULTS: Thirty-five studies with 16 747 individuals with schizophrenia were included. The pooled lifetime prevalence of suicide attempts was 26.8% (95% CI 22.1-31.9%; I2 = 97.0%), while the 1-year prevalence, 1-month prevalence and the prevalence of suicide attempts from illness onset were 3.0% (95% CI 2.3-3.7%; I2 = 95.6%), 2.7% (95% CI 2.1-3.4%; I2 = 78.5%) and 45.9% (95% CI 42.1-49.9%; I2 = 0), respectively. Earlier age of onset (Q = 4.38, p = 0.04), high-income countries (Q = 53.29, p < 0.001), North America and Europe and Central Asia (Q = 32.83, p < 0.001) were significantly associated with a higher prevalence of suicide attempts. CONCLUSIONS: Suicide attempts are common in individuals with schizophrenia, especially those with an early age of onset and living in high-income countries and regions. Regular screening and effective preventive measures should be implemented as part of the clinical care.

Objective optical assessment of tear-film quality dynamics in patients with meibomian gland dysfunction and aqueous-deficient dry eye optical quality changes in different dry eye subtypes.

Purpose: To evaluate the optical quality and tear-film dynamics in patients with aqueous-deficient or evaporative subtype of dry eye disease (DED). Methods: Twenty-five aqueous-deficient dry eye (ADDE) patients, 25 DED patients with meibomian gland dysfunction (MGD), and 25 healthy subjects were included in this study. Vision-related health-targeted quality of life was evaluated using the Ocular Surface Disease Index (OSDI) questionnaire. Dynamic recording with a double-pass system (Optical Quality Analysis System [OQAS]) was performed in right eyes. Scattered light was measured as the objective scatter index (OSI) at 0.5-second intervals over 20 seconds without blinking. Then, we recorded OSI every 0.5 seconds within a 20-second period with the subjects asked to blink freely. Several parameters were established to evaluate the dynamic alterations of optical quality and the effects of blinks: OSI, OSI standard deviation (SD), ΔOSI, ΔOSI/time, blinking change (BC), and blinking frequency (BF). Additional clinical examination included tear film break-up time (BUT), Schirmer I test (SIT), fluorescein staining grade (FL), meibomian gland quality, meibomian gland expressibility, and meibomian gland drop-out. Results: The OSI, SD, ΔOSI, ΔOSI/time, BC, and BF were significantly higher in DED patients than controls (P < 0.01, respectively). The OSI, SD, ΔOSI, ΔOSI/time, BC, and BF were significantly higher in patients with MGD than patients with ADDE (P < 0.01). In the MGD group, BUT, FL staining score, lid abnormality, meibomian gland expressibility, and meibomian gland drop-out were correlated with Δ OSI and Δ OSI/time. Conclusion: Dry eye patients with MGD had significant alterations of optical quality compared with ADDE patients. The double-pass system has potential to be a useful quantitative method to evaluate the optical quality and tear-film dynamics in patients with dry eye.

Adjunctive ketamine and electroconvulsive therapy for major depressive disorder: A meta-analysis of randomized controlled trials.

BACKGROUND: Adjunctive ketamine with electroconvulsive therapy (ECT) has been investigated for treating major depressive disorder (MDD), but the findings have been inconsistent. AIM: This is an updated meta-analysis of the efficacy and safety of ketamine augmentation of ECT in the treatment of MDD. METHODS: Randomized controlled trials (RCTs) reporting on the efficacy and safety of ketamine and ECT were identified and analyzed. RESULTS: Seventeen RCTs (n = 1,035) compared ketamine alone or ketamine plus other anesthetic drugs (n = 557) with other anesthetic agents (n = 478) in MDD patients who received ECT. Ketamine+other anesthetic drugs was superior in improving depressive symptoms over other anesthetic medications at early study time point, but not at post-ECT or end of study time points. Ketamine alone was not more efficacious in treating depressive symptoms than other anesthetic drugs at early study, post-ECT and end of study time points. Sensitivity analysis and 19 of the 20 subgroup analyses also confirmed the lack of significance of these findings. Eleven RCTs testing the effects of ketamine on neurocognitive functions with various test batteries found mixed results. Ketamine alone significantly increased blood pressure more than other anesthetic drugs in MDD treated with ECT. CONCLUSION: Compared to other anesthetic agents, ketamine alone does not appear to improve the efficacy of ECT. However, ketamine+other anesthetic combinations may confer a short-term advantage in improving depressive symptom at the early stages of ECT.

Dual-response detection of Ni2+ and Cu2+ ions by a pyrazolopyrimidine-based fluorescent sensor and the application of this sensor in bioimaging.

Herein, a dual-response fluorescent sensor, L, based on pyrazolopyrimidine was designed and developed for the simultaneous detection of Ni2+ and Cu2+ ions in the presence of other metal ions; the structural characterization of L was carried out by FTIR spectroscopy, NMR spectroscopy, HRMS and X-ray diffraction analysis. The sensor L effectively displayed fluorescence quenching towards the Ni2+ and Cu2+ ions with high sensitivity without interference from other metal ions. The results reveal that L binds to Ni2+ and Cu2+ in a 2 : 1 pattern, which matches well with the result of the Job's plot. The association constants of L with Ni2+ and Cu2+ were 3.2 × 104 M-1 and 7.57 × 104 M-1, respectively. The detection limits (DLs) are down to 8.9 nM for Ni2+ and 8.7 nM for Cu2+. The fluorescence imaging of L in T-24 cells was investigated because of the low cytotoxicity of L, indicating that L could be used to detect Ni2+ and Cu2+ in living cells.

Adjunctive intranasal oxytocin for schizophrenia: A meta-analysis of randomized, double-blind, placebo-controlled trials.

OBJECTIVE: Findings on the efficacy of intranasal oxytocin (IN-OT) in schizophrenia have been inconsistent. This meta-analysis of double-blind randomized controlled trials (RCTs) examined the efficacy and tolerability of adjunctive IN-OT in the treatment of schizophrenia. METHODS: Standardized mean differences or risk ratios (SMDs or RRs) with their 95% confidence intervals (CIs) were used to synthesize the results of studies included in the meta-analysis. RESULTS: Ten RCTs (n = 344) with 172 schizophrenia subjects on adjunctive IN-OT [range = 40-80 International Units (IU)/day] and 172 schizophrenia subjects on adjunctive placebo over 2-16 weeks were included. No significant differences regarding total psychopathology measured with the total Positive and Negative Syndrome Scale (PANSS) or the Brief Psychiatric Rating Scale (BPRS) [8 RCTs, n = 203; SMD: -0.08 (95%CI: -0.53, 0.37), P = 0.74, I2 = 59%] and the positive, negative and general symptom scores [SMD: -0.20 to -0.04 (95%CI: -0.75, 0.36), P = 0.28 to 0.78; I2 = 0% to 72%] were found between the IN-OT and placebo groups. Similarly, subgroup analyses for total psychopathology found no group differences. Dose-response effect analyses showed that only 80 IU/day IN-OT had superiority over placebo in improving total psychopathology (P = 0.02) and positive symptom score (P = 0.01). No group differences between adjunctive IN-OT and placebo regarding discontinuation due to any reason [RR: 1.12 (95%CI: 0.67, 1.88), P = 0.67, I2 = 0%] and adverse drug reactions were found. CONCLUSIONS: Although the meta-analysis did not show a positive effect in general, the higher dose of adjunctive IN-OT (80 IU/day) appears to be efficacious and safe in improving total psychopathology and positive symptoms in schizophrenia. REVIEW REGISTRATION: CRD42017080856.

Adjunctive Peony-Glycyrrhiza decoction for antipsychotic-induced hyperprolactinaemia: a meta-analysis of randomised controlled trials.

BACKGROUND: Hyperprolactinaemia is a common adverse effect of antipsychotics (APs). The results of Peony-Glycyrrhiza decoction (PGD) as a potentially useful adjunctive treatment for hyperprolactinaemia are inconsistent. AIM: This meta-analysis of randomised controlled trials (RCTs) examined the efficacy and safety of adjunctive PGD therapy for AP-induced hyperprolactinaemia. METHODS: English (PubMed, Embase, Cochrane Library, PsycINFO) and Chinese (Chinese National Knowledge Infrastructure, Wanfang Data) databases were systematically searched up to 10 June 2018. The inclusion criteria were based on PICOS-Participants: adult patients with schizophrenia; Intervention: PGD plus APs; Comparison: APs plus placebo or AP monotherapy; Outcomes: efficacy and safety; Study design: RCTs. The weighted mean difference (WMD) and risk ratio (RR) along with their 95% CIs were calculated using Review Manager (RevMan) V.5.3 software. RESULTS: Five RCTs (n=450) were included and analysed. Two RCTs (n=140) were double-blind and four RCTs (n=409) reported 'random' assignment with specific description. The PGD group showed a significantly lower serum prolactin level at endpoint than the control group (n=380, WMD: -32.69 ng/mL (95% CI -41.66 to 23.72), p<0.00001, I 2 =97%). Similarly, the superiority of PGD over the control groups was also found in the improvement of hyperprolactinaemia-related symptoms. No difference was found in the improvement of psychiatric symptoms assessed by the Positive and Negative Syndrome Scale (n=403, WMD: -0.62 (95% CI -2.38 to 1.15), p=0.49, I 2 =0%). There were similar rates of all-cause discontinuation (n=330, RR 0.93 (95% CI 0.63 to 1.37), p=0.71, I 2 =0%) and adverse drug reactions between the two groups. According to the Grading of Recommendations Assessment, Development and Evaluation approach, the level of evidence of primary and secondary outcomes ranged from 'very low' (14.3%), 'low' (42.8%), 'moderate' (14.3%), to 'high' (28.6%). CONCLUSIONS: Current evidence supports the adjunctive use of PGD to suppress elevated prolactin and improve prolactin-induced symptoms without significant adverse events in adult patients with AP-induced hyperprolactinaemia. High-quality RCTs with longer duration are needed to confirm these findings. TRIAL REGISTRATION NUMBER: 42016037017.

Electroconvulsive therapy for older adult patients with major depressive disorder: a systematic review of randomized controlled trials.

BACKGROUND: Electroconvulsive therapy (ECT) has been widely used in treating older adult patients with major depressive disorder. The results of randomized controlled trials (RCT) are mixed. This study systematically examined the efficacy and safety of ECT versus antidepressants (AD) in older adult patients with major depressive disorder. METHODS: A literature search was conducted independently by two reviewers using the PubMed, Embase, PsycINFO, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang, and SinoMed databases from their inceptions until 17 May 2017. The Cochrane risk of bias and Jadad scale were used to assess the quality of RCT included in the systematic review. RESULTS: Five RCT (n = 374; mean age: 66.0-66.4 years; men: 36.4-58.3%) all conducted in China were identified, including three RCT (n = 203) with ECT alone and two RCT (n = 171) with ECT-AD co-treatment. In two of the three RCT, ECT alone was superior to AD monotherapy in improving depressive symptoms as assessed by the Hamilton Depression Scale and by clinical judgement at the conclusion of the course of ECT. Both RCT of AD-ECT co-treatment showed a significant reduction in the Hamilton Depression Scale total score after ECT compared with AD monotherapy. The response rate ranged from 80% to 97.5% in the ECT groups and from 63.4% to 73.3% in the AD groups. Rates of adverse reactions were similar between ECT and AD groups in studies with available data. Only one RCT reported the discontinuation rate without a significant group difference. CONCLUSIONS: This systematic review showed that ECT appears to be an effective and safe treatment for older adult patients with major depressive disorder. Further high-quality studies with extended follow-up are warranted.

Adjunctive raloxifene for postmenopausal women with schizophrenia: A meta-analysis of randomized, double-blind, placebo-controlled trials.

OBJECTIVE: Raloxifene, a selective estrogen receptor modulator, has been used in treating postmenopausal women with schizophrenia with inconsistent results. This meta-analysis of randomized, double-blind, placebo-controlled trials (RCTs) examined its efficacy and safety for postmenopausal women with schizophrenia. METHOD: Standardized mean differences (SMDs) and risk ratio (RR) together with their 95% confidence intervals (CIs) were calculated using the random effects model. RESULTS: The meta-analysis included 5 RCTs (n = 240) comparing raloxifene (n = 125, 60 or 120 mg/day) with placebo (n = 115). Adjunctive raloxifene outperformed placebo with regard to the Positive and Negative Syndrome Scale (PANSS) total psychopathology [n = 240, SMD:-0.64 (95%CI:-0.90, -0.37), P < 0.00001; I2 = 0%], positive symptoms [n = 240, SMD:-0.49 (95%CI:-0.81, -0.16), P = 0.003; I2 = 29%], negative symptoms [n = 240, SMD:-0.43 (95%CI:-0.68, -0.17), P = 0.001; I2 = 0%], and general psychopathology scores [n = 240, SMD:-0.66 (95%CI:-0.92, -0.39), P < 0.00001; I2 = 0%]. Both groups had similar rates of adverse events and discontinuation (n = 159, RR: 1.32 (95%CI: 0.65, 2.70), P = 0.44, I2 = 0%). CONCLUSION: Adjunctive raloxifene appears to be effective and safe in improving psychotic symptoms for postmenopausal women with schizophrenia. Review registration: CRD 42017059946.