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Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Background: Biallelic variants in POLR1C are associated with POLR3-related leukodystrophy (POLR3-HLD), or 4H leukodystrophy (Hypomyelination, Hypodontia, Hypogonadotropic Hypogonadism), and Treacher Collins syndrome (TCS). The clinical spectrum of POLR3-HLD caused by variants in this gene has not been described. Methods: A cross-sectional observational study involving 25 centers worldwide was conducted between 2016 and 2018. The clinical, radiologic and molecular features of 23 unreported and previously reported cases of POLR3-HLD caused by POLR1C variants were reviewed. Results: Most participants presented between birth and age 6 years with motor difficulties. Neurological deterioration was seen during childhood, suggesting a more severe phenotype than previously described. The dental, ocular and endocrine features often seen in POLR3-HLD were not invariably present. Five patients (22%) had a combination of hypomyelinating leukodystrophy and abnormal craniofacial development, including one individual with clear TCS features. Several cases did not exhibit all the typical radiologic characteristics of POLR3-HLD. A total of 29 different pathogenic variants in POLR1C were identified, including 13 new disease-causing variants. Conclusions: Based on the largest cohort of patients to date, these results suggest novel characteristics of POLR1C-related disorder, with a spectrum of clinical involvement characterized by hypomyelinating leukodystrophy with or without abnormal craniofacial development reminiscent of TCS.
Loneliness and social networks have been extensively studied in relation to cognitive impairments, but how they interact with each other in relation to cognition is still unclear. This study aimed at exploring the interaction of loneliness and various types of social networks in relation to cognition in older adults.
a cross-sectional study.
497 older adults with normal global cognition were interviewed.
Loneliness was assessed with Chinese 6-item De Jong Gierverg’s Loneliness Scale. Confiding network was defined as people who could share inner feelings with, whereas non-confiding network was computed by subtracting the confiding network from the total network size. Cognitive performance was expressed as a global composite z-score of Cantonese version of mini mental state examination (CMMSE), Categorical verbal fluency test (CVFT) and delayed recall. Linear regression was used to test the main effects of loneliness and the size of various networks, and their interaction on cognitive performance with the adjustment of sociodemographic, physical and psychological confounders.
Significant interaction was found between loneliness and non-confiding network on cognitive performance (B = .002, β = .092, t = 2.099, p = .036). Further analysis showed a significant interaction between loneliness and the number of family members in non-confiding network on cognition (B = .021, β = .119, t = 2.775, p = .006).
Results suggested that a non-confiding relationship with family members might put lonely older adults at risk of cognitive impairment. Our study might have implications on designing psychosocial intervention for those who are vulnerable to loneliness as an early prevention of neurocognitive impairments.
While studies suggest that nutritional supplementation may reduce aggressive behavior in children, few have examined their effects on specific forms of aggression. This study tests the primary hypothesis that omega-3 (ω-3), both alone and in conjunction with social skills training, will have particular post-treatment efficacy for reducing childhood reactive aggression relative to baseline.
In this randomized, double-blind, stratified, placebo-controlled, factorial trial, a clinical sample of 282 children with externalizing behavior aged 7–16 years was randomized into ω-3 only, social skills only, ω-3 + social skills, and placebo control groups. Treatment duration was 6 months. The primary outcome measure was reactive aggression collected at 0, 3, 6, 9, and 12 months, with antisocial behavior as a secondary outcome.
Children in the ω-3-only group showed a short-term reduction (at 3 and 6 months) in self-report reactive aggression, and also a short-term reduction in overall antisocial behavior. Sensitivity analyses and a robustness check replicated significant interaction effects. Effect sizes (d) were small, ranging from 0.17 to 0.31.
Findings provide some initial support for the efficacy of ω-3 in reducing reactive aggression over and above standard care (medication and parent training), but yield only preliminary and limited support for the efficacy of ω-3 in reducing overall externalizing behavior in children. Future studies could test further whether ω-3 shows promise in reducing more reactive, impulsive forms of aggression.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
To identify predominant dietary patterns in four African populations and examine their association with obesity.
We used data from the Africa/Harvard School of Public Health Partnership for Cohort Research and Training (PaCT) pilot study established to investigate the feasibility of a multi-country longitudinal study of non-communicable chronic disease in sub-Saharan Africa. We applied principal component analysis to dietary intake data collected from an FFQ developed for PaCT to ascertain dietary patterns in Tanzania, South Africa, and peri-urban and rural Uganda. The sample consisted of 444 women and 294 men.
We identified two dietary patterns: the Mixed Diet pattern characterized by high intakes of unprocessed foods such as vegetables and fresh fish, but also cold cuts and refined grains; and the Processed Diet pattern characterized by high intakes of salad dressing, cold cuts and sweets. Women in the highest tertile of the Processed Diet pattern score were 3·00 times more likely to be overweight (95 % CI 1·66, 5·45; prevalence=74 %) and 4·24 times more likely to be obese (95 % CI 2·23, 8·05; prevalence=44 %) than women in this pattern’s lowest tertile (both P<0·0001; prevalence=47 and 14 %, respectively). We found similarly strong associations in men. There was no association between the Mixed Diet pattern and overweight or obesity.
We identified two major dietary patterns in several African populations, a Mixed Diet pattern and a Processed Diet pattern. The Processed Diet pattern was associated with obesity.
The glycaemic and insulin indices assess postprandial glycaemic and insulin response to foods, respectively, which may not reflect the long-term effects of diet on insulin response. We developed and evaluated the validity of four empirical indices to assess the insulinaemic potential of usual diets and lifestyles, using dietary, lifestyle and biomarker data from the Nurses’ Health Study (NHS, n 5812 for hyperinsulinaemia, n 3929 for insulin resistance). The four indices were as follows: the empirical dietary index for hyperinsulinaemia (EDIH) and the empirical lifestyle index for hyperinsulinaemia (ELIH); the empirical dietary index for insulin resistance (EDIR) and the empirical lifestyle index for insulin resistance (ELIR). We entered thirty-nine FFQ-derived food groups in stepwise linear regression models, and defined indices as patterns most predictive of fasting plasma C-peptide, for the hyperinsulinaemia pathway (EDIH and ELIH), and of theTAG:HDL-cholesterol ratio, for the insulin-resistance pathway (EDIR and ELIR). We evaluated the validity of indices in two independent samples from NHS-II and Health Professionals Follow-up Study (HPFS) using multivariable-adjusted linear regression analyses to calculate relative concentrations of biomarkers. The EDIH is comprised of eighteen food groups; thirteen were positively associated with C-peptide and five were inversely associated. The EDIR is comprised of eighteen food groups; ten were positively associated with TAG:HDL-cholesterol and eight were inversely associated. Lifestyle indices had fewer dietary components, and included BMI and physical activity as components. In the validation samples, all indices significantly predicted biomarker concentrations – for example, the relative concentrations of the corresponding biomarkers comparing extreme index quintiles in the HPFS were EDIH, 1·29 (95 % CI 1·22, 1·37); ELIH, 1·78 (95 % CI 1·68, 1·88); EDIR, 1·44 (95 % CI 1·34, 1·55); and ELIR, 2·03 (95 % CI 1·89, 2·19); all Ptrend<0·0001. The robust associations of these novel hypothesis-driven indices with insulin response biomarker concentrations suggest their usefulness in assessing the ability of whole diets and lifestyles to stimulate and/or sustain insulin secretion.
Intra-individual variability (IIV) and the change of attentional functions have been reported to be susceptible to both healthy ageing and pathological ageing. The current study aimed to evaluate the IIV of attention and the age-related effect on alerting, orienting, and executive control in cognitively healthy older adults.
We evaluated 145 Chinese older adults (age range of 65–80 years, mean age of 72.41 years) with a comprehensive neuropsychological battery and the Attention network test (ANT). A two-step strategy of analytical methods was used: Firstly, the IIV of older adults was evaluated by the intraindividual coefficient of variation of reaction time (ICV-RT). The correlation between ICV-RT and age was used to evaluate the necessity of subgrouping. Further, the comparisons of ANT performance among three age groups were performed with processing speed adjusted.
Person's correlation revealed significant positive correlations between age and IIV (r = 0.185, p = 0.032), age and executive control (r = 0.253, p = 0.003). Furthermore, one-way ANOVA comparisons among three age groups revealed a significant age-related disturbance on executive control (F = 4.55, p = 0.01), in which oldest group (group with age >75 years) showed less efficient executive control than young-old (group with age 65–70 years) (Conventional score, p = 0.012; Ratio score, p = 0.020).
Advancing age has an effect on both IIV and executive attention in cognitively healthy older adults, suggesting that the disturbance of executive attention is a sensitive indicator to reflect healthy ageing. Its significance to predict further deterioration should be carefully evaluated with prospective studies.
Genetic testing in psychiatry promises to improve patient care through
advances in personalised medicine. However, there are few clinically
To determine whether patients with a well-established genetic subtype of
schizophrenia show a different response profile to the antipsychotic
clozapine than those with idiopathic schizophrenia.
We retrospectively studied the long-term safety and efficacy of clozapine
in 40 adults with schizophrenia, half with a 22q11.2 deletion (22q11.2DS
group) and half matched for age and clinical severity but molecularly
confirmed to have no pathogenic copy number variant (idiopathic
Both groups showed similar clinical improvement and significant
reductions in hospitalisations, achieved at a lower median dose for those
in the 22q11.2DS group. Most common side-effects were similarly prevalent
between the two groups, however, half of the 22q11.2DS group experienced
at least one rare serious adverse event compared with none of the
idiopathic group. Many were successfully retried on clozapine.
Individuals with 22q11.2DS-schizophrenia respond as well to clozapine
treatment as those with other forms of schizophrenia, but may represent a
disproportionate number of those with serious adverse events, primarily
seizures. Lower doses and prophylactic (for example anticonvulsant)
management strategies can help ameliorate side-effect risks. This first
systematic evaluation of antipsychotic response in a genetic subtype of
schizophrenia provides a proof-of-principle for personalised medicine and
supports the utility of clinical genetic testing in schizophrenia.
The aims of the study were to determine the prevalence of cardiometabolic risk factors and establish the proportion of people with psychosis meeting criteria for the metabolic syndrome (MetS). The study also aimed to identify the key lifestyle behaviours associated with increased risk of the MetS and to investigate whether the MetS is associated with illness severity and degree of functional impairment.
Baseline data were collected as part of a large randomized controlled trial (IMPaCT RCT). The study took place within community mental health teams in five Mental Health NHS Trusts in urban and rural locations across England. A total of 450 randomly selected out-patients, aged 18–65 years, with an established psychotic illness were recruited. We ascertained the prevalence rates of cardiometabolic risk factors, illness severity and functional impairment and calculated rates of the MetS, using International Diabetes Federation (IDF) and National Cholesterol Education Program Third Adult Treatment Panel criteria.
High rates of cardiometabolic risk factors were found. Nearly all women and most men had waist circumference exceeding the IDF threshold for central obesity. Half the sample was obese (body mass index ≥ 30 kg/m2) and a fifth met the criteria for type 2 diabetes mellitus. Females were more likely to be obese than males (61% v. 42%, p < 0.001). Of the 308 patients with complete laboratory measures, 57% (n = 175) met the IDF criteria for the MetS.
In the UK, the prevalence of cardiometabolic risk factors in individuals with psychotic illnesses is much higher than that observed in national general population studies as well as in most international studies of patients with psychosis.
Plasmas are ubiquitous in nature, surround our local geospace environment, and permeate the universe. Plasma phenomena in space give rise to energetic particles, the aurora, solar flares and coronal mass ejections, as well as many energetic phenomena in interstellar space. Although plasmas can be studied in laboratory settings, it is often difficult, if not impossible, to replicate the conditions (density, temperature, magnetic and electric fields, etc.) of space. Single-point space missions too numerous to list have described many properties of near-Earth and heliospheric plasmas as measured both in situ and remotely (see http://www.nasa.gov/missions/#.U1mcVmeweRY for a list of NASA-related missions). However, a full description of our plasma environment requires three-dimensional spatial measurements. Cluster is the first, and until data begin flowing from the Magnetospheric Multiscale Mission (MMS), the only mission designed to describe the three-dimensional spatial structure of plasma phenomena in geospace. In this paper, we concentrate on some of the many plasma phenomena that have been studied using data from Cluster. To date, there have been more than 2000 refereed papers published using Cluster data but in this paper we will, of necessity, refer to only a small fraction of the published work. We have focused on a few basic plasma phenomena, but, for example, have not dealt with most of the vast body of work describing dynamical phenomena in Earth's magnetosphere, including the dynamics of current sheets in Earth's magnetotail and the morphology of the dayside high latitude cusp. Several review articles and special publications are available that describe aspects of that research in detail and interested readers are referred to them (see for example, Escoubet et al. 2005Multiscale Coupling of Sun-Earth Processes, p. 459, Keith et al. 2005Sur. Geophys.26, 307–339, Paschmann et al. 2005Outer Magnetospheric Boundaries: Cluster Results, Space Sciences Series of ISSI. Berlin: Springer, Goldstein et al. 2006Adv. Space Res.38, 21–36, Taylor et al. 2010The Cluster Mission: Space Plasma in Three Dimensions, Springer, pp. 309–330 and Escoubet et al. 2013Ann. Geophys.31, 1045–1059).
Abnormalities in the anterior inter-hemispheric connectivity have previously been implicated in major depressive disorder. Disruptions in fractional anisotropy in the callosum and fornix have been reported in schizophrenia and major depressive disorder. Oligodendrocyte density and overall size of the callosum and fornix show no alteration in either illness, suggesting that gross morphology is unchanged but more subtle organizational disruption may exist within these brain regions in mood and affective disorders.
Using high-resolution oil-immersion microscopy we examined the cross-sectional area of the nerve fibre and the axonal myelin sheath, and using standard high-resolution light microscopy we measured the density of myelinated axons. These measurements were made in the genu of the corpus callosum and the medial body of the fornix at its most dorsal point. Measures were taken in the sagittal plane in the callosal genu and in the coronal plane at the most dorsal part of the fornix body.
Cases of major depressive disorder had significantly greater mean myelin cross-sectional area (p = 0.017) and myelin thickness (p = 0.004) per axon in the genu than in control or schizophrenia groups. There was no significant change in the density of myelinated axons, and no changes observed in the fornix.
The results suggest a clear increase of myelin in the axons of the callosal genu in MDD, although this type of neuropathological study is unable to clarify whether this is caused by changes during life or has a developmental origin.
With the proportion of older adults in Hong Kong projected to double in size in the next 30 years, it is important to develop measures for detecting individuals in the earliest stage of Alzheimer's disease (AD, 0.5 in Clinical Dementia Rating, CDR). We tested the utility of a non-verbal prospective memory task (PM, ability to remember what one has to do when a specific event occurs in the future) as an early marker for AD in Hong Kong Chinese.
A large community dwelling sample of older adults who are healthy controls (CDR 0, N = 125), in the earliest stage of AD (CDR 0.5, N = 125), or with mild AD (CDR 1, N = 30) participated in this study. Their reaction time/accuracy data were analyzed by mixed-factor analyses of variance to compare the performance of the three CDR groups. Logistic regression analyses were performed to test the discriminative power of these measures for CDR 0 versus 0.5 participants.
Prospective memory performance declined as a function of AD severity: CDR 0 > CDR 0.5 > CDR 1, suggesting the effects of early-stage AD and AD progression on PM. After partialling out the variance explained by psychometric measures (e.g., ADAS-Cog), reaction time/accuracy measures that reflected the PM still significantly discriminated between CDR 0 versus 0.5 participants in most of the cases.
The effectiveness of PM measures in discriminating individuals in the earliest stage of AD from healthy older adults suggests that these measures should be further developed as tools for early-stage AD discrimination.
We aimed to investigate the diagnostic accuracy of contact endoscopy in evaluating oral and oropharyngeal mucosal lesions.
Between January 2010 and December 2011, 34 patients with lesions of the oral and oropharyngeal mucosa were enrolled in the study. Comparison between initial contact endoscopy results and ‘gold standard’ tissue biopsy was undertaken.
Nine patients had histologically confirmed squamous cell carcinoma, 2 had carcinoma in situ, 3 had dysplastic lesions and 20 patients had various benign lesions. Contact endoscopy demonstrated sensitivity and specificity of 89 and 100 per cent respectively in the evaluation of malignant lesions. Benign lesions were correctly categorised in 50 per cent of cases (10/20). The video images from contact endoscopy could not be interpreted in six cases.
Contact endoscopy demonstrates high sensitivity and specificity in the imaging of malignant lesions with reduced reliability in the evaluation of benign lesions. Significant shortcomings also exist in the design of current technology that we believe represent a significant barrier to the reliable collection of useful video data.
Cognitive–behavioural therapy (CBT) is considered to be effective for the symptoms of schizophrenia. However, this view is based mainly on meta-analysis, whose findings can be influenced by failure to consider sources of bias.
To conduct a systematic review and meta-analysis of the effectiveness of CBT for schizophrenic symptoms that includes an examination of potential sources of bias.
Data were pooled from randomised trials providing end-of-study data on overall, positive and negative symptoms. The moderating effects of randomisation, masking of outcome assessments, incompleteness of outcome data and use of a control intervention were examined. Publication bias was also investigated.
Pooled effect sizes were −0.33 (95% CI −0.47 to −0.19) in 34 studies of overall symptoms, −0.25 (95% CI −0.37 to −0.13) in 33 studies of positive symptoms and −0.13 (95% CI −0.25 to −0.01) in 34 studies of negative symptoms. Masking significantly moderated effect size in the meta-analyses of overall symptoms (effect sizes −0.62 (95% CI −0.88 to −0.35) v. −0.15 (95% CI −0.27 to −0.03), P = 0.001) and positive symptoms (effect sizes −0.57 (95% CI −0.76 to −0.39) v. −0.08 (95% CI −0.18 to 0.03), P<0.001). Use of a control intervention did not moderate effect size in any of the analyses. There was no consistent evidence of publication bias across different analyses.
Cognitive–behavioural therapy has a therapeutic effect on schizophrenic symptoms in the ‘small’ range. This reduces further when sources of bias, particularly masking, are controlled for.
To compare the image quality provided by rigid laryngoscopes versus flexible distal-chip laryngoscopes when documenting the same laryngeal pathology.
This paper reports a prospective single-blind study. Ten early stage glottic cancer cases were selected. Photographs of the pathologies were taken using both rigid and flexible distal-chip laryngoscopes (a total of 20 photographs). Nineteen clinicians were asked to review the laryngoscopic photographs; the clinicians were provided with a worksheet, which included questions regarding the clinical description, photograph quality and overall satisfaction with the images obtained. Clinicians' responses to the worksheet questions were then analysed.
The overall accuracy rate for lesion sidedness, anatomical sub-site involvement, anterior commissure involvement and tumour staging were 94.7 per cent, 46.6 per cent, 53.7 per cent and 47.1 per cent respectively. There were no statistically significant differences in terms of the accuracy rates, photograph quality or overall satisfaction with the photographs obtained by either modality.
There were no statistically significant differences demonstrated in overall clinical accuracy or perceived image quality between the use of the rigid or flexible endoscopes when interpreting images of early glottic cancer.
Over the past decade, the PV industry has witnessed tremendous growth in manufacturing scale and technology advancement, with PV generated electricity cost ever approaching grid parity. Among them, Si based thin film technology has made substantial progress in demonstrating its inherent advantages in lower material cost, ease of manufacturing and higher energy yield, etc. More recently, reduced product prices and competing technologies from crystalline silicon and other thin film technologies have made amorphous and microcrystalline silicon based thin film technology very challenging, and requires further increase in module efficiency and decrease in manufacturing cost. As one of the few companies in the world with significant manufacturing capacity for tandem thin film Si PV products, Chint Solar (Astronergy) has been at the forefront of technology development for the mass production of large-scale (Gen. 5, 1.43m2) Si thin film solar modules in the last 5 years. We will review major technology advancements which have been mass production proven and led to the mass produced tandem silicon thin film module with 10.0% plus stabilized efficiency, along with the field performance of those modules.