Objective
To systematically examine the randomized controlled trial (RCT) evidence regarding efficacy and tolerability of topiramate cotreatment with antipsychotics in schizophrenia‐spectrum ...disorders.
Methods
Random‐effects meta‐analysis of RCTs of topiramate cotreatment with antipsychotics vs. placebo/ongoing antipsychotic treatment in schizophrenia‐spectrum disorders. Standardized or weighted mean difference (SMD/WMD), risk ratio (RR) ±95% confidence intervals (CIs), and number needed to harm (NNH) were calculated.
Results
Across 16 RCTs (n = 934, duration = 11.8 ± 5.6 weeks), topiramate outperformed the comparator regarding change/endpoint of total (SMD: −0.58, 95% CI: −0.82, −0.35, P < 0.00001), positive (SMD: −0.37, 95% CI: −0.61, −0.14, P = 0.002), negative (SMD: −0.58, 95% CI: −0.87, −0.29, P < 0.0001), and general symptoms (SMD: −0.68, 95% CI: −0.95, −0.40, P < 0.00001). Furthermore, topiramate was superior regarding body weight (WMD: –2.75 kg, 95% CI: −4.03, −1.47, P < 0.0001), body mass index (BMI) (WMD: –1.77, 95% CI: −2.38, −1.15, P < 0.00001), triglycerides (P = 0.006), and insulin levels (P < 0.00001). Superiority regarding psychopathology and body weight/BMI was consistent across Chinese/Asian and Western RCTs, double‐blind and open designs, clozapine and non‐clozapine cotreatment, augmentation and co‐initiation RCTs, and higher and lower quality RCTs. In meta‐regression analyses, topiramate's efficacy for total symptoms was moderated by shorter illness duration (P = 0.047), while weight loss was greater in prevention/co‐initiation vs. intervention/augmentation RCTs (−4.11 kg, 95% CI: −6.70, −1.52 vs. −1.41 kg, 95% CI: −2.23, −0.59, P < 0.001). All‐cause discontinuation was similar between topiramate and comparators (RR: 1.28, 95% CI: 0.91, 1.81, P = 0.16). While topiramate led to more concentration/attention difficulties (P = 0.03, NNH = 8, 95% CI=4–25), psychomotor slowing (P = 0.02, NNH = 7, 95% CI = 4–25), and paresthesia (P = 0.05, NNH = 2, 95% CI = 4–33), it led to less ≥7% weight gain (P = 0.0001, NNH = 2, 95% CI = 2–3) and constipation (P = 0.04, NNH = 9, 95% CI = 5–100) than the comparator.
Conclusions
These results indicate that adjunctive topiramate to antipsychotics is an effective and safe treatment choice for symptomatic improvement and weight reduction in patients with schizophrenia‐spectrum disorders.
Objective
This systematic review and meta‐analysis of randomized controlled trials (RCTs) examined the efficacy and safety of adjunctive N‐acetylcysteine (NAC), an antioxidant drug, in treating major ...depressive disorder (MDD), bipolar disorder, and schizophrenia.
Methods
The PubMed, Cochrane Library, PsycINFO, CNKI, CBM, and WanFang databases were independently searched and screened by two researchers. Standardized mean differences (SMDs), risk ratios, and their 95% confidence intervals (CIs) were computed.
Results
Six RCTs (n = 701) of NAC for schizophrenia (three RCTs, n = 307), bipolar disorder (two RCTs, n = 125), and MDD (one RCT, n = 269) were identified and analyzed as separate groups. Adjunctive NAC significantly improved total psychopathology (SMD = −0.74, 95% CI: −1.43, −0.06; I2 = 84%, P = 0.03) in schizophrenia, but it had no significant effect on depressive and manic symptoms as assessed by the Young Mania Rating Scale in bipolar disorder and only a small effect on major depressive symptoms. Adverse drug reactions to NAC and discontinuation rates between the NAC and control groups were similar across the three disorders.
Conclusions
Adjunctive NAC appears to be a safe treatment that has efficacy for schizophrenia, but not for bipolar disorder or MDD. Further higher quality RCTs are warranted to determine the role of adjunctive NAC in the treatment of major psychiatric disorders.
Aims
To examine the average point prevalence of major depressive disorder in people with Type 2 diabetes and its associated factors in a comprehensive meta‐analysis.
Methods
Two researchers ...independently conducted a systematic literature search of PubMed, EMBASE, PsycINFO and Cochrane databases. Studies reporting the prevalence of major depressive disorder in people with Type 2 diabetes were identified and analysed using a random‐effects model.
Results
A total of 26 studies meeting the inclusion criteria were included in the study. The point prevalence of major depressive disorder was 14.5% (95% CI 7.9–25.3; I²=99.65). People with Type 2 diabetes were more likely to have major depressive disorder compared with the general population (odds ratio 1.73, 95% CI 1.38–2.16). Subgroup and meta‐regression analyses showed that study site, study type, diagnostic criteria and age significantly moderated the prevalence of major depressive disorder.
Conclusions
In this meta‐analysis, the average point prevalence of major depressive disorder in people with Type 2 diabetes was high. Routine screening and more effective interventions should be implemented for this population.
What's new?
This was the first meta‐analysis to examine the prevalence of major depressive disorder in people with Type 2 diabetes in studies using standardized diagnostic instruments.
People with Type 2 diabetes were more likely to have major depressive disorder compared with the general population.
Routine screening and more effective treatments and interventions should be implemented for people with Type 2 diabetes and major depressive disorder.
While oral antidepressants reach efficacy after weeks, single-dose intravenous (i.v.) ketamine has rapid, yet time-limited antidepressant effects. We aimed to determine the efficacy and safety of ...single-dose i.v. ketamine augmentation of escitalopram in major depressive disorder (MDD).
Thirty outpatients with severe MDD (17-item Hamilton Rating Scale for Depression total score ⩾ 24) were randomized to 4 weeks double-blind treatment with escitalopram 10 mg/day+single-dose i.v. ketamine (0.5 mg/kg over 40 min) or escitalopram 10 mg/day + placebo (0.9% i.v. saline). Depressive symptoms were measured using the Montgomery-Asberg Depression Rating Scale (MADRS) and the Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR). Suicidal ideation was evaluated with the QIDS-SR item 12. Adverse psychopathological effects were measured with the Brief Psychiatric Rating Scale (BPRS)-positive symptoms, Young Mania Rating Scale (YMRS) and Clinician Administered Dissociative States Scale (CADSS). Patients were assessed at baseline, 1, 2, 4, 24 and 72 h and 7, 14, 21 and 28 days. Time to response (⩾ 50% MADRS score reduction) was the primary outcome.
By 4 weeks, more escitalopram + ketamine-treated than escitalopram + placebo-treated patients responded (92.3% v. 57.1%, p = 0.04) and remitted (76.9% v. 14.3%, p = 0.001), with significantly shorter time to response hazard ratio (HR) 0.04, 95% confidence interval (CI) 0.01-0.22, p < 0.001 and remission (HR 0.11, 95% CI 0.02-0.63, p = 0.01). Compared to escitalopram + placebo, escitalopram + ketamine was associated with significantly lower MADRS scores from 2 h to 2 weeks (peak = 3 days-2 weeks; effect size (ES) = 1.08-1.18), QIDS-SR scores from 2 h to 2 weeks (maximum ES = 1.27), and QIDS-SR suicidality from 2 to 72 h (maximum ES = 2.24). Only YMRS scores increased significantly with ketamine augmentation (1 and 2 h), without significant BPRS or CADSS elevation.
Single-dose i.v. ketamine augmentation of escitalopram was safe and effective in severe MDD, holding promise for speeding up early oral antidepressant efficacy.
Breast cancer incidence rates are increasing among Asian women, likely due to the changes in risk factors caused by globalization. Trends in breast cancer rates among Chinese women may differ from ...other Asian regions due to the implementation of a nationwide family planning program and resulting changes in women's reproductive practices. Appraisal of cancer trends can direct cancer control and public health planning, but relevant studies in China are scarce due to a lack of long-term data. We sought to evaluate secular time trends in breast cancer incidence and mortality using 40 years of cancer registry data for women in urban Shanghai.
Data on invasive breast cancer incidence and mortality were collected by the Shanghai Cancer Registry. Age-standardized rates (ASRs) for incidence and mortality were calculated using the Segi/Doll 1960 world standard population. Age, period, and birth cohort effects were evaluated using age–period–cohort (APC) Poisson regression models. Overall linear trends, interpreted as the estimated annual percentage change (EAPC), were derived from the net drift in age–drift models.
A total of 53 885 breast cancer cases and 17 235 breast cancer-specific deaths were documented among women in urban Shanghai between 1 January 1973 and 31 December 2012. Breast cancer incidence and mortality ASRs increased by 141.2% and 26.6%, respectively. Significant age, cohort, and period effects were identified in both incidence and mortality APC models; cohort effects were pronounced. Overall, a substantial increase in breast cancer incidence (EAPC = 2.96%/year) and a moderate increase in breast cancer mortality (EAPC = 0.87%/year) was observed. A notable downward trend in mortality was identified among younger women born after 1960.
Forty years of cancer registry data document a tremendous increase in incidence and a slight increase in mortality for breast cancer among women in Shanghai. Effective, appropriate, and affordable breast cancer prevention and control strategies are urgently needed in China.
The authors provide an epidemiologic analysis of the first 425 confirmed cases of infection with the novel coronavirus in Wuhan, China. This analysis provides estimates of the epidemic doubling time ...and the basic reproductive number and shows clear evidence of sustained human-to-human transmission.
MYC (also known as c-MYC) overexpression or hyperactivation is one of the most common drivers of human cancer. Despite intensive study, the MYC oncogene remains recalcitrant to therapeutic ...inhibition. MYC is a transcription factor, and many of its pro-tumorigenic functions have been attributed to its ability to regulate gene expression programs. Notably, oncogenic MYC activation has also been shown to increase total RNA and protein production in many tissue and disease contexts. While such increases in RNA and protein production may endow cancer cells with pro-tumour hallmarks, this increase in synthesis may also generate new or heightened burden on MYC-driven cancer cells to process these macromolecules properly. Here we discover that the spliceosome is a new target of oncogenic stress in MYC-driven cancers. We identify BUD31 as a MYC-synthetic lethal gene in human mammary epithelial cells, and demonstrate that BUD31 is a component of the core spliceosome required for its assembly and catalytic activity. Core spliceosomal factors (such as SF3B1 and U2AF1) associated with BUD31 are also required to tolerate oncogenic MYC. Notably, MYC hyperactivation induces an increase in total precursor messenger RNA synthesis, suggesting an increased burden on the core spliceosome to process pre-mRNA. In contrast to normal cells, partial inhibition of the spliceosome in MYC-hyperactivated cells leads to global intron retention, widespread defects in pre-mRNA maturation, and deregulation of many essential cell processes. Notably, genetic or pharmacological inhibition of the spliceosome in vivo impairs survival, tumorigenicity and metastatic proclivity of MYC-dependent breast cancers. Collectively, these data suggest that oncogenic MYC confers a collateral stress on splicing, and that components of the spliceosome may be therapeutic entry points for aggressive MYC-driven cancers.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Schizophrenia is a severe psychiatric disorder with high premature mortality rates. This is a meta-analysis and systematic review of the prevalence of suicidal ideation (SI) and suicide plan (SP) ...among people with schizophrenia. PubMed, Web of Science, Embase, and PsycINFO were systematically searched from their respective inception to October 10, 2020. Data on prevalence of SI and/or SP were synthesized using the random effects model. Twenty-six studies covering 5079 people with schizophrenia were included for meta-analysis. The lifetime and point prevalence of SI were 34.5% (95% CI: 28.2-40.9%), and 29.9% (95% CI: 24.2-35.6%), respectively. The lifetime prevalence of SP was 44.3% and the point prevalence of SP ranged between 6.4 and 13%. Subgroup and meta-regression analyses revealed that source of patients, survey countries, and sample size were significantly associated with the point prevalence of SI, while male proportion and quality assessment scores were significantly associated with the lifetime and point prevalence of SI. Survey time and mean age were significantly associated with lifetime prevalence of SI. Both SI and SP are common in people living with schizophrenia, especially in males and inpatients. Routine screening and effective interventions for SI and SP should be implemented in this population.
Free radicals may be involved in the pathogenesis of tardive dyskinesia (TD). We conducted this meta-analysis to systematically examine the efficacy of extract of Ginkgo biloba (EGb), a potent ...antioxidant possessing free radical-scavenging properties, as a treatment for TD in schizophrenia using randomized controlled trial (RCT) data.
Drawn from English and Chinese databases, 3 RCTs of EGb augmentation of antipsychotics (APs) vs. AP plus placebo or AP monotherapy were identified. 2 evaluators extracted data. The primary outcome measure was the severity of TD symptoms assessed by the Abnormal Involuntary Movement Scale (AIMS). Weighted mean difference (WMD) and risk ratio (RR) ±95% confidence intervals (CI) were calculated. Statistical analyses were performed using Review Manager (version 5.1.7.0) and STATA (version 12.0).
The 3 RCTs (n=299) from China, of 12 weeks duration, involved schizophrenia patients with TD of 55.9±13.4 years old. EGb (240 mg/day) outperformed the control group in reducing the severity of TD and clinical symptoms as measured by the AIMS (trials=3, n=299, WMD: -2.30 (95%CI: - 3.04, -1.55), P<0.00001) and the adverse drug reactions as assessed by the Treatment Emergent Symptom Scale (TESS) (trials=2, n=142, WMD: -2.38 (95%CI: -4.01, -0.74), P=0.004). Both the Positive and Negative Syndrome Scale (PANSS) total score (trials=2, n=239, P=0.87) and all-cause discontinuation (trials=3, n=299, P=0.21) were similar between the EGb and control group.
This meta-analysis suggests that adjunctive EGb appeared to be an effective and safe option for improving TD in the treatment of schizophrenia patients. However, better RCTs are needed to demonstrate its efficacy and safety especially on cognitive function in TD.
CRD42015024930.
PDF
