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The aims of this study were to evaluate changes in inflammatory and oxidative stress levels following treatment with N-acetylcysteine (NAC) or mitochondrial-enhancing agents (CT), and to assess the how these changes may predict and/or moderate clinical outcomes primarily the Montgomery-Åsberg Depression Rating Scale (MADRS).
This study involved secondary analysis of a placebo-controlled randomised trial (n = 163). Serum samples were collected at baseline and week 16 of the clinical trial to determine changes in Interleukin-6 (IL-6) and total antioxidant capacity (TAC) following adjunctive CT and/or NAC treatment, and to explore the predictability of the outcome or moderator effects of these markers.
In the NAC-treated group, no difference was observed in serum IL-6 and TAC levels after 16 weeks of treatment with NAC or CT. However, results from a moderator analysis showed that in the CT group, lower IL-6 levels at baseline was a significant moderator of MADRS χ2 (df) = 4.90, p = 0.027) and Clinical Global Impression-Improvement (CGI-I, χ2 (df) = 6.28 p = 0.012). In addition, IL-6 was a non-specific but significant predictor of functioning (based on the Social and Occupational Functioning Assessment Scale (SOFAS)), indicating that individuals with higher IL-6 levels at baseline had a greater improvement on SOFAS regardless of their treatment (p = 0.023).
Participants with lower IL-6 levels at baseline had a better response to the adjunctive treatment with the mitochondrial-enhancing agents in terms of improvements in MADRS and CGI-I outcomes.
Imprinting, characterized by unequal expression of the offspring's genes in a parent-of-origin dependent manner, has been functionally implicated in brain development and in psychiatric disorders. In this study, unambiguous distortion in paternal but not maternal transmission of the disease-associated single-nucleotide polymorphism (SNP) rs6556547 (T/G) clearly indicated the presence of parent-of-origin effect (POE) in the GABAA receptor β2 subunit gene (GABRB2). ‘Flipping’ of allelic mRNA expression in heterozygotes of SNP rs2229944 (C/T) and the observed two-tiered distribution of mRNA expression levels in heterozygotes of the disease-associated SNP rs1816071 (G/A) furnished important support for the occurrence of imprinting at GABRB2. Imprinting in effect introduced heterozygotes from different parents-of-origin endowed with dissimilar mRNA expression capabilities. The deficit of upper-tiered expressions accounted for the lowered mRNA expression levels in the schizophrenic heterozygotes. This pointed to the necessity of differentiating between two kinds of heterozygotes of different parental origins in disease association studies on GABRB2. Bisulfite sequencing revealed hypermethylation in the neighborhood of SNP rs1816071, and methylation differences between controls and schizophrenia patients. Notably, allele-specific methylation was observed at the disease-associated SNPs rs6556547 and rs1816071. These findings raised the possibility that CpG methylation status of these sites could have an impact on the expression of GABRB2 and the risk of schizophrenia. Furthermore, the occurrence of imprinting and allele-specific methylation in the schizophrenia candidate gene GABRB2 was compatible with the epigenetic hypothesis for schizophrenia pathophysiology, thereby calling for the need to explore the role of epigenetic factors in mediating susceptibility to schizophrenia.
Previously the GABA(A) receptor beta-2 subunit gene GABRB2 was found to be associated with schizophrenia (SCZ). for SNPs and haplotypes in GRBRB2, the associations with bipolar disorder (BPD), the functional consequences on GABRB2 expression and their relationship to demographic and clinical characteristics in BPD and SCZ remain to be elucidated.
Case-control analysis was performed for association study of GABRB2 with BPD, and its mRNA expression in postmortem BPD brains was examined using quantitative real-time PCR. Quantitative trait analysis was subsequently employed to assess the covariate effects of demographic and clinical characteristics on genotypic correlation of GABRB2 expression in SCZ and BPD.
Significant association of GABRB2 with BPD and reduction in GABRB2 mRNA expression in BPD brains were observed in the present study. Duration of illness (DOI) was found to be a significant covariate for the correlation of the disease-associated SNPs rs1816071, rs1816072 and rs187269 with GABRB2 expression in both SCZ and BPD. for individuals with homozygous major genotypes of these SNPs, while GABRB2 expression increased with age in the controls, it decreased with DOI and age in SCZ, and with DOI in BPD. with age of onset as covariate, these three SNPs were significantly correlated with antipsychotic dosage in SCZ.
These results have thus revealed correlations of GABRB2 SNPs and expression not only with the occurrence of SCZ and BPD, but also with the clinical characteristics of patients, therefore providing support for a shared etiological role played by the gene in both diseases.
Depression is a common among palliative care patients but the reported prevalence varies in studies. This is due to the overlapping of the conventional diagnostic criteria with the somatic symptoms in palliative patients. Alternative diagnostic criteria for major depressive disorder (MDD) were introduced. However, the standard method to diagnose depression in palliative setting has not been established.
The aim of this study is to determine the prevalence of MDD among palliative care patients by comparing between four sets of diagnostic criteria.
This is a cross sectional study conducted at two hospitals in Malaysia. Palliative patients were interviewed for presence of depression based on DSM – IV Criteria,Modified DSM – IV Criteria,Cavanaugh Criteria and Endicott's Criteria. They were also requested to complete the Hospital Anxiety and Depression Scale, Distress Thermometer and McGill Quality of Life Questionnaire.
The prevalence of MDD among palliative care patients was the highest for Modified DSM – IV Criteria (23.3%), followed by Endicott Criteria (13.8%), DSM – IV Criteria (9.2%) and Cavanaugh Criteria (5%). It was found that 9 items: DSM – IV Criteria Item 1, 2, 3, 4, 6, 7, and 8; and Endicott Criteria Item 6 and 7 have the ability to differentiate between depressed and non depressed patients. The prevalence based on these 9 items (which we named as ‘Revised’ Diagnostic Criteria) is 10.8%.
The prevalence of depression varies depending on the criteria used. A ‘revised diagnostic criteria’ was formed for more accurate determination of depression in palliative patients.
Gene × environment (G × E) interactions in eating pathology have been increasingly investigated, however studies have been limited by sample size due to the difficulty of obtaining genetic data.
To synthesize existing G × E research in the eating disorders (ED) field and provide a clear picture of the current state of knowledge with analyses of larger samples.
Complete data from seven studies investigating community (n = 1750, 64.5% female) and clinical (n = 426, 100% female) populations, identified via systematic review, were included. Data were combined to perform five analyses: 5-HTTLPR × Traumatic Life Events (0–17 events) to predict ED status (n = 909), 5-HTTLPR × Sexual and Physical Abuse (n = 1097) to predict bulimic symptoms, 5-HTLPR × Depression to predict bulimic symptoms (n = 1256), and 5-HTTLPR × Impulsivity to predict disordered eating (n = 1149).
The low function (s) allele of 5-HTTLPR interacted with number of traumatic life events (P < .01) and sexual and physical abuse (P < .05) to predict increased likelihood of an ED in females but not males (Fig. 1). No other G × E interactions were significant, possibly due to the medium to low compatibility between datasets (Fig. 1).
Early promising results suggest that increased knowledge of G × E interactions could be achieved if studies increased uniformity of measuring ED and environmental variables, allowing for continued collaboration to overcome the restrictions of obtaining genetic samples.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
The introduction of endoscopic ear surgery has implications for the training of otolaryngology residents.
To report on the status of endoscopic ear surgery and assess the effects of this new technology on otolaryngology training in Singapore, from the residents’ perspective.
An anonymous survey was conducted amongst all Singaporean otolaryngology residents. Residents’ exposure to, and perceptions of, endoscopic ear surgery were assessed.
Residents from institutions that practise endoscopic ear surgery were more positive regarding its efficacy in various otological surgical procedures. Of residents in programmes with exposure to endoscopic ear surgery, 82.4 per cent felt that its introduction had adversely affected their training, with 88.3 per cent of residents agreeing that faculty members’ learning of endoscopic ear surgery had decreased their hands-on surgical load. Both groups expressed desire for more experience with endoscopy.
The majority of residents view endoscopic ear surgery as an expanding field with a potentially negative impact on their training. Mitigating measures should be implemented to minimise its negative impact on residents’ training.
Structure and optical properties have been successfully determined for a series of niobium- and tantalum-containing layered alkaline-earth silicate compounds, Ba3(Nb6−xTax)Si4O26 (x = 0.6, 1.8, 3.0, 4.2, 5.4). The structure of this solid solution was found to be hexagonal P-62m (No. 189), with Z = 1. With x increases from 0.6 to 5.4, the lattice parameter a increases from 8.98804(8) to 9.00565(9) Å and c decreases from 7.83721(10) to 7.75212(12) Å. As a result, the volume decreases from 548.304(11) to 544.479(14) Å3. The (Nb/Ta)O6 distorted octahedra form continuous chains along the c-axis. These (Nb/Ta)O6 chains are in turn linked with the Si2O7 groups to form distorted pentagonal channels in which Ba ions were found. These Ba2+ ions have full occupancy and a 13-fold coordination environment with neighboring oxygen sites. Another salient feature of the structure is the linear Si–O–Si chains. When x in Ba3(Nb6−xTax)Si4O26 increases, the bond valence sum (BVS) values of the Ba sites increase slightly (2.09–2.20), indicating the size of the cage becoming progressively smaller (over-bonding). While SiO cages are also slightly smaller than ideal (BVS range from 4.16 to 4.19), the (Nb/Ta)O6 octahedral cages are slightly larger than ideal (BVS range from 4.87 to 4.90), giving rise to an under-bonding situation. The bandgaps of the solid solution members were measured between 3.39 and 3.59 eV, and the x = 3.0 member was modeled by density functional theory techniques to be 3.07 eV. The bandgaps of these materials indicate that they are potential candidates for ultraviolet photocatalyst.
In Canada, recreational use of cannabis was legalized in October 2018. This policy change along with recent publications evaluating the efficacy of cannabis for the medical treatment of epilepsy and media awareness about its use have increased the public interest about this agent. The Canadian League Against Epilepsy Medical Therapeutics Committee, along with a multidisciplinary group of experts and Canadian Epilepsy Alliance representatives, has developed a position statement about the use of medical cannabis for epilepsy. This article addresses the current Canadian legal framework, recent publications about its efficacy and safety profile, and our understanding of the clinical issues that should be considered when contemplating cannabis use for medical purposes.
Background: Challenges in predicting risk of recurrence for individual patients with meningioma limits appropriate selection of patients who may benefit from adjuvant radiation therapy to delay recurrence. Here, we aimed to develop and validate a combined clinicomolecular predictor of early recurrence for individual patients with meningiomas. Methods: A methylation-based predictor of 5-year recurrence-free-survival (RFS) was developed using DNA-methylation profiles from a training cohort of 228 patients. Model performance was compared to a standard-of-care histological-based model using three independent cohorts (N=54 ;N=140; N=64 patients). Subsequently, a nomogram that integrated the methylome-based predictor with prognostic clinical factors was developed and validated. Results: The methylome-based predictor of 5-year RFS performed favorably compared to a grade-based predictor when tested using the three validation cohorts (ΔAUC=0.10, 95%CI 0.03 – 0.018) and was independently associated with RFS on multivariable Cox regression analysis (HR=3.6, 95%CI 1.8–7.2, P<0.001). A nomogram combining the methylome-predictor with clinical factors demonstrated greater discrimination for recurrence than a nomogram using clinical factors alone (ΔAUC=0.25, 95%CI 0.22–0.27) and resulted in two risk groups with distinct recurrence patterns (HR=7.7, 95%CI 5.3–11.1, P<0.001) and clinical implications. Conclusions: Our validated models provide important novel prognostic information that could be used to individualize decisions regarding post-operative therapeutic interventions in meningioma.
Introduction: Opioid overdoses (OODs) have become a public health emergency, yet little is known about their long-term outcomes following an OD. We determined the one-year all-cause mortality and associated risk factors in a cohort of patients treated in an urban emergency department (ED) for an OOD. Methods: We reviewed records of all patients who visited St. Paul's Hospital ED from January 2013 to August 2017 and had a discharge diagnosis of OOD or had received naloxone in the ED as per pharmacy records. Patients with a suspected OOD were identified on structured chart review. A patient's first visit for an OOD during the study period was used as the index visit, with subsequent visits excluded. The primary outcome was mortality during the year after the index visit. Mortality was assessed by linking patient electronic medical records with Vital Statistics data. Deaths that occurred in the ED on the index visit were excluded. Patients admitted to hospital following ED treatment were included in this study. We described patient characteristics, calculated mortality rates, and used Cox regression to identify risk factors. Results: A total of 2239 patients visited the ED for an OOD during the study period, with a median patient age of 37 years (IQR 29, 49). Males comprised 73% of patients, while 28% had no fixed address, and 21% received take-home naloxone at the index visit. In total, 137 patients (6.1%) died within 1 year of the index visit. Eighty-one deaths (3.6%) occurred within 6 months, including 24 deaths (1.1%) that occurred within 1 month. The highest mortality rate occurred in 2017, with 8.0% of patients entering the cohort that year dying within 1 year. Gender did not significantly impact mortality risk. A Cox regression analysis controlled for gender, housing status, and whether take-home naloxone was provided at the index visit indicated that advancing age (adjusted hazards ratio [AHR] 1.03; 95%CI: 1.01-1.04 for each year increase in age) and the index visit calendar year (AHR 1.30; 95%CI: 1.10-1.54 for each yearly increase in the study period) were significant factors for mortality within 1 year. Conclusion: The mortality rate following an opioid OD treated in the ED is high, with over 6% of patients in our study dying within 1 year. The rising mortality risk with increasing calendar year may reflect the growing harms of fentanyl-related OODs. Patients visiting the ED for an OOD should be considered high risk and offered preventative treatment and referrals prior to discharge.
Global inequity in access to and availability of essential mental health services is well recognized. The mental health treatment gap is approximately 50% in all countries, with up to 90% of people in the lowest-income countries lacking access to required mental health services. Increased investment in global mental health (GMH) has increased innovation in mental health service delivery in LMICs. Situational analyses in areas where mental health services and systems are poorly developed and resourced are essential when planning for research and implementation, however, little guidance is available to inform methodological approaches to conducting these types of studies. This scoping review provides an analysis of methodological approaches to situational analysis in GMH, including an assessment of the extent to which situational analyses include equity in study designs. It is intended as a resource that identifies current gaps and areas for future development in GMH. Formative research, including situational analysis, is an essential first step in conducting robust implementation research, an essential area of study in GMH that will help to promote improved availability of, access to and reach of mental health services for people living with mental illness in low- and middle-income countries (LMICs). While strong leadership in this field exists, there remain significant opportunities for enhanced research representing different LMICs and regions.
Death ideation (thinking about/wishing for one's own death, thinking that one would be better off dead) is linked to an increased mortality risk. However, comparatively little is known about more general thoughts of death (GTOD) where no wish to die or life value is expressed. This study examined whether GTOD predicted mortality in a community-based cohort of older adults.
Data came from the Komo-Ise cohort study in Gunma prefecture, Japan. The analytic sample comprised 8208 individuals (average age 61.3 (range 47–77)) who were asked in wave 2 of the study in 2000 if they had ‘Thought about death more than usual, either your own, someone else's or death in general?’ in the past 2 weeks. Death data were obtained from the municipal resident registration file. Cox proportional hazards regression analysis was used to examine associations.
During the follow-up period (2000–2008), there were 672 deaths. In a model adjusted for baseline covariates, GTOD were significantly associated with all-cause mortality (hazards ratio 1.66, 95% confidence interval 1.20–2.29). Stratified analyses showed an association between GTOD and mortality in men, older subjects (⩾70 years), married individuals and those with higher social support.
GTOD are associated with an increased mortality risk among older citizens in Japan. Research is now needed to determine the factors underlying this association and assess the clinical relevance of screening for GTOD in older individuals.
Analysis of injuries during military operations has focused on those related to combat. Non-combat complaints have received less attention, despite the need for many troops to be evacuated for non-battle illnesses in Iraq. This study aims to further characterize the disease and non-battle injuries (DNBIs) seen at a tertiary combat hospital and to describe the types of procedures and medications used in the management of these cases.
In this observational study, patients were enrolled from a convenience sample with non-combat-related diseases and injuries who were evaluated in the emergency department (ED) of a US military tertiary hospital in Iraq from 2007-2008. The treating emergency physician (EP) used a data collection form to enroll patients that arrived to the ED whose injury or illness was unrelated to combat.
Data were gathered on 1,745 patients with a median age of 30 years; 84% of patients were male and 85% were US military personnel. The most common diagnoses evaluated in the ED were abdominal disorders, orthopedic injuries, and headache. Many cases involved intravenous access, laboratory testing, and radiographic testing. Procedures performed included electrocardiogram, lumbar puncture, and intubation.
Disease and non-battle traumatic injuries are common in a tertiary combat hospital. Emergency providers working in austere settings should have the diagnostic and procedural skills to evaluate and treat DNBIs.
BebartaVS, MoraAG, NgPC, MasonPE, MuckA, MaddryJK. Disease and Non-Battle Traumatic Injuries Evaluated by Emergency Physicians in a US Tertiary Combat Hospital. Prehosp Disaster Med. 2018;33(1):53–57.
The Binary Population and Spectral Synthesis suite of binary stellar evolution models and synthetic stellar populations provides a framework for the physically motivated analysis of both the integrated light from distant stellar populations and the detailed properties of those nearby. We present a new version 2.1 data release of these models, detailing the methodology by which Binary Population and Spectral Synthesis incorporates binary mass transfer and its effect on stellar evolution pathways, as well as the construction of simple stellar populations. We demonstrate key tests of the latest Binary Population and Spectral Synthesis model suite demonstrating its ability to reproduce the colours and derived properties of resolved stellar populations, including well-constrained eclipsing binaries. We consider observational constraints on the ratio of massive star types and the distribution of stellar remnant masses. We describe the identification of supernova progenitors in our models, and demonstrate a good agreement to the properties of observed progenitors. We also test our models against photometric and spectroscopic observations of unresolved stellar populations, both in the local and distant Universe, finding that binary models provide a self-consistent explanation for observed galaxy properties across a broad redshift range. Finally, we carefully describe the limitations of our models, and areas where we expect to see significant improvement in future versions.
Suicide-related behaviours are common in schizophrenia and are significantly associated with premature death. The objective of this meta-analysis study was to estimate the pooled prevalence of suicide-related behaviours in schizophrenia patients in China.
The relevant literature was searched systematically via the relevant electronic databases (PubMed, Embase, PsycINFO, Chinese National Knowledge Infrastructure, Wanfang Databases and Chinese Biological Medical Literature Database) from their inception until 14 September 2016. Only original studies that reported the prevalence of suicide-related behaviours including suicidal ideation (SI), suicide plan, suicide attempt (SA) and completed suicide were selected.
Nineteen articles met the inclusion criteria and were analysed. The pooled lifetime prevalence of SI and SA were 25.8% (95% CI 14.7–41.1%) and 14.6% (95% CI 9.1–22.8%), respectively. The 1-month prevalence of SI was 22.0% (95% CI 18.2–26.4%). Subgroup analyses of lifetime SI and SA showed that gender, sample size, survey year, study location and source of patients have no significant mediating effects on the results.
Suicide-related behaviours are common in Chinese schizophrenia patients. Due to the high mortality risk, regular screening and effective suicide prevention programmes are warranted.
To evaluate the clinicopathological and mycological manifestations of fungal rhinosinusitis occurring in the Tengku Ampuan Rahimah Hospital, in Klang, Malaysia, which has a tropical climate.
Records of patients treated from 2009 to 2016 were analysed retrospectively. Data from the records were indexed based on age, gender, clinical presentations, symptom duration, clinical signs and mycological growth.
Of 80 samples, 27 (33.75 per cent) had fungal growth. Sixteen patients were classified as having non-invasive fungal rhinosinusitis and 11 as having invasive fungal rhinosinusitis. The commonest clinical presentation was nasal polyposis in non-invasive fungal rhinosinusitis patients (p < 0.05) and ocular symptoms in invasive fungal rhinosinusitis patients (p < 0.05). The commonest organism was aspergillus sp. (p < 0.05) in non-invasive fungal rhinosinusitis and mucorales in invasive fungal rhinosinusitis.
There is an almost equal distribution of both invasive and non-invasive fungal rhinosinusitis, as seen in some Asian countries. Invasive fungal rhinosinusitis, while slightly uncommon when compared to non-invasive fungal rhinosinusitis, is potentially life threatening, and may require early and extensive surgical debridement. The clinical presentation of nasal polyposis was often associated with non-invasive fungal rhinosinusitis, whereas ocular symptoms were more likely to be associated with invasive fungal rhinosinusitis.
Dysfunction of N-methyl-D-aspartate receptor (NMDAR) is involved in the pathophysiology of schizophrenia. A meta-analysis of randomized controlled trials (RCTs) was conducted to examine the efficacy and safety of memantine, a non-competitive NMDAR antagonist, in the treatment of schizophrenia.
Standardized/weighted mean differences (SMDs/WMDs), risk ratio (RR), and their 95% confidence intervals (CIs) were calculated and analyzed.
Included in the meta-analysis were eight RCTs (n = 452) of 11.5 ± 2.6 weeks duration, with 229 patients on memantine (20 mg/day) and 223 patients on placebo. Adjunctive memantine outperformed placebo in the measures of Positive and Negative Syndrome Scale and Brief Psychiatric Rating Scale negative symptoms [SMD: −0.63 (95% CI −1.10 to −0.16), p = 0.009, I2 = 77%], but not in the total, positive and general symptoms [SMD: −0.46 to −0.08 (95% CI −0.93 to 0.22), p = 0.06–0.60, I2 = 0–74%] or the Clinical Global Impression Severity Scale [WMD: 0.04 (95% CI −0.24 to 0.32), p = 0.78]. The negative symptoms remained significant after excluding one outlying RCT [SMD: −0.41 (95% CI −0.72 to −0.11), p = 0.008, I2 = 47%]. Compared with the placebo group, adjunctive memantine was associated with significant improvement in neurocognitive function using the Mini-Mental State Examination (MMSE) [WMD: 3.09, (95% CI 1.77–4.42), p < 0.00001, I2 = 22%]. There was no significant difference in the discontinuation rate [RR: 1.34 (95% CI 0.76–2.37), p = 0.31, I2 = 0%] and adverse drug reactions between the two groups.
This meta-analysis showed that adjunctive memantine appears to be an efficacious and safe treatment for improving negative symptoms and neurocognitive performance in schizophrenia. Higher quality RCTs with larger samples are warranted to confirm these findings.
Microdeletion syndrome is an important topic in intellectual disability, associated with various psychiatric symptoms, such as autism, attention deficit, hyperactivity, obsession and compulsion, and psychosis. In this article, we provide a clinical update on the following syndromes and their associated psychiatric disorders: Prader–Willi syndrome, Angelman syndrome, Williams syndrome, Wolf–Hirschhorn syndrome, cri du chat syndrome, DiGeorge syndrome and Rubinstein–Taybi syndrome.
• Gain an up-to-date understanding of the microdeletion syndromes commonly seen in daily practice
• Appreciate the association between underlying chromosomal abnormalities and the resultant intellectual disabilities in microdeletion syndromes
• Gain up-to-date knowledge about the treatment options for the various microdeletion syndromes commonly seen in daily practice
Traumatic events are common globally; however, comprehensive population-based cross-national data on the epidemiology of posttraumatic stress disorder (PTSD), the paradigmatic trauma-related mental disorder, are lacking.
Data were analyzed from 26 population surveys in the World Health Organization World Mental Health Surveys. A total of 71 083 respondents ages 18+ participated. The Composite International Diagnostic Interview assessed exposure to traumatic events as well as 30-day, 12-month, and lifetime PTSD. Respondents were also assessed for treatment in the 12 months preceding the survey. Age of onset distributions were examined by country income level. Associations of PTSD were examined with country income, world region, and respondent demographics.
The cross-national lifetime prevalence of PTSD was 3.9% in the total sample and 5.6% among the trauma exposed. Half of respondents with PTSD reported persistent symptoms. Treatment seeking in high-income countries (53.5%) was roughly double that in low-lower middle income (22.8%) and upper-middle income (28.7%) countries. Social disadvantage, including younger age, female sex, being unmarried, being less educated, having lower household income, and being unemployed, was associated with increased risk of lifetime PTSD among the trauma exposed.
PTSD is prevalent cross-nationally, with half of all global cases being persistent. Only half of those with severe PTSD report receiving any treatment and only a minority receive specialty mental health care. Striking disparities in PTSD treatment exist by country income level. Increasing access to effective treatment, especially in low- and middle-income countries, remains critical for reducing the population burden of PTSD.