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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: SMA is a neurodegenerative disease caused by biallelic deletion/mutation of SMN1. Copies of a similar gene (SMN2) modify disease severity. In a phase 1 study, SMN GRT onasemnogene abeparvovec (AVXS-101) improved outcomes of symptomatic SMA patients with two SMN2 copies (2xSMN2) dosed ≤6 months. Because motor neuron loss can be insidious and disease progression is rapid, early intervention is critical. This study evaluates AVXS-101 in presymptomatic SMA newborns. Methods: SPR1NT is a multicenter, open-label, phase 3 study enrolling ≥27 SMA patients with 2–3xSMN2. Asymptomatic infants ≤6 weeks receive a one-time intravenous AVXS-101 infusion (1.1x1014 vg/kg). Safety and efficacy are assessed through study end (18 [2xSMN2] or 24 months [3xSMN2]). Primary outcomes: independent sitting for ≥30 seconds (18 months [2xSMN2]) or assisted standing (24 months [3xSMN2]). Results: From April–September 2018, 7 infants received AVXS-101 (4 female; 6 with 2xSMN2) at ages 8–37 days. Mean baseline CHOP-INTEND score was 41.7 (n=6), which increased by 6.8, 11.0, 18.0, and 22.5 points at day 14 (n=4), month 1 (n=3), 2 (n=3), and 3 (n=2). Updated data available at the time of the congress will be presented. Conclusions: Preliminary data from SPR1NT show rapid motor function improvements in presymptomatic SMA patients.
Background: Spinal muscular atrophy (SMA) is a children’s neuromuscular disorder. Although motor neuron loss is a major feature of the disease, we have identified fatty acid abnormalities in SMA patients and in preclinical animal models, suggesting metabolic perturbation is also an important component of SMA. Methods: Biochemical, histological, proteomic, and high resolution respirometry were used. Results: SMA patients are more susceptible to dyslipidemia than the average population as determined by a standard lipid profile in a cohort of 72 pediatric patients. As well, we observed a non-alcoholic liver disease phenotype in apreclinical mouse model. Denervation alone was not sufficient to induce liver steatosis, as a mouse model of ALS, did not develop fatty liver. Hyperglucagonemia in Smn2B/-mice could explain the hepatic steatosis by increasing plasma substrate availability via glycogen depletion and peripheral lipolysis. Proteomic analysis identified mitochondrion and lipid metabolism as major clusters. Alterations in mitochondrial function were revealed by high-resolution respirometry. Finally, low-fat diets led to increased survival in Smn2B/-mice. Conclusions: These results provide strong evidence for lipid metabolism defects in SMA. Further investigation will be required to establish the primary mechanism of these alterations and understand how they lead to additional co-morbidities in SMA patients.
Commentary on the introduction of the Australian Curriculum (AC) has reflected a tension for educators of students with disabilities (SWD) between in-principle support for a curriculum that is inclusive of all students and the challenge of translating a general framework into relevant, individualised learning experiences appropriate for all SWD. In this paper, we report on findings from the second part of a national online survey in which we explored the perceptions and practices of 151 educators of SWD in specialist settings (special schools, disability units co-located at mainstream schools, special classes within mainstream schools) in relation to the AC. Specifically, these findings relate to the professional learning (PL) experiences and perceived needs of educators of SWD related to the AC and their advice to policymakers about the AC for SWD. Consistent with previous research, participants expressed a preference for PL experiences delivered on site, facilitated by content experts over extended periods, with opportunities for demonstration and targeted feedback, and in the context of collegial learning communities. In addition, participants raised concerns about the extent to which the AC is fully inclusive of all SWD. Implications for policy, practice, and future research are discussed.
Despite aspirations to be a world-class national curriculum, the Australian Curriculum (AC) has been criticised as ‘manifestly deficient’ (Australian Government Department of Education and Training, 2014 p. 5) as an inclusive curriculum, failing to meet the needs of all students with disabilities (SWD) and their teachers. There is a need for research into the daily attempts of educators to navigate the tension between a ‘top-down’ system-wide curriculum and a ‘bottom-up’ regard for individual student needs, with a view to informing both policy and practice. This article is the first of two research papers in which we report the findings from a national online Research in Special Education (RISE) Australian Curriculum Survey of special educators in special schools, classes, and units regarding their experience using the AC to plan for and teach SWD. Survey results indicated (a) inconsistent use of the AC as the primary basis for developing learning objectives and designing learning experiences, (b) infrequent use of the achievement standards to support assessment and reporting, and (c) considerable supplementation of the AC from other resources when educating SWD. Overall, participants expressed a lack of confidence in translating the AC framework into a meaningful curriculum for SWD. Implications for policy, practice, and future research are discussed.
Background: Spinal Muscular Atrophy (SMA) is an autosomal recessive neurodegenerative disease. In June 2017, Health Canada approved Nusinersen, currently the only available drug for SMA. Since 2016, patients in Ontario have been treated clinically with Nusinersen through different access programs. Methods: Retrospective case series of patients with SMA treated clinically with Nusinersen in Ontario, describing clinical characteristics and logistics of intrathecal Nusinersen administration. Results: Twenty patients have been treated across four centres. To date, we have reviewed 8 cases at one centre (seven SMA Type I, one SMA Type II). Age at first dose ranged from 3-156 months and disease duration 9-166 months. Patients had received 4-7 doses at last evaluation. Three patients with scoliosis (2 with spinal rods) required fluoroscopy-guided radiologist administration, and 4 required general anesthesia. No complications/adverse events were reported. At last follow up, 5/8 families reported improved daily activities. Of 5 patients with baseline and follow up motor function testing, 3 demonstrated improved scores. One patient died due to respiratory decline at age 9 months, despite improved motor outcome scores. Conclusions: We describe the first Canadian post-marketing experience with Nusinersen. Timely dissemination of this information is needed to guide clinicians, hospital administrators, and policy-makers.
Background:ATP8A2 mutations have only recently been associated with human disease. We present the clinical features from the largest cohort of patients with this disorder reported to date. Methods: An observational study of 9 unreported and 2 previously reported patients with biallelic ATP8A2 mutations was carried out at multiple centres. Results: The mean age of the cohort was 9.4 years old (range: 2.5-28 yrs). All patients demonstrated developmental delay, severe hypotonia and movement disorders: chorea/choreoathetosis (100%), dystonia (27%) or facial dyskinesia (18%). Hypotonia was apparent at birth (70%) or before 6 months old (100%). Optic atrophy was observed in 75% of patients who had a funduscopic examination. MRI of the brain was normal for most patients with a small proportion showing mild cortical atrophy (30%), delayed myelination (20%) and/or hypoplastic optic nerves (20%). Epilepsy was seen in two older patients. Conclusions:ATP8A2 gene mutations have emerged as a cause of a novel phenotype characterized by developmental delay, severe hypotonia and hyperkinetic movement disorders. Optic atrophy is common and may only become apparent in the first few years of life, necessitating repeat ophthalmologic evaluation. Early recognition of the cardinal features of this condition will facilitate diagnosis of this disorder.
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.
Water stored in and released from supraglacial lakes is an important factor when considering the seasonal and long-term evolution of the Greenland ice sheet. Here we use a radiative transfer model to estimate changes in the depth and volume of a supraglacial lake on the surface of Jakobshavn Isbræ, West Greenland, between 2002 and 2005. When compared to estimates of the lake depth determined from airborne lidar observations, we estimate that the root-mean-square departure of the modelled lake depths was 0.3 m during cloud-free conditions. The maximum lake area, depth and volume were 3.4 km2, 9.6 ±1.0 m and (18.6±3.7)×106 m3, respectively. When sequenced according to the number of positive degree-days (PDDs) accumulated prior to each image, we observe that the lake volume evolves in three distinct phases. At the start of the melting season, the rate of filling is slow; after approximately 80 PDDs the rate of filling increases by a factor ∽3, and after approximately 125 PDDs the lake drains rapidly. We estimate that the lake drains at a minimum rate of (2.66±0.53)×106 m3 d–1 over a 6 day period.
We are making accurate observations of the change in Doppler shift of stellar absorption lines. The purpose is to detect the oscillatory reflex motion due to planets orbiting stars. The scrambling of incident light by an optical fiber and the stability of wavelength calibration by a Fabry-Perot etalon provide immunity to systematic errors. Selecting several echelle diffraction orders in the vicinity of 4250–4600 A, which are imaged on a CCD, about 350 points on the profile of the stellar spectrum are sampled by successive orders of interferometric transmission through the etalon. At 4300 A each interference order is 47 milliangstroms wide and the sample points are 0.64 A apart, causing distinct, widely-spaced monochromatic images of the entrance aperture to be formed in the focal plane of the camera. Changes in Doppler shift modify the relative intensities of these images, according to the slope of the spectral profile at each point sampled. To simplify operation and enhance sensitivity, the instrument is being operated as a null-measurement accelerometer, responding only to changes in radial velocity. With an argon emission line lamp the interferometer is calibrated to two parts in 100 million; this corresponds to ± 6 meters/sec in Doppler shift. These calibrations show instrumental variations of ± 27 meters/sec on a time scale of months; observations of stars are corrected for such changes. The internal repeatability of observations of the differential Doppler shift of Arcturus (K1 IIIb; B=1.19) is ± 6 meters/sec for each exposure of 600 square meter-seconds. These exposures are obtained in 15–20 minutes with a 0.9-meter telescope. The external repeatability (day-to-day differential accuracy) of nightly averages of stellar observations is ± 20 meters/second.
Family caregivers are an integral and increasingly overburdened part of the health care system. There is a gap between what research evidence shows is beneficial to caregivers and what is actually provided. Using an integrated knowledge translation approach, a stakeholder meeting was held among researchers, family caregivers, caregiver associations, clinicians, health care administrators, and policy makers. The objectives of the meeting were to review current research evidence and conduct multi-stakeholder dialogue on the potential gaps, facilitators, and barriers to the provision of caregiver supports. A two-day meeting was attended by 123 individuals. Three target populations of family caregivers were identified for discussion: caregivers of seniors with dementia, caregivers in end-of-life care, and caregivers of frail seniors with complex health needs. The results of this meeting can and are being used to inform the development of implementation research endeavours and policies targeted at providing evidence-informed caregiver supports.
Individuals who seek asylum are frequently fleeing violent persecution and may experience head injury (HI). However, little is known about the prevalence of HI in asylum seekers and refugees (ASR) despite the potential for HI to significantly affect cognitive and emotional functioning and to compromise asylum outcomes. This preliminary study investigates the prevalence of HI in ASR referred to a complex psychological trauma service.
Participants were 115 adult ASR referred to a community psychological trauma service with moderate to severe mental health problems associated with psychological trauma. They were screened for a history of HI using a questionnaire developed for the study. Interpreters were used when required.
The overall prevalence of HI was 51%. At least 38% of those with HI had a moderate–severe HI that could cause persisting disability. In 53% of those with HI, the cause was torture, human trafficking or domestic violence. Repeat HI can have cumulative effects on function; it was common, and was reported in 68% of those with HI. An injury to the head was not known to mental health clinicians prior to screening in 64% of cases.
The emotional and cognitive consequences of HI in ASR may increase the vulnerability of this disadvantaged group, and can be associated with neurobehavioural problems affecting daily life and may compromise asylum outcomes. Routine screening for HI in ASR is needed, as are links to neuropsychology and brain injury services for advice, assessment and intervention.
Background: Planning for neurology training necessitated a reflection on the experience of graduates. We explored practice characteristics, and training experience of recent graduates. Methods: Graduates from 2010-2014 completed a survey. Results: Response rate was 37% of 211. 56% were female. 91% were adult neurologists. 65% practiced in an outpatient setting. 63% worked in academics. 85% completed subspecialty training (median 1 year). 36% work 3 days a week or less. 82% took general call (median 1 night weekly). Role preparation was considered very good or excellent for most; however poor or fair ratings were 17% in advocacy and 8% in leadership. Training feedback was at least “good” for 87%. Burnout a few times a week or more was noted by 5% (6% during residency, particularly PGY1 and 5). 64% felt overly burdened by paperwork. Although most felt training was adequate, it was poor or fair at preparing for practice management (85%) and personal balance (55%). Most conditions were under-observed in training environment. Many noted a need for more independent practice development and community neurology. Conclusions: Although our training was found to be very good, some identified needs included advocacy training, and more training in general neurology in the longitudinal outpatient/community settings.
Small < 10 m s−1 variations of radial velocity (RV) with multi-year periods in solar-type stars may be indistinguishable from the effects induced on lines by stellar activity cycles (Dravins 1985; Saar & Donahue 1997). Dravins (1992) recommended a resolving power R > 3 × 105 to measure accurately the subtle changes in the shapes of bisectors of photospheric absorption lines driven by changes of granular convection in slowly rotating dwarf stars. Butler et al. (1996) measure impressively small amplitudes of RVs by using echelle spectrographs that cover a broad spectrum. However, to cover a broad spectrum the resolving power is typically limited to < 7 × 104, and the necessary presence of the iodine absorption spectrum may make it difficult to measure convective line shifts contemporaneously with the RV time series. Furthermore, to reach an RV accuracy of ± 3 ms−1 the whole profile of each line is used, thus maximizing the possibility that changes in the shapes of the lines’ C-bisectors could induce an apparent variation of RV.
Dravins (1985) recommended the exclusive use of the steep flanks of photospheric absorption lines to minimize the effects of convection on apparent RV. McMillan et al. (1993, 1994) demonstrated that such RV measurements made with a Fabry-Perot etalon (FPE) interferometer in transmission can be stable in the presence of stellar line variations seen by other investigators whose measurements were not based exclusively on line flanks. Dravins also prescribed high resolving power, high signal-to-noise ratio, high instrumental contrast, and low instrumental wings to analyze the rest of the line profile for convectively-driven changes (Dravins 1978, 1987, 1992). A double- or multiple-pass FPE scanning whole line profiles can provide high R, high contrast, low wings, and a stable, symmetrical line spread function with small (portable) optics, although the low photon efficiency will restrict its use to a few carefully selected stars. The spectral classes of these stars should span the spectral classes of the stars being monitored by others for planets. We describe a possible implementation of this concept that has the potential for adequate photon flux: observing symbiotically through another instrument on a 6-m to 10-m class telescope.
Throughout the past decade, significant advances have been made in the size and scope of large-scale spectroscopic surveys, allowing for the opportunity to study in-depth the formation history of the Milky Way. Using the fourth data release of the RAdial Velocity Experiment (RAVE), we study the age-metallicity-velocity space of ~ 100,000 FGK stars in the extended solar neighborhood in order to explore evolutionary processes. Combining these three parameters, we better constrain our understanding of these interconnected, fundamental processes.
Transition metal nitrides containing metal ions in high oxidation states are a significant goal for the discovery of new families of semiconducting materials. Most metal nitride compounds prepared at high temperature and high pressure from the elements have metallic bonding. However amorphous or nanocrystalline compounds can be prepared via metal-organic chemistry routes giving rise to precursors with a high nitrogen:metal ratio. Using X-ray diffraction in parallel with high pressure laser heating in the diamond anvil cell this work highlights the possibility of retaining the composition and structure of a metastable nanocrystalline precursor under high pressure-temperature conditions. Specifically, a nanocrystalline Hf3N4 with a tetragonal defect-fluorite structure can be crystallized under high-P,T conditions. Increasing the pressure and temperature of crystallization leads to the formation of a fully recoverable orthorhombic (defect cottunite-structured) polymorph. This approach identifies a novel class of pathways to the synthesis of new crystalline nitrogen-rich transition metal nitrides.